Publications by authors named "Sievers J"

Article Synopsis
  • - The introduction of fluorine into drugs, specifically tetrafluorination of phthalimide in immunomodulatory drugs (IMiDs), enhances their ability to inhibit angiogenesis, a key process in cancer growth.
  • - Research examined a series of thalidomide analogs, revealing that neither fluorinated nor non-fluorinated versions effectively induced the degradation of certain neomorphic substrates linked to their activity, indicating that fluorine does not contribute to this degrading mechanism.
  • - A study of non-traditional IMiDs showed no effective angiogenesis inhibitors through endothelial cell tube formation tests, highlighting the limited scope of IMiD's antiangiogenic potential.
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Chronic progressive lymphedema (CPL) is a prevalent and progressive disease in Rhenish German draught horses. The objective of our follow-up study was to evaluate the heritability of this disease in Rhenish German draught horses using pedigree-based and genomic relationship matrices. We employed linear and threshold animal models.

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In GEMINI-1/-2, dolutegravir + lamivudine was non-inferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in achieving viral suppression (viral load [VL] < 50 copies/mL) in treatment-naive adults. Abbott's RealTime HIV-1 assay provides quantitative VL (40-10,000,000 copies/mL) and qualitative target detected or target not detected (TND) for VL < 40 copies/mL. This post hoc analysis assessed very-low-level viremia and "blips" through Week 144.

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Chronic progressive lymphedema (CPL) is a common disease in Rhenisch German draught horses. The objective of our study was to evaluate the prevalence of this disease and its progression with age in 493 Rhenish German draught horses from different regions in Germany. We employed generalized linear models with binomial, multinomial, and normal distributions to analyse the effects of breeding association, coat colour, sex and age within sex, time of examination, limb on which CPL was recorded, and farm-related factors on disease scores.

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Cancer progression is associated with extensive remodeling of the tumor microenvironment (TME), resulting in alterations of biochemical and biophysical cues that affect both cancer and stromal cells. In particular, the mechanical characteristics of the TME extracellular matrix undergo significant changes. Bioengineered polymer hydrogels can be instrumental to systematically explore how mechanically changed microenvironments impact cancer cell behavior, including proliferation, survival, drug resistance, and invasion.

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Background: For quantitative and qualitative evaluation of the imaging properties of IOLs, axial cross-sectional images can be obtained from the 3-dimensional light distribution by means of an optical bench, as is known from light sheet recordings in fluorescein baths. This paper presents a new image-processing algorithm to enhance the quality of generated axial cross-sectional images, and the two methods are then compared.

Material And Methods: The 3-dimensional point spread function of a diffractive trifocal IOL (AT LISA tri 839MP, Carl Zeiss Meditec AG, Jena, Germany) was recorded on an optical bench developed in Rostock for different pupil diameters.

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Article Synopsis
  • * Researchers used next-generation sequencing to analyze 13 complete genomes of DENV-4 from the outbreak, focusing on its evolutionary patterns and genetic changes.
  • * Findings revealed that selection pressure and genetic mutations, along with possible recombination events in the virus, may explain DENV-4's prevalence in East Java during the outbreak.
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The 2020 U.S. Presidential election was a campaign that could be characterized as 'one of the nastiest presidential campaigns in recent memory,' partly because the general election debates were highly contentious and featured frequent interruptions and several insults and invectives between candidates.

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Cross-sectional images of three-dimensional point spread functions of intraocular lenses are used to study their image formation. To obtain those, light sheet-based methods are established. Due to the non-negligible thicknesses of the light sheets, the image quality of the cross-sectional images is constrained.

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GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL at 48, 96, and 144 weeks in treatment-naive adults with HIV-1 infection. We present a post hoc analysis of the impact of treatment adherence on Week 48 virologic response.

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Article Synopsis
  • At week 48 of the DAWNING study, dolutegravir plus two nucleoside reverse transcriptase inhibitors showed better virologic suppression than ritonavir-boosted lopinavir in adults with HIV-1 who had previously failed treatment.
  • Among the 314 participants, 7 developed treatment-emergent INSTI resistance-associated mutations, indicating some resistance to dolutegravir, though they still achieved low HIV-1 RNA levels.
  • The study reveals that while mutations can confer some resistance to dolutegravir, this resistance comes with a significant trade-off: a decrease in the virus’s ability to replicate effectively.
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Macroporous cryogels have recently gained increasing interest for the controlled administration of signaling proteins in tissue engineering due to an advantageous combination of material properties. However, most of the previously reported cryogel systems did not allow for tunable, sustained protein release. We therefore designed a set of ready-to-use multi-armed polyethylene glycol (starPEG)-heparin cryogel systems containing different amounts of the protein-affine glycosaminoglycan component heparin to enable systematically tunable long-term delivery of different signaling proteins without affecting other cell-instructive properties.

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Objective: To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.

Design: Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).

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Background: Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mammalian target of rapamycin pathway. Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome.

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Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia.

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Background: To investigate antiviral potency of the 2-drug regimen (2DR) dolutegravir plus lamivudine vs the 3-drug regimen (3DR) dolutegravir plus tenofovir disoproxil fumarate/emtricitabine, we performed a post-hoc analysis assessing antiviral response rates in the phase III GEMINI-1 and GEMINI-2 studies by baseline viral load (VL).

Setting: One hundred ninety-two centers in 21 countries.

Methods: Treatment-naive HIV-1-infected participants with screening VL ≤500,000 copies/mL were randomized 1:1 to once-daily dolutegravir plus lamivudine or dolutegravir plus tenofovir disoproxil fumarate/emtricitabine.

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Background: The 2-drug regimen dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses.

Setting: One hundred eighty-seven centers in 21 countries.

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Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage.

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The cosmic microwave background (CMB) -mode signal is potentially weaker than the diffuse Galactic foregrounds over most of the sky at any frequency. A common method of separating the CMB from these foregrounds is via pixel-based parametric-model fitting. There are not currently enough all-sky maps to fit anything more than the most simple models of the sky.

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Thermoresponsive interpenetrating networks (IPNs) were prepared by sequential synthesis of a biohybrid network of star-shaped poly(ethylene glycol) [starPEG] and heparin and a poly(-isopropylacrylamide)-polymer network. Amide bond formation was used for cross-linking of the starPEG-heparin network and photo-cross-linking with ,'-methylenebis(acrylamide) was applied for the formation of the second polymer network. Both networks were linked by chain entanglements and hydrogen bonds only.

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Background: Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed.

Methods: DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries.

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Article Synopsis
  • The study evaluated the effectiveness and safety of a two-drug HIV treatment compared to a standard three-drug regimen in adults new to antiretroviral therapy (ART).
  • Both GEMINI-1 and GEMINI-2 trials were conducted in 21 countries, involving 1441 participants who were randomly assigned to either regimen to measure the proportion of individuals achieving adequate viral suppression at week 48.
  • Results indicated that the two-drug regimen was non-inferior to the three-drug regimen, with a significant percentage of participants on both treatments achieving viral loads below 50 copies per mL.
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