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The Traveling Salesman Problem (TSP) is an optimization problem in which the subject attempts to find the shortest possible route that passes through a set of fixed locations exactly once. The TSP is used in cognitive and behavioral research to study problem solving and spatial navigation. While the TSP has been studied in some depth from this perspective, the biological mechanisms underlying the behavior have not yet been explored. The hippocampus is a structure in the brain that is known to be involved in tasks that require spatial memory. Because the TSP requires spatial problem solving, we designed the current study to determine whether the hippocampus is required to find efficient solutions to the TSP, and if so, what role the hippocampus serves. Rats were pretrained on the TSP, which involved learning to retrieve bait from targets in a variety of spatial configurations. Matched for performance, rats were then divided into two groups, receiving either a hippocampal lesion or a control sham surgery. After recovering from surgery, the rats were tested on eight new configurations. A variety of behavioral measures were recorded, including distance travelled, number of revisits, memory span, and latency. The results showed that the sham group outperformed the lesion group on most of these measures. Based on the behavioral data and histological tissue analysis of each group, we determined that the hippocampus is involved in successful performance in the TSP, particularly regarding memory for which targets have already been visited., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Infectious complications are the major cause of morbidity and mortality after solid organ and stem cell transplantation. To better understand host and environmental factors associated with an increased risk of infection as well as the effect of infections on function and survival of transplanted organs, we established the DZIF Transplant Cohort, a multicentre prospective cohort study within the organizational structure of the German Center for Infection Research. At time of transplantation, heart-, kidney-, lung-, liver-, pancreas- and hematopoetic stem cell- transplanted patients are enrolled into the study. Follow-up visits are scheduled at 3, 6, 9, 12 months after transplantation, and annually thereafter; extracurricular visits are conducted in case of infectious complications. Comprehensive standard operating procedures, web-based data collection and monitoring tools as well as a state of the art biobanking concept for blood, purified PBMCs, urine, and faeces samples ensure high quality of data and biosample collection. By collecting detailed information on immunosuppressive medication, infectious complications, type of infectious agent and therapy, as well as by providing corresponding biosamples, the cohort will establish the foundation for a broad spectrum of studies in the field of infectious diseases and transplant medicine. By January 2020, baseline data and biosamples of about 1400 patients have been collected. We plan to recruit 3500 patients by 2023, and continue follow-up visits and the documentation of infectious events at least until 2025. Information about the DZIF Transplant Cohort is available at https://www.dzif.de/en/working-group/transplant-cohort .

This study examines the compatibility of multielectrolyte additives for NMC-silicon lithium-ion batteries. Research studies with Si-based anodes have shown stable reversible cycling using electrolytes containing fluoroethylene carbonate (FEC). At the same time, the electrolyte additive, tris(trimethylsilyl) phosphite (TTMSP), has shown to improve the electrochemical performance of nickel-rich layered cathodes, such as LiNi 0.5 Mn 0.3 Co 0.2 O 2 (NMC). However, the combination of these electrolyte additives for the realization of a full-cell NMC-Si lithium-ion battery has not been previously explored. Changes in the electrochemical performance (capacity retention, internal cell resistance, and electrochemical impedance) in half-cells are studied as the ratio of TTMSP and FEC is tuned. At the optimal TTMSP/FEC ratio of 0.33 (T1F3), the NMC-Si full-cells achieve a 2× longer cycle life when compared to the FEC-rich (T0F4) electrolyte. Moreover, T1F3 full-cells demonstrate 1.5 mAh/cm 2 areal capacities and high-capacity retention (25% more than T0F4). A detailed investigation of the electrode-electrolyte interfaces is conducted by using time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). The chemical species depth profiles and elemental analysis illustrate adequate hydrogen fluoride (HF) scavenging. These results demonstrate the synergistic effects of electrolyte additives in minimizing the capacity degradation in NMC-Si full-cells by effectively stabilizing the electrode-electrolyte interfaces.

Risk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22-92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Aim: Identify associations between attitudes of nurses towards people with dementia and their socio-demographic (age and gender) and work-related characteristics (employment, work experience, nursing degree, care setting)., Design: The study was designed in a cross-sectional way, collecting self-reported questionnaire data., Methods: Nurses ( N  = 417) completed the 20-item Dementia Attitude Scale questionnaire, including socio-demographic and work characteristics. Data were analysed using descriptive statistics, group mean comparison, correlation and regression analysis., Results: The attitudes of nurses towards people with dementia were only related to the care setting. Attitudes of nurses working in dementia-specialized long-term care institutions were significantly more positive compared with those working in mixed long-term care institutions and in the homecare setting. The other variables, such as age, gender, employment, nursing degree and work experience, were not associated with the attitudes.

Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dose-dependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability. Trk receptor expression determined GNF-5837 sensitivity. GNF-5837 caused downregulation of PI3K-Akt-mTOR signaling, Ras-Raf-MEK-ERK signaling, the cell cycle and increased apoptotic cell death. The combinational treatment of GNF-5837 with everolimus showed a significant enhancement in inhibition of cell viability vs single substance treatments, due to a cooperative PI3K-Akt-mTOR and Ras-Raf-MEK-ERK pathway downregulation, as well as an enhanced cell cycle component downregulation. Immunohistochemical staining for Trk receptors were performed using a tissue microarray containing 107 tumor samples of gastroenteropancreatic NETs. Immunohistochemical staining with TrkA receptor and pan-Trk receptor antibodies revealed a positive staining in pancreatic NETs in 24.2% (8/33) and 33.3% (11/33), respectively. We demonstrated that the pan-Trk inhibitor GNF-5837 has promising anti-tumoral properties in human NET cell lines expressing the TrkA receptor. Immunohistochemical or molecular screening for Trk expression particularly in pancreatic NETs might serve as predictive marker for molecular targeted therapy with Trk inhibitors., (© 2018 Society for Endocrinology.)

Context: Anaplastic thyroid carcinoma (ATC) is an orphan disease and confers a dismal prognosis. Standard treatment is not established., Objective: The aim of this study is to describe clinical characteristics, current treatment regimens and outcome of ATC and to identify clinical prognostic markers and treatment factors associated with improved prognosis., Design: Retrospective cohort study at five German tertiary care centers., Patients and Methods: Totally 100 ATC patients diagnosed between 2000 and 2015 were included in the analysis. Disease-specific overall survival (OS) was compared with the Kaplan-Meier method and log-rank test; Cox proportional hazard model was used to identify risk factors., Results: The 6-month, 1-year and 5-year disease-specific OS rates were 37, 28 and 5%, respectively. Stage-dependent OS at 6 months was 78, 54 and 18% for stage IVA, B and C, respectively. 29% patients survived >1 year. Multivariate analysis of OS identified age ≥70 years, incomplete local resection status and the presence of distant metastasis as significant risk factors associated with shorter survival. Radical surgery (hazard ratio [HR] 2.20, 95% confidence interval (CI) 1.19-4.09, P = 0.012), external beam radiation therapy (EBRT) ≥40 Gy (HR = 0.34, 0.15-0.76, P = 0.008) and any kind of chemotherapy (CTX) (HR = 11.64, 2.42-60.39, P = 0.003) were associated with longer survival in multivariate analyses adjusted for age and tumor stage. A multimodal treatment regimen was significantly associated with a survival benefit (HR = 1.04, 1.01-1.08, P < 0.0001) only in IVC patients., Conclusion: Disease-specific OS is still poor in ATC. Treatment factors associated with improved OS provide a rationale to devise treatment pathways for routine care. Collaborative research structures should be aimed to advance treatment of ATC., (© 2016 European Society of Endocrinology.)

Spontaneous recognition of a novel object is a popular measure of exploratory behavior, perception and recognition memory in rodent models. Because of its relative simplicity and speed of testing, the variety of stimuli that can be used, and its ecological validity across species, it is also an attractive task for comparative research. To date, variants of this test have been used with vertebrate and invertebrate species, but the methods have seldom been sufficiently standardized to allow cross-species comparison. Here, we review the methods necessary for the study of novel object recognition in mammalian and non-mammalian models, as well as the results of these experiments. Critical to the use of this test is an understanding of the organism's initial response to a novel object, the modulation of exploration by context, and species differences in object perception and exploratory behaviors. We argue that with appropriate consideration of species differences in perception, object affordances, and natural exploratory behaviors, the spontaneous object recognition test can be a valid and versatile tool for translational research with non-mammalian models.

Purpose: Localized prostate cancer affects younger and healthy patients as well as older patients with comorbidities. The purpose of this study was to evaluate the effect of age and comorbidities on the quality-of-life (QoL) course before and after radical retropubic prostatectomy., Patients and Methods: Overall, 374 patients with localized prostate cancer scheduled for radical prostatectomy were prospectively included. The QoL questionnaire QLQ-C30 (European Organisation for Research and Treatment of Cancer) was completed 1 day before surgery and 3, 6, 9, and 12 months after radical prostatectomy. Sexual and urinary functions were not assessed in this analysis. Subgroups according to age at diagnosis (≤60,>60 to≤70, and>70y) and comorbidities (Charlson scores≤2 and ≥3) were defined. Subgroups were compared using the Wilcoxon-Mann-Whitney test, whereas changes in a group over time were analyzed with the Wilcoxon signed rank test., Results: In all patient groups, no change was found 12 months after surgery compared with preoperative values in global health as well as functioning (role, physical, cognitive, and social). Emotional functioning improved significantly after surgery compared with preoperative functioning. Older patients (>70y) had better emotional and social functioning compared with younger patients (≤60y). The other scores were comparable between older and younger patients. Global health and physical, role, cognitive, and social functioning were independent of the number of comorbidities, although patients with a Charlson score≥3 did worse regarding fatigue and dyspnoe., Conclusion: The QoL of older patients or patients with multiple comorbidities is not negatively influenced by radical prostatectomy. This should be considered when discussing the indication for prostatectomy in older or comorbid patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy., Objective: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS., Design: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years., Patients: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease., Results: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses., Conclusions: Time to recovery of adrenal function is dependent on the underlying etiology of CS.