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Background: With the introduction of new therapy modalities and the resulting increase in survival rates, childhood brain cancers have become a focal point of research in pediatric oncology. In current protocols, besides surgical resection and chemotherapy, radiotherapy is required to ensure optimal survival. Our aim was to determine which of the two major irradiation options, proton (PT) or photon (XRT), was the least harmful yet effective for children with brain tumors., Methods: The protocol was registered on PROSPERO in advance (CRD42022374443). A systematic search was performed in four databases (MEDLINE via (PubMed), Embase, Cochrane Library, and Scopus) on 23 April 2024. Odd ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Survival and six major types of side effects were assessed based on data in the articles and reported using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Heterogeneity was assessed using Higgins and Thompson's I2 statistics., Results: Altogether, 5848 articles were screened, of which 33 were eligible for data extraction. The 5-year overall survival results showed statistically no significant difference between the two radiotherapy modalities (OR = 0.80, 95% CI: 0.51-1.23, p = 0.22, I2 = 0%). In terms of toxicity rates, an advantage was found for PT, particularly in terms of chronic endocrine side effects (hypothyroidism OR: 0.22, 95% CI: 0.10-0428, p = 0.002, I2 = 68%), neurocognitive decline (global IQ level MD: 13.06, 95% CI: 4.97-21.15, p = 0.009, I2 = 68%). As for hematological, acute side effects, neurological changes and ophthalmologic disorders PT can be beneficial for survivors in terms of reducing them., Conclusions: In comparison with XRT, PT can reduce most side effects, without significantly decreasing the survival rate. There is considerable clinical relevance in the findings, even not all of them are statistically significant, which may facilitate the development of protocols regarding the usage of radiotherapy methods, and may encourage the establishment of more proton centers, where more studies can be done., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kiss-Miki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Lymph node upstaging represents a quality criterion for standardized lymphadenectomy in lung cancer surgery. The aim of the study was to compare whether the quality of standardized lymphadenectomy in lung cancer surgery is comparable in minimally invasive (video-assisted thoracoscopic surgery) and the open approach (thoracotomy). Furthermore, factors associated with lymph node upstaging were assessed, as was its impact on overall survival and progression-free survival., Methods: This retrospective study reviewed data of all patients undergoing lobectomy at the Lung Tumor Center Munich between 2011 and 2020. Inclusion factors were non-small cell lung cancer without nodal involvement (N0) or metastasis (M0) and standardized lymphadenectomy. A propensity score matched analyses was performed. Frequency of categorical outcomes was compared with Chi [2]-test, mean values with t-test. We used logistic and Cox regression models to assess factors associated with upstaging, overall survival and progression-free survival, restrictively., Results: Of 1691 patients undergoing lobectomy, 637 met our inclusion criteria. After propensity score matching 198 patients remained in each group. Univariate analysis showed no significant difference in lymph node upstaging between the two groups. (p = 0.12). Overall affected lymph nodes (p = 0.45) and overall affected lymph node stations (p = 0.26) were not significantly different. Multivariate Cox regression analysis showed that overall survival and progression free survival were also independent of the surgical approach. L1 status was the only factor associated with progression-free survival., Conclusion: Minimally invasive approaches achieves comparable lymph node upstaging in patients undergone standardized lymphadenectomy., Competing Interests: Declarations. Ethics approval and consent to participate: Approval for this retrospective, non-interventional study was obtained from the Ethics Committee of the Ludwig-Maximilian’s University (reference number 21–0036). This study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, and local ethical and legal requirements. The need for written informed consent was waived by the above-mentioned ethics committee due to retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Respect for patient autonomy, the principle that patients are capable to make informed decisions about medical interventions, is fundamental in present-day medicine. However, if a patient's request is medically not indicated, the practitioner faces an ethical dilemma represented by the conflict of the principles of patient autonomy, beneficence, and maleficence. Adjacent to topics such as medical assistance in dying and healthy limb amputation, this ethical dilemma also manifests in the care of the maxillofacial region (the oral cavity and its surroundings), an area crucial to esthetic appearance, but also to everyday functions including mastication, speech, and facial expression, all of which are related to well-being. Our aim was to explore the manifestations and resolutions of the conflict between oral health and patient autonomy in relevant literature in order to contribute to the discourse of ethical challenges concerning patient autonomy, beneficence, and nonmaleficence., Methods: We screened all journal articles discussing the researched ethical dilemma obtained from three databases. Two researchers developed a hierarchical coding scheme, where the parent and grandparent codes were designated deductively as: Case (situations involving the researched ethical dilemma), Judgement (decisions made in the ethical dilemma), and Principle (ideas, rules, propositions explaining the judgements); child codes were developed inductively. After coding the sources, we utilized thematic analysis to construct code constellations., Results: Most themes identified in our sources advocated for the practitioner to choose the alternative that benefits the patient from a medical perspective, although no theme excluded the consideration of patient autonomy. Instances where respect for patient autonomy was encouraged concerned oral preventive care or when the requested intervention was expected to have an insignificant impact on oral health., Conclusions: Ethical conflicts concerning patient autonomy, beneficence, and nonmaleficence have a marked presence in oral care. These conflicts arise through the issue of body modification, evident in cosmetic dentistry and requests for tooth extraction. Our sources generally support the argumentation for beneficence, despite the rise of cosmetic procedures in dentistry., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Authors’ information: SKD is a dentist and a PhD student. ASI is a medical anthropologist and a PhD student. SZ is an assistant professor in medical anthropology with expertise in qualitative data analysis. JK is a professor in bioethics, physician, and philosopher., (© 2024. The Author(s).)

Background and Objectives: Antibiotic-impregnated shunts seem to be beneficial in preventing bacterial infections and decreasing mortality by effectively inhibiting microbial growth in the shunt system and reducing the risk of shunt-associated infections. This study aimed to evaluate the efficacy of antibiotic-impregnated shunt catheters (AISC) in reducing the incidence of bacterial shunt infection in patients with hydrocephalus., Methods: The protocol was registered on PROSPERO. A meta-analysis was conducted by searching 3 databases (PubMed, Scopus, CENTRAL) for relevant randomized controlled trials and observational studies. We included all studies published until November 2022 in any language. The primary outcome was the rate of bacterial infections, whereas the rate of shunt failure was our secondary endpoint. Odds ratios (OR) with 95% CI were calculated using a random-effects model., Results: A total of 27 articles with 27 266 shunt operations were included in this study. The results indicated that using AISC is significantly associated with reduction in infections (OR = 0.42; 95% CI: 0.33-0.54). Regarding shunt failure, there was a tendency in favor of AISC use (OR = 0.73; 95% CI: 0.51-1.06)., Conclusion: Our study provided evidence that AISC is significantly associated with the reduction in the rate of bacterial ventriculoperitoneal-shunt infection. In addition, there was a tendency toward AISC to decrease shunt failure compared with the standard shunt., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kleid, Walter, Moehnle, Wichmann, Kovács, Humpe, Schneider, Michel, Kneidinger, Irlbeck, Fertmann, Dick and Kauke.)

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS ( p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student's t-test and ANOVA to compare means and Chi 2 -test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care., (© 2023. The Author(s).)

Background: The role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated., Patients and Methods: We conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS). Secondary endpoints included postoperative complications and recurrence/progression-free survival (RFS/PFS)., Results: The primary tumour was non-small cell lung cancer in 12 (39%), ovarian cancer in 5 (16%), sarcoma in 3 (10%), pseudomyxoma peritonei in 3 (10%), and others in 8 (26%) patients. A macroscopic complete resection (R/1) could be achieved in 28 (90%) patients. Major postoperative complications as classified by Clavien-Dindo (III-V) were observed in 11 (35%) patients. The postoperative mortality rate was 10% (n=3). A total of 13 patients received additive chemotherapy (42%). The median time of follow up was 30 months (95% CI = 17- 43). The median OS was 39 months (95% CI: 34-44 months) with 1-month, 3-month, 1-, 3-, and 5-year survival estimates of 97%, 89%, 77%, 66%, and 41%. There was a significantly prolonged OS in patients who received additive chemotherapy compared to patients with only CRS+HITOC (median OS 69 vs 38 months; p= 0.048). The median RFS was 14 months (95% CI: 7-21 months)., Conclusions: We observed that CRS+HITOC is a feasible approach with reasonable complications and prolonged survival as a part of multimodal concept for highly selected patients with secondary pleural metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hassan, Zimmermann, Schmid, Passlick, Kovács, Hatz, Winter, Klotz, Eichhorn, Markowiak, Müller, Huppertz, Koller, Hofmann and Ried.)

Since February 24th, 2022, millions of Ukrainians have sought refuge in other, mainly European countries. Hungary, after Poland, is the second largest host of Ukrainian refugees. Only a portion of them are asylum seekers (~11.0% in Poland and ~ 1.1% in Hungary). The aim of the study is to compare the integrative acculturation attitudes between the war refugees residing in the two European countries. The comparison takes into account both the suffering of posttraumatic stress symptoms and social support. It is the first comparative study of this kind pertaining to the Ukrainian refugees in European countries. The data were obtained by a survey method using the modified CAPI (Computer Assisted Personal Interview) technique. The data analyzed were collected between November 21st and December 20th, 2022 from 728 adult Ukrainian individuals who crossed the borders of Poland and Hungary after February 24th, 2022. The research results show that refugees in Poland perceive significantly more social support and show stronger integrative attitudes than refugees in Hungary. The two samples do not differ regarding the presence of posttraumatic stress. The integrative attitudes proved not to be linked to gender and age, but linked to the host country. Besides social support and the host country, posttraumatic stress also proved to be a significant predictor of integrative attitudes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kovács, Csukonyi, Kovács, Liszka and Walawender.)

Histiocytic sarcoma is an uncommon hematological malignancy. Its occurrence in the lung is very rare. Due to the small number of cases and the clinical and pathological features of the disease, the diagnosis can be challenging. Its optimal treatment is not yet known, in locally confined cases - depending on the location and size - surgical removal is part of complex oncotherapy. We report the case of a 52-year-old man with a tumor of central localization in the left lung. Pulmonectomy was performed. Histology verified histiocytic sarcoma of the lung. An overview of clinical features of the entity is presented in connection with our case report. Orv Heti. 2023; 164(34): 1350-1357.

Objectives: Cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITOC) is effective on survival for patients with pleural metastatic thymic tumours., Methods: Multicentre, retrospective analysis of patients with stage IVa thymic tumours treated with surgical resection and HITOC. Primary end point was overall survival, secondary end points were recurrence-/progression-free survival and morbidity/mortality., Results: A total of n = 58 patients (thymoma, n = 42; thymic carcinoma, n = 15; atypical carcinoid of the thymus, n = 1) were included, who had primary pleural metastases (n = 50; 86%) or pleural recurrence (n = 8; 14%). Lung-preserving resection (n = 56; 97%) was the preferred approach. Macroscopically complete tumour resection was achieved in n = 49 patients (85%). HITOC was performed with cisplatin alone (n = 38; 66%) or in combination with doxorubicin (n = 20; 34%). Almost half of the patients (n = 28; 48%) received high-dose cisplatin > 125 mg/m2 body surface area. Surgical revision was required in 8 (14%) patients. In-hospital mortality rate was 2%. During follow-up, tumour recurrence/progression was evident in n = 31 (53%) patients. Median follow-up time was 59 months. The 1-, 3- and 5-year survival rates were 95%, 83% and 77%, respectively. Recurrence/progression-free survival rates were 89%, 54% and 44%, respectively. Patients with thymoma had significantly better survival compared to patients with thymic carcinoma (P-value ≤0.001)., Conclusions: Promising survival rates in patients with pleural metastatic stage IVa in thymoma (94%) and even in thymic carcinoma (41%) were achieved. Surgical resection and HITOC is safe and effective for treatment of patients with pleural metastatic thymic tumours stage IVa., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Case discussion of a 40-year-old male patient with a history of recurrent pneumothoraces due to Birt-Hogg-Dubé syndrome. In addition to conservative treatment of a pneumothorax on the left side, a subtotal parietal pleurectomy on the right side was performed after recurrence of a pneumothorax 6 years later. CT of the thorax showed high-grade structural remodelling of the lung parenchyma with cystic lung lesions on both sides with a diameter of up to 7.5 cm. After exclusion of alpha-1 antitrypsin deficiency, underlying immunological disease, unremarkable family and occupational history, Birt-Hogg-Dubé syndrome was suspected based on the morphological distribution pattern of the cystic lung lesions. Genetic examination helped detect a heterozygous pathogenic variant in the FLCN gene, namely c.1294_1298del;p.(Ser432Argfs*22). Birt-Hogg-Dubé syndrome is a rare genetic disorder clinically characterized by pulmonary cysts, fibrofolliculomas of the skin and occurrence of clustered renal tumors. In particular, the increased risk of renal malignancies and the risk of spontaneous pneumothoraces underlines the importance of early diagnosis and screening of affected patients and their families., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Our study aimed to identify preoperative predictors for perioperative allogenic blood transfusion (ABT) in patients undergoing major lung cancer resections in order to improve the perioperative management of patients at risk for ABT., Methods: Patients admitted between 2014 and 2016 in a high-volume thoracic surgery clinic were retrospectively evaluated in a cohort study based on a control group without ABT and the ABT group requiring packed red blood cell units within 15 days postoperatively until discharge. The association of ABT with clinically established parameters (sex, preoperative anemia, liver and coagulation function, blood groups, multilobar resections) was analyzed by contingency tables, receiver operating characteristics (ROC) and logistic regression analysis, taking into account potential covariates., Results: 60 out of 529 patients (11.3%) required ABT. N1 and non-T1 tumors, thoracotomy approach, multilobar resections, thoracic wall resections and Rhesus negativity were more frequent in the ABT group. In multivariable analyses, female sex, preoperative anemia, multilobar resections, as well as serum alanine-aminotransferase levels, thrombocyte counts and Rhesus negativity were identified as independent predictors of ABT, being associated with OR (95% Confidence interval, p-value) of 2.44 (1.23-4.88, p = 0.0112), 18.16 (8.73-37.78, p < 0.0001), 5.79 (2.50-13.38, p < 0.0001), 3.98 (1.73-9.16, p = 0.0012), 2.04 (1.04-4.02, p = 0.0390) and 2.84 (1.23-6.59, p = 0.0150), respectively., Conclusions: In patients undergoing major lung cancer resections, multiple independent risk factors for perioperative ABT apart from preoperative anemia and multilobar resections were identified. Assessment of these predictors might help to identify high risk patients preoperatively and to improve the strategies that reduce perioperative ABT., (© 2023. The Author(s).)

Introduction: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation., Methods: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19)., Results: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES., Conclusion: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Plants growing in proximity to other plants are exposed to a variety of metabolites that these neighbors release into the environment. Some species produce allelochemicals to inhibit growth of neighboring plants, which in turn have evolved ways to detoxify these compounds., Results: In order to understand how the allelochemical-receiving target plants respond to chemically diverse compounds, we performed whole-genome transcriptome analysis of Arabidopsis thaliana exposed to either the benzoxazinoid derivative 2-amino- 3H-phenoxazin-3-one (APO) or momilactone B. These two allelochemicals belong to two very different compound classes, benzoxazinoids and diterpenes, respectively, produced by different Poaceae crop species., Conclusions: Despite their distinct chemical nature, we observed similar molecular responses of A. thaliana to these allelochemicals. In particular, many of the same or closely related genes belonging to the three-phase detoxification pathway were upregulated in both treatments. Further, we observed an overlap between genes upregulated by allelochemicals and those involved in herbicide detoxification. Our findings highlight the overlap in the transcriptional response of a target plant to natural and synthetic phytotoxic compounds and illustrate how herbicide resistance could arise via pathways involved in plant-plant interaction., (© 2022. The Author(s).)

Abrupt and large-scale climate changes have occurred repeatedly and within decades during the last glaciation. These events, where dramatic warming occurs over decades, are well represented in both Greenland ice core mineral dust and temperature records, suggesting a causal link. However, the feedbacks between atmospheric dust and climate change during these Dansgaard-Oeschger events are poorly known and the processes driving changes in atmospheric dust emission and transport remain elusive. Constraining dust provenance is key to resolving these gaps. Here, we present a multi-technique analysis of Greenland dust provenance using novel and established, source diagnostic isotopic tracers as well as results from a regional climate model including dust cycle simulations. We show that the existing dominant model for the provenance of Greenland dust as sourced from combined East Asian dust and Pacific volcanics is not supported. Rather, our clay mineralogical and Hf-Sr-Nd and D/H isotopic analyses from last glacial Greenland dust and an extensive range of Northern Hemisphere potential dust sources reveal three most likely scenarios (in order of probability): direct dust sourcing from the Taklimakan Desert in western China, direct sourcing from European glacial sources, or a mix of dust originating from Europe and North Africa. Furthermore, our regional climate modeling demonstrates the plausibility of European or mixed European/North African sources for the first time. We suggest that the origin of dust to Greenland is potentially more complex than previously recognized, demonstrating more uncertainty in our understanding dust climate feedbacks during abrupt events than previously understood., (© 2022. The Authors.)

Background: Tumor 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., Methods: Internal 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., Results: We 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., Conclusion: Levels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sellmer, Kovács, Walter, Kumbrink, Neumann, Kauffmann-Guerrero, Kiefl, Schneider, Jung, Behr and Tufman.)

Background: Most SCLC patients are diagnosed with extensive disease (ED) and the prognosis in this cohort remains poor. However, some patients are diagnosed with limited (LD) or very limited (VLD, T1-2, N0-1, M0) disease and previous data suggest that surgical resection might improve outcomes in these patients. Most of the existing evidence comes from small case series. For this reason, we investigated clinical features and surgical outcomes in a large cohort of resected SCLC patients., Patients and Methods: We used a large pseudomized dataset (n = 32432) provided by the Munich Cancer Registry to analyze all documented SCLC patients (n = 5043) between 2002 and 2015. We correlated patients' characteristics as well as surgery modalities with survival data and describe trends in the role of surgery in SCLC over the time., Results: We analyzed 5043 SCLC patients. A total of 161 (3.2%) received either oncological (lobectomy, bilobectomy and pneumonectomy) or limited resection (segmentectomy and wedge resection). We found a significant trend suggesting that resections in SCLC patients become less common in all stages of disease, accompanied by an increased proportion of oncological resections. This suggests a more accurate preoperative staging. In VLD resection was significantly associated with longer survival compared to nonsurgical management (log-rank P = .013). Survival was better with oncological resection compared to atypical resection. Administration of adjuvant chemotherapy was associated with better outcome in all resected patients (P = .01)., Conclusion: VLD SCLC patients benefit from oncological resection. We recommend invasive staging in these patients to ensure VLD. Furthermore, adjuvant chemotherapy should be offered to all resected patients., (Copyright © 2022. Published by Elsevier Inc.)

Aim: To analyze immune cell populations in non-small-cell lung cancer (NSCLC) tumors and matched tumor-bearing and non-tumor-bearing lymph nodes (ntbLNs) to predict prognosis. Patients & methods: 71 patients with long-term disease-free survival and 80 patients with relapse within 3 years were included in this study. We used Cox regression to identify factors associated with overall survival (OS) and progression-free survival (PFS). Results: Sinus histiocytosis and tumor-infiltrating lymphocyte density in the tumor were positively associated with PFS and OS. CD4 expression in node 1 (hazard ratio = 0.72; p = 0.02) and node 2 (hazard ratio = 0.91; p = 0.04) ntbLNs were positively correlated with OS and PFS, respectively. Discussion: Immunological markers in ntbLNs could be used to predict survival in NSCLC.

Background:  The aim of this retrospective study was to investigate the implementation of measures to prevent perioperative COVID-19 in thoracic surgery during the first wave of the COVID-19 pandemic 2020 allowing a continued surgical treatment of patients., Methods:  The implemented preventive measures in patient management of the thoracic surgery department of the Asklepios Lung Clinic Munich-Gauting, Germany were retrospectively analyzed. Postoperative COVID-19 incidence before and after implementation of preventive measures was investigated. Patients admitted for thoracic surgical procedures between March and May 2020 were included in the study. Patient characteristics were analyzed. For the early detection of putative postoperative COVID-19 symptoms, typical post-discharge symptomatology of thoracic surgery patients was compared to non-surgical patients hospitalized for COVID-19., Results:  Thirty-five surgical procedures and fifty-seven surgical procedures were performed before and after implementation of the preventive measures, respectively. Three patients undergoing thoracic surgery before implementation of preventive measures developed a COVID-19 pneumonia post-discharge. After implementation of preventive measures, no postoperative COVID-19 cases were identified. Fever, dyspnea, dry cough and diarrhea were significantly more prevalent in COVID-19 patients compared to normally recovering thoracic surgery patients, while anosmia, phlegm, low energy levels, body ache and nausea were similarly frequent in both groups., Conclusions:  Based on the lessons learned during the first pandemic wave, we here provide a blueprint for successful easily implementable preventive measures minimizing SARS-CoV-2 transmission to thoracic surgery patients perioperatively. While symptoms of COVID-19 and the normal postoperative course of thoracic surgery patients substantially overlap, we found dyspnea, fever, cough, and diarrhea significantly more prevalent in COVID-19 patients than in normally recovering thoracic surgery patients. These symptoms should trigger further diagnostic testing for postoperative COVID-19 in thoracic surgery patients., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients ( n = 350) with malignant pleural mesothelioma ( n = 261; 75%) and thymic tumours with pleural spread ( n = 58; 17%) or pleural metastases ( n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone ( n = 212; 61%) or cisplatin plus doxorubicin ( n = 138; 39%). Low-dose cisplatin (≤125 mg/m 2 BSA) was given in 67% of patients ( n = 234), and high-dose cisplatin (>125 mg/m 2 BSA) was given in 33% of patients ( n = 116). Postoperative renal insufficiency appeared in 12% of the patients ( n = 41), and 1.4% ( n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% ( n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin ( p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range.

Background: Glucocorticoid (GC) pulse therapy is used for multiple sclerosis (MS) relapse treatment; however, GC resistance is a common problem. Considering that GC dosing is individual with several response-influencing factors, establishing a predictive model, which supports clinicians to estimate the maximum GC dose above which no additional therapeutic value can be expected presents a huge clinical need., Method: We established two, independent retrospective cohorts of MS patients. The first was an explorative cohort for model generation, while the second was established for its validation. Using the explorative cohort, a multivariate regression analysis with the GC dose used as the dependent variable and serum vitamin D (25D) concentration, sex, age, EDSS, contrast enhancement on cranial magnetic resonance imaging (MRI), immune therapy, and the involvement of the optic nerve as independent variables was established., Results: In the explorative cohort, 113 MS patients were included. 25-hydroxyvitamin D (25D) serum concentration and the presence of optic neuritis were independent predictors of the GC dose needed to treat MS relapses [(25D): -25.95 (95% confidence interval (CI)): -47.40 to -4.49; p  = 0.018; optic neuritis: 2040.51 (95% CI: 584.64-3496.36), p  = 0.006]. Validation of the multivariate linear regression model was performed within a second cohort. Here, the predicted GC dose did not differ significantly from the dose administered in clinical routine (mean difference: -843.54; 95% CI: -2078.08-391.00; n  = 30, p  = 0.173)., Conclusion: Our model could predict the GC dose given in clinical, routine MS relapse care, above which clinicians estimate no further benefit. Further studies should validate and improve our algorithm to help the implementation of predictive models in GC dosing., Competing Interests: Conflict of interest statement: J Gili-Kovács reports no disclosures. R Hoepner has received research and travel grants from Roche, Novartis, and Biogen Idec and speaker honoraria from Biogen, Novartis, Merck, Celgene, and Almirall, not related to this work. He reports no conflicts of interest related to this manuscript. A Salmen received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme, and research support by the Swiss MS Society, not related to this work. M Bagnoud reports no disclosures. R Gold received research support, and speaker’s honoraria from Bayer Schering, Biogen, Celgene, Chugai, Eisai, Janssen Pharmaceuticals, Merck Serono, Nikkiso Pharma, Novartis, Roche, Sandoz, Sanofi-Genzyme, and TEVA. They received consulting honoraria from ZLB Behring, Baxter, Novartis, and Talecris. They have personal stock options in Bayer, Merck, and Roche. A Chan has served on advisory boards for, and received funding for travel or speaker honoraria from, Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, and Teva, all for hospital research funds; and research support from Biogen, Genzyme, and UCB. A. Chan is associate editor of the European Journal of Neurology and serves on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. M Briner received travel grants from Merck, Biogen, and Genzyme., (© The Author(s), 2021.)

Összefoglaló. Bevezetés: Az atorvasztatin (koleszterincsökkentő), nifedipin (Ca2+-antagonista), kaptopril (angiotenzinkonvertáz-gátló) vegyületek a magas vérnyomás komplex kezelésének "alap"gyógyszerei. Mindhárom antioxidáns is. Célkitűzés: A tanulmány célja annak megválaszolása volt, hogy e molekulák gátolhatják-e a vérsejtek fagocitaműködését. Betegek és módszer: Magas vérnyomásos betegek: 15 fő, 39-80 éves, nő: 6, férfi: 9. Egészséges kontroll: 7 fő, 30-75 éves, nő: 3, férfi: 4. A vizsgálat a téli hónapokban zajlott. A zimozán- (Saccharomyces cerevisiae) részecskék fagocitózisa során képződő kemilumineszcencia mérése perifériás vérben a gyógyszerek jelenlétében történt luminométerrel. A gátlást a stimulációs index értékének csökkenésével jellemeztük. Eredmények: Mindhárom vegyület gátolta a kemilumineszcenciát (oxigénszabadgyök-képzést) a 65 év feletti, magas vérnyomásos betegek többségében: 11/13 főnél. Főleg magasabb életkorban és cukorbetegségben, de más társbetegségekben nőtt a gátlás. Következtetés: Az idős, magas vérnyomásos betegek fokozott orvosi figyelmet igényelnek a téli időszakokban, mivel antioxidáns hatással is rendelkező "alap"gyógyszereiknek, egyéntől függően, lehetnek gátló hatásaik a fagociták mikrobaölő, oxigénszabadgyök-termelő képességére. Orv Hetil. 2020; 161(45): 1908-1913., Introduction: Atorvastatin (cholesterol synthesis blocker), nifedipine (Ca2+ antagonist), captopril (angiotensin-convertase inhibitor) are basic drugs in the therapy of hypertension. They are also antioxidants., Objective: To investigate whether these molecules can inhibit the phagocytic activity of peripheral blood cells., Patients and Method: Hypertension group: 15 patients with ages between 39-80 years (6 women and 9 men). Healthy control group: 7 individuals with ages between 30-75 years (3 women and 4 men). The study was carried out in wintertime. The measurement of phagocytic activity was carried out by luminometry in peripheral blood samples. Chemiluminescence intensities were determined by the engulfment of zymosan (Saccharomyces cerevisiae) particles in the presence of drugs. The inhibitory effects were characterized by the decreased values of the stimulation index., Results: All three substances decreased the chemiluminescence (reactive oxygen species production) in the majority of samples from hypertensive patients over 65 years: in 11 of 13 patients. Stronger inhibition was detected in older, diabetic patients with other co-morbidities, too., Conclusion: Older patients with hypertension require a special attention in wintertime. Antihypertensive drugs with antioxidant capabilities may have individually different inhibitory effects on the production of reactive oxygen species by phagocytes, which decreases their antimicrobial potency. Orv Hetil. 2020; 161(45): 1908-1913.

Exploitation of engineered nanomaterials with unique properties has been dynamically growing in numerous fields, including the agricultural sector. Due to the increasing resistance of phytopathogenic microbes, human control over various plant pathogens in crop production is a big challenge and requires the development of novel antimicrobial materials. Photocatalytic active nanomaterials could offer an alternative solution to suppress the plant pathogens. In this work, titanium dioxide nanoparticles (TiO 2 NPs) with high photocatalytic activity were synthesized by hydrothermal post-treatment of amorphous titania at different temperatures (250 °C or 310 °C) without using any additives or doping agents. The obtained samples were investigated through X-ray diffraction, N 2 -sorption measurements, diffuse reflectance UV-Vis spectroscopy, transmission electron microscopy, electron paramagnetic resonance spectroscopy, and X-ray photoelectron spectroscopy. The applied hydrothermal treatment led to the formation of TiO 2 nanocrystallites with a predominant anatase crystal phase, with increasing crystallinity and crystallite size by prolonging treatment time. The photocatalytic activity of the TiO 2 NPs was tested for the photo-degradation of phenol and applied for the inactivation of various plant pathogens such as Erwinia amylovora , Xanthomonas arboricola pv. juglandis , Pseudomonas syringae pv. tomato and Allhorizobium vitis . The studied bacteria showed different susceptibilities; their living cell numbers were quickly and remarkably reduced by UV-A-irradiated TiO 2 NPs. The effectiveness of the most active sample prepared at 310 °C was much higher than that of commercial P25 TiO 2 . We found that fine-tuning of the structural properties by modulating the time and temperature of the hydrothermal treatment influenced the photocatalytic properties of the TiO 2 NPs considerably. This work provides valuable information to the development of TiO 2 -based antimicrobial photocatalysts.

Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator with diverse biological function mediated by S1P 1-5 receptors. Whereas S1P was shown to protect the heart against ischemia/reperfusion (I/R) injury, other studies highlighted its vasoconstrictor effects. We aimed to separate the beneficial and potentially deleterious cardiac effects of S1P during I/R and identify the signaling pathways involved. Wild type (WT), S1P 2 -KO and S1P 3 -KO Langendorff-perfused murine hearts were exposed to intravascular S1P, I/R, or both. S1P induced a 45% decrease of coronary flow (CF) in WT-hearts. The presence of S1P-chaperon albumin did not modify this effect. CF reduction diminished in S1P 3 -KO but not in S1P 2 -KO hearts, indicating that in our model S1P 3 mediates coronary vasoconstriction. In I/R experiments, S1P 3 deficiency had no influence on postischemic CF but diminished functional recovery and increased infarct size, indicating a cardioprotective effect of S1P 3 . Preischemic S1P exposure resulted in a substantial reduction of postischemic CF and cardiac performance and increased the infarcted area. Although S1P 3 deficiency increased postischemic CF, this failed to improve cardiac performance. These results indicate a dual role of S1P 3 involving a direct protective action on the myocardium and a cardiosuppressive effect due to coronary vasoconstriction. In acute coronary syndrome when S1P may be released abundantly, intravascular and myocardial S1P production might have competing influences on myocardial function via activation of S1P 3 receptors.

Campylobacter jejuni is one of the most common food-borne bacteria that causes gastrointestinal symptoms. In the present study we have investigated the molecular basis of the anti- Campylobacter effect of peppermint essential oil (PEO), one of the oldest EO used to treat gastrointestinal diseases. Transcriptomic, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and proteomic, two-dimensional polyacryl amid gel electrophoresis (2D-PAGE) methods have revealed that, in the presence of a sublethal concentration of PEO, the expression of several virulence-associated genes was decreased ( cheY 0.84x; flhB 0.79x; flgE 0.205x; cadF 0.08x; wlaB 0.89x; porA 0.25x; cbf2 4.3x) while impaired motility was revealed with a functional analysis. Scanning electron micrographs of the exposed cells showed that, unlike in the presence of other stresses, the originally curved C. jejuni cells straightened upon PEO exposure. Gaining insight into the molecular background of this stress response, we have revealed that in the presence of PEO C. jejuni dominantly exerts a general stress response that elevates the expression of general stress genes like dnaK , groEL , groES (10.41x, 3.63x, and 4.77x). The most important genes dps , sodB , and katA involved in oxidative stress responses showed however moderate transcriptional elevations (1,58x, 1,55x, and 1,85x).

Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro , their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization.

Centennial-scale mineral dust peaks in last glacial Greenland ice cores match the timing of lowest Greenland temperatures, yet little is known of equivalent changes in dust-emitting regions, limiting our understanding of dust-climate interaction. Here, we present the most detailed and precise age model for European loess dust deposits to date, based on 125 accelerator mass spectrometry 14 C ages from Dunaszekcső, Hungary. The record shows that variations in glacial dust deposition variability on centennial-millennial timescales in east central Europe and Greenland were synchronous within uncertainty. We suggest that precipitation and atmospheric circulation changes were likely the major influences on European glacial dust activity and propose that European dust emissions were modulated by dominant phases of the North Atlantic Oscillation, which had a major influence on vegetation and local climate of European dust source regions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2017 the Author(s). Published by PNAS.)

The research investigated three iron carbonate (siderite) sedimentary concretions from Nagykovácsi, Úri and Délegyháza, Hungary. To identify possible source rocks and effects of the glaze-like exposed surface of the concretions, we carried on comparative petrological, mineralogical, geochemical and isotopic studies. The samples were microbially mediated siderite concretions with embedded metamorphous and igneous mineral clasts, and had specific rim belts characterized by semi-concentric outer Fe-oxide layers, fluffy pyrite-rich outer belts and siderite inner parts. We investigated the cross section of the Fe-carbonate concretions by independent methodologies in order to identify their rim effects. Their surficial oxide layers showed evidence of degassing of the exposed surface caused most probably by elevated temperatures. The inner rim pyrite belt in the concretions excluded the possibility of a prolonged wet surface environment. Microtextural and mineralogical features did not support desert varnish formation. 10 Be nuclide values of the Nagykovácsi and Uri concretions were far above the level of terrestrial in-situ cosmogenic nuclides, but they were consistent with the lowest levels for meteorites. Though the data were not conclusive to confirm any kind of known origin, they are contradictary, and open possibilities for a scenario of terrestrial meteorite origin., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The proteasome is a nuclear-cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions, but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit-selective inhibitors and dual-color fluorescent activity-based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant-microbe interactions. Our data reveal that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both β1 and β5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1-1 [PtoDC3000(ΔhQ)] whilst the activity profile of the β1 subunit changes. Infection with wild-type PtoDC3000 causes proteasome activities that range from strongly induced β1 and β5 activities to strongly suppressed β5 activities, revealing that β1 and β5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community, and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species., (© 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.)

The stress proteasome in the animal kingdom facilitates faster conversion of oxidized proteins during stress conditions by incorporating different catalytic β subunits. Plants deal with similar kind of stresses and also carry multiple paralogous genes encoding for each of the three catalytic β subunits. Here, we investigated the existence of stress proteasomes upon abiotic stress (salt stress) in tomato roots. In contrast to Arabidopsis thaliana , tomato has a simplified proteasome gene set with single genes encoding each β subunit except for two genes encoding β2. Using proteasome activity profiling on tomato roots during salt stress, we discovered a transient modification of the catalytic subunits of the proteasome coinciding with a loss of cell viability. This stress-induced active proteasome disappears at later time points and coincides with the need to degrade oxidized proteins during salt stress. Subunit-selective proteasome probes and MS analysis of fluorescent 2D gels demonstrated that the detected stress-induced proteasome is not caused by an altered composition of subunits in active proteasomes, but involves an increased molecular weight of both labeled β2 and β5 subunits, and an additional acidic pI shift for labeled β5, whilst labeled β1 remains mostly unchanged. Treatment with phosphatase or glycosidases did not affect the migration pattern. This stress-induced proteasome may play an important role in PCD during abiotic stress.

Combined cluster and discriminant analysis (CCDA) as a chemometric tool in compound specific isotope analysis of diesel fuels was studied. The stable carbon isotope ratios (δ 13 C) of n-alkanes in diesel fuel can be used to characterize or differentiate diesels originating from different sources. We investigated 25 diesel fuel samples representing 20 different brands. The samples were collected from 25 different service stations in 11 European countries over a 2 year period. The n-alkane fraction of diesel fuels was separated using solid-state urea clathrate formation combined with silica gel fractionation. The stable carbon isotope ratios of C10-C24 n-alkanes were measured with gas chromatography-isotope ratio mass spectrometry (GC-IRMS) using perdeuterated n-alkanes as internal standards. Beside the 25 samples one additional diesel fuel was prepared and measured three times to get totally homogenous samples in order to test the performance of our analytical and statistical routine. Stable isotope ratio data were evaluated with hierarchical cluster analysis (HCA), principal component analysis (PCA) and CCDA. CCDA combines two multivariate data analysis methods hierarchical cluster analysis with linear discriminant analysis (LDA). The main idea behind CCDA is to compare the goodness of preconceived (based on the sample origins) and random groupings. In CCDA all the samples were compared pairwise. The results for the parallel sample preparations showed that the analytical procedure does not have any significant effect on the δ 13 C values of n-alkanes. The three parallels proved to be totally homogenous with CCDA. HCA and PCA can be useful tools when the examining of the relationship among several samples is in question. However, these two techniques cannot be always decisive on the origin of similar samples. The initial hypothesis that all diesel fuel samples are considered chemically unique was verified by CCDA. The main advantage of CCDA is that it gives an objective index number about the level of similarity among the investigated samples. Thus the application of CCDA supplemented by the traditionally used multivariate methods greatly improves the efficiency of statistical analysis in the CSIA of diesel fuel samples., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Pseudomonas syringae pv. tomato DC3000 (PtoDC3000) is an extracellular model plant pathogen, yet its potential to produce secreted effectors that manipulate the apoplast has been under investigated. Here we identified 131 candidate small, secreted, non-annotated proteins from the PtoDC3000 genome, most of which are common to Pseudomonas species and potentially expressed during apoplastic colonization. We produced 43 of these proteins through a custom-made gateway-compatible expression system for extracellular bacterial proteins, and screened them for their ability to inhibit the secreted immune protease C14 of tomato using competitive activity-based protein profiling. This screen revealed C14-inhibiting protein-1 (Cip1), which contains motifs of the chagasin-like protease inhibitors. Cip1 mutants are less virulent on tomato, demonstrating the importance of this effector in apoplastic immunity. Cip1 also inhibits immune protease Pip1, which is known to suppress PtoDC3000 infection, but has a lower affinity for its close homolog Rcr3, explaining why this protein is not recognized in tomato plants carrying the Cf-2 resistance gene, which uses Rcr3 as a co-receptor to detect pathogen-derived protease inhibitors. Thus, this approach uncovered a protease inhibitor of P. syringae, indicating that also P. syringae secretes effectors that selectively target apoplastic host proteases of tomato, similar to tomato pathogenic fungi, oomycetes and nematodes., Competing Interests: The authors have declared that no competing interests exist.

Background: One obstacle to organ donation is the high proportion of relatives who refuse consent in presumed-consent countries. The aim of this study was to survey the features of family approaches and to identify those that may have significant impact on family refusals., Methods: A 46-item validated questionnaire was designed and used in 2011 and 2012 to investigate factors around all family communications about brain death and organ donation. The data of 188 cases were collected by telephone calls. We asked for the demographic data of donors; place, timing, duration, type, and result of approach; number, age, gender, and qualification of the staff; affinity, gender, age, education, and religion of the involved relatives; and finally the applied method to treat family refusal if it existed., Results: Usually 1 physician talked with 2 relatives. Timing had significant impact on objection rate (χ 2  = 0.044). Single-discussion meetings (56.38%) were an average 1 hour 13 minutes before the brain death declaration, and they were initiated an average 19 hours 49 minutes before brain death when more than one meeting took place (43.62%). Conversations lasted for 11-22 minutes. Mann-Whitney U test revealed association between duration of donor family communication and occurrence of refusal (P = .021). It was found that the relatives' education level, the number of staff, and the number of family members strongly influenced the occurrence of refusals., Conclusions: The careful preparation, organized direction, and support by intensive care unit staff can decrease the number of family refusals., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Activity-based probes are powerful tools to interrogate the functional proteome. Their covalent and often irreversible labeling of proteins facilitates the purification, identification and quantification of labeled proteins. However, the detection of labeled proteins often requires a confirmation, especially when unexpected proteins are identified, or to unravel fluorescent activity profiles. Here, we review twelve approaches towards target confirmation, grouped in approaches by direct target detection, target expression or target depletion. We discuss their proper use and limitations and illustrate these approaches with examples from plant science., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The hypersensitive response (HR), a type of programmed cell death (PCD) during biotic stress is mediated by salicylic acid (SA). The aim of this work was to reveal the role of proteolysis and cysteine proteases in the execution of PCD in response of SA. Tomato plants were treated with sublethal (0.1 mM) and lethal (1 mM) SA concentrations through the root system. Treatment with 1 mM SA increased the electrolyte leakage and proteolytic activity and reduced the total protein content of roots after 6 h, while the proteolytic activity did not change in the leaves and in plants exposed to 0.1 mM SA. The expression of the papain-type cysteine protease SlCYP1, the vacuolar processing enzyme SlVPE1 and the tomato metacaspase SlMCA1 was induced within the first three hours in the leaves and after 0.5 h in the roots in the presence of 1 mM SA but the transcript levels did not increase significantly at sublethal SA. The Bax inhibitor-1 (SlBI-1), an antiapoptotic gene was over-expressed in the roots after SA treatments and it proved to be transient in the presence of sublethal SA. Protease inhibitors, SlPI2 and SlLTC were upregulated in the roots by sublethal SA but their expression remained low at 1 mM SA concentration. It is concluded that in contrast to leaves the SA-induced PCD is associated with increased proteolytic activity in the root tissues resulting from a fast up-regulation of specific cysteine proteases and down-regulation of protease inhibitors.

The salt stress triggered by sublethal, 100 mM and lethal, 250 mM NaCl induced ethylene production as well as rapid accumulation of superoxide radical and H2O2 in the root tips of tomato (Solanum lycopersicum cv. Ailsa Craig) wild type and ethylene receptor mutant, Never ripe (Nr/Nr) plants. In the wild type plants superoxide accumulation confined to lethal salt concentration while H2O2 accumulated more efficiently under sublethal salt stress. However, in Nr roots the superoxide production was higher and unexpectedly, H2O2 level was lower than in the wild type under sublethal salt stress. Nitric oxide production increased significantly under sublethal and lethal salt stress in both genotypes especially in mutant plants, while peroxynitrite accumulated significantly under lethal salt stress. Thus, the nitro-oxidative stress may be stronger in Nr roots, which leads to the programmed death of tissues, characterized by the DNA and protein degradation and loss of cell viability under moderate salt stress. In Nr mutants the cell death was induced in the absence of ethylene perception. Although wild type roots could maintain their potassium content under moderate salt stress, K(+) level significantly declined leading to small K(+)/Na(+) ratio in Nr roots. Thus Nr mutants were more sensitive to salt stress than the wild type and the viability of root cells decreased significantly under moderate salt stress. These changes can be attributed to a stronger ionic stress due to the K(+) loss from the root tissues., (Copyright © 2015. Published by Elsevier Masson SAS.)

Oyster mushroom (Pleurotus ostreatus) lignocellulolytic enzyme activity pattern and variation was investigated in a large-scale facility from spawning until the end of the second flush. In the first cultivation cycle laccase production reached its peak during vegetative growth stage, while manganese-peroxidase showed the highest activity during fruiting body induction. Cellulose and hemicellulose degrading enzymes had maximal activity at the beginning of flush and harvest stage. The enzyme activities showed similar tendencies among five different mushroom substrate blocks representing a production house. The spatial variability analysis of enzyme activities pointed out the within substrate block heterogeneity as the main source if variation. This result was confirmed by Combined Cluster and Discriminant Analysis (CCDA) method showing minimal among block heterogeneity considering the whole investigation period; furthermore in the first cultivation cycle all blocks were grouped into one cluster., (Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Palliative treatment of malignant gastroduodenal obstructions with enteral stents is an effective and safe method, and a viable alternative to gastroenterostomy., Aim: The authors present the most common malignancies behind gastroduodenal obstructions, the aspects of stent selections, insertion techniques, technical and clinical success rates, and possible procedure-related complications., Method: Between 1 March, 2013 and 9 April, 2015 nineteen patients were treated with uncovered, self-expandable enteral stents. Out of the 19 patients, 6 were females and 13 males, with an average age of 67 years. Indications of stenting were peripyloric ventricular tumour in five cases, malignancies of the duodenum, gastroenteralis anastomosis, Vater papilla and gallbladder in one case respectively, pancreatic tumor in seven cases and bile duct malignancies in three cases., Results: The technical success rate of stent placement was 100%. The evaluation of clinical success was analised on the basis of the Gastric Outlet Obstruction Scoring System., Conclusions: The use of enteral stents in malignant gastroduodenal obstructions is a reliable and safe method, which promptly decreases symptoms of the patients and improves their quality of life.

The reuse of industrial by-products is important for members of numerous industrial sectors. However, though the benefits of reuse are evident from an economical point of view, some compounds in these materials can have a negative effect on users' health. In this study, the radon emanation and exhalation features of red mud were surveyed using heat-treatment (100-1200 °C). As a result of the 1200°C-treated samples, massic radon exhalation capacity reduced from 75 ± 10 mBq kg(-1) h(-1) to 7 ± 4 mBq kg(-1) h(-1), approximately 10% of the initial exhalation rate. To find an explanation for internal structural changes, the porosity features of the heat-treated samples were also investigated. It was found that the cumulative pore volume reduced significantly in less than 100 nm, which can explain the reduced massic exhalation capacity in the high temperature treated range mentioned above. SEM snapshots were taken of the surfaces of the samples as visual evidence for superficial morphological changes. It was found that the surface of the high temperature treated samples had changed, proving the decrement of open pores on the surface., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The most essential requirement for water management is efficient and informative monitoring. Operating water quality monitoring networks is a challenge from both the scientific and economic points of view, especially in the case of river sections ranging over hundreds of kilometers. Therefore, spatio-temporal optimization is vital. In the present study, the optimization of the monitoring system of the River Tisza, the second largest river in Central Europe, is presented using a generally applicable and novel method, combined cluster and discriminant analysis (CCDA). This area for the study was chosen because, spatial inhomogeneity of a river's monitoring network can more easily be studied in a mostly natural watershed - as in the case of the River Tisza - since the effects of man-made obstacles: e.g water barrage systems, hydroelectric power plants, artificial lakes, etc. are more pronounced. Furthermore, since the temporal sampling frequency was bi-weekly, the opportunity of optimizing the monitoring system on a temporal (monthly) scale arose. In the research, 15 water quality parameters measured at 14 sampling sites in the Hungarian section of the River Tisza were assessed for the time period 1975-2005. First, four within-year sections ("hydrochemical seasons") were determined, characterized with unequal lengths, namely 2, 4, 2, and 4 months long starting with spring. Homogeneous groups of sampling sites were determined in space for every season, with the main separating factors being the tributaries and man-made obstacles. Similarly, an overall pattern of homogeneity was determined. As an overall result, the 14 sampling sites could be grouped into 11 homogeneous groups leading to the possibility of reducing the number of sampling locations and thus making the monitoring system more cost-efficient.

Background: We investigated in postmenopausal women with primary breast cancer prior to surgical intervention whether, serum levels of different steroid hormones and hormonal precursors associated with tumor tissue estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status., Methods: We enrolled 1,042 patients suffering invasive ductal carcinoma undergoing surgical resection in the National Institute of Oncology, Hungary between 2003 and 2011. Serum parameters were measured by RIA/IRMA assays; tumor tissue ER, PR and HER2 status was assessed histologically. Patients were classified according to tumor receptor status. Case-case analysis subjects were categorized into four subgroups based on serum hormone concentrations in ER, PR and HER2 receptor-negative cases, respectively., Results: Serum estrone sulfate and dehydroepiandrosterone sulfate levels correlated with each other and also with serum estrone and estradiol levels. According to case-case study the odds ratios in the highest quartile were 1.517 (p = 0.0305, Ptrend = 0.0394) for androstenedione, 1.495 (p = 0.0317, Ptrend < 0.0105) for estrone and 0.654 (p = 0.0273, Ptrend < 0.0151) for estrone sulfate/estrone ratio in PR+ vs. PR- tumors. Regarding HER2 status (HER2+ vs. HER2-), the odds ratios for estrone, estrone sulfate and estrone sulfate/estrone ratio were 0.530 (p = 0.0234, Ptrend = 0.0595), 2.438 (p = 0.0042, Ptrend < 0.0066) and 3.118 (p = 0.0001, Ptrend < 0.0001) in the highest quartile, respectively. Of note significantly increased BMI associates with PR+ and ER +/PR+ status while significantly decreased BMI was observed in HER2+ cases., Conclusions: Taken together, measurement of serum estrone and estrone sulfate concentrations prior to surgical intervention might support the individualization of regime in postmenopausal primary breast cancer patients.

Ochre is the common archaeological term for prehistoric pigments. It is applied to a range of uses, from ritual burials to cave art to medications. While a substantial number of Palaeolithic paint mining pits have been identified across Europe, the link between ochre use and provenance, and their antiquity, has never yet been identified. Here we characterise the mineralogical signature of core-shell processed ochre from the Palaeolithic paint mining pits near Lovas in Hungary, using a novel integration of petrographic and mineralogical techniques. We present the first evidence for core-shell processed, natural pigment that was prepared by prehistoric people from hematitic red ochre. This involved combining the darker red outer shell with the less intensely coloured core to efficiently produce an economical, yet still strongly coloured, paint. We demonstrate the antiquity of the site as having operated between 14-13 kcal BP, during the Epigravettian period. This is based on new radiocarbon dating of bone artefacts associated with the quarry site. The dating results indicate the site to be the oldest known evidence for core-shell pigment processing. We show that the ochre mined at Lovas was exported from the site based on its characteristic signature at other archaeological sites in the region. Our discovery not only provides a methodological framework for future characterisation of ochre pigments, but also provides the earliest known evidence for "value-adding" of products for trade.

The 20 residue long Trp-cage miniprotein is an excellent model for both computational and experimental studies of protein folding and stability. Recently, great attention emerged to study disease-related protein misfolding, aggregation, and amyloid formation, with the aim of revealing their structural and thermodynamic background. Trp-cage is sensitive to both environmental and structure-modifying effects. It aggregates with ease upon structure destabilization, and thus it is suitable for modeling aggregation and amyloid formation. Here, we characterize the amyloid formation of several sequence modified and side-chain phosphorylated Trp-cage variants. We applied NMR, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies, molecular dynamics (MD) simulations, and transmission electron microscopy (TEM) in conjunction with thioflavin-T (ThT) fluorescence measurements to reveal the structural consequences of side-chain phosphorylation. We demonstrate that the native fold is destabilized upon serine phosphorylation, and the resultant highly dynamic structures form amyloid-like ordered aggregates with high intermolecular β-structure content. The only exception is the D9S(P) variant, which follows an alternative aggregation process by forming thin fibrils, presenting a CD spectrum of PPII helix, and showing low ThT binding capability. We propose a complex aggregation model for these Trp-cage miniproteins. This model assumes an additional aggregated state, a collagen triple helical form that can precede amyloid formation. The phosphorylation of a single serine residue serves as a conformational switch, triggering aggregation, otherwise mediated by kinases in cell. We show that Trp-cage miniprotein is indeed a realistic model of larger globular systems of composite folding and aggregation landscapes and helps us to understand the fundamentals of deleterious protein aggregation and amyloid formation.

Migration of Tinuvin P (UV stabiliser) and Irganox 3114 (antioxidant) from high-density polyethylene (HDPE) was studied. HDPE pieces were soaked in either milk (1.5% or 3.5% fat content) or 50% (v/v) ethanol-water mixture - the food simulant for milk as specified in Regulation No. 10/2011/EC. The obtained extracts were analysed by LC-MS/MS. For statistical assessment variography was used. It proved to be a useful tool for making a distinction between the early migration range and the equilibrium, despite the variance of the data. Regulation No. 10/2011/EC specifies 10 days of contact time for milk at 5°C. Our experiments with the food simulant with 24 dm(2) kg(-1) surface/mass ratio showed that both Tinuvin P and Irganox 3114 need less than 1 h to reach equilibrium. Furthermore, 10-day experiments with daily sampling showed that these additives are stable in milk, as well as in the food simulant. The effect of the concentration of the additives in HDPE was studied in the 0.01-5% (m/m) range. For both Tinuvin P and Irganox 3114 and all three extractants the migrated amount became independent of the concentration of the additive in the HDPE approximately at 1% (m/m). For Tinuvin P the food simulant gave a close estimate for the milk samples. However, using the food simulant for modelling the migration of Irganox 3114 into milk gave an overestimation with a factor of minimum 3.5. In the case of Tinuvin P special care must be taken, since the recommended amount in the HDPE can result in additive concentrations near or even over the specific migration limit (SML). However, Irganox 3114 cannot reach the SML either in milk or in the food simulant.

The article analyzes some ethical problems in psychiatry that have been emerging in recent years. It deals with the ongoing intensive debates about the DSM-5 before its publication, and with some of the criticisms of the DSM-5 itself. Then it goes on to analyze the use of placebo. This is followed by the ethical problems of the treatment of ADHD with stimulant drugs, among which one is the question of authenticity, namely whether the pre-treatment or the post-treatment personality is the real, authentic self of the patient. This question has been raised not only in the case of the ADHD, but also in relation with the antidepressant treatment of depression earlier, and in relation with deep brain stimulation and dopamine replacement therapy now, all of which causes changes in the treated patient's personality and motivations. Finally the article describes some ethical problems of informed consent in the case of antidepressant medication, together with the necessity to involve psychiatric nurses and rating scales in the assessment of the patient's decision making capacity.