bluuebunny/crossref_metadata_2025 huggingface dataset:
Versorgungsforschung in der Kataraktchirurgie – eine Analyse der Patientenzufriedenheit nach Kataraktchirurgie in Mecklenburg-Vorpommern
Authors: Seifried Maria , Höh Helmut
Published: June 2017

Hintergrund Auf Grundlage eines Vertrags zwischen der AOK Mecklenburg-Vorpommern und den ambulanten Kataraktoperateuren/-zentren in Mecklenburg-Vorpommern erfolgte zwischen 2005 und 2008 die sektorenübergreifende Erfassung prä-, peri- und postoperativer Daten zur Eruierung der Qualität der ambulanten Kataraktchirurgie.

Material und Methoden Von ursprünglich 3058 (Operationen ausschließlich an unserem Zentrum) wurden 2952 vollständige und plausible Datensätze der Auswertung zugeführt. Visus, Refraktion, Komorbiditäten und weitere Daten wurden auf einen möglichen Zusammenhang mit der Patientenzufriedenheit mit der Kataraktoperation untersucht.

Ergebnisse Unsere Patienten waren durchschnittlich 74,5 Jahre alt, hatten mehrheitlich eine Cataracta senilis (96,5%) und wiesen einen mittleren dezimalen Visusanstieg von 0,4 ± 0,2 (LogMAR 0,5 ± 0,3) auf 0,8 ± 0,3 (LogMAR 0,2 ± 0,2) auf. Mit einer Genauigkeit von ± 1,0 dpt (respektive ± 0,5 dpt) erreichten 78,9% (respektive 49,9%) der Augen die Zielrefraktion. Faktoren, die mit der allgemeinen Zufriedenheit mit der Operation korrelierten, sind der postoperative Visusanstieg (Spearman, r = 0,404, p = 0,01) sowie die Abwesenheit von Komorbiditäten (Spearman, r = − 0,168, p = 0,01) und perioperativer Komplikationen (Spearman, r = − 0,104, p = 0,01). Trotz objektivierbar positiven Ergebnissen i. S. der Abwesenheit von Komorbiditäten sowie Komplikationen und trotz eines Visusanstiegs um dezimal ≥ 0,1 (Clinical Outcome Measure, COM+) waren durchschnittlich 1,7% unserer Patienten unzufrieden mit dem Operationsergebnis (Patient-reported Outcome Measure, PROM−). Den größten Anteil unzufriedener Patienten (3,9%) fanden wir im Bereich des Lesevermögens.

Schlussfolgerung Bei einem nicht selektierten Patientengut wurden international vergleichbare visuelle, refraktive und Zufriedenheitsergebnisse erzielt. Die allgemeine Zufriedenheit mit der Kataraktoperation war hoch. Es gilt, dass die Mehrheit der Patienten (84,2%) mit einem Visusanstieg ≥ 0,1 auch mit dem Ergebnis der Kataraktoperation zufrieden war (PROM+). Wenn Unzufriedenheit geäußert wurde, fand sich die Begründung im Bestehen von Komorbiditäten, perioperativen Komplikationen und in einem Poor Outcome (i. S. eines fehlenden Visusanstiegs ≥ 0,1). Ohne ophthalmologisch nachvollziehbaren Grund blieben dennoch 1,7% der Patienten mit dem Ergebnis der Kataraktoperation unzufrieden (COM+, PROM−), wobei zur Erklärung die Bedeutung der allgemeinen Lebenszufriedenheit herangezogen werden muss.
Sprachstörungen und deren Klassifikationen
Authors: Greitemann Georg
Published: June 2017

Sprache ist ein außerordentlich komplexes Konstrukt: Der aktive Wortschatz eines Durchschnittssprechers umfasst Schätzungen zufolge 12.000
bis 16.000 Wörter, die nach zahlreichen, oft komplexen Regeln zu Sätzen und Texten zusammengefügt werden.
„Raus aus der Komfortzone!“ – lautes Sprechen als Schlüssel zum Erfolg
Authors: Pichler Katharina , Peter Sina
Published: June 2017

Wer kennt es nicht – man versucht mit größter Anstrengung Veränderungen herbeizuführen, findet sich jedoch wie Sisyphus nach kurzer Zeit am
Ausgangspunkt wieder. Kleine Erfolge fallen umgehend dem Alltag zum Opfer. Frustration und Selbstzweifel sind die Folge. Um diesen
Teufelskreis aus Misserfolg und Frustration zügig und nachhaltig zu durchbrechen, bedarf es eines wirkungsvollen „Generalschlüssels“. Dieser
soll die Tür zum Verlassen der Komfortzone öffnen und dem Patienten zu einem mutigen Neubeginn verhelfen.
Einfluss von Geschlecht und Alter auf die Kontrastempfindlichkeit in Abhängigkeit der verwendeten Methodik
Authors: Darius Sabine , Bergmann Lisa , Blaschke Saskia , Böckelmann Irina
Published: June 2017

Ziel Ziel der Studie war es, den Einfluss von Geschlecht und Alter auf die photopische Kontrastempfindlichkeit sowie das Dämmerungssehen, insbesondere im Hinblick auf die Fahrerlaubnisverordnung (FeV), mit unterschiedlichen Verfahren zu untersuchen.

Methodik An der Studie nahmen 134 freiwillige augengesunde Probanden (53 Männer, 81 Frauen) mit gutem Visus im Alter von 18 – 76 Jahren teil. Die Probanden wurden in 2 Altersgruppen eingeteilt (AG I < 45 Jahre, AG II ≥ 45 Jahre). Die Prüfung des Dämmerungssehens erfolgte mit dem Mesotest II. Die photopische Kontrastempfindlichkeit wurde mit den Einblickgeräten Optovist und Rodatest 302 sowie mit der VISTECH-Tafel und den Mars-Tafeln bei standardisierter Beleuchtung erfasst.

Ergebnisse Es wurden keine Geschlechterunterschiede gefunden. Bei Verwendung altersangepasster Grenzwerte entsprechend den jeweiligen Herstellerangaben wurden keine Unterschiede zwischen den Altersgruppen gefunden bei Testung mit dem Rodatest-Gerät und den Mars-Tafeln. Bei allen anderen Testverfahren schnitten die Jüngeren signifikant besser ab.

Schlussfolgerungen Je nach Verfahren gelten altersabhängige Bestehenskriterien. Hinsichtlich der Fahrsicherheit der Verkehrsteilnehmer sollte jedoch altersunabhängig auf ein ausreichendes Kontrast- oder Dämmerungssehen geachtet werden. Insofern ist zu überlegen, ob altersabhängige Grenzwerte weiterhin Bestand haben sollten.
Das wettbewerbsfähige Krankenhaus – Worauf es ankommt
Authors: Hellmann Wolfgang
Published: June 2017

Knappe finanzielle Ressourcen erschweren die Sicherung von guter Qualität im Krankenhaus. Folge ist eine zunehmende Arbeitsdichte für Ärzte
und Pflegepersonal. Neue Herausforderungen ergeben sich aus neuen Patienten- und Mitarbeiterklientelen. Insgesamt stellt sich die Frage, was
unter zunehmenden schlechter werdenden Arbeitsbedingungen im Krankenhaus noch machbar und möglich ist. Der vorliegende Beitrag zeigt zentral
bestehende Defizite im Management von Krankenhäusern auf und gibt Anregungen zur Steigerung der Wettbewerbsfähigkeit.

Zielsetzung Aufzeigen von grundlegenden Defiziten im Krankenhausmanagement wie mangelnde Kommunikation, eingeschränkte Sicht auf
Qualitäts- und Risikomanagement, einseitiges Verständnis von Qualität und Vorschläge zur Optimierung zwecks Erhöhung der
Wettbewerbsfähigkeit des Krankenhauses.

Methodik Kritische Reflexion wichtiger Konzepte für das Krankenhausmanagement zur Entwicklung einer neuen Sicht von Qualität im
Kontext einschlägiger Literatur anderer Autoren.

Ergebnisse Beschreibung vom Autor entwickelter Konzepte zu einem neuen Verständnis von Qualität, einer ganzheitlichen Sicht von
Risikomanagement, einer neuen Logik von Qualitätssicherung und einem prospektiver Gesamtansatz zur Qualität.

Schlussfolgerung Es ergibt sich ein innovativer prospektiver Gesamtansatz für Qualität im Krankenhaus, der Qualitätsmanagement,
Risikomanagement und Qualitätssicherung einschließt. Angemessene Kommunikation und Kooperation sind Voraussetzung für eine erfolgreiche
Implementierung. Ein vergleichbares Konzept gibt es bisher in Deutschland nicht.
Composite Shell Strain Detection for SRM Based on Optical Fiber Sensors
Authors: Zhang Lei , Chang Xin-Long , Zhang You-hong , Chen Xiang-dong
Published: June 2017

As a new passive sensor, fiber Bragg grating (FBG) sensors have provided a new idea for the SRM shell damage detection, which is to integrate the FBG sensor network in the material interior or to the surface to monitor the shell structure. However, it is difficult to embed the FBG sensor in filament wound composite material structure for the reason of large tension and high temperature in process of manufacture. Therefore we propose a new method that embed FBG sensor network between the composite shell surface and the thermal protective coating. The calibration of sensor is presented by tensile test and the strain transfer coefficient is gotten. It is certified by the hydrostatic test that the FBG sensors could precisely describe the strain variation and distribution of the composite shell and effectively improve the survival rate by embedding the FBG sensors between the composite shell surface and the thermal protective coating.
Mechanical Behavior of PBO Fiber Used for Lunar Soil Sampler
Authors: Gao Xingwen , Tang Dewei , Yue Honghao , Qiao Fei , Li Yanwei
Published: June 2017

The stability of the mechanical properties of the materials used for lunar soil sampler at different temperatures is one of the key factors to ensure the success of the lunar sampling task. In this paper, two kinds of poly(pphenylene-2,6-benzobisoxazole) (PBO) fiber fabric used for lunar soil sampler, flexible tube and wireline, are tested for mechanical properties. The results show that the mechanical properties of the PBO flexible tube and wireline raised 8.3% and 5.7% respectively in -194°C environment comparing with the room temperature of 25°C. When the temperature rises to 300°C, the deviation is -38.6% and -46.4% respectively.
NLPReViz: an interactive tool for natural language processing on clinical text
Authors: Trivedi Gaurav , Pham Phuong , Chapman Wendy W , Hwa Rebecca , Wiebe Janyce , Hochheiser Harry
Published: June 2017

The gap between domain experts and natural language processing expertise is a barrier to extracting understanding from clinical text. We describe a prototype tool for interactive review and revision of natural language processing models of binary concepts extracted from clinical notes. We evaluated our prototype in a user study involving 9 physicians, who used our tool to build and revise models for 2 colonoscopy quality variables. We report changes in performance relative to the quantity of feedback. Using initial training sets as small as 10 documents, expert review led to final F1scores for the “appendiceal-orifice” variable between 0.78 and 0.91 (with improvements ranging from 13.26% to 29.90%). F1for “biopsy” ranged between 0.88 and 0.94 (−1.52% to 11.74% improvements). The average System Usability Scale score was 70.56. Subjective feedback also suggests possible design improvements.
White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes
Authors: Wheelock Kevin M , Saulnier Pierre-Jean , Tanamas Stephanie K , Vijayakumar Pavithra , Weil E Jennifer , Looker Helen C , Hanson Robert L , Lemley Kevin V , Yee Berne , Knowler William C , Hadjadj Samy , Najafian Behzad , Mauer Michael , Nelson Robert G
Published: June 2017

Background

Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study.

Methods

Associations of WBC variables with morphometric parameters were assessed by linear regression. RFL was defined as≥40% loss of estimated glomerular filtration rate from baseline. Associations with RFL were evaluated by Cox regression. Hazard ratios (HRs) were reported per standard deviation increment of each WBC variable.

Results

After multivariable adjustment, lymphocyte (r  = −0.20, P = 0.043) and eosinophil (r = 0.21, P = 0.032) fractions in the Pima Indians correlated with glomerular basement membrane width. Eosinophil fraction also correlated with glomerular filtration surface density (r  = −0.21, P = 0.031). Lymphocyte fraction (r = 0.25, P = 0.013), neutrophil fraction (r  = −0.23, P = 0.021) and the neutrophil:lymphocyte ratio (r  = −0.22, P = 0.024) correlated with percentage of normally fenestrated endothelial cells. During median follow-up of 4.5 years, 321 SURDIAGENE participants developed RFL. Lower lymphocyte fraction [HR = 0.67, 95% confidence interval (95% CI) 0.60–0.76] and higher neutrophil fraction (HR = 1.35, 95% CI 1.20–1.52), total WBC count (HR = 1.20, 95% CI 1.08–1.35) and neutrophil:lymphocyte ratio (HR = 1.44, 95% CI 1.28–1.62) each predicted RFL in this cohort.

Conclusions

WBC fractions associate with morphometric lesions of DKD and predict RFL in individuals with Type 2 diabetes.
A Direct Aspiration First Pass Technique vs Standard Endovascular Therapy for Acute Stroke: A Systematic Review and Meta-Analysis
Authors: Phan Kevin , Dmytriw Adam A , Teng Ian , Moore Justin M , Griessenauer Christoph , Ogilvy Christopher , Thomas Ajith
Published: June 2017

BACKGROUND

The direct aspiration first pass technique (ADAPT) is a recent endovascular treatment for ischemic stroke due to large vessel occlusion that has been gaining popularity due to the rapidity of the technique and the potential for cost savings in comparison to standard thrombectomy methods such as stent retrievers. However, few studies have directly compared these 2.

OBJECTIVE

To compare ADAPT with stent retrievers for thrombectomy via systematic review and meta-analysis.

METHODS

Ovid Medline, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ACP Journal Club, and Database of Abstracts of Review of Effectiveness limited to English through September 2016 were systematically searched. Eligible studies included those in which patient cohorts underwent ADAPT for acute stroke. Recanalization efficiency, clinical outcomes, and complication rates of ADAPT were compared with the current standard of endovascular thrombectomy techniques.

RESULTS

Seventeen studies on ADAPT and 5 randomized controlled trials on endovascular therapy were included. ADAPT achieved higher rates of complete revascularisation (89.4% vs 71.7%, P < .001) but similar clinical outcomes compared to front-line endovascular therapy. Seventy-one point four percent of ADAPT cases were successfully recanalized with aspiration alone, and a trend towards reduced time from groin puncture to recanalization time was noted (44.77 vs 61.46 min, P = .088).

CONCLUSION

The pooled results are comparable with recent randomized studies that demonstrate the benefit of endovascular therapy over intra-arterial medical therapy. Future direct comparative studies and randomized trials are required to confirm the benefit of the ADAPT strategy compared to standard endovascular therapy for acute ischemic stroke.
Puncture of Cerebellar Horizontal Fissure for Retrosigmoid Approach: A Prospective and Quantitative Analysis
Authors: Park Chang Kyu , Lee Sung Ho , Rhee Bong Arm , Choi Seok Keun
Published: June 2017

BACKGROUND

Cerebrospinal fluid (CSF) drainage is important in retrosigmoid approached surgery; however, in some cases, it is not feasible due to cerebellar swelling.

OBJECTIVE

To introduce a method, puncture of the horizontal fissure of the cerebellum, which can reduce the cerebellum to easily obtain a good operative corridor and slowly drain CSF.

METHODS

Between January and December 2014, we estimated the precise location of the horizontal fissure in 56 patients who underwent surgery via a retrosigmoid approach. Then, we collected and analyzed CSF drained by puncturing the horizontal fissure. We investigated whether a good operative corridor was obtained with this method.

RESULTS

The location of the precise horizontal fissure was a mean of 3.97 mm caudal to transverse sinus and the mean amount of CSF drained in 56 patients was 50.4 mL. A good corridor was obtained in 46 (82.1%) of 56 patients without additional cistern puncture.

CONCLUSION

The puncture of the horizontal fissure can be useful in retrosigmoid approach surgery. Moreover, inexperienced surgeons can use this method to effectively avoid injury of the cerebellum.
Behavior in Children with Fetal Alcohol Spectrum Disorders in Remote Australia: A Population-Based Study
Authors: Tsang Tracey W. , Carmichael Olson Heather , Latimer Jane , Fitzpatrick James , Hand Marmingee , Oscar June , Carter Maureen , Elliott Elizabeth J.
Published: June 2017

Objective:

To document behavior in children residing in very remote Western Australian communities as rated by parent/caregivers and teachers. We hypothesized that children with fetal alcohol spectrum disorders (FASD) would have higher rates of problematic behavior than children without FASD.

Methods:

The Child Behavior Checklist (CBCL; n = 97), and Teacher Report Form (TRF; n = 106) were used in this population-based study. Raw scores, proportions scoring within “Normal/Borderline/Clinical” ranges, and frequencies of Critical items were determined. Mann–Whitney U and χ2 tests were used for between-group comparisons.

Results:

Children were aged from 7.5 to 9.6 years, and 19% had FASD. Academic performance was commonly rated in the “Borderline/Clinical” range (73%). Teacher-rated scores were poorer in the FASD group on 15 scales encompassing total and internalizing problems, adaptive function, academic performance, attention, withdrawn/depressed, social problems, posttraumatic stress, thought problems, and sluggish cognitive tempo (p < .05). More children in the FASD group had scores in the “Borderline/Clinical” range on 11 TRF scales (p < .05). “Physically attacks people” was the most prevalent Critical item endorsed by teachers for the total cohort (22%). “Talks about killing self” was endorsed by teachers more often in the FASD group (14%) than the Non-FASD group (1%; p = .03). There were no significant differences between groups in parent-reported CBCL scores after adjustment for multiple comparison testing.

Conclusion:

This study demonstrates that children with FASD have more teacher-reported behavioral impairment than children without FASD. In remote Australian communities, academic performance is poor.
Use of Extracorporeal Membrane Oxygenation and Mortality in Pediatric Cardiac Surgery Patients With Genetic Conditions: A Multicenter Analysis*
Authors: Furlong-Dillard Jamie M. , Amula Venugopal , Bailly David K. , Bleyl Steven B. , Wilkes Jacob , Bratton Susan L.
Published: June 2017

Objective:

Congenital heart disease is commonly a manifestation of genetic conditions. Surgery and/or extracorporeal membrane oxygenation were withheld in the past from some patients with genetic conditions. We hypothesized that surgical care of children with genetic conditions has increased over the last decade, but their cardiac extracorporeal membrane oxygenation use remains lower and mortality greater.

Design:

Retrospective cohort study.

Setting:

Patients admitted to the Pediatric Health Information System database 18 years old or younger with cardiac surgery during 2003–2014. Genetic conditions identified by International Classification of Diseases, 9th Edition codes were grouped as follows: trisomy 21, trisomy 13 or 18, 22q11 deletion, and all “other” genetic conditions and compared with patients without genetic condition.

Patients:

A total of 95,253 patients met study criteria, no genetic conditions (85%), trisomy 21 (10%), trisomy 13 or 18 (0.2%), 22q11 deletion (1%), and others (5%).

Interventions:

None.

Measurements and Main Results:

Annual surgical cases did not vary over time. Compared to patients without genetic conditions, trisomy 21 patients, extracorporeal membrane oxygenation use was just over half (odds ratio, 0.54), but mortality with and without extracorporeal membrane oxygenation were similar. In trisomy 13 or 18 patients, extracorporeal membrane oxygenation use was similar to those without genetic condition, but all five treated with extracorporeal membrane oxygenation died. 22q11 patients compared with those without genetic condition had similar extracorporeal membrane oxygenation use, but greater odds of extracorporeal membrane oxygenation mortality (odds ratio, 3.44). Other genetic conditions had significantly greater extracorporeal membrane oxygenation use (odds ratio, 1.22), mortality with extracorporeal membrane oxygenation (odds ratio, 1.42), and even greater mortality odds without (odds ratio, 2.62).

Conclusions:

The proportion of children undergoing cardiac surgery who have genetic conditions did not increase during the study. Excluding trisomy 13 or 18, all groups of genetic conditions received and benefited from extracorporeal membrane oxygenation, although extracorporeal membrane oxygenation mortality was greater for those with 22q11 deletion and other genetic conditions.
Observational Study of the Effect of Patient Outreach on Return to Care: The Earlier the Better
Authors: Rebeiro Peter F. , Bakoyannis Giorgos , Musick Beverly S. , Braithwaite Ronald S. , Wools-Kaloustian Kara K. , Nyandiko Winstone , Some Fatma , Braitstein Paula , Yiannoutsos Constantin T.
Published: June 2017

Background:

The burden of HIV remains heaviest in resource-limited settings, where problems of losses to care, silent transfers, gaps in care, and incomplete mortality ascertainment have been recognized.

Methods:

Patients in care at Academic Model Providing Access to Healthcare (AMPATH) clinics from 2001–2011 were included in this retrospective observational study. Patients missing an appointment were traced by trained staff; those found alive were counseled to return to care (RTC). Relative hazards of RTC were estimated among those having a true gap: missing a clinic appointment and confirmed as neither dead nor receiving care elsewhere. Sample-based multiple imputation accounted for missing vital status.

Results:

Among 34,522 patients lost to clinic, 15,331 (44.4%) had a true gap per outreach, 2754 (8.0%) were deceased, and 837 (2.4%) had documented transfers. Of 15,600 (45.2%) remaining without active ascertainment, 8762 (56.2%) with later RTC were assumed to have a true gap. Adjusted cause-specific hazard ratios (aHRs) showed early outreach (a ≤8-day window, defined by grid-search approach) had twice the hazard for RTC vs. those without (aHR = 2.06; P < 0.001). HRs for RTC were lower the later the outreach effort after disengagement (aHR = 0.86 per unit increase in time; P < 0.001). Older age, female sex (vs. male), antiretroviral therapy use (vs. none), and HIV status disclosure (vs. none) were also associated with greater likelihood of RTC, and higher enrollment CD4 count with lower likelihood of RTC.

Conclusion:

Patient outreach efforts have a positive impact on patient RTC, regardless of when undertaken, but particularly soon after the patient misses an appointment.
Addressing current challenges in cancer immunotherapy with mathematical and computational modeling
Authors: Konstorum Anna , Vella Anthony T. , Adler Adam J. , Laubenbacher Reinhard
Published: June 2017

The goal of cancer immunotherapy is to boost a patient’s immune response to a tumor. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumor microenvironment, immune-modulating effects of conventional treatments, and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modeling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumor classification, optimal treatment scheduling, and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modelers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumor-immune biology. We conclude the review with recommendations for modelers both with respect to methodology and biological direction that might help keep modelers at the forefront of cancer immunotherapy development.
Cameo: A Python Library for Computer Aided Metabolic Engineering and Optimization of Cell Factories
Authors: Cardoso João G. R. , Jensen Kristian , Lieven Christian , Hansen Anne Sofie Lærke , Galkina Svetlana , Beber Moritz , Özdemir Emre , Herrgård Markus J. , Redestig Henning , Sonnenschein Nikolaus
Published: June 2017

Computational systems biology methods enable rational design of cell factories on a genomescale and thus accelerate the engineering of cells for the production of valuable chemicals and proteins. Unfortunately, for the majority of these methods’ implementations are either not published, rely on proprietary software, or do not provide documented interfaces, which has precluded their mainstream adoption in the field. In this work we present cameo, a platform-independent software that enablesin silicodesign of cell factories and targets both experienced modelers as well as users new to the field. It is written in Python and implements state-of-the-art methods for enumerating and prioritizing knock-out, knock-in, over-expression, and down-regulation strategies and combinations thereof. Cameo is an open source software project and is freely available under the Apache License 2.0. A dedicated website including documentation, examples, and installation instructions can be found athttp://cameo.bio. Users can also give cameo a try athttp://try.cameo.bio.
Differential Mast Cell Outcomes Are Sensitive to FcεRI-Syk Binding Kinetics
Authors: Schwartz Samantha L. , Cleyrat Cédric , Olah Mark , Relich Peter , Phillips Genevieve , Hlavacek William S. , Lidke Keith A. , Wilson Bridget S. , Lidke Diane S.
Published: June 2017

Crosslinking of IgE-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single molecule imaging in live cells, we directly visualized and quantified the binding of individual mNeonGreen-tagged Syk molecules as they associated with the plasma membrane after FcεRI activation. We found that Syk colocalizes transiently to FcεRI and that Syk-FcεRI binding dynamics are independent of receptor aggregate size. Substitution of glutamic acid for tyrosine between the Syk SH2 domains (SykY130E) led to an increased Syk-FcεRI off-rate, loss of site-specific Syk autophosphorylation, and impaired downstream signaling. CRISPR-Cas9 engineered cells expressing only SykY130E were deficient in antigen-stimulated calcium release, degranulation and production of some cytokines (TNF-a, IL-3) but not others (MCP-1, IL-4). We propose that kinetic discrimination along the FcεRI signaling pathway occurs at the level of Syk-FcεRI interactions, with key outcomes dependent upon sufficiently long-lived Syk binding events.

Schwartz et al. use single molecule imaging to quantify the transient nature of FcεRI-Syk interactions in live mast cells. A functional mutation that increases Syk off-rate leads to loss of site-specific Syk phosphorylation and impaired signaling, highlighting the importance of finely tuned protein interactions in directing cellular outcomes.
De-novoassembly of zucchini genome reveals a whole genome duplication associated with the origin of theCucurbitagenus
Authors: Montero-Pau Javier , Blanca José , Bombarely Aureliano , Ziarsolo Peio , Esteras Cristina , Martí-Gómez Carlos , Ferriol María , Gómez Pedro , Jamilena Manuel , Mueller Lukas , Picó Belén , Cañizares Joaquín
Published: June 2017

TheCucurbitagenus (squashes, pumpkins, gourds) includes important domesticated species such asC. pepo,C. maximaandC. moschata. In this study, we present a high-quality draft of the zucchini (C. pepo) genome. The assembly has a size of 263 Mb, a scaffold N50 of 1.8 Mb, 34,240 gene models, includes 92% of the conserved BUSCO core gene set, and it is estimated to cover 93.0% of the genome. The genome is organized in 20 pseudomolecules, that represent 81.4% of the assembly, and it is integrated with a genetic map of 7,718 SNPs. Despite its small genome size three independent evidences support that theC. pepogenome is the result of a Whole Genome Duplication: the topology of the gene family phylogenies, the karyotype organization, and the distribution of 4DTv distances. Additionally, 40 transcriptomes of 12 species of the genus were assembled and analyzed together with all the other published genomes of the Cucurbitaceae family. The duplication was detected in all theCucurbitaspecies analyzed, includingC. maximaandC. moschata, but not in the more distant cucurbits belonging to theCucumisandCitrullusgenera, and it is likely to have happened 30 ± 4 Mya in the ancestral species that gave rise to the genus.
A single-cell anatomical blueprint for intracortical information transfer from primary visual cortex
Authors: Han Yunyun , Kebschull Justus M , Campbell Robert AA , Cowan Devon , Imhof Fabia , Zador Anthony M , Mrsic-Flogel Thomas D
Published: June 2017

The wiring diagram of the neocortex determines how information is processed across dozens of cortical areas. Each area communicates with multiple others via extensive long-range axonal projections1–6, but the logic of inter-area information transfer is unresolved. Specifically, the extent to which individual neurons send dedicated projections to single cortical targets or distribute their signals across multiple areas remains unclear5,7–20. Distinguishing between these possibilities has been challenging because axonal projections of only a few individual neurons have been reconstructed. Here we map the projection patterns of axonal arbors from 591 individual neurons in mouse primary visual cortex (V1) using two complementary methods: whole-brain fluorescence-based axonal tracing21,22and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq)23. Although our results confirm the existence of dedicated projections to certain cortical areas, we find these are the exception, and that the majority of V1 neurons broadcast information to multiple cortical targets. Furthermore, broadcasting cells do not project to all targets randomly, but rather comprise subpopulations that either avoid or preferentially innervate specific subsets of cortical areas. Our data argue against a model of dedicated lines of intracortical information transfer via “one neuron – one target area” mapping. Instead, long-range communication between a sensory cortical area and its targets may be based on a principle whereby individual neurons copy information to, and potentially coordinate activity across, specific subsets of cortical areas.
Single-cell RNA-seq of mouse dopaminergic neurons informs candidate gene selection for sporadic Parkinson’s disease
Authors: Hook Paul W. , McClymont Sarah A. , Cannon Gabrielle H. , Law William D. , Morton A. Jennifer , Goff Loyal A. , McCallion Andrew S.
Published: June 2017

Genetic variation modulating risk of sporadic Parkinson’s disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population andsubstantia nigra(SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised inCplx1null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research.
Population genomics of bank vole populations reveals associations between immune related genes and the epidemiology of Puumala hantavirus in Sweden
Authors: Rohfritsch Audrey , Galan Maxime , Gautier Mathieu , Gharbi Karim , Olsson Gert , Gschloessl Bernhard , Zeimes Caroline , VanWambeke Sophie , Vitalis Renaud , Charbonnel Nathalie
Published: June 2017

Infectious pathogens are major selective forces acting on individuals. The recent advent of high-throughput sequencing technologies now enables to investigate the genetic bases of resistance/susceptibility to infections in non-model organisms. From an evolutionary perspective, the analysis of the genetic diversity observed at these genes in natural populations provides insight into the mechanisms maintaining polymorphism and their epidemiological consequences. We explored these questions in the context of the interactions between Puumala hantavirus (PUUV) and its reservoir host, the bank voleMyodes glareolus. Despite the continuous spatial distribution ofM. glareolusin Europe, PUUV distribution is strongly heterogeneous. Different defence strategies might have evolved in bank voles as a result of co-adaptation with PUUV, which may in turn reinforce spatial heterogeneity in PUUV distribution. We performed a genome scan study of six bank vole populations sampled along a North/South transect in Sweden, including PUUV endemic and non-endemic areas. We combined candidate gene analyses (Tlr4,Tlr7,Mx2genes) and high throughput sequencing of RAD (Restriction-site Associated DNA) markers. We found evidence for outlier loci showing high levels of genetic differentiation. Ten outliers among the 52 that matched to mouse protein-coding genes corresponded to immune related genes and were detected using ecological associations with variations in PUUV prevalence. One third of the enriched pathways concerned immune processes, including platelet activation and TLR pathway. In the future, functional experimentations should enable to confirm the role of these these immune related genes with regard to the interactions betweenM. glareolusand PUUV.
SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly Accurate SNP Based Parentage Verification and Identification
Authors: McClure M.C. , McCarthy J. , Flynn P. , McClure J. , O’Connell K. , Kearney J.F.
Published: June 2017

A major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP) based verification inBos tauruscattle has been the ISAG 100 and 200 SNP panels. While these SNP sets have provided an increased level of parentage accuracy over microsatellite markers (MS), they can validate the wrong parent for an animal at ≤1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61Bos taurusbreeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF) analysed different SNP densities to determine that at a minimum ≥500 SNP are needed to consistently predict only one set of parents at a ≤1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele frequency (MAF) in the Irish cattle population. Large datasets require sample and SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here a genomic sample QC pipeline to deal with the unique challenges of >1,000,000 genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise.
Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury
Authors: Koch Marta , Nicolas Maya , Zschaetzsch Marlen , de Geest Natalie , Claeys Annelies , Yan Jiekun , Morgan Matthew , Erfurth Marie-Luise , Holt Matthew , Schmucker Dietmar , Hassan Bassem A
Published: June 2017

Injury to the adult central nervous systems (CNS) results in severe long-term disability because damaged CNS connections rarely regenerate. Although several axon regeneration regulators have been proposed, intrinsic regenerative mechanisms remain largely unexplored. Here, we use aDrosophilaCNS injury model to identify a novel pro-regeneration signaling pathway. We conducted a genetic screen of approximately three hundred candidate genes and identified three strong inducers of axonal growth and regeneration: the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3’-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.
Hammondia hammondihas a developmental programin vitrothat mirrors its stringent two host life cycle
Authors: Sokol Sarah L. , Primack Abby S. , Nair Sethu C. , Wong Zhee S. , Tembo Maiwase , Dubey J.P. , Verma Shiv K. , Boyle Jon P.
Published: June 2017

Hammondia hammondiis the nearest relative ofToxoplasma gondii,but unlikeT. gondiiis obligately heteroxenous. We have comparedH. hammondiandT. gondiidevelopmentin vitroand identified multipleH. hammondi-specific growth states. Despite replicating slower thanT. gondii,H. hammondiwas resistant to pH-induced tissue cyst formation early after excystation. However, in the absence of stressH. hammondispontaneously converted to a terminally differentiated tissue cyst stage whileT. gondiidid not. CulturedH. hammondicould infect new host cells for up to 8 days following excystation, and this period was exploited to generate stably transgenicH. hammondi. Coupled with RNAseq analyses, our data clearly show thatH. hammondizoites grow as stringently regulated life stages that are fundamentally distinct fromT. gondiitachyzoites and bradyzoites.
Metabolic engineering ofEscherichia colifor production of valerenadiene
Authors: Eric Nybo S. , Saunders Jacqueline , McCormick Sean P.
Published: June 2017

Valeriana officinalisis a medicinal herb which produces a suite of compounds in its root tissue useful for treatment of anxiety and insomnia. The sesquiterpene components of the root extract, valerenic acid and valerena-1,10-diene, are thought to contribute to most of the observed anxiolytic of Valerian root preparations. However, valerenic acid and its biosynthetic intermediates are only produced in low quantities in the roots ofV. officinalis. Thus, in this report,Escherichia coliwas metabolically engineered to produce substantial quantities of valerena-1,10-diene in shake flask fermentations with decane overlay. Expression of the wildtype valerenadiene synthase gene (pZE-wvds) resulted in production of 12 μg/mL in LB cultures using endogenous FPP metabolism. Expression of a codon-optimized version of the valerenadiene synthase gene (pZE-cvds) resulted in 3-fold higher titers of valerenadiene (32 μg/mL). Co-expression of pZE-cvdswith an engineered methyl erythritol phosphate (MEP) pathway improved valerenadiene titers 65-fold to 2.09 mg/L valerenadiene. Optimization of the fermentation medium to include glycerol supplementation enhanced yields by another 5.5-fold (11.0 mg/L valerenadiene). The highest production of valerenadiene resulted from engineering the codon-optimized valerenadiene synthase gene under strong Ptrcand PT7promoters and via co-expression of an exogenous mevalonate (MVA) pathway. These efforts resulted in anE. coliproduction strain that produced 62.0 mg/L valerenadiene (19.4 mg/L/OD600specific productivity). ThisE. coliproduction platform will serve as the foundation for the synthesis of novel valerenic acid analogues potentially useful for the treatment of anxiety disorders.
Challenges in estimating the motility parametersn of single processive motor proteins
Authors: Ruhnow F. , Kloß L. , Diez S.
Published: June 2017

Cytoskeletal motor proteins are essential to the function of a wide range of intracellular mechanosystems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Towards this end, single-molecule,in vitrostepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods. Here, we investigate the movement of fluorescently-labeled, processive, dimeric motor proteins and propose a unified algorithm to correct the measurements for finite filament length as well as photobleaching. Particular emphasis is put on estimating the statistical errors associated with the proposed evaluation method as knowledge of these values is crucial when comparing measurements from different experiments. Testing our approach with simulated and experimental data from GFP-labeled kinesin-1 motors stepping along immobilized microtubules, we show (i) that velocity distributions should be fitted by atlocation-scale probability density function rather than by a norm*al distribution, (ii) that the impossibility to measure events shorter than the image acquisition time needs to be accounted for, (iii) that the interaction time and run length of the motors can be estimated independent of the filament length distribution, and (iv) that the dimeric nature of the motors needs to be considered when correcting for photobleaching. Moreover, our analysis reveals that controlling the temperature during the experiments with a precision below 1 K is of importance. We believe, our method will not only improve the evaluation of experimental data, but will also allow for better statistical comparisons between different populations of motor proteins (e.g. with distinct mutations or linked to different cargos) and filaments (e.g. in distinct nucleotide states or with different posttranslational modifications).
Gaining insights from RNA-Seq data using iDEP
Authors: Ge Steven Xijin , Son Eun Wo
Published: June 2017

The analysis and interpretation of the RNA-Seq data can be time-consuming and challenging. We aim to streamline the bioinformatic analyses of gene-level data by developing a user-friendly web application for exploratory data analysis, differential expression, and pathway analysis. iDEP (integrated Differential Expression and Pathway analysis) seamlessly connects 63 R/Bioconductor packages, 208 annotation databases for plant and animal species, and 2 web services. The workflow can be reproduced by downloading customized R code and related files. As demonstrated by two examples, iDEP (http://ge-lab.org/idep/) democratizes access to bioinformatics resources and empowers biologists to easily gain actionable insights from transcriptomic data.
Age differentiation within grey matter, white matter and between memory and white matter in an adult lifespan cohort
Authors: Mooij Susanne M. M. de , Henson Richard N. A. , Waldorp Lourens J. , Cam-CAN  , Kievit Rogier A.
Published: June 2017

It is well-established that brain structures and cognitive functions change across the lifespan. A longstanding hypothesis calledage differentiationadditionally posits that the relations between cognitive functions also change with age. To date however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multi-group Structural Equation Modeling and SEM Trees to study differenceswithinandbetweenbrain and cognition across the adult lifespan (18-88 years) in a large (N>646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of grey-matter volume (from T1- and T2-weighted MRI) and white-matter organisation (fractional anisotropy from Diffusion-weighted MRI), we found evidence for differentiation of grey and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation between fluid intelligence, language and memory, suggesting a relatively stable covariance pattern between cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.

Significance statement

The theory of age differentiation posits age-related changes in the relationships between cognitive domains, either weakening (differentiation) or strengthening (de-differentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult lifespan sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change between cognitive factors of fluid intelligence, language and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.
Incarcerated youth mental and physical health: parity of esteem
Authors: Singh Yolisha , Kasinathan John , Kennedy Andrew
Published: June 2017

Purpose

The purpose of this paper is to describe physical and mental health characteristics of incarcerated youth both internationally and in New South Wales (NSW) Australia. To outline current practices in the provision of mental and physical healthcare for incarcerated youth internationally and in NSW.

Design/methodology/approach

Population relevant literature will be outlined as applicable. Health service delivery will be discussed, with an emphasis on the experiences of NSW physical and mental health service provision for incarcerated youth.

Findings

This paper illustrates that in NSW there was a parity of provision between physical and mental healthcare, though there were deficits in what should ideally be provided. Internationally there was clear evidence that current minimum standards of healthcare in both physical and mental healthcare domains remain unmet.

Practical implications

Provision of physical and mental healthcare for incarcerated youth warrants global improvement. Further research into current provisions, across jurisdictions and subsequent standardisation of practice, will improve health outcomes for this vulnerable group.

Originality/value

This is the first paper to describe mental and physical healthcare provision in NSW for incarcerated youth framed within the broader context of international health service provision for similar populations.