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Background: Major depressive disorder (MDD) is often marked by impaired motivation and reward processing, known as anhedonia. Many patients do not respond to first-line treatments, and improvements in motivation can be slow, creating an urgent need for rapid interventions. Recently, we demonstrated that transcutaneous auricular vagus nerve stimulation (taVNS) acutely boosts effort invigoration in healthy participants, but its effects on depression remain unclear. Objective: To assess the impact of taVNS on effort invigoration and maintenance in a sample that includes patients with MDD, evaluating the generalizability of our findings. Methods: We used a single-blind, randomized crossover design in 30 patients with MDD and 29 matched (age, sex, and BMI) healthy control participants (HCP). Results: Consistent with prior findings, taVNS increased effort invigoration for rewards in both groups during Session 1 (p = .040), particularly for less wanted rewards in HCP (pboot

AbstractWe report on a 21-year-old male patient, suffering from bilateral acute hearing loss and vertigo. The article presents the clinical course of autoimmune inner ear disease, including diagnostic approaches and challenges, as well as therapeutic strategies and clinical follow-up. Response to corticosteroids often decreases during the course of the disease, requiring a more targeted treatment, such as the use of biological agents to block cytokines like interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFα). In our case, hearing thresholds improved considerably under immune-modulating therapy, while vestibular function remained reduced. In case of autoimmune inner ear disease, therapies targeting IL-1 and TNFα for consecutive reduction of cytokine activity represent an effective remedy for the measurable restoration of sensory function.

The public debate on the use of the German nonbinary gender asterisk ("Lehrer*in" 'teacher') is emotionally charged. While it has been adopted by political and educational institutions, opponents argue that it is inappropriate for making persons identifying themselves beyond the male-female-dichotomy more visible. We investigated this claim by using a word-picture matching task directly assessing mental representations activated by the asterisk. Students evaluated whether pictures of persons read as male, female, or nonbinary were suitable illustrations of immediately preceding role nouns in masculine, feminine, or star form. Processing difficulties for female pictures following masculine nouns confirmed that the latter was not automatically read as generic. High acceptance rates and low reaction times for all pictures following the asterisk suggest it leads to inclusive mental representations including men, women, and persons beyond the gender binary. These results are the first to confirm that the asterisk elicits the intended inclusive interpretation.

The wave nature of matter is a cornerstone of modern physics and has been demonstrated for a wide range of fundamental and composite particles. While diffraction at nanomechanical masks is usually regarded to be independent of internal atomic or molecular states, the particles' polarizabilities and dipole moments lead to dispersive interactions with the grating surface. In prior experiments, such forces largely prevented coherent diffraction of polar molecules as they induce dephasing of the matter wave in the presence of randomly distributed charges inside the grating. Here, we show that surface milling using neon ions facilitates the fabrication of lowly charged nanomasks in gold-capped silicon nitride membranes. This allows us to observe diffraction of polar molecules with over four times larger electric dipole moment than in previous experiments, opening a path towards distinction of structural conformers in matter-wave experiments.

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive Non-Hodgkin lymphoma (NHL) characterised by the presence of neoplastic lymphoid cells within small- and medium-sized blood vessels. According to the clinical presentation, the current WHO classification distinguishes the ‘classic’ (formerly ‘Western’) from a hemophagocytic syndrome-associated (formerly ‘Asian’) variant. A third ‘cutaneous’ variant has been proposed, characterised by a good prognosis and unique clinical features. While laboratory findings can hint at diagnosis, symptoms are rather nonspecific, and deep skin biopsy supported by further measures such as bone marrow aspiration and positron emission tomography-computed tomography scanning is needed to make a definite diagnosis. Treatment is comprised of anthracycline-based chemotherapy supplemented with rituximab and central nervous system prophylaxis. While there are various prognostic models for NHL, only one is specific to IVLBCL, which does not sufficiently represent some patient groups, especially regarding the lack of differentiation within the patient collective with skin involvement. This underlines the necessity for the establishment of further prognostic models in particular for IVLBCL patients with cutaneous manifestations.

Malignancies can cause severe stenosis of the biliary tract and therefore predispose a patient to bacterial cholangitis. Upon endoscopic drainage, antibiotic therapy (AT) is performed according to individual clinical judgement, as the optimal duration of AT is unclear to date, especially in the case of multidrug-resistant organisms (MDROs). In a case-based retrospective study, patients with malignant biliary strictures and acute cholangitis were included upon endoscopic retrograde cholangiography (ERC). The outcome of cases treated with short AT (≤6 days) was compared to that of long AT (≥7 days). Recurrent cholangitis (RC) before scheduled stent exchange was the primary end point. In total, 124 patients were included, with 183 cases of proven cholangitis in total. The overall median duration of AT was 7 days (range 1–20), with 74 cases (40%) receiving short AT and 109 (60%) receiving long AT. Short AT was not an independent risk factor for RC (HR = 0.66, p > 0.2), while colonization with MDROs was associated with a higher risk of RC (HR = 2.21, p = 0.005). Placement of a metal stent was associated with minor risk of RC (HR = 0.4, p = 0.038). In conclusion, short AT is possible in selected patients with non-severe cholangitis and malignant biliary strictures. Scheduled screening for MDROs is recommended and placement of a metal stent should be performed if possible.

Background Indonesia is one of the world's largest asbestos importing countries. While asbestos is the main contributor to work-related lung cancer, studies or reports regarding the CT findings of asbestos-related lung cancer have been limited in the country. The objective of this study was to compare CT findings of the size of the tumor and pleural and lung parenchymal changes between lung cancer patients exposed to asbestosis and those not exposed. Methods This cross-sectional study involved 96 lung cancer patients consisting of 48 subjects who had been exposed to asbestos and 48 who had not been exposed. They underwent thoracic CT scans at the Radiology Department of Persahabatan Hospital. Asbestos exposure was determined using interviews that followed a protocol similar to that of a previous study about asbestos-related lung cancer. Senior radiologists investigated the existence of pleural and parenchymal changes. An independent T- test and chi-square test to compare CT scan features between the two groups. Results The mean age was 57.75 ± 8.56 years in the asbestos-exposed group and 58.56 ± 7.99 years in the unexposed group. The proportion of tumor sizes of more than five cm, pleural plaques, and subpleural dot-like or branching opacities were significantly higher among asbestos-exposed subjects compared to the non-exposed group (p = 0.044;p=0.37;p=0.041, respectively). Conclusions Asbestos exposure is significantly related to the size of the tumor and the existence of pleural plaques and asbestosis. These findings may help further management of lung cancer patients and the policy of asbestos use in Indonesia.

We performed a retrospective single-center analysis to investigate the diagnostic yield of bone marrow puncture in patients with liver cirrhosis and cytopenia. Liver cirrhosis patients receiving bone marrow aspiration or biopsy for the diagnostic work-up of otherwise unexplained peripheral blood cytopenia at our institution between 2004 and 2020 were enrolled in this study. We evaluated findings from cytologic, histologic and immunologic assessment and final diagnostic outcomes. A total of 118 patients with a median age of 55 years and a median Child–Pugh score of B (8 points) were enrolled. The main etiologies of liver cirrhosis were viral hepatitis (B and C) or chronic alcohol consumption. The majority of patients (60%) exhibited concurrent anemia, leukocytopenia and thrombocytopenia. Bone marrow assessment revealed normal, unspecific or reactive alterations in 117 out of 118 patients (99%). One patient was diagnosed with myelodysplastic syndrome. Our findings suggest that peripheral blood cytopenia in patients with liver cirrhosis is rarely associated with a primary bone marrow pathology.

The use of gender-fair language is an important measure to boost gender equality. However, there is wide-spreadscepticism as to the usefulness of avoiding male bias in language, even in gendered languages. For instance, in German allnouns carry grammatical gender, and role names are considered generic, even when their gender is masculine. We used asentence-picture matching task to test whether male references in language induce gendered representations. After presentinga sentence with a role name, a picture of a person was shown. In 48 trials, the factors gender of the role name (masculinevs. feminine) and sex of the person in the picture (woman vs. man) were crossed. The results of 40 participants showed thatwomen after masculine referents were more readily accepted than men after feminine referents, but reaction times increased.Thus, readers interpret some masculine forms as generic, but only with considerable cognitive effort.

Teeth with different chemical compositions can show vastly different physical properties, so knowledge of elemental composition is required to use animal teeth as substitutes for human teeth in research. In vitro, energy dispersive X-ray spectroscopy (EDX), improved by calibration standards and Si3N4-window material, enables determining local elemental compositions of inorganic and organic compounds without sample destruction. Six human molars, bovine incisors, murine incisors, and murine molars were analyzed. EDX-field scans and line scans were analyzed for elements Ca, P, O, C, N, F, Na, Mg, Fe, Cl, and S. Furthermore, Ca/P- and Ca/N-Ratios were calculated. The presence of iron in murine incisor enamel was investigated using additional wavelength dispersive X-ray spectroscopy measurements (WDX) near the enamel surface. Bovine and human enamel and dentin revealed close similarities regarding elemental composition. The median (25–75% percentiles) of At%Ca was 21.1 (20.8–21.3) in human enamel, 21.0 (20.7–21.2) in bovine enamel, and in murine enamel, 18.3 (17.85–18.88) for molars and 18.35 (18.00–18.75) for incisors. In dentin, murine teeth revealed a higher At%Ca compared to human and bovine teeth. Significant differences between human and bovine teeth were found for nitrogen in dentin, with a median of 4.5 (3.3–5) At%N for human dentin and 2.7 (2.3–3.2) At%N for bovine dentin. The Ca/P-Ratio was the highest in human and bovine enamel, which did not differ significantly. Enamel from murine molars had a higher Ca/P-Ratio than murine incisors and the highest Ca/P-Ratio in dentin was observed for human teeth and murine molars (1.49). WDX revealed iron in the outer 10 µm of pre- and post-eruptive enamel of murine incisors. Pre- and post-eruptive enamel on murine incisors only differed significantly in At%Ca (p = 0.041) and At%P (p = 0.026) with both At% higher in the pre-eruptive enamel. Murine teeth differ significantly from human and bovine teeth in terms of the elemental composition of enamel and dentin.

Since 2015, the research project Ludwig Tieck’s Library. Anatomy of a Romantic Comparatist Book Collection has conducted the virtual reconstruction of the library of German romanticist Ludwig Tieck. About 4.000 volumes have already been located all over Europe, and have been recorded in a database according to current bibliographical standards. Polish libraries verifiably contain a couple dozen of books from Tieck’s collection – it is, however, very probable that many more books from it have been dispersed in Poland after 1945 via the library of Count Yorck von Wartenburg (which was located in today’s Oleśnica Mała in the vicinity of Wrocław). The history of Tieck’s library and its dispersion, and its relevance to Polish library holdings, will be detailed in this paper. In closing, a description of material traits and distinctive features particular to books of Tieck/Yorck provenance will provide information useful to identify respective holdings in Polish libraries.

Many theories of verbal humour postulate that the funniness of jokes is caused by an incongruency in the punchline whose resolution yields a feeling of mirth. While there are studies testing the prediction that this situation model updating leads to increases in processing costs, there are few studies directly assessing the time course of when the alternative situation models are entertained. In a visual world paradigm, stories were presented auditorily and displays were presented illustrating either the situation implied by the context or the final interpretation after the punchline. Eye movement data confirmed the switch from the initial to the final interpretation for jokes as well as for non-funny control stories that also required a situation model revision. In addition to these effects of the cognitive revision requirements, the pupil dilations were sensitive to the affective component of joke comprehension. These results are discussed in light of incongruency theories of verbal humour.

Summary: Background: Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany. Methods: We analyzed the data of all hospital admissions in Germany within diagnosis-related groups from 2005 to 2018. The diagnostic records of cirrhosis and other categories of diseases were based on ICD-10-GM codes. The primary outcome measurement was in-hospital mortality. Trends were analyzed through Poisson regression of annual number of admissions. The impact of cirrhosis on overall in-hospital mortality were assessed through the multivariate multilevel logistic regression model adjusted for age, sex, and comorbidities. Findings: Of the 248,085,936 admissions recorded between 2005 and 2018, a total of 2,302,171(0•94%) were admitted with the diagnosis of cirrhosis, mainly as a comorbidity. Compared with other chronic diseases, patients admitted with cirrhosis were younger, mainly male and had the highest in-hospital mortality rate. Diagnosis of cirrhosis was an independent risk factor of in-hospital mortality with the highest odds ratio (OR:6•2[95%CI:6.1-6•3]) among all diagnoses. The prevalence of non-alcoholic fatty liver disease has increased four times from 2005 to 2018, while alcoholic cirrhosis is 20 times than other etiologies. Bleeding was found to be decreasing over time, but ascites remained the most common complication and was increasing. Interpretation: This nationwide study demonstrates that cirrhosis represents a considerable healthcare burden, as shown by the increasing in-hospital mortality, also in combination with other chronic diseases. Alcohol-related cirrhosis and complications are on the rise. More resources and better management strategies are warranted. Funding: The funders had no influence on this study.

Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.

The accumulation of caries-preventive compounds on sound enamel is crucial in order to improve the inhibition of carious lesion initiation. The aim of this research was to investigate the initial accumulation of cerium, oligopeptide p11-4, and fluoride from NaF or amine fluoride (AmF) on sound enamel in vitro by means of energy dispersive X-ray spectroscopy (EDX). Polished bovine enamel specimens (n = 120 from 60 teeth) were fabricated. Out of these, 12 specimens each were treated with CeCl3 (cerium(III) chloride heptahydrate 25%), oligopeptide p11-4 (Curodont Repair, Credentis), NaF (10,000 ppm F−), AmF (amine fluoride, Elmex Fluid, CP-GABA GmbH, 10,000 ppm F−), or Aqua demin (control). After rinsing with water, the surface elemental composition (Ce, N, F, Ca, P, O, Na, Mg) was measured (EDX; EDAX Octane Elect detector, APEX v2.0), expressed in atomic percent (At%) and analyzed (non-parametric statistics, α = 0.05, error rates method). Another 12 specimens per treatment group were fabricated and used for analyzing accumulation in cross-sections with EDX linescans and two-dimensional EDX-mappings. The surface median atomic percent of cerium (At%Ce) was 0.8 for CeCl3, but no Ce was found for any other group. N, specifically for oligopeptide p11-4, could not be detected. Fluorine could only be detected on fluoridated surfaces. The median atomic percent of fluorine (At%F) was 15.2 for NaF and 17.0 for AmF. The Ca/P ratio increased significantly compared to the control following the application of NaF and AmF (p < 0.001), but decreased significantly for CeCl3 (p < 0.001). In cross-sectioned specimens of the CeCl3-group, 12.5% of the linescans revealed cerium at the enamel surface, whereas 83.3% of the NaF linescans and 95.8% of the AmF linescans revealed fluorine at the enamel surface. Following the application of oligopeptide p11-4, no traces of N were detectable. In the depth of the samples, no signal was detected for any of the corresponding elements exceeding the background noise. Cerium and fluorine (from both NaF and AmF), but not the oligopeptide p11-4, precipitated on sound enamel.

The conical pendulum is a classic introductory physics problem for teaching circular motion--a topic about which students frequently carry alternative conceptions. As teachers provide lessons to untangle these conceptions, it is good to allow students to practice their new knowledge in varied settings. This is one possible experiment that builds off the conical pendulum. The experiment can be modified to fit the level of complexity the instructor wishes to pursue. Although the context of this article is about the physics of the amusement park flying carousel swing, the analysis techniques discussed can be used in a variety of situations.

Abstract Very‐low‐carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno‐nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T‐cell responses. CD4+, CD8+, and regulatory T‐cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very‐low‐carbohydrate diet as a clinical tool to improve human T‐cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required.

Abstract Asthma is a heterologous disease that is influenced by complex interactions between multiple environmental exposures, metabolism, and host immunoregulatory processes. Specific metabolites are increasingly recognized to influence respiratory inflammation. However, the role of protein‐derived metabolites in regulating inflammatory responses in the lung are poorly described. The aims of the present study were to quantify polyamine levels in bronchoalveolar lavages (BALs) from healthy volunteers and asthma patients, and to evaluate the impact of each polyamine on inflammatory responses using in vitro models and in a house dust mite (HDM)‐induced respiratory allergy model. Spermidine levels were decreased, while cadaverine levels were increased in BALs from asthma patients compared to healthy controls, using Ultra Performance Liquid Chromatography (UPLC). Both spermine and spermidine inhibit lipopolysaccharide (LPS)‐induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in vitro. In addition, oral gavage with spermine or spermidine modulate HDM‐induced cell infiltration, cytokine secretion, and epithelial cell tight junction expression in murine models. Spermidine also reduces airway hyper‐responsiveness. These results suggest that modulation of polyamine metabolism, in particular spermidine, is associated with respiratory inflammation and these molecules and pathways should be further explored as biomarkers of disease and potential targets for novel therapies.

Reducing the risk of periprosthetic joint infections (PJI) requires a multi-pronged strategy including usage of a prophylactic antibiotic. A history of penicillin or cephalosporin allergy often leads to a change in prophylactic antibiotic regimen to avoid serious side effects. The purpose of the present retrospective study was to determine incidence of PJI based on perioperative antibiotic regimen in total hip arthroplasty (THA), total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA). A review of all primary THAs, primary TKAs and primary UKAs, undertaken between 2011 and 2020 in a tertiary referral hospital, was performed. The standard perioperative antibiotic for joint arthroplasty (JA) in the analyzed tertiary hospital is cefuroxime. There were no differences in prophylactic antibiotic regimen over time. In 7.9% (211 of 2666) of knee arthroplasties and in 6.0% (206 of 3419) of total hip arthroplasties, a second-line prophylactic antibiotic was used. There was no statistically significant higher occurrence of PJI between the first-line and second-line prophylactic antibiotic in knee arthroplasties (p = 0.403) as well as in total hip arthroplasties (p = 0.309). No relevant differences in age, American Society of Anesthesiologists (ASA) score and body mass index (BMI) between the groups were observed.

Phonemic awareness is the ability to notice and manipulate language sounds in their base form (phonemes). It is associated with emerging literacy skills and predictive of skilled reading. The aim of the present study was to investigate phonemic awareness in German and its association with speaking a German-origin, but predominantly unwritten language. We investigated speakers of Hunsrückisch, a Brazilian minority language predominantly used in its spoken form. Participants were literate Brazilian Portuguese speakers who spoke Hunsrückisch and German or Hunsrückisch only. The results show faster, more accurate performance in the phonemic awareness task among participants who spoke Hunsrückisch and German, relative to those who spoke Hunsrückisch only. Participants who spoke Hunsrückisch only were able to perform the phonemic awareness tasks but having learned to read and write in German allowed for faster, more accurate performance, especially in relation to pseudowords.