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1

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Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial

Behr, Jürgen ; Prasse, Antje ; Kreuter, Michael ; [et al.]

Elsevier BV ; 2021

In: The Lancet Respiratory Medicine Vol. 9, No. 5 ( 2021-05), p. 476-486

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In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 9, No. 5 ( 2021-05), p. 476-486

Type of Medium: Online Resource

ISSN: 2213-2600

URL: Article

DOI: 10.1016/S2213-2600(20)30554-3

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2704917-6

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A chromosome-based draft sequence of the hexaploid bread wheat ( Triticum aestivum ) genome

The International Wheat Genome Sequencing Consortium (IWGSC) ; Mayer, Klaus F. X. ; Rogers, Jane ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2014

In: Science Vol. 345, No. 6194 ( 2014-07-18)

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In: Science, American Association for the Advancement of Science (AAAS), Vol. 345, No. 6194 ( 2014-07-18)

Abstract: An ordered draft sequence of the 17-gigabase hexaploid bread wheat ( Triticum aestivum ) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.

Type of Medium: Online Resource

ISSN: 0036-8075 , 1095-9203

URL: Article

DOI: 10.1126/science.1251788

RVK:

TA 1000

RVK:

WA 15000

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2014

detail.hit.zdb_id: 128410-1

detail.hit.zdb_id: 2066996-3

detail.hit.zdb_id: 2060783-0

SSG: 11

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3

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Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

Weuster, Matthias ; Mommsen, Philipp ; Pfeifer, Roman ; [et al.]

Hindawi Limited ; 2015

In: Mediators of Inflammation Vol. 2015 ( 2015), p. 1-11

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In: Mediators of Inflammation, Hindawi Limited, Vol. 2015 ( 2015), p. 1-11

Abstract: Background . The deterioration of hemodynamics instantly endangers the patients’ life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods . We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results . Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals’ hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions . Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia.

Type of Medium: Online Resource

ISSN: 0962-9351 , 1466-1861

URL: Article

DOI: 10.1155/2015/829195

Language: English

Publisher: Hindawi Limited

Publication Date: 2015

detail.hit.zdb_id: 2008065-7

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Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial

Barco, Stefano ; Schmidtmann, Irene ; Ageno, Walter ; [et al.]

Oxford University Press (OUP) ; 2020

In: European Heart Journal Vol. 41, No. 4 ( 2020-01-21), p. 509-518

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In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. 4 ( 2020-01-21), p. 509-518

Abstract: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 ( & lt;6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). Conclusion Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

Type of Medium: Online Resource

ISSN: 0195-668X , 1522-9645

URL: Article

DOI: 10.1093/eurheartj/ehz367

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

detail.hit.zdb_id: 2001908-7

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5

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Targeted Therapy With the T-Cell–Engaging Antibody Blinatumomab of Chemotherapy-Refractory Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia Patients Results in High Response Rate and Prolonged Leukemia-Free Survival

Topp, Max S. ; Kufer, Peter ; Gökbuget, Nicola ; [et al.]

American Society of Clinical Oncology (ASCO) ; 2011

In: Journal of Clinical Oncology Vol. 29, No. 18 ( 2011-06-20), p. 2493-2498

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In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 18 ( 2011-06-20), p. 2493-2498

Abstract: Blinatumomab, a bispecific single-chain antibody targeting the CD19 antigen, is a member of a novel class of antibodies that redirect T cells for selective lysis of tumor cells. In acute lymphoblastic leukemia (ALL), persistence or relapse of minimal residual disease (MRD) after chemotherapy indicates resistance to chemotherapy and results in hematologic relapse. A phase II clinical study was conducted to determine the efficacy of blinatumomab in MRD-positive B-lineage ALL. Patients and Methods Patients with MRD persistence or relapse after induction and consolidation therapy were included. MRD was assessed by quantitative reverse transcriptase polymerase chain reaction for either rearrangements of immunoglobulin or T-cell receptor genes, or specific genetic aberrations. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dose of 15 μg/m 2 /24 hours. Results Twenty-one patients were treated, of whom 16 patients became MRD negative. One patient was not evaluable due to a grade 3 adverse event leading to treatment discontinuation. Among the 16 responders, 12 patients had been molecularly refractory to previous chemotherapy. Probability for relapse-free survival is 78% at a median follow-up of 405 days. The most frequent grade 3 and 4 adverse event was lymphopenia, which was completely reversible like most other adverse events. Conclusion Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2010.32.7270

RVK:

XA 52760

RVK:

XA 10000

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2011

detail.hit.zdb_id: 2005181-5

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6

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Ancient hybridizations among the ancestral genomes of bread wheat

Marcussen, Thomas ; Sandve, Simen R. ; Heier, Lise ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2014

In: Science Vol. 345, No. 6194 ( 2014-07-18)

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In: Science, American Association for the Advancement of Science (AAAS), Vol. 345, No. 6194 ( 2014-07-18)

Abstract: The allohexaploid bread wheat genome consists of three closely related subgenomes (A, B, and D), but a clear understanding of their phylogenetic history has been lacking. We used genome assemblies of bread wheat and five diploid relatives to analyze genome-wide samples of gene trees, as well as to estimate evolutionary relatedness and divergence times. We show that the A and B genomes diverged from a common ancestor ~7 million years ago and that these genomes gave rise to the D genome through homoploid hybrid speciation 1 to 2 million years later. Our findings imply that the present-day bread wheat genome is a product of multiple rounds of hybrid speciation (homoploid and polyploid) and lay the foundation for a new framework for understanding the wheat genome as a multilevel phylogenetic mosaic.

Type of Medium: Online Resource

ISSN: 0036-8075 , 1095-9203

URL: Article

DOI: 10.1126/science.1250092

RVK:

TA 1000

RVK:

WA 15000

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2014

detail.hit.zdb_id: 128410-1

detail.hit.zdb_id: 2066996-3

detail.hit.zdb_id: 2060783-0

SSG: 11

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7

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The Gq signalling pathway inhibits brown and beige adipose tissue

Klepac, Katarina ; Kilić, Ana ; Gnad, Thorsten ; [et al.]

Springer Science and Business Media LLC ; 2016

In: Nature Communications Vol. 7, No. 1 ( 2016-03-09)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-03-09)

Abstract: Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the G q family, and inhibition of G q signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of G q signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of G q signalling in brown adipocytes. Expression of a constitutively active G q protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of G q in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that G q signalling regulates brown/beige adipocytes and inhibition of G q signalling may be a novel therapeutic approach to combat obesity.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms10895

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2553671-0

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8

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Structure of trans-Isoshinanolone in the Crystal and in Solution

Bringmann, Gerhard ; Pfeifer, Robert-Michael ; Breuning, Matthias ; [et al.]

Walter de Gruyter GmbH ; 2004

In: Zeitschrift für Naturforschung B Vol. 59, No. 1 ( 2004-1-1), p. 100-105

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In: Zeitschrift für Naturforschung B, Walter de Gruyter GmbH, Vol. 59, No. 1 ( 2004-1-1), p. 100-105

Abstract: The first X-ray structure analysis of authentic, not derivatized (racemic) trans-isoshinanolone, a wide-spread acetogenic tetralone, is described. In the crystal, two slightly different conformers are found, along with the corresponding enantiomers. The ‘homomeric’ conformers differ by their H-bonding interactions with the respective neighboring molecules. Rows of a single enantiomeric species, but with the two conformers linked ‘head-to-head’, ‘tail-to-tail’, are surrounded by four analogous rows of the corresponding enantiomers. Apparently the interactions between these heterochiral rows are the reason for the enhanced crystallization tendency of the racemate as compared to that of enantiomerically pure isoshinanolone. The structures in the crystal are compared with those calculated (gas phase) and with the structure in solution.

Type of Medium: Online Resource

ISSN: 1865-7117 , 0932-0776

URL: Article

DOI: 10.1515/znb-2004-0114

RVK:

WA 15000

RVK:

VA 8360

Language: English

Publisher: Walter de Gruyter GmbH

Publication Date: 2004

detail.hit.zdb_id: 2078109-X

detail.hit.zdb_id: 124635-5

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A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure

Müller, Thomas ; Philipp, Alois ; Luchner, Andreas ; [et al.]

Springer Science and Business Media LLC ; 2009

In: Critical Care Vol. 13, No. 6 ( 2009), p. R205-

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In: Critical Care, Springer Science and Business Media LLC, Vol. 13, No. 6 ( 2009), p. R205-

Type of Medium: Online Resource

ISSN: 1364-8535

URL: Article

DOI: 10.1186/cc8213

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2009

detail.hit.zdb_id: 2051256-9

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Induced hypothermia reduces the hepatic inflammatory response in a swine multiple trauma model

Fröhlich, Matthias ; Hildebrand, Frank ; Weuster, Matthias ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2014

In: Journal of Trauma and Acute Care Surgery Vol. 76, No. 6 ( 2014-06), p. 1425-1432

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In: Journal of Trauma and Acute Care Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. 6 ( 2014-06), p. 1425-1432

Type of Medium: Online Resource

ISSN: 2163-0755

URL: Article

DOI: 10.1097/TA.0000000000000224

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2014

detail.hit.zdb_id: 2651313-4

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Kooperativer Bibliotheksverbund

Berlin Brandenburg