bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation
Authors: Rojas Camilo , Barnaeva Elena , Thomas Ajit G. , Hu Xin , Southall Noel , Marugan Juan , Chaudhuri Amrita Datta , Yoo Seung-Wan , Hin Niyada , Stepanek Ondrej , Wu Ying , Zimmermann Sarah C. , Gadiano Alexandra G. , Tsukamoto Takashi , Rais Rana , Haughey Norman , Ferrer Marc , Slusher Barbara S. 
Published: December 2018

AbstractBrain injury and inflammation induces a local release of extracellular vesicles (EVs) from astrocytes carrying proteins, RNAs, and microRNAs into the circulation. When these vesicles reach the liver, they stimulate the secretion of cytokines that mobilize peripheral immune cell infiltration into the brain, which can cause secondary tissue damage and impair recovery. Recent studies suggest that suppression of EV biosynthesis through neutral sphingomyelinase 2 (nSMase2) inhibition may represent a new therapeutic strategy. Unfortunately, currently available nSMase2 inhibitors exhibit low potency (IC50 ≥ 1 μM), poor solubility and/or limited brain penetration. Through a high throughput screening campaign of >365,000 compounds against human nSMase2 we identified 2,6-Dimethoxy-4-(5-Phenyl-4-Thiophen-2-yl-1H-Imidazol-2-yl)-Phenol (DPTIP), a potent (IC50 30 nM), selective, metabolically stable, and brain penetrable (AUCbrain/AUCplasma = 0.26) nSMase2 inhibitor. DPTIP dose-dependently inhibited EV release in primary astrocyte cultures. In a mouse model of brain injury conducted in GFAP-GFP mice, DPTIP potently (10 mg/kg IP) inhibited IL-1β-induced astrocyte-derived EV release (51 ± 13%; p < 0.001). This inhibition led to a reduction of cytokine upregulation in liver and attenuation of the infiltration of immune cells into the brain (80 ± 23%; p < 0.01). A structurally similar but inactive analog had no effect in vitro or in vivo.
The expression of ecdysteroid UDP-glucosyltransferase enhances cocoon shell ratio by reducing ecdysteroid titre in last-instar larvae of silkworm, Bombyx mori
Authors: Shen Guanwang , Wu Jinxin , Wang Yong , Liu Hongling , Zhang Haiyan , Ma Sanyuan , Peng Chuyue , Lin Ying , Xia Qingyou 
Published: December 2018

AbstractEcdysteroid UDP glucosyltransferase (EGT) is a baculovirus-encoded protein which can hinder the normal molting of insects by inactivating 20-hydroxyecdysone (20E). Here we expressed EGT in the last-instar silkworm larvae using the GAL4/ UAS system. Compared with the control, for the EGT overexpressed silkworm, the hemolymph 20E content was significantly decreased, the feeding and spinning periods of the last-instar silkworm larvae were extended, the cocoon shell ratio was significantly increased, and the transformation from silkworm larvae to pupa was blocked. Increasing EGT expression resulted in the decrease of 20E content in the hemolymph of silkworm larvae, treating the EGT overexpressed male silkworm with 20E decreased the larval weight and cocoon shell ratio, confirming that the increase in the availability of nutrients to the cocoon and an increase in the cocoon shell weight in the hybrid transgenic silkworms is because of the EGT-induced reduction in active 20E content. Furthermore, though the sericin and flavonoid contents were increased in the cocoon of the EGT overexpressing silkworm, the production of silk fibroin didn’t change.
Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence
Authors: Khan Saif , Mandal Raju K. , Elasbali Abdulbaset Mohamed , Dar Sajad A. , Jawed Arshad , Wahid Mohd , Mahto Harishankar , Lohani Mohtashim , Mishra Bhartendu Nath , Akhter Naseem , Rabaan Ali A. , Haque Shafiul 
Published: December 2018

Abstract
Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C&gt;T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G&gt;A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G&gt;A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.
LncRNA HAND2-AS1 inhibits non-small cell lung cancer migration, invasion and maintains cell stemness through the interactions with TGF-β1
Authors: Miao Feng , Chen Ji , Shi Meng , Song Yang , Chen Zhiming , Pang Liewen 
Published: December 2018

Abstract
LncRNA HAND2-AS1 is characterized as a tumor suppressor involved in several types of malignancies, but its role in non-small cell lung cancer (NSCLC) is unknown. Our study was carried out to investigate the involvement of lncRNA HAND2-AS1 in NSCLC. In our study, we observed that levels of HAND2-AS1 were lower in tumor tissues than that in adjacent healthy tissues. Compared with healthy controls, plasma levels of HAND2-AS1 were lower, while levels of transforming growth factor β (TGF-β) were higher in NSCLC patients. A significant negative correlation between plasma levels of HAND2-AS1 and TGF-β1 was found in NSCLC patients but not in healthy controls. LncRNA HAND2-AS1 overexpression inhibits, while exogenous TGF-β1 treatment promotes cell migration and invasion ability and cancer cell stemness. Cancer cells with lncRNA HAND2-AS1 overexpression showed down-regulated TGF-β1, while TGF-β1 treatment showed no significant effects on lncRNA HAND2-AS1 expression. TGF-β1 attenuated the inhibitory effects of lncRNA HAND2-AS1 overexpression on cell migration, invasion and stemness. We concluded that lncRNA HAND2-AS1 may regulate the migration, invasion and stemness of NSCLC cells through interactions with TGF-β1.
Hepatitis-C-Therapie: State of the Art 2018
Authors: Zeuzem Stefan 
Published: December 2018

Was ist neu?
Ziele der antiviralen Therapie Ziel der individuellen antiviralen Therapie ist die dauerhafte Viruseradikation, populationsbezogen die Elimination des Hepatitis-C-Virus (HCV) (Ziel der WHO bis 2030).
Antivirale Medikamente und Medikamenteninteraktionen Zur antiviralen Therapie stehen Inhibitoren der RNA-abhängigen RNA-Polymerase, der NS3/4A-Protease und des NS5A-Proteins des HCV sowie Ribavirin zur Verfügung. Typischerweise werden 2 spezifische Inhibitoren kombiniert, die Therapiedauer liegt für die Mehrheit der Patienten bei 8 – 12 Wochen.
Pan-genotypische und Genotypen-restringierte Kombinationstherapien Zwei pan-genotypische Kombinationstherapien stehen zur Verfügung: Sofosbuvir/Velpatasvir sowie Glecaprevir/Pibrentasvir. In der Differenzialtherapie sind die Leber- und Nierenfunktion sowie Medikamenteninteraktionen zu berücksichtigen. Die dauerhaften virologischen Ansprechraten liegen über 95 %, die Sicherheit und Verträglichkeit der Medikamente ist sehr gut.
Therapie spezieller Patientenpopulationen Protease-Inhibitoren sind bei Patienten mit einer dekompensierten Zirrhose kontraindiziert. Sofosbuvir ist bei Patienten mit schwerer Niereninsuffizienz nicht zugelassen. Die Re-Therapie von Nonrespondern auf die Interferon-freie Therapie erfolgt mit Sofosbuvir/Velpatasvir/ Voxilaprevir.
Diagnostik und Therapie bei interstitiellen Lungenerkrankungen
Authors: Jakubczyc Anna , Neurohr Claus 
Published: December 2018

Was ist neu?
Anamnese Der neue Fragebogen der Deutschen Gesellschaft für Pneumologie (DGP) erleichtert die Erhebung der komplexen Anamnese bei interstitiellen Lungenerkrankungen.
Bildgebende Diagnostik Die Veröffentlichung des Fleischner Society White Papers betont die Bedeutung der hochauflösenden Computertomografie (HRCT) bei der Diagnostik der IPF. Die neuen internationalen Leitlinien betonen den Stellenwert der interdisziplinären Diskussion auch bereits vor der invasiven Diagnostik, insbesondere bei nicht eindeutigen interstitiellen Veränderungen.
Invasive Diagnostik Die histologische Diagnostik der fibrotischen Veränderungen wird bei untypischen CT-Befunden bzw. bei den unstimmigen Ergebnissen der Anamnese, der Laborbefunde und der bildgebenden Diagnostik gefordert. Die videoassistierte Thorakoskopie (VATS) mit Keilexzision ist weiterhin der Goldstandard. Die Bronchoskopie mit transbronchialer Kryobiopsie als diagnostische Alternative hat zunehmend an Bedeutung gewonnen.
Therapie Die 2017 veröffentlichten deutschen Leitlinien zur medikamentösen Therapie der IPF standardisieren das therapeutische Vorgehen. Die Behandlung mit einem der beiden zugelassenen antifibrotischen Medikamente (Pirfenidon, Nintedanib) sollte zeitnah nach Diagnosestellung begonnen werden und ist als Dauertherapie durchzuführen. Bei Unverträglichkeit bzw. Krankheitsprogress kann auf ein Alternativpräparat umgestellt werden. Von Kombinationstherapie beider Wirkstoffe wird abgeraten.
Opportunistische Infektionen: Was gibt es Neues?
Authors: Boesecke Christoph , Rockstroh Jürgen , Thoden Jan 
Published: December 2018

Was ist neu?
Zerebrale Toxoplasmose Als intravenöse Therapie ist die Gabe von Trimethoprim und Sulfamethoxazol möglich. Auch als orale Prophylaxe können sie nun schon ab einer CD4-T-Helferzellzahl von < 200/µl eingesetzt werden.
Pneumocystis jiroveci Zur Prophylaxe und Therapie der Pneumocystis-jiroveci-Pneumonie ist die Kombination aus Trimethoprim und Sulfamethoxazol weiterhin Mittel der Wahl.
Kryptokokkose Eine neue Therapieoption besteht aus liposomalem Amphotericin B plus Fluconazol.
Tuberkulose Um ein Immunrekonstitutions-Inflammations-Syndrom (IRIS) zu vermeiden, kann eine präventive Steroidbehandlung in Betracht gezogen werden.
Humanes Herpes-Virus Typ 8 (HHV8) Das „Kaposi-Sarkom-Herpesvirus-Inflammations-Zytokin-Syndrom“ (KICS) wurde als neue HHV8-assoziierte Erkrankung beschrieben.
Varizella zoster In der Therapie sollte man Lokalisation und Ausbreitung berücksichtigen.
Die Pathophysiologie des Lungenemphysems – Laënnec (1781–1826) hatte Recht!
Authors: Koehler U. , Hildebrandt O. , Dittrich M. , Koehler N. , Weissflog A. 
Published: December 2018

ZusammenfassungDas Lungenemphysem ist definiert als irreversible Erweiterung des Luftraums distal der terminalen Bronchiolen. Die kleinen Atemwege < 2 mm Durchmesser sind der Bereich, bei dem es bei Patienten mit einer chronischen obstruktiven Atemwegserkrankung (COPD) zu einer chronischen Inflammation mit bronchialer Obstruktion kommt. 80 – 90 % der terminalen Bronchiolen sind bei Patienten mit schwergradiger COPD zerstört. Neuere Daten belegen, dass bereits bei leichter bis moderater COPD GOLD 1 und 2 etwa 40 % der terminalen und 60 % der transitionalen Bronchiolen destruiert sind. Morphologische Zeichen des Emphysems weisen diese Patienten jedoch noch nicht auf. Erst bei einer kritischen Prozentzahl zerstörter terminaler und respiratorischer Bronchiolen scheint es zum Auftreten einer klinischen Symptomatik sowie zur Emphysementstehung zu kommen.
Acute Exercise Increases the Expression of KIR2DS4 by Promoter Demethylation in NK Cells
Authors: Schenk Alexander , Pulverer Walter , Koliamitra Christine , Bauer Claus , Ilic Suzana , Heer Rudolf , Schier Robert , Schick Volker , Böttiger Bernd , Gerhäuser Clarissa , Bloch Wilhelm , Zimmer Philipp 
Published: December 2018

AbstractPositive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50–60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention. Blood samples (pre-, post-GXT and post-training) were used for isolation of DNA/RNA of NK cells to assess DNA promoter methylation by targeted deep-amplicon sequencing and gene expression by qRT-PCR. Potential changes in NK cell subsets were determined by flow cytometry. Acute and chronic exercise did not provoke significant alterations of NK cell proportions. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. A high gene expression correlated with a low methylation of CpGs that were altered by acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression. Acute exercise provokes epigenetic modifications, affecting the balance between the activating KIR2DS4 and the inhibiting KIR3DL1, with potential benefits on NK cell function.
Sex Differences in Aortic Hemodynamics Following Acute Exercise: Wave Separation Analysis
Authors: Wee Sang , Yan Huimin , Lane-Cordova Abbi , Ranadive Sushant , Rosenberg Alexander , White Daniel , Fernhall Bo 
Published: December 2018

AbstractThe importance of sex differences in the control of blood pressure responses to exercise is controversial. It is unknown whether the potential sex differences are a result of magnitude differences in forward or reflected pressure waves. The purpose of this study was to investigate sex differences in BP following acute exercise using wave separation analysis. Sixty-eight adults (36 females) participated in the study. Aerobic capacity was measured during a graded cycle ergometry test. Central pulse wave analysis was derived from the radial pulse using applanation tonometry and separated into forward and reflected pressure waves before, and 15 min and 30 min after maximum aerobic exercise. Both males and females exhibited significantly decreased brachial SBP (p<0.05) following acute exercise. However, only males exhibited a significant decrease in forward wave pressure (p<0.05). Reflected wave pressure was decreased following exercise in both sex (p<0.05) with no sex difference. Males and females differ in blood pressure control following maximal exercise. Results show that males rely on both central and peripheral hemodynamic modifications, whereas females mostly rely on peripheral modifications. The preferential peripheral adaptations in females may provide insight regarding mechanisms of blood pressure control and the disproportionate development of hypertension in young men compared to women.
Beeinflussung der Muskelaktivität von Unterarm und Schultergürtel durch verschiedene Computer-Eingabegeräte am Arbeitsplatz
Authors: Sturm Jeanette , Brockhaus Fabienne , Briest Juliane , Gutenbrunner Christoph , Sturm Christian 
Published: December 2018

Zusammenfassung
Fragestellung Wegen epidemiologisch hoher Prävalenz von Schulter- und Nackenschmerzen besteht Anlass zur Ursachenforschung, weshalb wir Muskelaktivitäten bei Nutzung verschiedener PC-Eingabegeräte verglichen.
Material und Methoden Wir maßen bei 34 Probanden die Muskelaktivität des Armes und Schultergürtels mittels Oberflächen-EMG in standardisiertem Arbeitsplatzsetting und erhoben durch Fragebögen die Nutzerakzeptanz.
Ergebnisse Bei Nutzung einer weit verbreiteten Standard-Maus zeigte sich in allen gemessenen Muskeln statistisch signifikant gegenüber ergonomischeren Eingabegeräten die höchste Aktivität. Die Auswertung der Fragebögen ergab stark variierende Bewertungen: geringere Aktivierung der Muskulatur korrelierte nicht mit subjektivem Komfort.
Diskussion und Schlussfolgerung Zur Reduktion von Muskelbeanspruchungen im Schulter-/Nackenbereich kann der Wechsel auf ein ergonomischeres Eingabegerät hilfreich sein. Je nach Beschwerdebild kann das passende Gerät nach unseren Daten ausgewählt werden. Zu berücksichtigen ist die zu erwartende Akzeptanz der Nutzer.
In Würde zu sich stehen – Konzept und Wirksamkeit eines peer-geleiteten Programms zu Offenlegung und Stigmabewältigung
Authors: Rüsch Nicolas , Oexle Nathalie , Reichhardt Lea , Ventling Stephanie 
Published: December 2018

Zusammenfassung
Hintergrund Menschen mit psychischen Erkrankungen stehen aufgrund verbreiteter Stigmatisierung oft vor der schwierigen Entscheidung, ob sie ihre Erkrankung anderen gegenüber offenlegen sollen.
Methode Konzept und Inhalte von ‚In Würde zu sich stehen‘ (IWS), einem kompakten peer-geleiteten Gruppenprogramm, werden beschrieben.
Ergebnisse IWS unterstützt Teilnehmer mit psychischen Erkrankungen bei Offenlegungsentscheidungen und Stigmabewältigung. Drei RCTs zeigen positive Effekte von IWS.
Schlussfolgerungen Fragen der Wirksamkeit, Implementierung und Weiterentwicklung von IWS werden diskutiert.
The Hantzsch Pyrrole Synthesis: Non-conventional Variations and Applications of a Neglected Classical Reaction
Authors: Menéndez J. , Leonardi Marco , Estévez Verónica , Villacampa Mercedes 
Published: December 2018

Pyrrole is one of the most important one-ring heterocycles because of its widespread presence in natural products and unnatural bioactive compounds and drugs in clinical use. The preparation of pyrroles by reaction between primary amines, β-dicarbonyl compounds, and α-halo ketones, known as the Hantzsch pyrrole synthesis, is reviewed here for the first time. In spite of its age and its named reaction status, this method has received little attention in the literature. Recent work involving the use of non-conventional conditions has rejuvenated this classical reaction and this is emphasized in this review. Some applications of the Hantzsch reaction in target-oriented synthesis are also discussed.1	Introduction2	The Conventional Hantzsch Pyrrole Synthesis3	Hantzsch Pyrrole Synthesis under Non-conventional Conditions4	Applications of the Hantzsch Pyrrole Synthesis5	Conclusions
Accuracy Validation of 8 Equations to Estimate 24-Hour Sodium by Spot Urine in Young Adolescents
Authors: Dong Jie , Yan Yinkun , Fan Hui , Zhao Xiaoyuan , Mi Jie 
Published: December 2018

AbstractBACKGROUNDSeveral formulas using spot urine have been developed to estimate 24-hour sodium excretion, but none of them have been validated in pediatrics. We aimed to evaluate the performance of 8 formulas—Kawasaki; Tanaka; International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT1); INTERSALT without potassium (INTERSALT2); Mage; Whitton; Uechi simple-mean; and Uechi regression—in estimating 24-hour sodium excretion at both population and individual levels in Chinese young adolescents.METHODSThis cross-sectional study consisted of 284 students aged 10–15 years from Hunan, China. Two spot urine and 24-hour urine samples were collected from each participant.RESULTSThe median 24-hour urinary sodium excretion was 2,742 mg. The mean differences (95% confidence intervals) of 24-hour sodium excretion by the 8 equations were 1,613 (1,491 to 1,735) mg for Kawasaki, −12 (−97 to 73) mg for Tanaka, −214 (−319 to −110) mg for INTERSALT1, −289 (−394 to −185) mg for INTERSALT2, −615 (−730 to −500) mg for Mage, 1,082 (967 to 1,198) mg for Whitton, −479 (−610 to −348) mg for Uechi simple-mean, and −620 (−716 to −525) mg for Uechi regression. The Tanaka formula performed best in relative and absolute difference distributions, with 35.2% participants having relative differences within 10%, and 45.8% participants having absolute differences within 393 mg. The misclassification rates were all &gt;50% except for the Tanaka formula (43.7%).CONCLUSIONSIn our study, Tanaka could offer a plausible alternative of mean populational 24-hour sodium estimation for young adolescents. However, the results did not support the use of these equations in pediatrics at individual levels.
Gender differences in cognitive function and grip strength: a cross-national comparison of four European regions
Authors: Ahrenfeldt Linda Juel , Scheel-Hincke Lasse Lybecker , Kjærgaard Søren , Möller Sören , Christensen Kaare , Lindahl-Jacobsen Rune 
Published: December 2018

Abstract

Background
Cross-national comparison studies on gender differences have mainly focussed on life expectancy, while less research has examined differences in health across countries. We aimed to investigate gender differences in cognitive function and grip strength over age and time across European regions.

Methods
We performed a cross-sectional study including 51 292 men and 62 007 women aged 50 + participating in the Survey of Health, Ageing and Retirement in Europe between 2004–05 and 2015. Linear regression models were used to examine associations.

Results
In general, women had better cognitive function than men, whereas men had higher grip strength measures. Sex differences were consistent over time, but decreased with age. Compared with men, women had higher cognitive scores at ages 50–59, corresponding to 0.17 SD (95% CI 0.14, 0.20) but slightly lower scores at ages 80–89 (0.08 SD, 95% CI 0.14, 0.00). For grip strength, the sex difference decreased from 18.8 kg (95% CI 18.5, 19.1) at ages 50–59 to 8.5 kg (95% CI 7.1, 9.9) at age 90 + . Northern Europeans had higher cognitive scores (19.6%) and grip strength measures (13.8%) than Southern Europeans. Gender differences in grip strength were similar across regions, whereas for cognitive function they varied considerably, with Southern Europe having a male advantage from ages 60–89.

Conclusion
Our results illustrate that gender differences in health depend on the selected health dimension and the age group studied, and emphasize the importance of considering regional differences in research on cognitive gender differences.