julilili42/papers huggingface dataset:
Using Springs as Sentinels of Climate Change in Nature Parks North and South of the Alps: A Critical Evaluation of Methodological Aspects and Recommendations for Long-Term Monitoring
2022-09-12

Spring ecosystems are diverse transition zones between ground- and surface-water habitats. Due to their characteristics and vulnerable species assemblages, springs are considered indicator systems for monitoring environmental change. In particular, climate change is expected to alter spring-ecosystem features, such as water temperature and discharge, affecting otherwise typically stable biotic and abiotic conditions. However, reliable trend-development recognition and analysis require a uniform methodology and comparable data series over long periods of time. Spring research findings in the Berchtesgaden National Park and the Adamello-Brenta Nature Park have been consolidated to develop methodological recommendations to create lasting societal-added value. The successful transfer of the methodology to the Bavarian Forest National Park and the experienced contribution of the Bavarian Association for the Protection of Nature (Bavarian Climate Alliance) strongly improved method validations. Our resulting, newly developed recommendations for long-term spring monitoring have a focus on climate change impacts and aim at providing a decision-making basis for establishing programs in similar ecological and climatic zones. Uniform site-selection criteria and selected climate-sensitive parameters are indicated. This includes documenting the spring’s environment and structure, measuring abiotic parameters, and determining selected floristic and faunistic groups. We recommend measurement and sampling-survey intervals ranging from 3(4) times yearly to every 5 years, depending on the parameter. We further suggest a database system that integrates all monitoring parameters to ensure consistent data management and storage. Analysing the data resulting from our new holistic spring monitoring methodology should provide critical knowledge about putatively changing ecosystems that can then be used as evidence of climate-change impact on spring ecosystems.
Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells
2022-09-12

Background. A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers’ attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2 <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mo>′</a:mo> </a:math> -chloro-5 <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mo>′</c:mo> </c:math> -nitrobenzenesulfonyl)−2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results. In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion. CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition.
Last Interglacial decadal sea surface temperature variability in the eastern Mediterranean
2022-09-12

Abstract The Last Interglacial (~129,000–116,000 years ago) is the most recent geologic period with a warmer-than-present climate. Proxy-based temperature reconstructions from this interval can help contextualize natural climate variability in our currently warming world, especially if they can define changes on decadal timescales. Here, we established a ~4.800-year-long record of sea surface temperature (SST) variability from the eastern Mediterranean Sea at 1–4-year resolution by applying mass spectrometry imaging of long-chain alkenones to a finely laminated organic-matter-rich sapropel deposited during the Last Interglacial. We observe the highest amplitude of decadal variability in the early stage of sapropel deposition, plausibly due to reduced vertical mixing of the highly stratified water column. With the subsequent reorganization of oceanographic conditions in the later stage of sapropel deposition, when SST forcing resembled the modern situation, we observe that the maximum amplitude of reconstructed decadal variability did not exceed the range of the recent period of warming climate. The more gradual, centennial SST trends reveal that the maximal centennial scale SST increase in our Last Interglacial record is below the projected temperature warming in the twenty-first century.
A complex systems model of temporal fluctuations in depressive symptomatology
2022-09-12

Symptom fluctuation is one of the hallmarks of major depression. However, a principled, quantitative framework explaining when and how symptoms change remains elusive. Following a complex systems perspective, we model clusters of depressive symptomatology across N = 2059 longitudinal biweekly measurements using a mobile phone app from N = 113 patients based on Beck Depression Inventory-I (BDI-I). We show that 1) the five largest clusters cover more than 60% of all symptom profiles, 2) in close to 90% of all cases, major temporal fluctuations in depression scores (i.e. sum of BDI-I items) coincides temporally with the change between the symptom clusters, 3) the probability of an approaching transition increases the further away the symptoms move from the center of the clusters (r = 0.78, p &amp;lt; 0.008), and 4) the approaching symptoms clusters are those that are closest to the BDI measurement at any given moment (r = 0.42, p &amp;lt; 0.0001). Taken together these results support the notion that symptom fluctuations can be predicted with high precision, potentially opening the possibility to augment interventions by predicting upcoming shifts in symptom structures.
Phosphoproteome Dynamics of Streptomyces rimosus during Submerged Growth and Antibiotic Production
2022-09-12

Streptomyces rimosus is best known as a primary source of oxytetracycline (OTC). The significant global market value of OTC highlights the need for a better understanding of the regulatory mechanisms that lead to production of this antibiotic.
Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage
2022-09-12

Results of three randomized clinical trials (RCTs) comparing adjuvant radiotherapy (ART) and early salvage radiotherapy (eSRT) of prostate carcinoma and a subsequent meta-analysis of the individual patient data from these RCTs were recently published. The results suggest that early eSRT is as effective and potentially less toxic than ART. Therefore, eSRT should be considered the standard of care. However, due to limitations in the RCTs, ART remains a valid treatment option in patients with the combination of high-risk features such as Gleason Score (GS) 8–10, positive surgical margins (R1) and pathological T-stage 3 or 4 (pT3/4). This article provides a critical appraisal of the RCTs and the rationale for recommendations adopted in the current national guidelines regarding patients with high-risk features after radical prostatectomy (RP): ART should be offered in case of pT3/pT4 and R1 and Gleason Score 8–10; ART can be offered in case of pT3/pT4 and R0 and Gleason Score 8–10 as well as in case of multifocal R1 (including pT2) and Gleason Score 8–10. In any case, the alternative treatment option of eSRT in case of rising PSA should be discussed with the patient.
Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study
2022-09-12

<title>Abstract</title> Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship of medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (<italic>p</italic> &lt; 0.001) was associated with better global functioning but showed no impact on the cognitive domains <italic>learning and memory</italic>, <italic>executive function</italic>, and <italic>psychomotor speed</italic>. The hierarchical cluster analysis resulted in three clusters with different cognitive performance, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not by medication adherence.
Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome
2022-09-12

Brief Summary: In this multicentre, randomized, double-dummy, double-blind crossover trial the authors investigated differences in metabolic parameters between the individuals with complete androgen insensitivity syndrome (CAIS) receiving testosterone versus estradiol replacement therapy. This is the first study investigating these different treatment options in CAIS. It finds no major differences in metabolic and safety parameters between the treatments.
Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
2022-09-13

Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be &gt;2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial.
Long-term memory representations for audio-visual scenes
2022-09-13

Abstract In this study, we investigated the nature of long-term memory representations for naturalistic audio-visual scenes. Whereas previous research has shown that audio-visual scenes are recognized more accurately than their unimodal counterparts, it remains unclear whether this benefit stems from audio-visually integrated long-term memory representations or a summation of independent retrieval cues. We tested two predictions for audio-visually integrated memory representations. First, we used a modeling approach to test whether recognition performance for audio-visual scenes is more accurate than would be expected from independent retrieval cues. This analysis shows that audio-visual integration is not necessary to explain the benefit of audio-visual scenes relative to purely auditory or purely visual scenes. Second, we report a series of experiments investigating the occurrence of study-test congruency effects for unimodal and audio-visual scenes. Most importantly, visually encoded information was immune to additional auditory information presented during testing, whereas auditory encoded information was susceptible to additional visual information presented during testing. This renders a true integration of visual and auditory information in long-term memory representations unlikely. In sum, our results instead provide evidence for visual dominance in long-term memory. Whereas associative auditory information is capable of enhancing memory performance, the long-term memory representations appear to be primarily visual.
Does intraocular straylight predict night driving visual performance? Correlations between straylight levels and contrast sensitivity, halo size, and hazard recognition distance with and without glare
2022-09-13

Purpose To evaluate the relationship between intraocular straylight perception and: (i) contrast sensitivity (CS), (ii) halo size, and (iii) hazard recognition distance, in the presence and absence of glare. Subjects and methods Participants were 15 (5 female) ophthalmologically healthy adults, aged 54.6–80.6 (median: 67.2) years. Intraocular straylight (log s) was measured using a straylight meter (C-Quant; Oculus GmbH, Wetzlar, Germany). CS with glare was measured clinically using the Optovist I device (Vistec Inc., Olching, Germany) and also within a driving simulator using Landolt Cs. These were presented under both static or dynamic viewing conditions, and either with or without glare. Hazard detection distance was measured for simulated obstacles of varying contrast. For this, the participant was required to maintain a speed of 60 km/h within a custom-built nighttime driving simulator. Glare was simulated by LED arrays, moved by cable robots to mimic an oncoming car’s headlights. Halo size (“halometry”) was measured by moving Landolt Cs outward originating from the center of a static glare source. The outcome measure from “halometry” was the radius of the halo (angular extent, in degrees visual angle). Results The correlation between intraocular straylight perception, log s, and hazard recognition distance under glare was poor for the low contrast obstacles (leading/subdominant eye: r = 0.27/ r = 0.34). Conversely, log CS measured with glare strongly predicted hazard recognition distances under glare. This was true both when log CS was measured using a clinical device (Optovist I: r = 0.93) and within the driving simulator, under static ( r = 0.69) and dynamic ( r = 0.61) conditions, and also with “halometry” ( r = 0.70). Glare reduced log CS and hazard recognition distance for almost all visual function parameters. Conclusion Intraocular straylight was a poor predictor of visual function and driving performance within this experiment. Conversely, CS was a strong predictor of both hazard recognition and halo extent. The presence of glare and motion lead to a degradation of CS in a driving simulator. Future studies are necessary to evaluate the effectiveness of all above-mentioned vision-related parameters for predicting fitness to drive under real-life conditions.
Laser-Induced Action Potential-Like Measurements of Cardiomyocytes on Microelectrode Arrays for Increased Predictivity of Safety Pharmacology
2022-09-13

Life-threatening drug-induced cardiac arrhythmia is often preceded by prolonged cardiac action potentials (AP), commonly accompanied by small proarrhythmic membrane potential fluctuations. The shape and time course of the repolarizing fraction of the AP can be pivotal for the presence or absence of arrhythmia. Microelectrode arrays (MEA) allow easy access to cardiotoxic compound effects via extracellular field potentials (FP). Although a powerful and well-established tool in research and cardiac safety pharmacology, the FP waveform does not allow to infer the original AP shape due to the extracellular recording principle and the resulting intrinsic alternating current (AC) filtering. A novel device, described here, can repetitively open the membrane of cardiomyocytes cultivated on top of the MEA electrodes at multiple cultivation time points, using a highly focused nanosecond laser beam. The laser poration results in transforming the electrophysiological signal from FP to intracellular-like APs (laser-induced AP, liAP) and enables the recording of transcellular voltage deflections. This intracellular access allows a better description of the AP shape and a better and more sensitive classification of proarrhythmic potentials than regular MEA recordings. This system is a revolutionary extension to the existing electrophysiological methods, permitting accurate evaluation of cardiotoxic effect with all advantages of MEA-based recordings (easy, acute, and chronic experiments, signal propagation analysis, etc.).
Protocol to analyze the transmigration efficiency of T. brucei using an in vitro model of the blood-cerebrospinal fluid barrier
2022-09-13

At present, the only approach to investigate the transmigration of Trypanosoma brucei, the causative agent of human African trypanosomiasis, from blood to cerebrospinal fluid is through animal experiments. This protocol details how to analyze the transmigration efficiency using an in vitro model of the blood-cerebrospinal fluid (blood-CSF) barrier. We describe how to grow human choroid plexus epithelial cells on cell culture filter inserts to form the barrier, followed by isolating and quantifying genomic DNA of transmigrated parasites by qPCR. For complete details on the use and execution of this protocol, please refer to Speidel et al. (2022).
Comparative multi-OMICS single cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action
2022-09-13

Abstract COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to optimization of future vaccination strategies, schedules, and combinations. Thus, we investigated a cohort of individuals pre- and post-vaccination to understand the humoral and cellular immune response against different COVID-19 vaccines, including recombinant adenoviral vector (rAdVV) and mRNA-based vaccines. Single-cell RNA sequencing allowed characterization of monocytes, T, NK and B cell activation at the transcriptomics/proteomic level, in response to different COVID-19 vaccines. Our data revealed that different COVID-19 vaccines elicit a unique and distinct mechanism of action. Specifically, we revealed that rAdVV vaccines negatively regulate CD4 + T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation by monocytes whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was already observed following the 1 st vaccine dose and was not further augmented after the subsequent 2 nd dose of the same vaccine and it was dependent on the type of vaccination used. Our integrated three layered-analyses highlights that COVID-19 vaccines evoke a strong but divergent immune response at the RNA, protein, and cellular levels. Our approach is able to pinpoint efficacy and mechanisms controlling immunity to vaccination and open the door for better vaccination which could induce innate and adaptive immunity equally in the long term. Key findings Decrease in major three cell types classical and non-classical monocytes and NK type III cells after COVID-19 vaccination Individual vaccination (AZ, JJ, MD, PB) has differential effect on various immune cell subsets and regulates unique cell populations, whilst no change was observed for CV vaccination rAdVV and mRNA vaccines have different mechanism of action for activation of lymphocytes and monocytes, respectively rAdVV vaccines negatively regulates CD4 + T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was prompted after the 1 st vaccine dose and not augmented after the subsequent 2 nd dose of the same vaccine. Graphical abstract
Supercritical Fluid Extraction with CO2 of Curcuma longa L. in Comparison to Conventional Solvent Extraction
2022-09-14

Curcuma longa L. is a traditional medicinal and spice plant containing a variety of lipophilic active substances with promising therapeutic properties. In this work, the solvent properties of supercritical carbon dioxide in a pressure and temperature range of 75–425 bar and 35–75 °C were investigated when Curcuma longa rhizomes were extracted. The three main curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, together with the three main constituents of the essential oil, i.e., ar-turmerone, α-turmerone, and β-turmerone, were analyzed in the resulting extracts. For statistical evaluation, experiments were performed employing a full factorial design, in which flow rate, extraction time, and drug load were kept constant. Within the given conditions, the experimental design revealed an optimum yield of all aforementioned substances, when supercritical carbon dioxide extraction was performed at 425 bar and 75 °C. For comparison, solvent extracts using methanol and n-hexane were prepared and their main components were characterized using LC-MS. The stability of the extracts was monitored upon storage for 6 months at 22 and 40 °C under protection from light. The decomposition of individual compounds was mainly observed in the presence of residual water in the extracts.