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Human papilloma virus (HPV) infection is linked to cervical cancer, which represents the world's fourth most common cancer in women. So far, no detailed map of the worldwide HPV research architecture has been constructed. Hence, this study focuses on the chronological development and geographical distribution of the global HPV-specific publications and evaluates citation-based parameters as well as socioeconomic features of the publishing countries.
In total, 29,330 HPV-related publications were identified. The US was the leading country with 12,270 publications. Only high-income-countries were found in the ranking of the fifteen most active countries with Germany, France, and Japan among the top five. Analysis of HPV research activity in relation to the economic strength demonstrated a lead position of Finland and Sweden with an average of 2248.78 and 1924.67 HPV-related publications per GDP in 1000 bn US-$, respectively. The most active upper-middle-income country was Mexico (416.78 HPV-related publications per GDP in 1000 bn US-$). India as lower-middle-income country reached a value of 279.78 HPV-related publications per GDP in 1000 bn US-$. Collaboration analysis pointed to the US as the center of the 4517 international HPV collaborations.
The worldwide HPV-research landscape is dominated by North American and Western European countries. By contrast, a high prevalence of HPV-related cervical cancer is documented for low-income countries. Hence, HPV-related public health interventions and prevention research specifically tailored to these countries needs to be fostered by monetary support and international collaborations.
The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
The method of relative self absorption is based on the technique of nuclear resonance fluorescence measurements. It allows for a model-independent determination of ground-state transition widths, natural level widths, and, consequently, of branching ratios to the ground state for individual excitations. Relative self–absorption experiments have been performed on the nuclei 6Li and 140Ce. In order to investigate the total level width for the 0+1, T = 1 level at 3563 keV in 6Li, a high-precision self-absorption measurement has been performed. In the case of 140Ce, self absorption has been applied for the first time to study decay widths of dipole-excited states in the energy regime of the pygmy dipole resonance.
The antibacterial properties of nanosilver have led to a versatile application spectrum including medical purposes and personal care products. However, the increasing use of nanosilver has raised concerns about its environmental impacts. Long-term exposure studies with aquatic invertebrates are essential to assess possible adverse effects on aquatic ecosystems. In the present study, acute (48 h), chronic (21 d) and long-term effects of nanosilver (primary size 15 nm) on five successive generations of three Daphnia species (D. magna, D. pulex, and D. galeata) were investigated. Acute EC50 values of nanosilver were 121 µg Ag L−1 for D. magna being the least sensitive species and 8.95 and 13.9 µg Ag L−1 for D. pulex and D. galeata, respectively. Chronic exposure provided EC10 values of 0.92 µg Ag L−1 for D. magna showing the most sensitive chronic reaction and 2.25 and 3.45 µg Ag L−1 for D. pulex and D. galeata, respectively. Comparative exposure to AgNO3 revealed a generally higher toxicity of the soluble form of silver. The multi-generation experiments resulted in effects on the population level for all tested species. Exposure of D. magna indicated an increased toxicity of nanosilver in the fifth generation of animals exposed to 10 µg Ag L−1. Neonates from pre-exposed parental daphnids did not completely recover when transferred into clean water. Exposure of D. pulex and D. galeata revealed not only increasing toxicity in some generations, but also greater tolerance to nanosilver. This study contributes to the assessment of the risk potential of nanosilver on aquatic ecosystems. It shows that effects of nanosilver vary within one genus and change with exposure duration. Therefore, long-term studies considering different aquatic species are needed to better understand the possible effects of nanosilver on aquatic ecosystems.
A recent randomized study of whipworm Trichuris suis ova (TSO) in ileal Crohn’s disease failed to demonstrate a clinical benefit compared to placebo after 12 weeks. Nonetheless, it has recently been shown that the spontaneous small intestinal inflammatory changes in Nod2-/- (Nucleotide-binding oligomerization domain 2) mice could be substantially ameliorated when these mice were colonized by Trichuris muris. Those and complementary epidemiologic findings in humans lead to the hypothesis that helminths may be advantageous only in patients carrying defective NOD2 variants. Thus, 207 participants of the TSO trial were retrospectively genotyped for six functional NOD2 genetic variants to evaluate whether the treatment outcome differed in patients carrying NOD2 variants. We observed no significant association of the NOD2 variants or their haplotypes with clinical outcome after TSO treatment.
The exposure to tobacco smoke during pregnancy is considered to be amongst the most harmful avoidable risk factors. In this scientometric and gender study scientific data on smoking and pregnancy was analyzed using a variety of objective scientometric methods like the number of scientific contributions, the number of citations and the modified h-index in combination with gender-specific investigations. Covering a time period from 1900 to 2012, publishing activities of 27,955 authors, institutions and countries, reception within the international scientific community and its reactions were analyzed and interpreted. Out of 10,043 publications the highest number of scientific works were published in the USA (35.5%), followed by the UK (9.9%) and Canada (5.3%). These nations also achieve the highest modified h-indices of 128, 79 and 62 and the highest citation rates of 41.4%, 8.6% and 5.3%, respectively. Out of 12,596 scientists 6,935 are female (55.1%), however they account for no more than 49.7% of publications (12,470) and 42.8% of citations (172,733). The highest percentage of female experts about smoking and pregnancy is found in Australasia (60.7%), while the lowest is found in Asia (41.9%). The findings of the study indicate an increase in gender equality as well as in quantity and quality of international scientific research about smoking and pregnancy in the future.
Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.
Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.
Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.
Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.
Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing
(2019)
Background: Pollinex Quattro Grass (PQ Grass) is an effective, well-tolerated, short pre-seasonal subcutaneous immunotherapy to treat seasonal allergic rhinoconjunctivitis (SAR) due to grass pollen. In this Phase II study, 4 cumulative doses of PQ Grass and placebo were evaluated to determine its optimal cumulative dose.
Methods: Patients with grass pollen-induced SAR were randomised to either a cumulative dose of PQ Grass (5100, 14400, 27600 and 35600 SU) or placebo, administered as 6 weekly subcutaneous injections over 31–41 days (EudraCT number 2017-000333-31). Standardized conjunctival provocation tests (CPT) using grass pollen allergen extract were performed at screening, baseline and post-treatment to determine the total symptom score (TSS) assessed approximately 4 weeks after dosing. Three models were pre-defined (Emax, logistic, and linear in log-dose model) to evaluate a dose response relationship.
Results: In total, 95.5% of the 447 randomized patients received all 6 injections. A highly statistically significant (p < 0.0001), monotonic dose response was observed for all three pre-specified models. All treatment groups showed a statistically significant decrease from baseline in TSS compared to placebo, with the largest decrease observed after 27600 SU (p < 0.0001). The full course of 6 injections was completed by 95.5% of patients. Treatment-emergent adverse events were similar across PQ Grass groups, and mostly mild and transient in nature.
Conclusions: PQ Grass demonstrated a strong curvilinear dose response in TSS following CPT without compromising its safety profile.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
LICE is one of the four major LHC experiments at CERN. When the accelerator enters the Run 3 data-taking period, starting in 2021, ALICE expects almost 100 times more Pb-Pb central collisions than now, resulting in a large increase of data throughput. In order to cope with this new challenge, the collaboration had to extensively rethink the whole data processing chain, with a tighter integration between Online and Offline computing worlds. Such a system, code-named ALICE O2, is being developed in collaboration with the FAIR experiments at GSI. It is based on the ALFA framework which provides a generalized implementation of the ALICE High Level Trigger approach, designed around distributed software entities coordinating and communicating via message passing.
We will highlight our efforts to integrate ALFA within the ALICE O2 environment. We analyze the challenges arising from the different running environments for production and development, and conclude on requirements for a flexible and modular software framework. In particular we will present the ALICE O2 Data Processing Layer which deals with ALICE specific requirements in terms of Data Model. The main goal is to reduce the complexity of development of algorithms and managing a distributed system, and by that leading to a significant simplification for the large majority of the ALICE users.