@article{BeierlePryssAizawa2023, author = {Beierle, Felix and Pryss, R{\"u}diger and Aizawa, Akiko}, title = {Sentiments about mental health on Twitter — before and during the COVID-19 pandemic}, series = {Healthcare}, volume = {11}, journal = {Healthcare}, number = {21}, issn = {2227-9032}, doi = {10.3390/healthcare11212893}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355192}, year = {2023}, abstract = {During the COVID-19 pandemic, the novel coronavirus had an impact not only on public health but also on the mental health of the population. Public sentiment on mental health and depression is often captured only in small, survey-based studies, while work based on Twitter data often only looks at the period during the pandemic and does not make comparisons with the pre-pandemic situation. We collected tweets that included the hashtags \#MentalHealth and \#Depression from before and during the pandemic (8.5 months each). We used LDA (Latent Dirichlet Allocation) for topic modeling and LIWC, VADER, and NRC for sentiment analysis. We used three machine-learning classifiers to seek evidence regarding an automatically detectable change in tweets before vs. during the pandemic: (1) based on TF-IDF values, (2) based on the values from the sentiment libraries, (3) based on tweet content (deep-learning BERT classifier). Topic modeling revealed that Twitter users who explicitly used the hashtags \#Depression and especially \#MentalHealth did so to raise awareness. We observed an overall positive sentiment, and in tough times such as during the COVID-19 pandemic, tweets with \#MentalHealth were often associated with gratitude. Among the three classification approaches, the BERT classifier showed the best performance, with an accuracy of 81\% for \#MentalHealth and 79\% for \#Depression. Although the data may have come from users familiar with mental health, these findings can help gauge public sentiment on the topic. The combination of (1) sentiment analysis, (2) topic modeling, and (3) tweet classification with machine learning proved useful in gaining comprehensive insight into public sentiment and could be applied to other data sources and topics.}, language = {en} } @article{HennesHuflageGrunzetal.2023, author = {Hennes, Jan-Lucca and Huflage, Henner and Grunz, Jan-Peter and Hartung, Viktor and Augustin, Anne Marie and Patzer, Theresa Sophie and Pannenbecker, Pauline and Petritsch, Bernhard and Bley, Thorsten Alexander and Gruschwitz, Philipp}, title = {An intra-individual comparison of low-keV photon-counting CT versus energy-integrating-detector CT angiography of the aorta}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {24}, issn = {2075-4418}, doi = {10.3390/diagnostics13243645}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355568}, year = {2023}, abstract = {This retrospective study aims to provide an intra-individual comparison of aortic CT angiographies (CTAs) using first-generation photon-counting-detector CT (PCD-CT) and third-generation energy-integrating-detector CT (EID-CT). High-pitch CTAs were performed with both scanners and equal contrast-agent protocols. EID-CT employed automatic tube voltage selection (90/100 kVp) with reference tube current of 434/350 mAs, whereas multi-energy PCD-CT scans were generated with fixed tube voltage (120 kVp), image quality level of 64, and reconstructed as 55 keV monoenergetic images. For image quality assessment, contrast-to-noise ratios (CNRs) were calculated, and subjective evaluation (overall quality, luminal contrast, vessel sharpness, blooming, and beam hardening) was performed independently by three radiologists. Fifty-seven patients (12 women, 45 men) were included with a median interval between examinations of 12.7 months (interquartile range 11.1 months). Using manufacturer-recommended scan protocols resulted in a substantially lower radiation dose in PCD-CT (size-specific dose estimate: 4.88 ± 0.48 versus 6.28 ± 0.50 mGy, p < 0.001), while CNR was approximately 50\% higher (41.11 ± 8.68 versus 27.05 ± 6.73, p < 0.001). Overall image quality and luminal contrast were deemed superior in PCD-CT (p < 0.001). Notably, EID-CT allowed for comparable vessel sharpness (p = 0.439) and less pronounced blooming and beam hardening (p < 0.001). Inter-rater agreement was good to excellent (0.58-0.87). Concluding, aortic PCD-CTAs facilitate increased image quality with significantly lower radiation dose compared to EID-CTAs}, language = {en} } @article{HampfScherfClavelWeissetal.2023, author = {Hampf, Chantal and Scherf-Clavel, Maike and Weiß, Carolin and Kl{\"u}pfel, Catherina and Stonawski, Saskia and Hommers, Leif and Lichter, Katharina and Erhardt-Lehmann, Angelika and Unterecker, Stefan and Domschke, Katharina and Kittel-Schneider, Sarah and Menke, Andreas and Deckert, J{\"u}rgen and Weber, Heike}, title = {Effects of anxious depression on antidepressant treatment response}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {24}, issn = {1422-0067}, doi = {10.3390/ijms242417128}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355801}, year = {2023}, abstract = {Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50\%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.}, language = {en} } @article{SchuhmannLanghauserZimmermannetal.2023, author = {Schuhmann, Michael K. and Langhauser, Friederike and Zimmermann, Lena and Bellut, Maximilian and Kleinschnitz, Christoph and Fluri, Felix}, title = {Dimethyl fumarate attenuates lymphocyte infiltration and reduces infarct size in experimental stroke}, series = {International journal of molecular sciences}, volume = {24}, journal = {International journal of molecular sciences}, number = {21}, doi = {10.3390/ijms242115540}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357731}, year = {2023}, abstract = {Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood-brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke.}, language = {en} } @article{TessmerMargison2023, author = {Tessmer, Ingrid and Margison, Geoffrey P.}, title = {The DNA alkyltransferase family of DNA repair proteins: common mechanisms, diverse functions}, series = {International Journal of Molecular Sciences}, volume = {25}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms25010463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355790}, year = {2023}, abstract = {DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O\(^6\)-alkylguanine and O\(^4\)-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O\(^6\)-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms. Nevertheless, between species, subtle as well as more extensive differences that affect target lesion preferences and/or introduce additional protein functions have evolved. Examining these differences and their functional consequences is intricately entwined with understanding the details of their DNA repair mechanism(s) and their biological roles. In this review, we will present and discuss various aspects of the current status of knowledge on this intriguing protein family.}, language = {en} } @article{ScheupleinLohrVivoliVegaetal.2023, author = {Scheuplein, Nicolas Julian and Lohr, Theresa and Vivoli Vega, Mirella and Ankrett, Dyan and Seufert, Florian and Kirchner, Lukas and Harmer, Nicholas J. and Holzgrabe, Ulrike}, title = {Fluorescent probe for the identification of potent inhibitors of the macrophage infectivity potentiator (Mip) protein of Burkholderia pseudomallei}, series = {SLAS Discovery}, volume = {28}, journal = {SLAS Discovery}, number = {5}, doi = {10.1016/j.slasd.2023.03.004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349784}, pages = {211-222}, year = {2023}, abstract = {Highlights • Synthesis of a new tracer molecule. • Robust and easy screening method for a broad range of compound activities. • FP assay validation considering limited use of starting material, DMSO tolerance, variation in incubation time and temperature. • Possibility of extension to HTP assay. Abstract The macrophage infectivity potentiator (Mip) protein belongs to the immunophilin superfamily. This class of enzymes catalyzes the interconversion between the cis and trans configuration of proline-containing peptide bonds. Mip has been shown to be important for the virulence of a wide range of pathogenic microorganisms, including the Gram-negative bacterium Burkholderia pseudomallei. Small molecules derived from the natural product rapamycin, lacking its immunosuppression-inducing moiety, inhibit Mip's peptidyl-prolyl cis-trans isomerase (PPIase) activity and lead to a reduction in pathogen load in vitro. Here, a fluorescence polarization assay (FPA) to enable the screening and effective development of BpMip inhibitors was established. A fluorescent probe was prepared, derived from previous pipecolic scaffold Mip inhibitors labeled with fluorescein. This probe showed moderate affinity for BpMip and enabled a highly robust FPA suitable for screening large compound libraries with medium- to high-throughput (Z factor ∼ 0.89) to identify potent new inhibitors. The FPA results are consistent with data from the protease-coupled PPIase assay. Analysis of the temperature dependence of the probe's binding highlighted that BpMip's ligand binding is driven by enthalpic rather than entropic effects. This has considerable consequences for the use of low-temperature kinetic assays.}, language = {en} } @article{SchuergerEngel2023, author = {Sch{\"u}rger, Peter and Engel, Volker}, title = {On the relation between nodal structures in quantum wave functions and particle correlation}, series = {AIP Advances}, volume = {13}, journal = {AIP Advances}, number = {12}, doi = {10.1063/5.0180004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350361}, year = {2023}, abstract = {We study the influence of nodal structures in two-dimensional quantum mechanical densities on wave packet entanglement. This is motivated by our recent study [Entropy, 25, 970 (2023)], which showed that the mutual information derived from the momentum-space probability density of a coupled two-particle system exhibits an unusual time dependence, which is not encountered if the position-space density is employed in the calculation. In studying a model density, here, we identify cases where the mutual information increases with the number of nodes in the wave function and approaches a finite value, whereas in this limit, the linear correlation vanishes. The results of the analytical model are then applied to interpret the correlation measures for coupled electron-nuclear dynamics, which are treated by numerically solving the time-dependent Schr{\"o}dinger equation.}, language = {en} } @article{SchadeBaderHuberetal.2023, author = {Schade, A. and Bader, A. and Huber, T. and Kuhn, S. and Czyszanowski, T. and Pfenning, A. and Rygała, M. and Smołka, T. and Motyka, M. and Sęk, G. and Hartmann, F. and H{\"o}fling, S.}, title = {Monolithic high contrast grating on GaSb/AlAsSb based epitaxial structures for mid-infrared wavelength applications}, series = {Optics Express}, volume = {31}, journal = {Optics Express}, number = {10}, doi = {10.1364/OE.487119}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350346}, pages = {16025-16034}, year = {2023}, abstract = {We demonstrate monolithic high contrast gratings (MHCG) based on GaSb/AlAs0.08Sb0.92 epitaxial structures with sub-wavelength gratings enabling high reflection of unpolarized mid-infrared radiation at the wavelength range from 2.5 to 5 µm. We study the reflectivity wavelength dependence of MHCGs with ridge widths ranging from 220 to 984 nm and fixed 2.6 µm grating period and demonstrate that peak reflectivity of above 0.7 can be shifted from 3.0 to 4.3 µm for ridge widths from 220 to 984 nm, respectively. Maximum reflectivity of up to 0.9 at 4 µm can be achieved. The experiments are in good agreement with numerical simulations, confirming high process flexibility in terms of peak reflectivity and wavelength selection. MHCGs have hitherto been regarded as mirrors enabling high reflection of selected light polarization. With this work, we show that thoughtfully designed MHCG yields high reflectivity for both orthogonal polarizations simultaneously. Our experiment demonstrates that MHCGs are promising candidates to replace conventional mirrors like distributed Bragg reflectors to realize resonator based optical and optoelectronic devices such as resonant cavity enhanced light emitting diodes and resonant cavity enhanced photodetectors in the mid-infrared spectral region, for which epitaxial growth of distributed Bragg reflectors is challenging.}, language = {en} } @article{PozziBolzoniBiellaetal.2023, author = {Pozzi, Nicol{\´o} Gabriele and Bolzoni, Francesco and Biella, Gabriele Eliseo Mario and Pezzoli, Gianni and Ip, Chi Wang and Volkmann, Jens and Cavallari, Paolo and Asan, Esther and Isaias, Ioannis Ugo}, title = {Brain noradrenergic innervation supports the development of Parkinson's tremor: a study in a reserpinized rat model}, series = {Cells}, volume = {12}, journal = {Cells}, number = {21}, issn = {2073-4409}, doi = {10.3390/cells12212529}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357721}, year = {2023}, abstract = {The pathophysiology of tremor in Parkinson's disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (\% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic-rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.}, language = {en} } @article{LuDreyerDickinsonetal.2023, author = {Lu, Jinping and Dreyer, Ingo and Dickinson, Miles Sasha and Panzer, Sabine and Jaślan, Dawid and Navarro-Retamal, Carlos and Geiger, Dietmar and Terpitz, Ulrich and Becker, Dirk and Stroud, Robert M. and Marten, Irene and Hedrich, Rainer}, title = {Vicia faba SV channel VfTPC1 is a hyperexcitable variant of plant vacuole two pore channels}, series = {eLife}, volume = {12}, journal = {eLife}, doi = {10.7554/eLife.86384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350264}, year = {2023}, abstract = {To fire action-potential-like electrical signals, the vacuole membrane requires the two-pore channel TPC1, formerly called SV channel. The TPC1/SV channel functions as a depolarization-stimulated, non-selective cation channel that is inhibited by luminal Ca\(^{2+}\). In our search for species-dependent functional TPC1 channel variants with different luminal Ca\(^{2+}\) sensitivity, we found in total three acidic residues present in Ca\(^{2+}\) sensor sites 2 and 3 of the Ca\(^{2+}\)-sensitive AtTPC1 channel from Arabidopsis thaliana that were neutral in its Vicia faba ortholog and also in those of many other Fabaceae. When expressed in the Arabidopsis AtTPC1-loss-of-function background, wild-type VfTPC1 was hypersensitive to vacuole depolarization and only weakly sensitive to blocking luminal Ca\(^{2+}\). When AtTPC1 was mutated for these VfTPC1-homologous polymorphic residues, two neutral substitutions in Ca\(^{2+}\) sensor site 3 alone were already sufficient for the Arabidopsis At-VfTPC1 channel mutant to gain VfTPC1-like voltage and luminal Ca\(^{2+}\) sensitivity that together rendered vacuoles hyperexcitable. Thus, natural TPC1 channel variants exist in plant families which may fine-tune vacuole excitability and adapt it to environmental settings of the particular ecological niche.}, language = {en} }