Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer:a systematic review and meta-analysis

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely

Quality of life after treatment with immune checkpoint inhibitors for lung cancer:the impact of age

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients’ HRQoL scores with normative data of an age-matched non-cancer general population.Methods: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (&lt;60, 60–69 and ≥ 70 years).Results: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(β = -3.28,CI95%-6.42;-0.14), physical(β = -4.8, CI95% −8.71;-0.88), cognitive(β = −4.51,CI95%-8.24;−0.78), role functioning(β = −5.41,CI95%-10.78;−0.05), symptom burden(β = −3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(β = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium.Conclusion: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population.</p

An improved nearest neighbor method for the estimation of the gamma photon entry point in monolithic scintillator detectors for PET

Several improvements of the k-nearest neighbor (k-NN) method for the determination of the entry point (x, y) of a gamma photon in a monolithic scintillator PET detector have been investigated with the aim to obtain better spatial resolution and/or to enable faster detector calibration by reducing the amount of required reference data and by allowing for calibrating with a line source. These methods were tested on a dataset measured with a SiPM-array-based monolithic LYSO detector. It appears that 10% to 25% better spatial resolution can be obtained compared to the standard approach. Moreover, some of the improved methods using two orders of magnitude less reference data, yield essentially the same spatial resolution as the standard method, which reduces the time needed for calibration as well as entry point computation. Finally, line source calibration is shown to be possible with some of the methods, yielding better results than the standard method and allowing much faster and easier collection of the reference data.</p

Abatement of particulate-laden SO2 in tapered bubble column with internals

The performance of particulate-laden SO2 scrubbing in a modified tapered bubble column with internals is reported in this article. The presence of particles improved the particulate-laden SO2 removal efficiency to about 15% that was elucidated by the facilitated adsorptive mass transport. Experimentation revealed that nearly 100% removal efficiency of particulate-laden SO2 was achievable without any additives or pretreatment under certain operating condition of the scrubber. An empirical correlation was developed to predict the performance of the modified tapered scrubber. Experimental values fitted excellently well with the predicted values through the correlation (within ±5% deviation). The performance of the modified tapered bubble scrubber with column internals has been found to be better than a tapered bubble column without any internals

Association of Endogenous Erythropoietin Levels and Iron Status With Cognitive Functioning in the General Population

Background: Emerging data suggest that erythropoietin (EPO) promotes neural plasticity and that iron homeostasis is needed to maintain normal physiological brain function. Cognitive functioning could therefore be influenced by endogenous EPO levels and disturbances in iron status. Objective: To determine whether endogenous EPO levels and disturbances in iron status are associated with alterations in cognitive functioning in the general population. Materials and Methods: Community-dwelling individuals from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a general population-based cohort in Groningen, Netherlands, were surveyed between 2003 and 2006. Additionally, endogenous EPO levels and iron status, consisting of serum iron, transferrin, ferritin, and transferrin saturation were analyzed. Cognitive function was assessed by scores on the Ruff Figural Fluency Test (RFFT), as a reflection of executive function, and the Visual Association Test (VAT), as a reflection of associative memory. Results: Among 851 participants (57% males; mean age 60 ± 13 years), higher endogenous EPO levels were independently associated with an improved cognitive function, reflected by RFFT scores (ß = 0.09, P = 0.008). In multivariable backward linear regression analysis, EPO levels were among the most important modifiable determinants of RFFT scores (ß = 0.09, P = 0.002), but not of VAT scores. Of the iron status parameters, only serum ferritin levels were inversely associated with cognitive function, reflected by VAT scores, in multivariable logistic regression analysis (odds ratio, 0.77; 95% confidence interval 0.63–0.95; P = 0.02 for high performance on VAT, i.e., ≥11 points). No association between iron status parameters and RFFT scores was identified. Conclusion: The findings suggest that endogenous EPO levels and serum ferritin levels are associated with specific cognitive functioning tests in the general population. Higher EPO levels are associated with better RFFT scores, implying better executive function. Serum ferritin levels, but not other iron status parameters, were inversely associated with high performance on the VAT score, implying a reduced ability to create new memories and recall recent past. Further research is warranted to unravel underlying mechanisms and possible benefits of therapeutic interventions

Der Umzug der Menschheit: Die transformative Kraft der Städte

Die Wucht der derzeitigen Urbanisierungsdynamik und ihre Auswirkungen sind so groß, dass sich weltweit Städte, Stadtgesellschaften, Regierungen und Internationale Organisationen diesem Trend stellen müssen. Ein „Weiter so wie bisher“, würde ohne gestaltende Urbanisierungspolitik zu einer nicht-nachhaltigen Welt-Städte-Gesellschaft führen. Nur wenn Städte und Stadtgesellschaften ausreichend handlungsfähig werden, können sie ihre Kraft für eine nachhaltige Entwicklung entfalten: In den Städten wird sich entscheiden, ob die Große Transformation zur Nachhaltigkeit gelingt. In diesem Buch werden die Erfolgsbedingungen dafür diskutiert

Humanity on the move: Unlocking the transformative power of cities

The momentum of urbanization and its impacts are so massive that we must face up to this trend. In view of the existing cognitive, technical, economic and institutional path dependencies, a policy of business as usual – i.e. an unstructured, quasi-automatic urbanization – would lead to a non-sustainable ‘world cities society’. Only if cities and urban societies are sufficiently empowered can they make use of the opportunities for sustainability and successfully follow the urban transformation pathways. The success or failure of the Great Transformation will be decided in the cities. The WBGU discusses the relevant conditions for the success of this transformation in this report

Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model

Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several wasting states. Methods Monocrotaline (MCT) was injected over eight weeks into mice to establish pulmonary hypertension as a murine model for cardiac cachexia. The effects on skeletal muscle atrophy, myofiber force, and selected muscle proteins were evaluated in wild-type (WT), MuRF1, and MuRF2-KO mice by determining muscle weights, in vitro muscle force and enzyme activities in soleus and tibialis anterior (TA) muscle. Results In WT, MCT treatment induced wasting of soleus and TA mass, loss of myofiber force, and depletion of citrate synthase (CS), creatine kinase (CK), and malate dehydrogenase (MDH) (all key metabolic enzymes). This suggests that the murine MCT model is useful to mimic peripheral myopathies as found in human cardiac cachexia. In MuRF1 and MuRF2-KO mice, soleus and TA muscles were protected from atrophy, contractile dysfunction, while metabolic enzymes were not lowered in MuRF1 or MuRF2-KO mice. Furthermore, MuRF2 expression was lower in MuRF1KO mice when compared to C57BL/6 mice. Conclusions In addition to MuRF1, inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia. The protection of metabolic enzymes in both MuRF1KO and MuRF2KO mice as well as the dependence of MuRF2 expression on MuRF1 suggests intimate relationships between MuRF1 and MuRF2 during muscle atrophy signaling

The Role of Thailand in the International Trade in CITES-Listed Live Reptiles and Amphibians

BACKGROUND: International wildlife trade is one of the leading threats to biodiversity conservation. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is the most important initiative to monitor and regulate the international trade of wildlife but its credibility is dependent on the quality of the trade data. We report on the performance of CITES reporting by focussing on the commercial trade in non-native reptiles and amphibians into Thailand as to illustrate trends, species composition and numbers of wild-caught vs. captive-bred specimens. METHODOLOGY/PRINCIPAL FINDINGS: Based on data in the WCMC-CITES trade database, we establish that a total of 75,594 individuals of 169 species of reptiles and amphibians (including 27 globally threatened species) were imported into Thailand in 1990-2007. The majority of individuals (59,895, 79%) were listed as captive-bred and a smaller number (15,699, 21%) as wild-caught. In the 1990s small numbers of individuals of a few species were imported into Thailand, but in 2003 both volumes and species diversity increased rapidly. The proportion of captive-bred animals differed greatly between years (from 0 to >80%). Wild-caught individuals were mainly sourced from African countries, and captive-bred individuals from Asian countries (including from non-CITES Parties). There were significant discrepancies between exports and imports. Thailand reports the import of >10,000 individuals (51 species) originating from Kazakhstan, but Kazakhstan reports no exports of these species. Similar discrepancies, involving smaller numbers (>100 individuals of 9 species), can be seen in the import of reptiles into Thailand via Macao. CONCLUSION/SIGNIFICANCE: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES

Novel materials for solid oxide fuel cells cathodes and oxygen separation membranes: Fundamentals of oxygen transport and performance

In the field of modern hydrogen energy, obtaining pure hydrogen and syngas and then being able to use them for green energy production are significant problems. Developing solid oxide fuel cells (SOFC) and catalytic membranes for oxygen separation as well as materials for these devices is one of the most likely ways to solve these problems. In this work, the authors’ recent studies in this field are reviewed; the fundamentals of developing materials for SOFC cathodes and oxygen separation membranes’ permselective layers based on research of their oxygen mobility and surface reactivity are presented. Ruddlesden – Popper phases Ln2–xCaxNiO4+δ (LnCNO) and perovskite-fluorite nanocomposites PrNi0.5Co0.5O3–δ–Ce0.9Y0.1O2–δ (PNC–YDC) were studied by isotope exchange of oxygen with C18O2 and 18O2 in flow and closed reactors. For LnCNO a high oxygen mobility was shown (D* ~ 10–7 cm2/s at 700 °C), being provided by the cooperative mechanism of oxygen migration involving both regular and highly-mobile interstitial oxygen. For PNC–YDC dominated a wide fast diffusion channel via fluorite phase and interphases due to features of the redistribution of cations resulting in superior oxygen mobility (D* ~ 10–8 cm2/s at 700 °C). After optimization of composition and nanodomain structure of these materials, as cathodes of SOFC they provided a high power density, while for asymmetric supported oxygen separation membranes – a high oxygen permeability. © 2020Support of different parts of the work by the Russian Science Foundation (Project 16-13-00112) and the budget project №AAAA-A17-117041110045-9 for Boreskov Institute of Catalysis is gratefully acknowledged. The authors from the Ural Federal University are grateful to the Government of the Russian Federation (Agreement 02.A03.21.0006, Act 211). Ce 0.9 Y 0.1 O 2–δ |Ce 0.9 Gd 0.1 O 2–δ |Ni/Zr 0.84 Y 0.16 O 2–δ anodic half-cells and Ni/Al foam substrates were kindly provided by H.C. Starck, Germany and Powder Metallurgy Institute NAN Belarus, respectively. Authors would like to appreciate International Conference on Advances in Energy Systems and Environmental Engineering (ASEE19, Wroclaw, Poland, June 9-12, 2019) Organization Committee