bluuebunny/crossref_metadata_2025 huggingface dataset:
Zusammenhang des Antrags- und Bewilligungsgeschehen in der psychosomatischen Rehabilitation mit der regionalen medizinischen und psychotherapeutischen Versorgung in Westfalen
Authors: Köckerling Elena , Breckenkamp Jürgen , Hesse Bettina
Published: May 2018

Ziel der Studie Regionale Unterschiede in der Versorgung von psychischen Erkrankungen sind bekannt und zeigen sich mitunter in unzureichenden Behandlungskapazitäten und langen Wartezeiten auf eine Psychotherapie. Es wird daher eine Verlagerung von der Kuration in die Rehabilitation vermutet. Ziel dieser Studie ist, den Zusammenhang des Antrags- und Bewilligungsgeschehens in der psychosomatischen Rehabilitation der Deutschen Rentenversicherung (DRV) Westfalen mit der regionalen ärztlichen und psychotherapeutischen Versorgung für das Jahr 2013 zu analysieren.

Methodik Regionale Daten zur ärztlichen und psychotherapeutischen Versorgung im Einzugsgebiet der DRV Westfalen wurden in öffentlichen Datenbanken des Bundes und der Länder ermittelt. Daten zum Antrags- und Bewilligungsgeschehen der psychosomatischen Rehabilitation sowie Daten zu demografischen und rentenversicherungsbezogenen Merkmalen der Versicherten wie z. B. Versicherungszeiten wurden von der DRV Westfalen für das Jahr 2013 bereitgestellt. Zur Analyse der Zusammenhänge wurden logistische 2-Ebenen Modelle gerechnet.

Ergebnisse Die regionalen Versorgungsdaten zeigen, dass eine niedrige medizinische Versorgung mit einer signifikant höheren Chance für hohe Reha-Antragszahlen verbunden ist. Die demografischen und rentenversicherungsbezogenen Merkmale der Versicherten weisen hohe Zusammenhänge sowohl mit der Beantragung wie auch der Bewilligung einer psychosomatischen Rehabilitation auf. So weisen Personen mit Hinweisen auf eine nichtkontinuierliche Erwerbstätigkeit innerhalb des Jahres 2013 höhere Chancen auf Beantragung und Bewilligung einer psychosomatischen Rehabilitation auf. Es konnten keine signifikanten Zusammenhänge zwischen regionalen Versorgungsmerkmalen und dem Bewilligungsgeschehen ermittelt werden.

Schlussfolgerung Die gefundenen Zusammenhänge zwischen den demografischen und rentenversicherungsbezogenen Merkmalen der Versicherten und der Beantragung und Bewilligung einer psychosomatischen Rehabilitation bestätigen, dass das Bewilligungsverfahren der DRV Westfalen primär an den persönlichen Voraussetzungen der Versicherten orientiert ist. Die erhöhten Antrags- und Bewilligungsquoten in Gebieten mit einer niedrigeren medizinischen Versorgung können als kompensatorische Versorgungsmaßnahme interpretiert werden und weisen auf einen Nachbesserungsbedarf in der regionalen Versorgung hin.
Enantioselective Bromocyclization of Allylic Amides Mediated by Phosphorus Catalysis
Authors: Hamashima Yoshitaka , Kawato Yuji
Published: May 2018

Halocyclization of alkenes is commonly employed to increase molecular complexity during organic synthesis because it enables double installation of heteroatoms on a carbon–carbon double bond. Moreover, stereodefined halogenated compounds are widely found among naturally occurring compounds and can serve as versatile chiral building blocks. Therefore, the development of asymmetric halocyclization reactions is of great interest and, in recent years, there has been remarkable progress in catalytic asymmetric halogenation reactions. This account summarizes recent progress made by our group on phosphorus-­catalyzed enantioselective bromocyclization of allylic amides. Building on a comprehensive study of the reaction mechanism, we discovered an intriguing catalytic reaction in which P+Br species serves as a fine-tuning element for substrate fixation. We also describe the application of this bromocyclization to asymmetric desymmetrization of 1,4-diene substrates and a concise synthesis of the HIV-protease inhibitor ­nelfinavir using the newly developed desymmetrization reaction as a key step.

1 Introduction

2 Enantioselective Bromocyclization of Allylic Amides with a BINAP Catalyst

2.1 Bromocyclization with a P/P Catalyst

2.2 Bromocyclization with a P/P=O Catalyst

3 Desymmetrization of Bisallylic Amides through Enantioselective Bromocyclization

3.1 Desymmetrization of Bisallylic Amides

3.2 Enantioselective Synthesis of Nelfinavir

4 Summary
Mano zamba radial con radio presente, reporte de un caso, propuesta de manejo quirúrgico y revisión de la literatura
Authors: Gómez Ramírez Jairo , Lores García Francisco , Martínez Villegas José
Published: May 2018

Introducción Se describe una forma inusual de deformidad congénita de la mano, que consiste en una deformidad en mano zamba radial con radio presente pero luxado en extremos proximal y distal. Es una variedad infrecuente, por lo que proponemos una opción de corrección quirúrgica. Solo existe un caso descrito en la literatura con la característica de tener radio presente completo y no existen reportes de tratamiento, por tanto, ese sería el primer reporte de un tratamiento.

Materiales y Métodos Reporte de caso de un paciente de 4 años de edad con mano zamba radial con radio presente congénita, valorado en un hospital de nivel III en la ciudad de Bogotá, Colombia, el cual fue llevado a corrección quirúrgica en el año 2010. Se realizó una osteotomía de acortamiento del radio con cierre del espacio radiocubital distal, capsulotomía ulno carpiana con reinserción de la cápsula al radio distal y centralización del carpo sobre el remanente del radio.

Resultados Paciente con corrección de la deformidad radiológica y clínicamente con mejoría del agarre en seguimiento realizado en el primer mes de posoperatorio.

Conclusiones Se puede realizar una corrección quirúrgica de la deformidad en mano zamba radial con radio presente, utilizando la técnica quirúrgica descrita.
S3-Leitlinie: Lungenerkrankung bei Mukoviszidose – Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa
Authors: Schwarz C. , Schulte-Hubbert B. , Bend J. , Abele-Horn M. , Baumann I. , Bremer W. , Brunsmann F. , Dieninghoff D. , Eickmeier O. , Ellemunter H. , Fischer R. , Grosse-Onnebrink J. , Hammermann J. , Hebestreit H. , Hogardt M. , Hügel C. , Hug M. , Illing S. , Jung A. , Kahl B. , Koitschev A. , Mahlberg R. , Mainz J. , Mattner F. , Mehl A. , Möller A. , Muche-Borowski C. , Nüßlein T. , Puderbach M. , Renner S. , Rietschel E. , Ringshausen F. , Schmidt S. , Sedlacek L. , Sitter H. , Smaczny C. , Tümmler B. , Vonberg R. , Wielpütz M. , Wilkens H. , Wollschläger B. , Zerlik J. , Düesberg U. , van Koningsbruggen-Rietschel S.
Published: May 2018

Mukoviszidose (Cystic Fibrosis, CF) ist die häufigste, autosomal-rezessiv vererbte Multisystemerkrankung. In Deutschland sind ca. 8000 Menschen betroffen.

Die Erkrankung wird durch Mutationen im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR-) Gen verursacht; diese führen zu einer Fehlfunktion des Chloridkanals CFTR. Dadurch kommt es in den Atemwegen zu einer unzureichenden Hydrierung des epithelialen Flüssigkeitsfilms und somit zu einer chronischen Inflammation.

Rezidivierende Infektionen der Atemwege sowie pulmonale Exazerbationen der Lunge führen im Verlauf zu zunehmender Inflammation, pulmonaler Fibrose und fortschreitender Lungendestruktion bis hin zur respiratorischen Globalinsuffizienz, die für über 90 % der Mortalität verantwortlich ist.

Das Ziel der medikamentösen Therapie ist die pulmonale Inflammation und v. a. die Infektion der Atemwege zu reduzieren.

Der Kolonisation und chronischen Infektion mit Pseudomonas aeruginosa (Pa) kommt die größte Bedeutung zu. Diese führt zu weiterem Verlust an Lungenfunktion.

Für die medikamentöse Therapie der chronischen Pa-Infektion stehen viele unterschiedliche Therapieoptionen zur Verfügung.

Mit dieser S3-Leitlinie wird eine einheitliche Definition für die chronische Pa-Infektion implementiert sowie eine evidenzbasierte Diagnostik und Therapie dargelegt, um eine Orientierung bei der individuellen Therapieentscheidung zu geben.
Healthy publics: enabling cultures and environments for health
Authors: Hinchliffe Stephen , Jackson Mark A. , Wyatt Katrina , Barlow Anne E. , Barreto Manuela , Clare Linda , Depledge Michael H. , Durie Robin , Fleming Lora E. , Groom Nick , Morrissey Karyn , Salisbury Laura , Thomas Felicity
Published: May 2018

Despite extraordinary advances in biomedicine and associated gains in human health and well-being, a growing number of health and well-being related challenges have remained or emerged in recent years. These challenges are often ‘more than biomedical’ in complexion, being social, cultural and environmental in terms of their key drivers and determinants, and underline the necessity of a concerted policy focus on generating healthy societies. Despite the apparent agreement on this diagnosis, the means to produce change are seldom clear, even when the turn to health and well-being requires sizable shifts in our understandings of public health and research practices. This paper sets out a platform from which research approaches, methods and translational pathways for enabling health and well-being can be built. The term ‘healthy publics’ allows us to shift the focus of public health away from ‘the public’ or individuals as targets for intervention, and away from the view that culture acts as a barrier to efficient biomedical intervention, towards a greater recognition of the public struggles that are involved in raising health issues, questioning what counts as healthy and unhealthy and assembling the evidence and experience to change practices and outcomes. Creating the conditions for health and well-being, we argue, requires an engaged research process in which public experiments in building and repairing social and material relations are staged and sustained even if, and especially when, the fates of those publics remain fragile and buffeted by competing and often more powerful public formations.
Perspective: 2D for beyond CMOS
Authors: Robinson Joshua A.
Published: May 2018

Two-Dimensional (2D) materials have been a “beyond CMOS” focus for more than a decade now, and we are on the verge of a variety of breakthroughs in the science to enable their incorporation into next generation electronics. This perspective discusses some of the challenges that must be overcome, as well as various opportunities that await us in the world of 2D for beyond CMOS.
Review of medication errors that are new or likely to occur more frequently with electronic medication management systems
Authors: Van de Vreede Melita , McGrath Anne , de Clifford Jan
Published: May 2018

Objective
The aim of the present study was to identify and quantify medication errors reportedly related to electronic medication management systems (eMMS) and those considered likely to occur more frequently with eMMS. This included developing a new classification system relevant to eMMS errors.

Methods
Eight Victorian hospitals with eMMS participated in a retrospective audit of reported medication incidents from their incident reporting databases between May and July 2014. Site-appointed project officers submitted deidentified incidents they deemed new or likely to occur more frequently due to eMMS, together with the Incident Severity Rating (ISR). The authors reviewed and classified incidents.

Results
There were 5826 medication-related incidents reported. In total, 93 (47 prescribing errors, 46 administration errors) were identified as new or potentially related to eMMS. Only one ISR2 (moderate) and no ISR1 (severe or death) errors were reported, so harm to patients in this 3-month period was minimal. The most commonly reported error types were ‘human factors’ and ‘unfamiliarity or training’ (70%) and ‘cross-encounter or hybrid system errors’ (22%).

Conclusions
Although the results suggest that the errors reported were of low severity, organisations must remain vigilant to the risk of new errors and avoid the assumption that eMMS is the panacea to all medication error issues.

What is known about the topic?
eMMS have been shown to reduce some types of medication errors, but it has been reported that some new medication errors have been identified and some are likely to occur more frequently with eMMS. There are few published Australian studies that have reported on medication error types that are likely to occur more frequently with eMMS in more than one organisation and that include administration and prescribing errors.

What does this paper add?
This paper includes a new simple classification system for eMMS that is useful and outlines the most commonly reported incident types and can inform organisations and vendors on possible eMMS improvements. The paper suggests a new classification system for eMMS medication errors.

What are the implications for practitioners?
The results of the present study will highlight to organisations the need for ongoing review of system design, refinement of workflow issues, staff education and training and reporting and monitoring of errors.
Dormancy-breaking and germination requirements of seeds of the Hawaiian endemic Dianella sandwicensis (Xanthorrhoeaceae)
Authors: Wolkis Dustin , Baskin Carol C. , Baskin Jerry M.
Published: May 2018

One problem with including some wild plant species in restoration projects is that seeds are dormant and fail to germinate. Thus, information on the dormancy-breaking and germination requirements facilitates propagation of species, such as the Hawaiian endemic Dianella sandwicensis Hook. & Arn., for conservation. In seeds of this species the embryo is shorter than the endosperm, and seeds sown in early summer in Hawai‘i did not germinate until autumn. Thus, we hypothesised that seeds have morphophysiological dormancy (MPD) and that germination is promoted by low (autumn) temperatures. Studies on embryo growth and the temperature requirements for dormancy-break and germination were conducted on seeds of D. sandwicensis collected on three Hawaiian Islands. Prior to germination the embryo length : seed length ratio increased 16.3 to 17.6%; thus, seeds have MPD. Since both embryo growth and germination occurred at 25/15°C, seeds have a simple level of MPD. Seeds germinated to 90–100% at both 20/10 and 25/15°C, but germination was faster at 20/10°C. However, seeds incubated for 12 weeks at 25/15°C then moved to 20/10°C reached 100% germination as rapidly as seeds kept at 20/10°C. Our results show that exposure of seeds to relatively cool autumn (20/10°C) conditions facilitates propagation of this species from seeds.
Synthesis, Photophysical, and Antioxidant Properties of Rhodamine B Decorated Novel Dendrimers
Authors: Savithri Jothinathan Sathiya , Rajakumar Perumal
Published: May 2018

Novel triazole bridged dendrimers with rhodamine B derivative as surface groups have been achieved using click chemistry by both divergent and convergent approaches. Rhodamine B decorated dendrimers 1, 2, and 3 were synthesised up to the second generation with spirolactam grafted at the terminal. The UV and fluorescence intensity increases with the increase in the dendritic generation. The synthesised rhodamine B decorated dendrimers show significant antioxidant behaviour compared with the standards butylated hydroxy toluene (BHT) and gallic acid when tested by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay and hydroxyl radical scavenging assay methods, respectively. Rhodamine B decorated higher generation dendrimers exhibit better antioxidant activity than the lower generation dendrimers due to the presence of a greater number of triazole branching units and rhodamine B derivative surface units.
The role of the permanent wilting point in controlling the spatial distribution of precipitation
Authors: Hohenegger Cathy , Stevens Bjorn
Published: May 2018

Significance

One basic distinction between land and ocean is that the land can dry out. We show that this is of fundamental importance for the precipitation distribution over land as it brings precipitation from the precipitating region to the nonprecipitating region. This process prevents the land–atmosphere system from sustaining precipitation over the same region and thus acts against drought or the formation of desert. Paradoxically, although dry atmospheres are known to hamper moist convection, drying the soil to its permanent wilting point generates circulations that are strong enough to overcome this inhibition. Our findings help understand why tropical rain bands broaden poleward over land, the more so the drier the soils are.
Nouns slow down speech across structurally and culturally diverse languages
Authors: Seifart Frank , Strunk Jan , Danielsen Swintha , Hartmann Iren , Pakendorf Brigitte , Wichmann Søren , Witzlack-Makarevich Alena , de Jong Nivja H. , Bickel Balthasar
Published: May 2018

Significance

When we speak, we unconsciously pronounce some words more slowly than others and sometimes pause. Such slowdown effects provide key evidence for human cognitive processes, reflecting increased planning load in speech production. Here, we study naturalistic speech from linguistically and culturally diverse populations from around the world. We show a robust tendency for slower speech before nouns as compared with verbs. Even though verbs may be more complex than nouns, nouns thus appear to require more planning, probably due to the new information they usually represent. This finding points to strong universals in how humans process language and manage referential information when communicating linguistically.
An operando X-ray diffraction study of chloroaluminate anion-graphite intercalation in aluminum batteries
Authors: Pan Chun-Jern , Yuan Chunze , Zhu Guanzhou , Zhang Qian , Huang Chen-Jui , Lin Meng-Chang , Angell Michael , Hwang Bing-Joe , Kaghazchi Payam , Dai Hongjie
Published: May 2018

Significance

Operando X-ray diffraction experiments are performed to investigate chloroaluminate anion intercalation into a graphite positive electrode during electrochemical charging and discharging of rechargeable aluminum batteries in situ. The results revealed surprisingly ordered anion intercalation staging behavior in graphite despite the large anion size and the remarkably stable graphite structure upon repeated intercalation and deintercalation by the large anions. The basic understanding will guide the design and development of new battery materials and new batteries.
On the precipitation behaviour of 7055 aluminium alloy during high-speed cutting
Authors: Zhang Ping , Wang Youqiang , Wang Qing
Published: May 2018

The following paper examined changes in the microstructure of 7055 aluminium alloy before and after high-speed cutting (HSC) were examined, for various (T6, T7, and T84) heat treatment conditions. In the T6 state, the results demonstrated that the number of η″ particles gradually reduced and there was pinning in the η″ particles. After both the T7 and T84 heat treatments, a dislocation was observed in the microstructure by transmission electron microscopy. Grain boundaries in the T6 state were continuous with no obvious non-precipitate zone before HSC. The grain boundary width in the T7 state before HSC was double the T6 value. The grain boundary width for the T84 state alloy was similar to that in the T7 state, but less clearly defined.

This is part of a thematic issue on Small Scale Mechanics - EUROMAT.
A comparison of mechanistic signaling pathway activity analysis methods
Authors: Amadoz Alicia , Hidalgo Marta R , Çubuk Cankut , Carbonell-Caballero José , Dopazo Joaquín
Published: May 2018

Understanding the aspects of cell functionality that account for disease mechanisms or drug modes of action is a main challenge for precision medicine. Classical gene-based approaches ignore the modular nature of most human traits, whereas conventional pathway enrichment approaches produce only illustrative results of limited practical utility. Recently, a family of new methods has emerged that change the focus from the whole pathways to the definition of elementary subpathways within them that have any mechanistic significance and to the study of their activities. Thus, mechanistic pathway activity (MPA) methods constitute a new paradigm that allows recoding poorly informative genomic measurements into cell activity quantitative values and relate them to phenotypes. Here we provide a review on the MPA methods available and explain their contribution to systems medicine approaches for addressing challenges in the diagnostic and treatment of complex diseases.
Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA
Authors: Sarafidis Pantelis A , Mallamaci Francesca , Loutradis Charalampos , Ekart Robert , Torino Claudia , Karpetas Antonios , Raptis Vasileios , Bikos Athanasios , Papagianni Aikaterini , Balafa Olga , Siamopoulos Konstantinos , Pisani Giovanni , Morosetti Massimo , Del Giudice Antonio , Aucella Filippo , Di Lullo Luca , Tripepi Rocco , Tripepi Giovanni , Jager Kitty , Dekker Friedo , London Gerard , Zoccali Carmine
Published: May 2018

Background

Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association.

Methods

A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents.

Results

The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P <0.001). In all, 290 participants were receiving antihypertensive treatment. In all, 9.1% of haemodialysis patients were categorized as normotensives, 12.6% had controlled hypertension confirmed by the two BP techniques, while 46.0% had uncontrolled hypertension with both techniques. The prevalence of white coat hypertension was 18.2% and that of masked hypertension 14.1%. Of note, hypertension was confined only to night-time in 22.2% of patients while just 1% of patients had only daytime hypertension. Pre-dialysis BP ≥140/90 mmHg had 76% sensitivity and 54% specificity for the diagnosis of BP ≥130/80 mmHg by 48-h ABP monitoring.

Conclusions

The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.
Is Spending More Time Associated With Less Missed Care?
Authors: McNair Norma , Baird Jennifer , Grogan Tristan R. , Walsh Catherine M. , Liang Li-Jung , Worobel-Luk Pamela , Needleman Jack , Nuckols Teryl K.
Published: May 2018

OBJECTIVE:

The aim of this study is to examine the relationship between nursing time use and perceptions of missed care.

BACKGROUND:

Recent literature has highlighted the problem of missed nursing care, but little is known about how nurses’ time use patterns are associated with reports of missed care.

METHODS:

In 15 nursing units at 2 hospitals, we assessed registered nurse (RN) perceptions of missed care, observed time use by RNs, and examined the relationship between time spent and degree of missed care at the nursing unit level.

RESULTS:

Patterns of time use were similar across hospitals, with 25% of time spent on documentation. For 6 different categories of nursing tasks, no association was detected between time use, including time spent on documentation, and the degree of missed care at the nursing unit level.

CONCLUSIONS:

Nursing time use cannot fully explain variation in missed care across nursing units. Further work is needed to account for patterns of missed care.
Noise Exposure on Pediatric Inpatient Units
Authors: Daraiseh Nancy M. , Hoying Cheryl L. , Vidonish William P. , Lin Li , Wagner Michael
Published: May 2018

BACKGROUND:

Noise is a problem placing registered nurses (RNs) at risk for safety events, decreased job performance, fatigue, irritability, and hearing loss.

OBJECTIVE:

The purpose of this study is to measure noise levels and sources on pediatric inpatient units as well as to explore the health impact of noise on RNs.

METHODS:

This was a descriptive nonexperimental study with 65 pediatric RNs from 14 units. Noise (levels, source, location, and activity), heart rate (HR), and stress were measured. Correlations between sound pressure levels (SPLs), HR, and stress were examined.

RESULTS:

Mean (SD) SPLs were 75.8 (8.9) dBA and were significantly higher than SPLs for patients. Noise was significantly associated with HR but not with time in tachycardia or stress. Primary sources of noise were employee conversations in patient rooms.

CONCLUSIONS:

On all units, SPLs exceeded protection agency guidelines. Cost-prohibitive structural changes underscore the importance of using behavioral and culture modification to reduce noise.
Effects of Attentional Bias Modification on Residual Symptoms in depression. A Randomized Controlled Trial
Authors: Jonassen Rune , Harmer Catherine J. , Hilland Eva , Maglanoc Luigi A. , Kraft Brage , Browning Michael , Stiles Tore C. , Haaland Vegard Ø. , Berge Torkil , Landrø Nils Inge
Published: May 2018

Background

Following treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. When Attention bias modification training (ABM) leads to more positive emotional biases, associated changes in clinical symptoms have been reported. A broader and more transparent picture of the true advantage of ABM based on larger and more stringent clinical trials have been requested.

Aims

To evaluate the early effect of two weeks ABM training on blinded clinician-rated and self-reported residual symptoms, and whether changes towards more positive attentional biases (AB) would be associated with symptom reduction.

Method

A total of 321 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training.

Results

ABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards relatively more positive stimuli associated with greater symptom reduction.

Conclusion

The current study demonstrates that ABM produces early changes in both AB and blinded clinician-rated depressive symptoms. ABM may have practical potential in the treatment of residual depression.

ClinicalTrials.govID:NCT02658682
Optogenetic dissection of mitotic spindle positioning in vivo
Authors: Fielmich Lars-Eric , Schmidt Ruben , Dickinson Daniel J. , Goldstein Bob , Akhmanova Anna A. , van den Heuvel Sander J.L.
Published: May 2018

The position of the mitotic spindle determines the plane of cell cleavage, and thereby the location, size, and content of daughter cells. Spindle positioning is driven by dynein-mediated pulling forces exerted on astral microtubules. This process requires an evolutionarily conserved complex of Gα-GDP, GPR-1/2Pins/LGN, and LIN-5Mud/NuMAproteins. It remains unknown whether this complex merely forms a membrane anchor for dynein, or whether the individual components have additional functions, for instance through Gα-GTP or dynein activation. To functionally dissect this system, we developed a genetic strategy for light-controlled localization of endogenous proteins inC. elegansembryos. Controlled germline expression and membrane recruitment of the Gα regulators RIC-8Ric-8Aand RGS-7Loco/RGS3, and replacement of Gα with a light-inducible membrane anchor demonstrated that Gα-GTP signaling is dispensable for pulling force generation. In the absence of Gα, cortical recruitment of GPR-1/2 or LIN-5, but not dynein itself, induced high pulling forces. Local recruitment of LIN-5 overruled normal cell-cycle and polarity regulation, and provided experimental control over the spindle and cell cleavage plane. Our results define Gα∙GDP–GPR-1/2Pins/LGNas a regulatable membrane anchor, and LIN-5Mud/NuMAas a potent activator of dynein-dependent spindle positioning forces. This study also highlights the possibilities for optogenetic control of endogenous proteins within an animal system.
Enzymatic evolution driven by entropy production
Authors: Arango-Restrepo A. , Rubi J.M. , Barragán D.
Published: May 2018

We show that the structural evolution of enzymes is largely influenced by the entropy produced in the enzymatic process. We have computed this quantity for the case in which the process has unstable and metastable intermediate states. By assuming that the kinetics takes place along a potential barrier, we have found that the behavior of the total entropy produced is a non-monotonic function of the intermediate state energy. By diminishing the number of metastable intermediate states, the total entropy produced decreases and consequently the enzyme kinetics and the thermodynamic efficiency are enhanced. Minimizing locally the total entropy produced for an enzymatic process with metastable intermediate states, the kinetics and the thermodynamic efficiency are raised. In contrast, in the absence of metastable intermediate states, a maximum of the entropy produced results in an improvement of the kinetic performance although the thermodynamic efficiency diminishes. Our results show that the enzymatic evolution proceeds not only to enhance the kinetics but also to optimize the total entropy produced.
Diversity of active viral infections within theSphagnummicrobiome
Authors: Stough Joshua M.A. , Kolton Max , Kostka Joel E. , Weston David J. , Pelletier Dale A. , Wilhelm Steven W.
Published: May 2018

Sphagnum-dominatedpeatlands play an important role in global carbon storage and represent significant sources of economic and ecological value. While recent efforts to describe microbial diversity and metabolic potential of theSphagnummicrobiome have demonstrated the importance of its microbial community, little is known about the viral constituents. We used metatranscriptomics to describe the diversity and activity of viruses infecting microbes within theSphagnumpeat bog. The vegetative portions of 6Sphagnumplants were obtained from a peatland in northern Minnesota and total RNA extracted and sequenced. Metatranscriptomes were assembled and contigs screened for the presence of conserved virus marker genes. Using bacteriophage capsid protein, gp23, as a marker for phage diversity, we identified 33 contigs representing undocumented phage s that were active in the community at the time of sampling. Similarly, RNA-dependent RNA polymerase and the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) major capsid protein were used as markers for ssRNA viruses and NCLDV, respectively. In total 114 contigs were identified as originating from undescribed ssRNA viruses, 22 of which represent near-complete genomes. An additional 64 contigs were identified as being from NCLDVs. Finally, 7 contigs were identified as putative virophage or polinto-like viruses. We developed co-occurrence networks with these markers in relation to the expression of potential-host housekeeping generpb1to predict virus-host relationships, identifying 13 groups. Together, our approach offers new tools for the identification of virus diversity and interactions in understudied clades, and suggest viruses may play a considerable role in the ecology of theSphagnummicrobiome.

Significance

Sphagnum-dominatedpeatlands play an important role in maintaining atmospheric carbon dioxide levels by modifying conditions in the surrounding soil to favor its own growth over other plant species. This slows rates of decomposition and facilitates the accumulation of fixed carbon in the form of partially decomposed biomass. The unique environment produced bySphagnumenriches for the growth of a diverse microbial consortia that benefit from and support the moss’s growth, while also maintaining the hostile soil conditions. While a growing body of research has begun to characterize the microbial groups that colonizeSphagnum, little is currently known about the ecological factors that constrain community structure and define ecosystem function. Top-down population control by viruses is almost completely undescribed. This study provides insight into the significant viral influence on theSphagnummicrobiome, and identifying new potential model systems to study virus-host interactions in the peatland ecosystem.
Monitoring changes in the Gene Ontology and their impact on genomic data analysis
Authors: Jacobson Matthew , Sedeño-Cortés Adriana Estela , Pavlidis Paul
Published: May 2018

The Gene Ontology (GO) is one of the most widely used resources in molecular and cellular biology, largely through the use of “enrichment analysis”. To facilitate informed use of GO, we present GOTrack (https://gotrack.msl.ubc.ca), which provides access to historical records and trends in the Gene Ontology and GO annotations (GOA). GOTrack gives users access to gene- and term-level information on annotations for nine model organisms as well as an interactive tool that measures the stability of enrichment results over time for user-provided “hit lists” of genes. To document the effects of GO evolution on enrichment, we analyzed over 2500 published hit lists of human genes (most over 9 years old). 53% of hit lists were considered to yield significantly stable enrichment results. Because stability is far from assured for any individual hit list, GOTrack can lead to more informed and cautious application of GO to genomics research.
Discovery of New CDK8 ligands with a Novel Virtual Drug Screening Tool
Authors: Chen Wei , Ren Xiaodong , Chang Chia-en A.
Published: May 2018

Selective inhibition of CDK8 could be a promising strategy for reducing mitogenic signals in cancer cells with reduced toxic effects on normal cells. As compared with type I ligands, binding of a type II compound often achieves longer residence time. We developed a novel virtual drug screening package which takes advantage of two energy evaluation methods: Superposition and Single-Point Energy Evaluation, and VM2 free energy calculation, and applied it to the discovery of new CDK8 type II ligands. In this research we analyzed binding thermodynamics of 11 published CDK8 type II ligands, and extracted the key binding information to assist virtual drug screening for new ligands. The free energy and MD calculations on the reference CDK8-ligand complexes revealed the important factors in the binding. The urea moiety was found to be the critical structural contributor of the reference ligands. Starting with the urea moiety we implemented virtual drug screening and singled out three compounds for bio-assay testing. The ranking from the experimental result for the three compounds is completely consistent with the predicted rankings by both energy evaluation methods. A potent drug-like compound was discovered to have a Kd value of 42.5 nM with CDK8, which is comparable to the most potent reference ligands and provided a good starting point to design and synthesize a series of highly selective and potent CDK8 ligands. Therefore, our novel virtual drug screening package is accurate and efficient enough to be used in drug design projects. We believe this work has significant impact to the field of drug discovery.
Identification of regulatory elements from nascent transcription using dREG
Authors: Wang Zhong , Chu Tinyi , Choate Lauren A. , Danko Charles G.
Published: May 2018

Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvements in accuracy, 3-4-fold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly-transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-I-hypersensitivity. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. We provide a web interface to dREG that can be used by the scientific community (http://dREG.DNASequence.org).
Effect of Inhibitory Spike-Timing-Dependent Plasticity on Fast Sparsely Synchronized Rhythms in A Small-World Neuronal Network
Authors: Kim Sang-Yoon , Lim Woochang
Published: May 2018

We consider the Watts-Strogatz small-world network (SWN) consisting of inhibitory fast spiking Izhikevich interneurons. This inhibitory neuronal population has adaptive dynamic synaptic strengths governed by the inhibitory spike-timing-dependent plasticity (iSTDP). In previous works without iSTDP, fast sparsely synchronized rhythms, associated with diverse cognitive functions, were found to appear in a range of large noise intensities for fixed strong synaptic inhibition strengths. Here, we investigate the effect of iSTDP on fast sparse synchronization (FSS) by varying the noise intensity D. We employ an asymmetric anti-Hebbian time window for the iSTDP update rule [which is in contrast to the Hebbian time window for the excitatory STDP (eSTDP)]. Depending on values of D, population-averaged values of saturated synaptic inhibition strengths are potentiated [long-term potentiation (LTP)] or depressed [long-term depression (LTD)] in comparison with the initial mean value, and dispersions from the mean values of LTP/LTD are much increased when compared with the initial dispersion, independently of D. In most cases of LTD where the effect of mean LTD is dominant in comparison with the effect of dispersion, good synchronization (with higher spiking measure) is found to get better via LTD, while bad synchronization (with lower spiking measure) is found to get worse via LTP. This kind of Matthew effect in inhibitory synaptic plasticity is in contrast to that in excitatory synaptic plasticity where good (bad) synchronization gets better (worse) via LTP (LTD). Emergences of LTD and LTP of synaptic inhibition strengths are intensively investigated via a microscopic method based on the distributions of time delays between the pre- and the post-synaptic spike times. Furthermore, we also investigate the effects of network architecture on FSS by changing the rewiring probability p of the SWN in the presence of iSTDP.
Axon-seq decodes the motor axon transcriptome and its modulation in response to ALS
Authors: Nijssen Jik , Benitez Julio Aguila , Hoogstraaten Rein , Kee Nigel , Hedlund Eva
Published: May 2018

Spinal motor axons traverse large distances to innervate target muscles, thus requiring local control of cellular events for proper functioning. To interrogate axon-specific processes we developed Axon-seq, a refined method incorporating microfluidics, RNA-seq and bioinformatic-QC. We show that the axonal transcriptome is distinct from somas and contains fewer genes. We identified 3,500-5,000 transcripts in mouse and human stem cell-derived spinal motor axons, most of which are required for oxidative energy production and ribogenesis. Axons contained transcription factor mRNAs, e.g. Ybx1, with implications for local functions. As motor axons degenerate in amyotrophic lateral sclerosis (ALS), we investigated their response to the SOD1G93A mutation, identifying 121 ALS-dysregulated transcripts. Several of these are implicated in axonal function, including Nrp1, Dbn1 and Nek1, a known ALS-causing gene. In conclusion, Axon-seq provides an improved method for RNA-seq of axons, increasing our understanding of peripheral axon biology and identifying novel therapeutic targets in motor neuron disease.
Patient-specific detection of cancer genes reveals recurrently perturbed processes in esophageal adenocarcinoma
Authors: Mourikis Thanos P. , Benedetti Lorena , Foxall Elizabeth , Temelkovski Damjan , Nulsen Joel , Perner Juliane , Cereda Matteo , Lagergren Jesper , Howell Michael , Yau Christopher , Fitzgerald Rebecca C. , Scaffidi Paola , Ciccarelli Francesca D. ,   on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Published: May 2018

The identification of somatic alterations with a cancer promoting role is challenging in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we developed a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously (mutations, copy number alterations and structural rearrangements). Analysing 261 EACs from the OCCAMS Consortium, we discovered a large number of novel cancer genes that, together with well-known drivers, help promote cancer. Validation using 107 additional EACs confirmed the robustness of the approach. Unlike known drivers whose alterations recur across patients, the large majority of the newly discovered cancer genes are rare or patient-specific. Despite this, they converge towards perturbing cancer-related processes, including intracellular signalling, cell cycle regulation, proteasome activity and Toll-like receptor signalling. Recurrence of process perturbation, rather than individual genes, divides EACs into six clusters that differ in their molecular and clinical features and suggest patient stratifications for personalised treatments. By experimentally mimicking or reverting alterations of predicted cancer genes, we validated their contribution to cancer progression and revealed EAC acquired dependencies, thus demonstrating their potential as therapeutic targets.
Barriers and incentives for conducting research amongst the Ophthalmologists in Sub-Sahara Africa
Authors: Dhalla Kazim A , Guirguis Micheal
Published: May 2018

Background

Research is a critical component amongst the strategies to improve health outcomes of any country. The role of research assumes greater importance in Africa as it carries a larger share of global burden of diseases, blindness and low vision. “Vision 2020- the Right to Sight” is a WHO-IAPB collaborated initiative aiming to eliminate preventable blindness by the year 2020. High quality research in eye care is imperative for the initiative to succeed, however, there is a dearth of research in eye care in sub Saharan Africa in general and specifically in the Eastern, Central and Southern African (ECSA) region. Identifying the barriers that hamper research in this region is an important step towards elimination of preventable blindness.

Methods

A structured questionnaire using the SurveyMonkey program was sent to ophthalmologists in the ECSA region and South Africa through their respective regional professional bodies. Data was analyzed using the SPSS program version.

Results

Lack of funding, inadequate time and poor research knowledge were the main research barriers while ability to improve eye health care through research was the main incentive for conducting research.

Conclusion

The barriers mainly center on financial, human and administrative infrastructure and resources. In spite of the barriers, ophthalmologists in the study region are enthusiastic in research aiming to increase evidence based knowledge to improve eye health care in line with the goals of “Vision 2020- the Right to Sight” initiative.
Replication fork collapse at a protein-DNA roadblock leads to fork reversal, promoted by the RecQ helicase
Authors: Weaver Georgia M. , Mettrick Karla A. , Corocher Tayla-Ann , Graham Adam , Grainge Ian
Published: May 2018

There are numerous impediments that DNA replication can encounter while copying a genome, including the many proteins that bind DNA. Collapse of the replication fork at a protein roadblock must be dealt with to enable replication to eventually restart; failure to do so efficiently leads to mutation or cell death. Several prospective models have been proposed that process a stalled or collapsed replication fork. This study shows that replication fork reversal (RFR) is the preferred pathway for dealing with a collapsed fork inEscherichia coli, along with exonuclease activity that digests the two nascent DNA strands. RFR moves the Y-shaped replication fork DNA away from the site of the blockage and generates a four-way DNA structure, the Holliday junction (HJ). Direct endo-nuclease activity at the replication fork is either slow or does not occur. The protein that had the greatest effect on HJ processing/RFR was found to be the RecQ helicase. RecG and RuvABC both played a lesser role, but did affect the HJ produced: mutations in these known HJ processing enzymes produced longer-lasting HJ intermediates, and delayed replication restart. The SOS response is not induced by the protein-DNA roadblock under these conditions and so does not affect fork processing.

Author Summary

To transfer genetic material to progeny, a cell must replicate its DNA accurately and completely. If a cell does not respond appropriately to inhibitors of the DNA replication process, genetic mutation and cell death will occur. Previous works have shown that protein-DNA complexes are the greatest source of replication fork stalling and collapse in bacteria. This work examines how the cell deals with replication fork collapse at a persistent protein blockage, at a specific locus on the chromosome ofEscherichia coli. Cells were found to process the DNA at the replication fork, moving the branch point away from the site of blockage by replication fork reversal and exonuclease activity. Our data indicate that it is the RecQ helicase that has the main controlling role in this process, and not the proteins RecG and RuvABC, as currently understood. RecQ homologs have been shown to be involved in replication fork processing in eukaryotes and their mutation predisposes humans to genome instability and cancer. Our findings suggest that RecQ proteins could play more important role in replication fork reversal than previously understood, and that this role could be conserved across domains.