bluuebunny/crossref_metadata_2025_split huggingface dataset:
GC-Recomposition-Olfactometry (GC-R) and multivariate study of three terpenoid compounds in the aroma profile of Angostura bitters
Authors: Johnson Arielle J. , Hjelmeland Anna K. , Heymann Hildegarde , Ebeler Susan E. 
Published: May 2019

AbstractFoods and beverage aroma results from multicomponent mixtures of volatile compounds present in the food that interact with olfactory receptors and produce a perceptual response in the brain. However, the perceptual interactions that occur when complex odor mixtures are combined are not well understood. Here we used Gas chromatography-Recomposition-Olfactometry (GC-R) to better understand the role that individual compounds have on the perceived sensory aroma of bitters. Bitters are the concentrated alcoholic extract of flavorful plant materials with a wide range of complex sensory and chemical aroma profiles that have not been extensively studied. Previously, we demonstrated that Angostura bitters are characterized by complex aroma attributes described as cola, ginger, orange peel, and black pepper and that the volatile composition of Angostura bitters is predominantly composed of terpenoids. Using GC-R to create in-instrument mixtures of the Angostura headspace extracts, the sensory attributes of Angostura extracts with linalool, α-terpinyl-acetate and caryophyllene omitted were evaluated. The omission experiments demonstrated direct and indirect effects of the individual compounds on the aroma attributes of Angostura bitters, through masking, additive, and synergistic interactions. Caryophyllene in particular, which was present in the headspace extracts at concentration only slightly above sensory threshold levels, had a large and unexpected impact on the sensory properties of the mixtures and may be most responsible for the aromas associated with the whole sample. The GC-R and statistical approaches used here provided valuable tools to reveal relationships among individual compounds and aroma attributes of foods that have not been currently theorized using existing analytical approaches.
Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031
Authors: Sarr Awa , Bré Jennifer , Um In Hwa , Chan Tsz Huen , Mullen Peter , Harrison David J. , Reynolds Paul A. 
Published: May 2019

AbstractGemcitabine is a fluoropyrimidine analogue that is used as a mainstay of chemotherapy treatment for pancreatic and ovarian cancers, amongst others. Despite its widespread use, gemcitabine achieves responses in less than 10% of patients with metastatic pancreatic cancer and has a very limited impact on overall survival due to intrinsic and acquired resistance. NUC-1031 (Acelarin), a phosphoramidate transformation of gemcitabine, was the first anti-cancer ProTide to enter the clinic. We find it displays important in vitro cytotoxicity differences to gemcitabine, and a genome-wide CRISPR/Cas9 genetic screening approach identified only the pyrimidine metabolism pathway as modifying cancer cell sensitivity to NUC-1031. Low deoxycytidine kinase expression in tumour biopsies from patients treated with gemcitabine, assessed by immunostaining and image analysis, correlates with a poor prognosis, but there is no such correlation in tumour biopsies from a Phase I cohort treated with NUC-1031.
Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
Authors: Iwasaki Ryo , Tsuge Kyoshiro , Kishimoto Koichiro , Hayashi Yuta , Iwaana Takuya , Hohjoh Hirofumi , Inazumi Tomoaki , Kawahara Atsuo , Tsuchiya Soken , Sugimoto Yukihiko 
Published: May 2019

AbstractLymphatic endothelial cells arise from the venous endothelial cells in embryonic lymphatic development. However, the molecular mechanisms remain to be elucidated. We here report that prostaglandin (PG) E2 plays essential roles in the embryonic lymphatic development through the EP3 receptor, one of the PGE2 receptors. Knockdown of the EP3 receptor or inhibition of cyclooxygenases (COX; rate-limiting enzymes for PG synthesis) impaired lymphatic development by perturbing lymphatic specification during zebrafish development. These impairments by COX inhibition were recovered by treatment with sulprostone (EP1/3 agonist). Knockdown of the EP3 receptor further demonstrated its requirement in the expression of sex determining region Y-box 18 (sox18) and nuclear receptor subfamily 2, group F, member 2 (nr2f2), essential factors of the lymphatic specification. The EP3 receptor was expressed in the posterior cardinal vein (region of embryonic lymphatic development) and the adjacent intermediate cell mass (ICM) during the lymphatic specification. COX1 was expressed in the region more upstream of the posterior cardinal vein relative to the EP3 receptor, and the COX1-selective inhibitor impaired the lymphatic specification. On the other hand, two COX2 subtypes did not show distinct sites of expression around the region of expression of the EP3 receptor. Finally, we generated EP3-deficient zebrafish, which also showed defect in lymphatic specification and development. Thus, we demonstrated that COX1-derived PGE2-EP3 pathway is required for embryonic lymphatic development by upregulating the expression of key factors for the lymphatic specification.
The effect of 808 nm and 905 nm wavelength light on recovery after spinal cord injury
Authors: Svobodova Barbora , Kloudova Anna , Ruzicka Jiri , Kajtmanova Ludmila , Navratil Leos , Sedlacek Radek , Suchy Tomas , Jhanwar-Uniyal Meena , Jendelova Pavla , Machova Urdzikova Lucia 
Published: May 2019

AbstractWe investigated the effect of a Multiwave Locked System laser (with a simultaneous 808 nm continuous emission and 905 nm pulse emission) on the spinal cord after spinal cord injury (SCI) in rats. The functional recovery was measured by locomotor tests (BBB, Beam walking, MotoRater) and a sensitivity test (Plantar test). The locomotor tests showed a significant improvement of the locomotor functions of the rats after laser treatment from the first week following lesioning, compared to the controls. The laser treatment significantly diminished thermal hyperalgesia after SCI as measured by the Plantar test. The atrophy of the soleus muscle was reduced in the laser treated rats. The histopathological investigation showed a positive effect of the laser therapy on white and gray matter sparing. Our data suggests an upregulation of M2 macrophages in laser treated animals by the increasing number of double labeled CD68+/CD206+ cells in the cranial and central parts of the lesion, compared to the control animals. A shift in microglial/macrophage polarization was confirmed by gene expression analysis by significant mRNA downregulation of Cd86 (marker of inflammatory M1), and non-significant upregulation of Arg1 (marker of M2). These results demonstrated that the combination of 808 nm and 905 nm wavelength light is a promising non-invasive therapy for improving functional recovery and tissue sparing after SCI.
Effect of endogenous microbiota on the molecular composition of cloud water: a study by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS)
Authors: Bianco Angelica , Deguillaume Laurent , Chaumerliac Nadine , Vaïtilingom Mickaël , Wang Miao , Delort Anne-Marie , Bridoux Maxime C. 
Published: May 2019

AbstractA cloud water sample collected at the puy de Dôme observatory (PUY) has been incubated under dark conditions, with its endogenous microbiota at two different temperatures (5 and 15 °C), and the change in the molecular organic composition of this sample was analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Microorganisms were metabolically active and strongly modified the dissolved organic matter since they were able to form and consume many compounds. Using Venn diagrams, four fractions of compounds were identified: (1) compounds consumed by microbial activity; (2) compounds not transformed during incubation; (3) compounds resulting from dark chemistry (i.e., hydrolysis and Fenton reactions) and, finally, (4) compounds resulting from microbial metabolic activity. At 15 °C, microorganisms were able to consume 58% of the compounds initially present and produce 266 new compounds. For this cloud sample, the impact of dark chemistry was negligible. Decreasing the temperature to 5 °C led to the more efficient degradation of organic compounds (1716 compounds vs. 1094 at 15 °C) but with the less important production of new ones (173). These transformations were analyzed using a division into classes based on the O/C and H/C ratios: lipid-like compounds, aliphatic/peptide-like compounds, carboxylic-rich alicyclic molecule (CRAM)-like structures, carbohydrate-like compounds, unsaturated hydrocarbons, aromatic structures and highly oxygenated compounds (HOCs). Lipid-like, aliphatic/peptide-like and CRAMs-like compounds were the most impacted since they were consumed to maintain the microbial metabolism. On the contrary, the relative percentages of CRAMs and carbohydrates increased after incubation.
Risk factors for distant metastasis of patients with primary triple-negative breast cancer
Authors: Yao Yi , Chu Yuxin , Xu Bin , Hu Qinyong , Song Qibin 
Published: May 2019

AbstractObjective: Triple-negative breast cancer (TNBC) involves higher rates of recurrence and distant metastasis. The present study sought to characterize the risk factors for distant metastasis of TNBC.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was exploited to enroll patients diagnosed with TNBC from 2010 to 2015. The eligible patients were dichotomized into locoregional and distant metastasis at the time of diagnosis. Patients’ demographics and tumor features, and treatment were evaluated to identify the risk factors for distant metastasis of primary TNBC. The categorical variables were examined by chi-square tests. Univariate and multivariate logistic regression analyses were used to determine the risk factors for distant metastasis. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated by Kaplan–Meier plots with log-rank tests.Results: We collected 26863 patients with primary TNBC, 1330 (5.0%) of them presented with distant metastasis. In the univariate analysis, all the variables indicated statistical significance. The significant variables were subsequently enlisted into the multivariate logistic regression analysis. Age &gt; 50, higher clinical stage T and N, and tumor size &gt; 5 cm were independent risk factors for distant metastasis of primary TNBC. Moreover, higher clinical stage T and stage N were independent risk factors for bone metastasis of the patients. TNBC patients with either bone or visceral metastasis have poor survival, with brain metastasis worst of all, though the OS difference was not statistically significant.Conclusions: TNBC patients with larger age, higher clinical stage, larger tumor size were more predisposed to have distant metastasis. Great attention should be paid to the prognosis of these patients with distant metastasis.
Quantifying CRISPR off-target effects
Authors: Gkazi Soragia Athina 
Published: May 2019

Abstract
Recent advances in the era of genetic engineering have significantly improved our ability to make precise changes in the genomes of human cells. Throughout the years, clinical trials based on gene therapies have led to the cure of diseases such as X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency (ADA-SCID) and Wiskott–Aldrich syndrome. Despite the success gene therapy has had, there is still the risk of genotoxicity due to the potential oncogenesis introduced by utilising viral vectors. Research has focused on alternative strategies like genome editing without viral vectors as a means to reduce genotoxicity introduced by the viral vectors. Although there is an extensive use of RNA-guided genome editing via the clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein-9 (Cas9) technology for biomedical research, its genome-wide target specificity and its genotoxic side effects remain controversial. There have been reports of on- and off-target effects created by CRISPR–Cas9 that can include small and large indels and inversions, highlighting the potential risk of insertional mutagenesis. In the last few years, a plethora of in silico, in vitro and in vivo genome-wide assays have been introduced with the sole purpose of profiling these effects. Here, we are going to discuss the genotoxic obstacles in gene therapies and give an up-to-date overview of methodologies for quantifying CRISPR–Cas9 effects.
The Finite Verb Morphology Composite: Values From a Community Sample
Authors: Rudolph Johanna M. , Dollaghan Christine A. , Crotteau Simone 
Published: May 2019

Purpose
We investigated the finite verb morphology composite (FVMC), a measure associated with developmental language disorder (DLD), in a large community sample to provide evidence on its distribution, its association with other variables, and its sensitivity and specificity.

Method

We coded percent occurrence of FVMC morphemes in obligatory contexts in archival language samples from 676 six-year-olds conversing with an adult family member. Using multiple regression, we quantified the variance in FVMC scores accounted for by language sample characteristics (number of utterances and obligatory contexts) and child/family variables (performance IQ, family history, maternal education, and adult FVMC). We calculated sensitivity and specificity of low (< 85%) FVMC scores for predicting low (−1
SD
) scores on measures of utterance length, receptive vocabulary, and nonword repetition.

Results

FVMC scores ranged from 33% to 100% (
M
= 93%). Number of obligatory contexts (
R
2
= 3%), performance IQ (
R
2
= 11%), and adult FVMC (
R
2
= 18%) were significant covariates. Sensitivity ranged from 25% to 35%; specificity was from 91% to 92%.

Conclusion
FVMC scores at the age of 6 years were generally high, but 12% of the participants had FVMCs below 85%, and scores were significantly associated with characteristics of the language samples, children, and adult interlocutors. Sensitivity of the FVMC was considerably lower in this community sample than in previous studies comparing groups of children who met criteria for DLD or typical language. Evidence from large representative samples is important when developing and validating potential clinical markers of DLD.
Sexual Function and Socio-Sexual Difficulties in Women with Polycystic Ovary Syndrome (PCOS)
Authors: Fliegner Maike , Richter-Appelt Hertha , Krupp Kerstin , Brunner Franziska 
Published: May 2019

Abstract
Introduction PCOS is the most common endocrine syndrome in women of the reproductive age that has manifold effects on the life of affected women. Little scientific attention has been devoted to these womenʼs sexual lives.
Aim To investigate sexual quality of life in women with PCOS.
Methods The sample size was n = 44. Measures employed were: An extended list of sexual dysfunctions and perceived distress based on DSM-IV-TR, Female Sexual Function Index (FSFI), German Questionnaire on Feelings of Inadequacy in Social and Sexual Situations (FUSS), Rosenberg Self-Esteem Scale (RSE), Brief Symptom Inventory (BSI) subscale depression. The relationships of these components were examined including further variables (body mass index, degree of hirsutism using the Ferriman-Gallwey Score, wish for a child). An open question about what participants see as the source of their sexual problems was presented.
Results Only moderate impairment in sexual function was detected, but feelings of inadequacy in social and sexual situations were markedly elevated and positively correlated with the degree of hirsutism. Depression showed to be a major problem.
Conclusion Patients with PCOS should be screened for socio-sexual difficulties and emotional problems. Specialized psychological and sexological counselling can complement patient care.
Zum „konkurrierenden Fluss“ in der Shuntchirurgie
Authors: Krönung Gerhard 
Published: May 2019

ZUSAMMENFASSUNGEin „konkurrierender Fluss“ ist eine nicht seltene hämodynamische Variante in der Shuntchirurgie. Er muss assoziiert/bemerkt, die relative Anteiligkeit der konkurrierenden Strombahnen an der venösen Drainage beschrieben und bewertet werden und beeinflusst dann regelhaft die Taktik bei Indikation und Operation/Intervention.
Update Mammakarzinom 2018 (Teil 3) – Genomforschung, individualisierte Medizin und Immuntherapien – mitten in einer neuen Ära: Prävention und Therapie des frühen Mammakarzinoms
Authors: Wöckel Achim , Lux Michael , Janni Wolfgang , Hartkopf Andreas , Nabieva Naiba , Taran Florin-Andrei , Overkamp Friedrich , Hadji Peyman , Tesch Hans , Ettl Johannes , Lüftner Diana , Müller Volkmar , Welslau Manfred , Belleville Erik , Brucker Sara , Schütz Florian , Fasching Peter , Fehm Tanja , Schneeweiss Andreas , Kolberg Hans-Christian 
Published: May 2019

ZusammenfassungBeim primären, frühen Mammakarzinom zielt die Behandlungsplanung auf ein immer besseres Verständnis der Erkrankung ab. Die Identifikation von Patientinnen mit einer exzellenten Prognose könnte dieser Gruppe helfen, unnötige Therapien zu vermeiden.Weiterhin wird die Planung der Therapie immer weiter auf die Patientin abgestimmt. Das Wissen über Patientinnen, die besonders von einer Chemotherapie profitieren, wächst genauso wie das Wissen um Patientinnen, die von einer Immuntherapie profitieren könnten. Hinsichtlich der Immuntherapien stehen die durchgeführten Studien kurz vor der Publikation. Einzelne kleinere Studien bieten einen ersten Einblick in die Wirksamkeit der Checkpoint-Inhibitoren (Anti-PD1 / PDL1-Therapien). Nicht zuletzt konnte kürzlich eine der größten Brustkrebsstudien aller Zeiten zu Ende geführt werden. Die Anwendung eines Multigentests konnte zeigen, dass er ausreicht, um Patientinnen mit einer so guten Prognose zu identifizieren, dass keine Chemotherapie nötig ist. Dieser Review-Artikel soll die aktuellen Studien zusammenfassen und einen Ausblick der gegenwärtigen Entwicklungen geben.
Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis
Authors: Hartkopf Andreas , Müller Volkmar , Wöckel Achim , Lux Michael , Janni Wolfgang , Nabieva Naiba , Taran Florin-Andrei , Ettl Johannes , Lüftner Diana , Belleville Erik , Schütz Florian , Fasching Peter , Fehm Tanja , Kolberg Hans-Christian , Overkamp Friedrich , Schneeweiss Andreas , Tesch Hans 
Published: May 2019

ZusammenfassungIn der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt.
Informationen im Internet zu humangenetischen Untersuchungen (bei Kindern) zur Ursachenklärung von Intelligenzminderung oder Epilepsien
Authors: Borusiak Peter , Mazheika Yuliya 
Published: May 2019

Zusammenfassung
Hintergrund Genetische Untersuchungsmethoden haben eine bedeutsame Rolle bei der Abklärung der Ätiologie bei Kindern mit Entwicklungsstörungen, Intelligenzminderungen und Epilepsien. Angesichts des Klientel und der Komplexität der Untersuchungsmethoden ist eine angemessene Aufklärung eine Herausforderung. Internetbasierte Informationen könnten hierbei hilfreich sein.
Methoden Es erfolgte eine systematische Recherche und Bewertung von internetbasierten Informationen der pädiatrischen Fachverbände und der bei den humangenetischen Fachgesellschaften gelisteten Institute und Praxen mittels standardisierter und validierter Instrumente (u. a. DISCERN Genetics, LIDA, LIX).
Ergebnisse Auf 111 Homepages waren Informationen zu finden. Die Darstellung der Seiten und die Navigation können als zufriedenstellend eingeordnet werden. Die Inhalte sind teilweise lückenhaft und schwer verständlich formuliert. Die Einverständniserklärungen bieten z. T. eingeschränkte Möglichkeiten der Entscheidung. Der Schwierigkeitsgrad der Texte ist überwiegend in den Bereichen „hoch“ bis „sehr hoch“ einzuordnen. Informationen in einfacher Sprache fehlen komplett. Fremdsprachige Informationen sind nur eingeschränkt verfügbar.
Schlussfolgerung Eine Verbesserung der Aufklärung könnte über die Bereitstellung von geeigneten internetbasierten Materialien als Vorbereitung auf das Aufklärungsgespräch erfolgen. Eine barrierefreie Umsetzung könnte bspw. durch die Verwendung von einfacher Sprache, Audioversionen, grafischer Unterstützung und fremdsprachigen Informationen erfolgen.
NADia – Netzwerk Assistierte Dialyse
Authors: Iseke Kerstin-Brigitte , Oleimeulen Ursula , Greuèl Marius , Rockenbach Jörg , Kitsche Benno 
Published: May 2019

ZUSAMMENFASSUNGTrotz der Vielfalt der in Deutschland angebotenen Dialyseformen klafft noch immer eine Versorgungslücke für hilfebedürftige dialysepflichtige Patienten, die sich für ein Heimdialyseverfahren entschieden haben. Versorgungsformen der assistierten Dialyse wie assistierte Peritonealdialyse (aPD) und assistierte Heimhämodialyse (aHHD) sind bislang nicht als anerkannte Therapiemöglichkeiten im Richtlinienkatalog der häuslichen Krankenpflege vorgesehen. Daher werden die Kostenerstattungen für die Leistungserbringer bislang nur durch Einzelfallentscheidungen bewilligt. Um diese Lücke zu schließen, gründete sich 2017 das Netzwerk NADia – Netzwerk Assistierte Dialyse, eine Initiative von Ärzten, Pflegekräften, Patienten, Mitarbeitern von Pflegediensten, Pflegeeinrichtungen und Gesundheitsunternehmen. Ziel von NADia ist es, bundesweite Strukturen zur Umsetzung der assistierten Dialyse zu etablieren.
Telemedizin mit Blick auf die Heimdialyseverfahren
Authors: Jahn Michael , Kopecky Jens , Meister Sven , Mülling Nils , Kribben Andreas , Becker Stefan 
Published: May 2019

ZUSAMMENFASSUNGDie Digitalisierung des Gesundheitswesens und auch der Nephrologie in Deutschland schreitet schnell voran. Nahezu täglich werden neue Teilprozesse in der Versorgung digitalisiert. Dabei können telemedizinische Ansätze die Betreuung von Heimdialysen und chronisch Nierenkranken verbessern. Die praktische Umsetzung ist allerdings im Hinblick auf die Datenschutzgrundverordnung, ärztliche Schweigepflicht, Medizinprodukteverordnung und einer vielschichtigen Gemengelage von Bedürfnissen sowie Rechten von Patienten, Ärzte und Industrie komplex.