julilili42/papers huggingface dataset:
The semi-automatic classification of an open-ended question on panel survey motivation and its application in attrition analysis
2022-08-11

In this study, we demonstrate how supervised learning can extract interpretable survey motivation measurements from a large number of responses to an open-ended question. We manually coded a subsample of 5,000 responses to an open-ended question on survey motivation from the GESIS Panel (25,000 responses in total); we utilized supervised machine learning to classify the remaining responses. We can demonstrate that the responses on survey motivation in the GESIS Panel are particularly well suited for automated classification, since they are mostly one-dimensional. The evaluation of the test set also indicates very good overall performance. We present the pre-processing steps and methods we used for our data, and by discussing other popular options that might be more suitable in other cases, we also generalize beyond our use case. We also discuss various minor problems, such as a necessary spelling correction. Finally, we can showcase the analytic potential of the resulting categorization of panelists' motivation through an event history analysis of panel dropout. The analytical results allow a close look at respondents' motivations: they span a wide range, from the urge to help to interest in questions or the incentive and the wish to influence those in power through their participation. We conclude our paper by discussing the re-usability of the hand-coded responses for other surveys, including similar open questions to the GESIS Panel question.
Encapsulated vaterite-calcite CaCO3 particles loaded with Mg2+ and Cu2+ ions with sustained release promoting osteogenesis and angiogenesis
2022-08-11

Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO 3 particles were loaded with copper (Cu 2+ ) and magnesium (Mg 2+ ). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO 3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu 2+ in 2 months without initial burst release. Mg 2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering.
Mobilization with reduced cyclophosphamide for autologous stem cell transplantation is feasible in patients with systemic sclerosis
2022-08-11

Abstract Objectives To assess the feasibility of reduced cyclophosphamide dosing in the setting of mobilization chemotherapy prior to high dose chemotherapy and autologous stem cell transplantation in patients with SSc. The primary end point was the occurrence of ‘poor mobilization’ when using different cyclophosphamide dosing. The second end point was to analyse potential risk factors for difficult stem cell mobilization in this cohort of patients with SSc. Methods This single-centre study retrospectively reviewed 32 patients with SSc who underwent autologous stem cell transplantation. We analysed the occurrence of ‘poor mobilization’ (defined as CD34+ progenitor cell count &amp;lt;2 × 106/kg body weight, the use of increasing G-CSF dose, the use of plerixafor, or leukapheresis on &amp;gt;2 consecutive days) in different cyclophosphamide mobilization regimens: We herein compared low dose (2 × 1–1.5 g/m2) cyclophosphamide vs high dose (2 × 2 g/m2) for mobilization. Results Higher dosing of cyclophosphamide seems not to be beneficial regarding stem cell collection as there was no significant difference in stem cell yield between high dose and reduced dose cyclophosphamide (6.2 vs 5.2 × 106/kg bodyweight after CD34+ enrichment). Furthermore, higher doses of cyclophosphamide might be associated with more side effects; this difference was, however, not statistically significant. Lower bodyweight and BMI (P &amp;lt; 0.001) as well as rituximab pre-therapy (P &amp;lt; 0.05) and cardiac involvement (P &amp;lt; 0.01) might negatively impact stem cell collection independently from the chosen regimen. Conclusion Our data demonstrate that a reduced cyclophosphamide mobilization regimen seems to be feasible. Risk factors for poor mobilization might be low bodyweight, prior rituximab therapy and cardiac involvement.
Current and future aspects of IBD research and treatment: The 2022 perspective
2022-08-11

Inflammatory bowel diseases (IBD) have seen major progress in current concepts and treatment regimes. Based on the theory of an inadequate “overshoot” of the mucosal immune response to the intestinal microbiome, therapies have been developed to interfere with the key mediators of inflammation from cytokines, including TNF and IL12/23, to integrins such as α4ß7 and intracellular cytokine signal transducers such as janus kinases. Recently, sphingosine-1-receptor agonists were marketed to suppress mucosal inflammation by sequestering lymphocytes in peripheral lymph nodes. However, the aim of these regimes targeting immunity to induce a long-term deep remission, including mucosal healing, is missed in most patients. Contrasting these anti-inflammatory mechanisms of action, the pathogenic focus has finally shifted to the mucosal antibacterial barrier in both Crohn ́s disease and ulcerative colitis. Translating this novel concept requires a completely different approach but, in the end, may come closer to a cure of these devastating diseases, in which an incomplete immune modulation fails to achieve the key endpoints: halting disease activity and progression. This review aims to give an overview of past, current, and future concepts in IBD, focusing on both pathogenesis and consequent therapy. A cure is in sight only if both reflect the actual key mechanisms of slow bacterial entry into the mucosa and are harmonized and in line.
Inference of affordances and active motor control in simulated agents
2022-08-11

Flexible, goal-directed behavior is a fundamental aspect of human life. Based on the free energy minimization principle, the theory of active inference formalizes the generation of such behavior from a computational neuroscience perspective. Based on the theory, we introduce an output-probabilistic, temporally predictive, modular artificial neural network architecture, which processes sensorimotor information, infers behavior-relevant aspects of its world, and invokes highly flexible, goal-directed behavior. We show that our architecture, which is trained end-to-end to minimize an approximation of free energy, develops latent states that can be interpreted as affordance maps. That is, the emerging latent states signal which actions lead to which effects dependent on the local context. In combination with active inference, we show that flexible, goal-directed behavior can be invoked, incorporating the emerging affordance maps. As a result, our simulated agent flexibly steers through continuous spaces, avoids collisions with obstacles, and prefers pathways that lead to the goal with high certainty. Additionally, we show that the learned agent is highly suitable for zero-shot generalization across environments: After training the agent in a handful of fixed environments with obstacles and other terrains affecting its behavior, it performs similarly well in procedurally generated environments containing different amounts of obstacles and terrains of various sizes at different locations.
Ancient DNA reveals interstadials as a driver of the common vole population dynamics during the last glacial period
2022-08-11

1 Abstract Aim The common vole is a temperate rodent widespread across Europe. It was also one of the most abundant small mammal species throughout the Late Pleistocene. Phylogeographic studies of its extant populations suggested the Last Glacial Maximum (LGM, 26.5–19 ka ago) as one of the main drivers of the species’ population dynamics. However, analyses based solely on extant genetic diversity may not recover the full complexity of past population history. The main aim of this study was to investigate the evolutionary history and identify the main drivers of the common vole population dynamics during the Late Pleistocene. Location Europe Taxon Common vole ( Microtus arvalis ) Methods We generated a dataset comprising 4.2 kb-long fragment of mitochondrial DNA from 148 ancient and 51 modern specimens sampled from multiple localities across Europe and covering the last 60 thousand years (ka). We used Bayesian inference to reconstruct their phylogenetic relationships and to estimate the age of specimens that were not directly dated. Results We estimate the time to the most recent common ancestor of all Last Glacial and extant common vole lineages to 90 ka ago and the divergence of the main mtDNA lineages present in extant populations to between 55 and 40 ka ago, earlier than previous estimates. We find multiple lineage turnovers in Europe in the period of high climate variability at the end of Marine Isotope Stage 3 (MIS 3; 57–29 ka ago) in addition to those found previously around the Pleistocene/Holocene transition. Conversely, data from the Western Carpathians suggest continuity throughout the LGM even at high latitudes. Main conclusions Our results suggest that the main factor affecting the common vole populations during the last glacial period was the reduction of open habitats during the interstadial periods while the climate deterioration during the LGM had little impact on species’ population dynamics.
Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety
2022-08-11

Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus’s prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
Staff councils and their power resources – Workplace representation in German municipalities
2022-08-11

Purpose The paper examines the work and interactions of staff councils in German municipalities and the power resources the staff councils have at disposal. The paper also discusses the relationship between staff councils and trade unions and suggests a modification of the prominent concept of the “dual system of interest representation” to a “trimorphic system of interest representation” for the public sector. Design/methodology/approach The paper draws on case studies of staff councils in municipalities and administrative districts, relying on semi-structured interviews, group discussions and document analysis. Findings Staff councils operate in an extensively regulated field. The major task of staff councils is to monitor that employers follow collective agreements and the law. Staff councils' existence and co-determination rights of staff councils are provided by law; however, staff councils not only use institutional, but also organisational and – occasionally – political power resources, whereas structural and societal power resources are rarely actively used. The relationship between staff councils and trade unions often plays an important role and is in many cases characterised by mutual support. Originality/value Although staff councils are a widespread and a very interesting type of representation because staff councils represent both employees and civil servants who are employed in two distinctly different employment systems, staff councils are widely under-researched. This paper enriches empirical knowledge about labour relations and introduces the notion of a “trimorphic system of interest representation”.
The transcriptional regulator JAZ8 interacts with the C2 protein from geminiviruses and limits the viral infection in Arabidopsis
2022-08-11

ABSTRACT Jasmonates (JAs) are phytohormones that finely regulate critical biological processes, including plant development and defense. JASMONATE ZIM-DOMAIN (JAZ) proteins are crucial keeping JA-responsive genes in a repressed state. In the presence of JA-Ile, JAZ repressors are ubiquitinated and targeted for degradation by the ubiquitin/proteasome system, allowing the activation of the downstream transcription factors and, consequently, the activation of JA-responsive genes. A growing body of evidence has shown that JA signalling is crucial in defending against plant viruses and their insect vectors. Here, we describe the interaction of C2 proteins from two geminiviruses from the genus Begomovirus, tomato yellow curl Sardinia virus (TYLCSaV) and tomato yellow leaf curl virus (TYLCV), with the transcriptional repressor JAZ8 from Arabidopsis thaliana and its closest orthologue in tomato, SlJAZ9. Both JAZ and C2 proteins colocalize in the nucleus, forming discrete nuclear speckles. Overexpression of JAZ8 did not lead to altered responses to TYLCV infection; however, knock-down of JAZ8 favours the geminiviral infection in plants. Low levels of JAZ8 likely affect the viral infection specifically since JAZ8 -silenced plants do not display developmental phenotypes nor present differences in their interaction with the viral insect vector. Our results show that JAZ8 interacts with geminiviral C2 proteins and exerts an anti-geminiviral effect.
Structure-Based Identification of Naphthoquinones and Derivatives as Novel Inhibitors of Main Protease Mpro and Papain-like Protease PLpro of SARS-CoV-2
2022-08-12

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (M<sup>pro</sup>) and papain-like protease (PL<sup>pro</sup>) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In this study, we virtually screened 688 naphthoquinoidal compounds and derivatives against M<sup>pro</sup> of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against M<sup>pro</sup> using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PL<sup>pro</sup>. Four compounds inhibited M<sup>pro</sup> with half-maximal inhibitory concentration (IC<sub>50</sub>) values between 0.41 μM and 9.0 μM. In addition, three compounds inhibited PL<sup>pro</sup> with IC<sub>50</sub> ranging from 1.9 μM to 3.3 μM. To verify the specificity of M<sup>pro</sup> and PL<sup>pro</sup> inhibitors, our experiments included an assessment of common causes of false positives such as aggregation, high compound fluorescence, and inhibition by enzyme oxidation. Altogether, we confirmed novel classes of specific M<sup>pro</sup> and PL<sup>pro</sup> inhibitors. Molecular dynamics simulations suggest stable binding modes for M<sup>pro</sup> inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PL<sup>pro</sup> inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.
Dosimetric Evaluation of Dose Calculation Uncertainties for MR-Only Approaches in Prostate MR-Guided Radiotherapy
2022-08-12

Purpose: Magnetic resonance imaging guided radiotherapy (MRgRT) allows treatment plan adaptation on the MRI of the day. For dose calculations, a structure-specific bulk relative electron density (RED) overwrite derived from a planning computed tomography (CT) poses as one possible treatment workflow. However, this approach introduces uncertainties due to assignment of mean densities and requires a planning CT. The aim of this study was to investigate the uncertainty of the used patient-specific (PSCT) dose calculation in contrast to the correct calculation on a CT and compare to MR-only workflows using population-based bulk ED (PBCT) and artificial intelligence–based pseudo-CTs (AICT). Methods: Twenty primary prostate cancer patients treated on the 1.5 T MR-Linac were chosen from the clinical database, based on best visual congruence between the planning CT and daily MRI. CT-based reference dose distribution was compared to different pseudo-CT approaches. 1) For PSCT, mean REDs for the femur, pelvis, sacrum, rectum, bladder, and patient were assigned based on individual mean CT densities. 2) Population-based mean REDs were derived based on 50 previous, independent patients and assigned to the structures for the PBCT approach. 3) An AI model for pseudo-CT generation was trained using end-to-end ensembled self-supervised GANs and used to create AICTs from T2w-MRIs. For comparison, the CT was registered to the MRI, structures rigidly propagated, and treatment plans recalculated. Differences of DVH parameters were analyzed, and dose distributions were compared using gamma analysis. Results: All approaches were able to reproduce the dose distribution accurately, according to a gamma criterion of 3%/3 mm, with pass rates greater than 98%. Applying a 2%/2 mm criterion, the median gamma pass rates for PSCT, PBCT, and AICT resulted in 98.6%, 98.2%, and 99.0%, respectively. The median differences for PTV D 98% resulted in 0.13 Gy for AICT, −0.31 Gy for PBCT, and −0.32 Gy for PSCT. The OAR-related DVH parameter showed similar results between the three investigated methods. Conclusion: In this study, a detailed analysis of uncertainties of MR-only treatment planning concepts for pelvic MRgRT was performed. Both a PBCT and an AICT approach, which bypass the need for a planning CT, may be considered clinically acceptable while reducing imaging dose and registration issues.
Diagnostic Value of CRP and Serum WBC Count during Septic Two-Stage Revision of Total Hip Arthroplasties
2022-08-12

The diagnostic value of C-reactive protein (CRP) and the serum white blood cell (WBC) count is still barely defined for decision making during septic two-stage revision surgery of hip arthroplasty. We, therefore, compared these values between stages as well as between the groups without and with reinfection in 117 patients. A total of 106 patients were reinfection-free (91%). The median follow-up was 51 months. With a ΔCRP of −10 mg/L and a ΔWBC count of −1000/μL, a significant decrease between stages (p = 0.001) could be observed. When comparing the CRP and WBC count values between groups, however, no significant difference was found at stage one, stage two and even the difference between these two time points (reinfection-free ΔCRP of −11 mg/L and ΔWBC count of −1000/μL vs. reinfection ΔCRP of −5 mg/L (p = 0.131) and ΔWBC count of −1100/μL) (p = 0.424). The diagnostic value was poor for the calculated parameters (area under the curve (AUC) 0.5–0.6). The courses of the mean CRP values of both groups were similar. We conclude that the CRP and WBC count are not helpful to guide the decision making in individual cases.
Combination of PI-RADS score and mRNA urine test—A novel scoring system for improved detection of prostate cancer
2022-08-12

Available tests to detect clinically significant prostate cancer frequently lead to overdiagnosis and overtreatment. Our study assessed the feasibility of combining a urinary biomarker-based risk score (SelectMDx ® ) and multiparametric MRI outcomes in order to identify patients with prostate cancer on prostate biopsy with increased accuracy and reliability. Samples of 74 men with suspicion of prostate cancer and available multiparametric MRI were analysed in a prospective cross-sectional study design. First-voided urine for determination of HOXC6 and DLX1 mRNA levels was collected after digital rectal examination and prior to MRI/ultrasound fusion-guided prostate biopsy. All multiparametric MRI images were centrally reviewed by two experienced radiologists blinded for urine test results and biopsy outcome. The PI-RADS v2 was used. SelectMDx ® score, PI-RADS and Gleason Sore were obtained. Associations between Gleason Score, PI-RADS scores and SelectMDx ® were assessed using ANOVA and t-test. Sensitivity and specificity were assessed and evaluated as area-under-the-curve of the receiver operating characteristic. Upon biopsy, 59.5% of patients were diagnosed with prostate cancer, whereby 40.6% had high-grade prostate cancer (GS ≥ 7a). SelectMDx ® scores were significantly higher for patients with positive biopsy findings (49.07 ± 25.99% vs. 22.00 ± 26.43%; p &lt; 0.001). SelectMDx ® scores increased with higher PI-RADS scores. Combining SelectMDx ® , history of prior biopsy with benign histology and PI-RADS scores into a novel scoring system led to significant prostate cancer detection rates with tiered detection rate of 39%, 58%, 81% and 100% for Gleason grade group II, III, IV, and V, respectively. The area-under-the-curve for our novel sum score in receiver operating characteristic analysis was 0.84. The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.