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Abstract Whether it is listening to a piece of music, learning a new language, or solving a mathematical equation, people often acquire abstract notions in the sense of motifs and variables—manifested in musical themes, grammatical categories, or mathematical symbols. How do we create abstract representations of sequences? Are these abstract representations useful for memory recall? In addition to learning transition probabilities, chunking, and tracking ordinal positions, we propose that humans also use abstractions to arrive at efficient representations of sequences. We propose and study two abstraction categories: projectional motifs and variable motifs. Projectional motifs find a common theme underlying distinct sequence instances. Variable motifs contain symbols representing sequence entities that can change. In two sequence recall experiments, we train participants to remember sequences with projectional and variable motifs, respectively, and examine whether motif training benefits the recall of novel sequences sharing the same motif. Our result suggests that training projectional and variables motifs improve transfer recall accuracy, relative to control groups. We show that a model that chunks sequences in an abstract motif space may learn and transfer more efficiently, compared to models that learn chunks or associations on a superficial level. Our study suggests that humans construct efficient sequential memory representations according to the two types of abstraction we propose, and creating these abstractions benefits learning and out-of-distribution generalization. Our study paves the way for a deeper understanding of human abstraction learning and generalization.

María José Valencia López,1,* Brigitte Stephan,1,* Anna Meineke,1 Sandra Wolf,1 Diamant Thaci,2 Ulrich Mrowietz,3 Valerie Andrees,1 Stephan Jeff Rustenbach,1 Kristian Reich,1 Linus Thalmann,1 Henriette Bogena,1 Petra Staubach,4 Ralph Michael von Kiedrowski,5 Matthias Augustin1 1Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; 2Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 3Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany; 4Department of Dermatology and Allergy, University Medical Center Mainz, Mainz, Germany; 5Dermatological Practice Selters, Selters, Germany*These authors contributed equally to this workCorrespondence: Matthias Augustin, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, Hamburg, 20246, Germany, Tel +49 040 7410 55428, Fax +49 040 7410 55348, Email m.augustin@uke.deBackground: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany.Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies.Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others.Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (> 92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients.Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.Keywords: psoriasis, COVID-19, SARS-CoV-2, pandemic, patient perception, risk factors

For Brandenburg, a region in Germany with increasing water shortage and drought events, water reuse can counteract competition scenarios between drinking water supply, agricultural irrigation, and industrial use. Centralized and decentralized sources for reclaimed water are found to potentially substitute 245 or 28% of irrigation water, respectively, in agriculture production in Brandenburg. For such a reuse scenario, the fate of organic micro-pollutants is examined for diatrizoate (DZA) and carbamazepine (CBZ). Retention in local sandy soil and transfer into roots and leaves of arugula are analyzed in lysimeter studies and greenhouse pot experiments. Vertical transport was found for DZA and accumulation in or on arugula roots with a root concentration factor of 1,925 ± 34% but a low bioconcentration factor due to intrinsic molecule properties. CBZ was not found to be mobile in the sandy soil but accumulates in arugula roots and leaves by factors of 70 ± 7% and 155 ± 12%, respectively. Further research on potential plant uptake and groundwater enrichment for more substances is highly recommended as well as tertiary wastewater treatment prior to water reuse. HIGHLIGHTS The volume of treated wastewater exceeds irrigation water by a factor of 2.5 in Brandenburg.; Water reuse could reduce competition between drinking water supply, industry and agriculture.; Organic micro-pollutant pathways for sandy soil to groundwater and to plants are assessed.; Carbamazepine did not reach 10 cm depth in lysimeter studies probably due to acidic soil pH.; Diatrizoate obtained very high concentrations in arugula roots but were low in leaves.;

Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. Results: 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. Conclusion: ED after RP is a known long-term side effect with significant impact on patients’ QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.

The ultrafast relaxation dynamics of tetracene following UV excitation to the bright singlet state S6 has been studied with time-resolved photoelectron spectroscopy. With the help of high-level ab initio multireference perturbation theory calculations, we assign photoelectron signals to intermediate dark electronic states S3, S4, and S5 as well as to a low-lying electronic state S2. The energetic structure of these dark states has not been determined experimentally previously. The time-dependent photoelectron yields assigned to the states S6, S5, and S4 have been analyzed and reveal the depopulation of S6 within 60 fs, while S5 and S4 are populated with delays of about 50 and 80 fs. The dynamics of the lower-lying states S3 and S2 seem to agree with a delayed population coinciding with the depopulation of the higher-lying states S4–S6 but could not be elucidated in full detail due to the low signal levels of the corresponding two-photon ionization probe processes. [ABSTRACT FROM AUTHOR]

Abstract There is growing interest in the use of the enzyme, insulin regulated aminopeptidase (IRAP), as a biomarker for conditions such as cardio-metabolic diseases and ischemic stroke, with upregulation in its tissue expression in these conditions. However, quantification of circulating IRAP has been hampered by difficulties in detecting release of the truncated, soluble form of this enzyme into the blood stream. The current study aimed to develop a sandwich ELISA using novel antibodies directed towards the soluble portion of IRAP (sIRAP), to improve accuracy in detection and quantification of low levels of sIRAP in plasma. A series of novel anti-IRAP antibodies were developed and found to be highly specific for sIRAP in Western blots. A sandwich ELISA was then optimised using two distinct antibody combinations to detect sIRAP in the low nanogram range (16–500 ng/ml) with a sensitivity of 9 ng/ml and intra-assay variability

Abstract Background Short stems were introduced into total hip arthroplasty (THA) to preserve bone stock, to transmit more load to the proximal femur, and to enable minimal invasive approaches. This study is the first long-term study (with a follow-up of 10 years) of the survival as well as the clinical and radiographic outcomes of the Fitmore hip stem, a short curved uncemented stem. Methods In total, 123 Fitmore hip stems were prospectively evaluated. At the final 10-year follow-up, 80 Fitmore stems (78 patients: 30 female, 48 male) were eligible for evaluation. Clinical parameters were thigh pain, EQ-5D, Harris Hip Score (HHS) and Oxford Hip Score. Radiographic parameters were cortical hypertrophy (CH), bone condensation, cortical thinning, radiolucency, reactive lines, calcar rounding, calcar resorption, subsidence and varus/valgus position. Results After 10 years, there was a survival rate of 99% (1 revision because of aseptic stem loosening). HHS had improved from 59 to 94 and Oxford Hip Score from 22 to 43. CH rate after 1 year was 69% and after 10 years 74%. In the first year, radiolucency was found in 58% and in 17.5% after 10 years. Subsidence after 1 year was 1.6 ± 1.6 mm and 5.0 ± 3.1 mm after 10 years. Conclusions The Fitmore hip stem showed a survival rate of 99% as well as good clinical and radiographic outcomes in the long-term follow-up of 10 years.

Abstract Background Prostate cancer is morphologically and molecularly heterogeneous. Genomic heterogeneity might be mirrored by variability in DNA ploidy. Aneuploidy is a hallmark of genomic instability and associated with tumor aggressiveness. Little attention has been paid to the biological significance of the diploid tumor cell population that often coexists with aneuploid populations. Here, we investigated the role of DNA ploidy in tumor heterogeneity and clonal evolution. Methods Three radical prostatectomy specimens with intratumoral heterogeneity based on nuclear features on H&E were selected. DNA content of each subpopulation was determined by DNA image cytometry and silver in situ hybridization (SISH). Genomic evolution was inferred from array comparative genomic hybridization (aCGH). Additionally, immunohistochemistry was used to examine the stemness‐associated marker ALDH1A1. Results Nuclear morphology reliably predicted DNA ploidy status in all three cases. In one case, aCGH analysis revealed several shared deletions and one amplification in both the diploid and the aneuploid population, suggesting that these populations could be related. In the other two cases, a statement about relatedness was not possible. Furthermore, ALDH1A1 was expressed in 2/3 cases and exclusively observed in their diploid populations. Conclusions In this proof‐of‐concept study, we demonstrate the feasibility to predict the DNA ploidy status of distinct populations within one tumor by H&E morphology. Future studies are needed to further investigate the clonal relationship between the diploid and the aneuploid subpopulation and test the hypothesis that the aneuploid population is derived from the diploid one. Finally, our analyses pointed to an enrichment of the stemness‐associated marker ALDH1A1 in diploid populations, which warrants further investigation in future studies.

Background Screening for atrial fibrillation (AF) may reveal incidental arrhythmias of relevance. The aim of this study was to describe incidental arrhythmias detected during screening for AF in the STAR‐FIB (Predicting SilenT AtRial FIBrillation in Patients at High Thrombembolic Risk) cohort study. Methods and Results In the STAR‐FIB cohort study, we screened hospitalized patients for AF with 3 repeat 7‐day Holter ECGs. We analyzed all Holter ECGs for the presence of the following incidental arrhythmias: (1) sinus node dysfunction, defined as sinus pause of ≥3 seconds’ duration; (2) second‐degree (including Wenckebach) or higher‐degree atrioventricular block (AVB); (3) sustained supraventricular tachycardia of ≥30 seconds’ duration; and (4) sustained ventricular tachycardia of ≥30 seconds’ duration. We furthermore report treatment decisions because of incidental arrhythmias. A total of 2077 Holter ECGs were performed in 794 patients (mean age, 74.7 years; 49% women), resulting in a mean cumulative duration of analyzable ECG signal of 414±136 hours/patient. We found incidental arrhythmias in 94 patients (11.8%). Among these were sinus node dysfunction in 14 patients (1.8%), AVB in 41 (5.2%), supraventricular tachycardia in 42 (5.3%), and ventricular tachycardia in 2 (0.3%). Second‐degree AVB was found in 23 patients (2.9%), 2:1 AVB in 10 (1.3%), and complete AVB in 8 (1%). Subsequently, 8 patients underwent pacemaker implantation, 1 for sinus node dysfunction (post‐AF conversion pause of 9 seconds) and 7 for advanced AVB. One patient had an implantable cardioverter‐defibrillator implanted for syncopal ventricular tachycardia. Conclusions Incidental arrhythmias were frequently detected during screening for AF in the STAR‐FIB study and resulted in device therapy in 1.1% of our cohort patients.

Nonlinear force-free extrapolations are a common approach to estimate the 3D topology of coronal magnetic fields based on photospheric vector magnetograms. The force-free assumption is a valid approximation at coronal heights, but for the dense plasma conditions in the lower atmosphere, this assumption is not satisfied. In this study, we utilize multiheight magnetic field measurements in combination with physics-informed neural networks to advance solar magnetic field extrapolations. We include a flexible height-mapping, which allows us to account for the different formation heights of the observed magnetic field measurements. The comparison to analytical and simulated magnetic fields demonstrates that including chromospheric magnetic field measurements leads to a significant improvement of our magnetic field extrapolations. We also apply our method to chromospheric line-of-sight magnetograms from the Vector Spectromagnetograph (VSM) on the Synoptic Optical Long-term Investigations of the Sun (SOLIS) observatory, in combination with photospheric vector magnetograms from the Helioseismic Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO). The comparison to observations in extreme-ultraviolet wavelengths shows that the additional chromospheric information leads to a better agreement with the observed coronal structures. In addition, our method intrinsically provides an estimate of the corrugation of the observed magnetograms. With this new approach, we make efficient use of multiheight magnetic field measurements and advance the realism of coronal magnetic field simulations.

Background: Ticks represent very important vectors of human and zoonotic pathogens, and tick-borne diseases (TBDs) are diagnosed with increasing frequency. Therefore, the aim of this retrospective study was to describe patients presenting with a complaint of tick bite in the emergency department (ED) of a large university hospital in Switzerland. Methods: Data were collected by searching for keywords in the routine clinic database to identify cases from 1 July 2012 to 30 June 2020. The patients’ data were screened for preexisting diseases and demographic and clinical characteristics. Results: We included 415 patients collected over a period of 8 years, with highest admission frequencies from May to July. Of these, 82% were outpatients, 15.9% admitted to a hospital ward, and five to intensive care. The patients were allocated to three groups. The first group represented patients with erythema chronica migrans (ECM), which is pathognomonic for Lyme borreliosis (n = 45). Accordingly, 89% of cases in this group of patients were treated with antibiotics. The second group represented patients with other tick bite-associated erythema (n = 139). In this group, no particular clinical symptoms or laboratory findings were found. Finally, the largest group represented patients in which the tick bite was no longer visible (n = 201). This group of patients had significantly more evidence of neurological disorders (52%) and were treated at a higher rate with non-steroidal anti-inflammatory (29%) or antiviral (13%) drugs. Although the vaccination status for tick-borne encephalitis virus (TBEV) was not systematically evaluated, at least 10% of the latter group was vaccinated, indicating another source for neurological disease. Furthermore, only 14% of the tested patients were positive for IgM or IgG against TBEV. Conclusion: This retrospective study indicates the presence of many undiagnosed neurological diseases following tick bites that could be caused by TBEV or an unknown infectious agent. Taken together, although tick bites were not very frequently seen in the present tertiary ED, the frequent presence of neurological symptoms demands a more systematic assessment of vaccination status and TBEV serology as well as further diagnostic evaluations in patients that report tick bites and neurological symptoms.