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Abstract Background Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation. Methods We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients. Results We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential. Conclusion Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students’ t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Abstract Background Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. Methods Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. Results In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p

Abstract As a result of advances in the treatment of lung cancer, the life expectancy of lung cancer patients has improved significantly, but it remains the leading cause of cancer death worldwide. For decades, most of the initial tumor biopsies have been obtained by bronchoscopy or computed tomography (CT)-guided transthoracic lung biopsy without concerning reports of cancer seeding following the latter. In this case report we discuss the patient history of a 56-year old women with low-differentiated squamous cell lung cancer who developed tumor seeding following a CT-guided transthoracic biopsy 11 months after the intervention. This is put into context reviewing former and current literature.

Abstract Introduction Trials of CT‐based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. Methods We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6‐year risk thresholds of 1.0%/6 year and 1.7%/6 year. Results Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small‐cell and large‐cell carcinomas (non‐significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. Conclusion Using a risk‐based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large‐scale lung cancer screening program.

Background: A debate persists on the prognostic value of the pre-therapeutic standardized uptake value (SUV) of non-tumorous lung tissue for the risk assessment of therapy-related pneumonitis, with most studies lacking significant correlation. However, the influence of patient comorbidities on the pre-therapeutic lung SUV has not yet been systematically evaluated. Thus, we aimed to elucidate the association between comorbidities, biological variables and lung SUVs in pre-therapeutic [18F]FDG-PET/CT. Methods: In this retrospective study, the pre-therapeutic SUV in [18F]FDG-PET/CT was measured in non-tumorous areas of both lobes of the lung. SUVMEAN, SUVMAX and SUV95 were compared to a multitude of patient characteristics and comorbidities with Spearman’s correlation analysis, followed by a Bonferroni correction and multilinear regression. Results: In total, 240 patients with lung cancer were analyzed. An elevated BMI was significantly associated with increased SUVMAX (β = 0.037, p < 0.001), SUVMEAN (β = 0.017, p < 0.001) and SUV95 (β = 0.028, p < 0.001). Patients with chronic obstructive pulmonary disease (COPD) showed a significantly decreased SUVMAX (β = −0.156, p = 0.001), SUVMEAN (β = −0.107, p < 0.001) and SUV95 (β = −0.134, p < 0.001). Multiple other comorbidities did not show a significant correlation with the SUV of the non-tumorous lung. Conclusions: Failure to consider the influence of BMI and COPD on the pre-therapeutic SUV measurements may lead to an erroneous interpretation of the pre-therapeutic SUV and subsequent treatment decisions in patients with lung cancer.

Abstract In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p

Abstract Background The novel coronavirus SARS-CoV-2 has caused a global COVID-19 pandemic, leading to worldwide changes in public health measures. In addition to changes in the public sector (lockdowns, contact restrictions), hospitals modified care to minimize risk of infection and to mobilize resources for COVID-19 patients. Our study aimed to assess the impact of these measures on access to care and behaviour of patients with thoracic malignancies. Methods Thoracic oncology patients were surveyed in October 2020 using paper-based questionnaires to assess access to ambulatory care services and tumor-directed therapy during the COVID-19 pandemic. Additionally, behaviour regarding social distancing and wearing of face masks were assessed, as well as COVID-19 exposure, testing and vaccination. Results are presented as absolute and relative frequencies for categorical variables and means with standard deviation for numerical variables. We used t-test, and ANOVA to compare differences in metric variables and Chi2-test to compare proportions between groups. Results 93 of 245 (38%) patients surveyed completed the questionnaire. Respiration therapy and physical therapy were unavailable for 57% to 70% of patients during March/April. Appointments for tumor-directed therapy, tumor imaging, and follow-up care were postponed or cancelled for 18.9%, 13.6%, and 14.8% of patients, respectively. Patients reported their general health as mostly unaffected. The majority of patients surveyed did not report reducing their contacts with family. The majority reduced contact with friends. Most patients wore community masks, although a significant proportion reported respiratory difficulties during prolonged mask-wearing. 74 patients (80%) reported willingness to be vaccinated against SARS-CoV-2. Conclusions This survey provides insights into the patient experience during the second wave of the COVID-19 pandemic in Munich, Germany. Most patients reported no negative changes to cancer treatments or general health; however, allied health services were greatly impacted. Patients reported gaps in social distancing, but were prepared to wear community masks. The willingness to get vaccinated against SARS-CoV-2 was high. This information is not only of high relevance to policy makers, but also to health care providers.

Abstract Hydrology is a major environmental factor determining plant fitness, and hydrological niche segregation (HNS) has been widely used to explain species coexistence. Nevertheless, the distribution of plant species along hydrological gradients does not only depend on their hydrological niches but also depend on their seed dispersal, with dispersal either weakening or reinforcing the effects of HNS on coexistence. However, it is poorly understood how seed dispersal responds to hydrological conditions. To close this gap, we conducted a common‐garden experiment exposing five wind‐dispersed plant species (Bellis perennis, Chenopodium album, Crepis sancta, Hypochaeris glabra, and Hypochaeris radicata) to different hydrological conditions. We quantified the effects of hydrological conditions on seed production and dispersal traits, and simulated seed dispersal distances with a mechanistic dispersal model. We found species‐specific responses of seed production, seed dispersal traits, and predicted dispersal distances to hydrological conditions. Despite these species‐specific responses, there was a general positive relationship between seed production and dispersal distance: Plants growing in favorable hydrological conditions not only produce more seeds but also disperse them over longer distances. This arises mostly because plants growing in favorable environments grow taller and thus disperse their seeds over longer distances. We postulate that the positive relationship between seed production and dispersal may reduce the concentration of each species to the environments favorable for it, thus counteracting species coexistence. Moreover, the resulting asymmetrical gene flow from favorable to stressful habitats may slow down the microevolution of hydrological niches, causing evolutionary niche conservatism. Accounting for context‐dependent seed dispersal should thus improve ecological and evolutionary models for the spatial dynamics of plant populations and communities.

For the first time, the symposium on the History of Architectural History, organised by Henrik Karge (Dresden) and Sabine Frommel (Paris) at the Accademia Nazionale di San Luca in Rome, analysed architectural history as a European phenomenon. The participants – renowned experts from Italy, Germany, France, Spain, Denmark, Poland, Hungary and Greece – described the genesis and development of the historiography of architecture within the panorama of historical sciences, especially in relation to the history of art. Of particular importance is the role that architectural history played in the constitution of national identities in the course of nation building, and thus also national conflicts, in 19th and 20th century Europe. In various contributions, the historians of architecture were examined: art historians, architectural theorists and practical architects have each developed specific perspectives. In this way, the special feature of the Roman school of architecture was elaborated, which consisted in keeping alive the awareness of historical models in the training of architects, even under the reign of 20th century modernism and postmodernism. Finally, current aspects of digital techniques and global aspects in the analysis and visualisation of architecture were also dealt with.

Background: Due to the effects of climate change, winter sport enthusiasts will be increasingly forced to stay at higher altitudes. High altitude (HA) environmental factors such as cold temperature, physical exertion, and hypoxia with subsequent hypocapnia due to hyperventilation have been shown to induce bronchoconstriction. With bronchial asthma being highly prevalent, asthmatics also will be increasingly exposed to HA environment and might experience increasing symptoms. Methods: We analysed the effects of HA factors at around 2600 m a.s.l. (metres above sea level) on lung function in mild seasonal asthmatics while they were routinely off (January) and on (March, after start of lowland pollen season) low-dose inhaled corticosteroid (ICS) treatment (n = 10), and matched healthy controls (n = 11). Results: Without inhaled corticosteroid (ICS) treatment mean FEV1 in asthmatics was 230 ml lower after exercise at HA compared to low altitude (LA, p

Background: The COVID-19 vaccines, face masks, and social distancing are effective interventions to prevent SARS-CoV-2 infections. In this study, we aimed to determine lung cancer patients’ attitudes toward vaccination, changes in behavior after vaccination, and willingness to continue mask wearing after the pandemic. Methods: We sent out questionnaires to 220 thoracic oncology patients treated at our lung cancer center in May 2021. The questionnaire focused on patients’ vaccination status, self-reported experiences surrounding vaccination, and assessed changes in behaviors before and after vaccination as well as opinions toward mask wearing after the pandemic. Results are presented as absolute and relative frequencies and means with standard deviation and compared using t test, paired t test, and analysis of variance test as well as chi 2 test, and Fisher exact text. Results: About 91.0% of patients reported having received at least 1 vaccination. About 73.3% of patients reported having at least 1 reaction to the vaccination. The most common reactions were pain at the injection site, fatigue, and headache. After vaccination, patients increased contact with family and friends, use of public transport, and grocery shopping. Overall, the level of willingness to wear masks beyond the end of the pandemic differed according to vaccination status. Conclusions: Acceptance of the COVID-19 vaccination among thoracic oncology patients in Germany was high. Overall, patients with thoracic malignancies tolerated the COVID-19 vaccination well. Rate of adverse reaction was not higher compared with the general population. After the vaccination, patients increased social contacts and usage of public transport. These changes suggest positive psychological effects on quality of life. While reducing social distancing can increase the risk of infection, our results indicate that an extension of mask mandates after the pandemic would likely be accepted by a majority of thoracic oncology patients, suggesting that our cohort was still aware and in support of other measure of protection.

Abstract Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

BackgroundTumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.MethodsInternal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.ResultsWe identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.ConclusionLevels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.

Abstract Litter decomposition is a key process of nutrient and carbon cycling in terrestrial ecosystems. The decomposition process will likely be altered under ongoing climate change, both through direct effects on decomposer activity and through indirect effects caused by changes in litter quality. We studied how hydrological change indirectly affects decomposition via plant functional community restructuring caused by changes in plant species’ relative abundances (community‐weighted mean (CWM) traits and functional diversity). We further assessed how those indirect litter quality effects compare to direct effects. We set up a mesocosm experiment, in which sown grassland communities and natural turf pieces were subjected to different hydrological conditions (dryness and waterlogging) for two growing seasons. Species‐level mean traits were obtained from trait databases and combined with species’ relative abundances to assess functional community restructuring. We studied decomposition of mixed litter from these communities in a common “litterbed.” These indirect effects were compared to effects of different hydrological conditions on soil respiration and on decomposition of standard litter (direct effects). Dryness reduced biomass production in sown communities and natural turf pieces, while waterlogging only reduced biomass in sown communities. Hydrological stress caused profound shifts in species’ abundances and consequently in plant functional community composition. Hydrologically stressed communities had higher CMW leaf dry matter content, lower CMW leaf nitrogen content, and lower functional diversity. Lower CWM leaf N content and functional diversity were strongly related to slower decomposition. These indirect effects paralleled direct effects, but were larger and longer‐lasting. Species mean traits from trait databases had therefore considerable predictive power for decomposition. Our results show that stressful soil moisture conditions, that are likely to occur more frequently in the future, quickly shift species’ abundances. The resulting functional community restructuring will decelerate decomposition under hydrological stress.

Abstract Background Filamentous cyanobacteria represent model organisms for investigating multicellularity. For many species, nitrogen-fixing heterocysts are formed from photosynthetic vegetative cells under nitrogen limitation. Intracellular Ca2+ has been implicated in the highly regulated process of heterocyst differentiation but its role remains unclear. Ca2+ is known to operate more broadly in metabolic signalling in cyanobacteria, although the signalling mechanisms are virtually unknown. A Ca2+-binding protein called the Ca2+ Sensor EF-hand (CSE) is found almost exclusively in filamentous cyanobacteria. Expression of asr1131 encoding the CSE protein in Anabaena sp. PCC 7120 was strongly induced by low CO2 conditions, and rapidly downregulated during nitrogen step-down. A previous study suggests a role for CSE and Ca2+ in regulation of photosynthetic activity in response to changes in carbon and nitrogen availability. Results In the current study, a mutant Anabaena sp. PCC 7120 strain lacking asr1131 (Δcse) was highly prone to filament fragmentation, leading to a striking phenotype of very short filaments and poor growth under nitrogen-depleted conditions. Transcriptomics analysis under nitrogen-replete conditions revealed that genes involved in heterocyst differentiation and function were downregulated in Δcse, while heterocyst inhibitors were upregulated, compared to the wild-type. Conclusions These results indicate that CSE is required for filament integrity and for proper differentiation and function of heterocysts upon changes in the cellular carbon/nitrogen balance. A role for CSE in transmitting Ca2+ signals during the first response to changes in metabolic homeostasis is discussed.

Climate change is altering precipitation patterns, with higher frequency and magnitude of extreme events. Specifically, longer and more pronounced waterlogged conditions are predicted after rain spells as well as more frequent droughts, especially in Central Europe. Such hydrological changes can severely affect species performance and alter the function of ecosystems, as well as favor plant invasions. Competition with native communities may change depending on water stress. Bunias orientalis is an invasive plant that may benefit from disturbance or precipitation changes. We conducted a 3-year mesocosm experiment in a common garden to investigate how invasion success of B. orientalis in native German grassland communities is affected by varying hydrological conditions (from very dry to waterlogged). We measured the establishment and growth of B. orientalis in varying water table depths in bare soil (simulating disturbance) vs. in the community. Establishment and biomass of B. orientalis was generally highest under non-stress conditions. The species was also highly tolerant to dry conditions, but only when growing in bare soil. However, performance of B. orientalis was generally low, whereby interspecific competition in communities greatly limited invasion success. This might be due to the low competitive ability of the species in conditions of hydrological stress and the near-natural grassland communities with an extensive mowing regime used in our experiment. Our results suggest that invasion success of B. orientalis in grasslands will not increase if precipitation patterns change toward more extreme events. However, disturbance that creates bare soil patches might favor B. orientalis under drought conditions.

Abstract Background When patients die in a hospital their quality of life is lower than when they die at home or in a hospice. Despite efforts to improve palliative care supply structures, still about 60% of lung cancer patients die in a hospital. Studies have examined factors related to inhospital death in lung cancer patients, yet none used data of a representative German population, additionally including economic aspects. This study aimed to identify factors related to inhospital death in German lung cancer patients and analysed resulting costs. Methods We analysed a dataset of health insurance claims of 17,478 lung cancer patients (incident 2009) with 3 year individual follow-up. We grouped patients into inhospital death and death elsewhere. Studied factors were indicators of healthcare utilization, palliative care, comorbidities and disease spread. We used logistic regression models with LASSO selection method to identify relevant factors. We compared all-cause healthcare expenditures for the last 30 days of life between both groups using generalized linear models with gamma distribution. Results Twelve thousand four hundred fifty-seven patients died in the observation period, thereof 6965 (55.9%) in a hospital. The key factors for increased likelihood of inhospital death were receipt of inpatient palliative care (OR = 1.85), chemotherapeutic treatments in the last 30 days of life (OR = 1.61) and comorbid Congestive Heart Failure (OR = 1.21), and Renal Disease (OR = 1.19). In contrast, higher care level (OR = 0.16), nursing home residency (OR = 0.25) and receipt of outpatient palliative care (OR = 0.25) were associated with a reduced likelihood. All OR were significant (p-values

A real-time polymerase chain reaction (qPCR) is considered the gold standard for the laboratory diagnosis of canine parvovirus (CPV) infection but can only be performed in specialized laboratories. Several point-of-care tests (POCT), detecting CPV antigens in faeces within minutes, are commercially available. The aim of this study was to evaluate eight POCT in comparison with qPCR. Faecal samples of 150 dogs from three groups (H: 50 client-owned, healthy dogs, not vaccinated within the last four weeks; S: 50 shelter dogs, healthy, not vaccinated within the last four weeks; p = 50 dogs with clinical signs of CPV infection) were tested with eight POCT and qPCR. Practicability, sensitivity, specificity, positive (PPV) and negative predictive values (NPV), as well as overall accuracy were determined. To assess the differences between and agreement among POCT, McNemar’s test and Cohen’s Kappa statistic were performed. Specificity and PPV were 100.0% in all POCT. Sensitivity varied from 22.9–34.3% overall and from 32.7–49.0% in group P. VetexpertRapidTestCPVAg® had the highest sensitivity (34.3% overall, 49.0% group P) and differed significantly from the 3 POCT with the lowest sensitivities (Fassisi®Parvo (27.7% overall, 36.7% group P), Primagnost®ParvoH+K (24.3% overall, 34.7% group P), FASTest®PARVOCard (22.9% overall, 32.7% group P)). The agreement among all POCT was at least substantial (kappa >0.80). A positive POCT result confirmed the infection with CPV in unvaccinated dogs, whereas a negative POCT result did not definitely exclude CPV infection due to the low sensitivity of all POCT.

BackgroundAlthough lung cancer is most commonly diagnosed in elderly patients, evidence about tumor-directed therapy in elderly patients is sparse, and it is unclear to what extent this affects treatment and care. Our study aimed to discover potential disparities in care between elderly patients and those under 65 years of age.MethodsWe studied claims from 13 283 German patients diagnosed with lung cancer in 2009 who survived for at least 90 days after diagnosis. We classified patients as "non-elderly" (≤ 65), "young-old" (65-74), "middle-old" (75-84), and "old-old" (≥ 85). We compared receipt of tumor-directed therapy (6 months after diagnosis), palliative care, opioids, antidepressants, and pathologic diagnosis confirmation via logistic regression. We used generalized linear regression (gamma distribution) to compare group-specific costs of care for 3 months after diagnosis. We adjusted all models by age, nursing home residency, nursing care need, comorbidity burden, and area of residence (urban, rural). The age group "non-elderly" served as reference group.ResultsCompared with the reference group "non-elderly", the likelihood of receiving any tumor-directed treatment was significantly lower in all age groups with a decreasing gradient with advancing age. Elderly lung cancer patients received significantly fewer resections and radiotherapy than non-elderly patients. In particular, treatment with antineoplastic therapy declined with increasing age ("young-old" (OR = 0.76, CI = [0.70,0.83]), "middle-old" (OR = 0.45, CI = [0.36,0.50]), and "old-old" (OR = 0.13, CI = [0.10,0.17])). Patients in all age groups were less likely to receive structured palliative care than "non-elderly" ("young-old" (OR = 0.84, CI = [0.76,0.92]), "middle-old" (OR = 0.71, CI = [0.63,0.79]), and "old-old" (OR = 0.57, CI = [0.44,0.73])). Moreover, increased age was significantly associated with reduced quotas for outpatient treatment with opioids and antidepressants. Costs of care decreased significantly with increasing age.ConclusionThis study suggests the existence of age-dependent care disparities in lung cancer patients, where elderly patients are at risk of potential undertreatment. To support equal access to care, adjustments to public health policies seem to be urgently required.

Bacterial periplasmic binding proteins (PBPs) undergo a pronounced ligand-induced conformational change which can be employed to monitor ligand concentrations. The most common strategy to take advantage of this conformational change for a biosensor design is to use a Förster resonance energy transfer (FRET) signal. This can be achieved by attaching either two fluorescent proteins (FPs) or two organic fluorescent dyes of different colors to the PBPs in order to obtain an optical readout signal which is closely related to the ligand concentration. In this study we compare a FP-equipped and a dye-labeled version of the glucose/galactose binding protein MglB at the single-molecule level. The comparison demonstrates that changes in the FRET signal upon glucose binding are more pronounced for the FP-equipped sensor construct as compared to the dye-labeled analog. Moreover, the FP-equipped sensor showed a strong increase of the FRET signal under crowding conditions whereas the dye-labeled sensor was not influenced by crowding. The choice of a labeling scheme should therefore be made depending on the application of a FRET-based sensor.

The purpose of this study was to explore the skin transcriptional profile in pediatric localized scleroderma (LS) to provide a better understanding of the altered immune and fibrotic pathways promoting disease. LS is a progressive disease of the skin and underlying tissue that causes significant functional disability and disfigurement, especially in developing children. RNA sequencing (RNAseq) technology allows for improved understanding of relevant cellular expression through transcriptome analysis of phases during LS disease progression (more active/inflammatory vs. inactive/fibrotic) and also permits the use of RNA extracted from existing paraffin-embedded skin tissue, which is important in pediatrics. A strong correlation was observed between the comparison of genes expressed between fresh (RNAlater) and paraffinized skin in healthy and LS subjects, supporting the use of paraffinized tissue. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ-, IFNα-, and TNFα-associated genes. GSEA© enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNγ itself, was more highly expressed in LS patients with more inflammatory lesions. The use of paraffinized skin for sequencing was proven to be an effective substitute for fresh skin by comparing gene expression profiles. The prevalence of the IFNγ signature in the lesion biopsies of active LS patients indicates that these genes reflect clinical activity parameters and may be the promoters of early, inflammatory disease.