julilili42/papers huggingface dataset:
Regional specificity of cathodal transcranial direct current stimulation effects on spatial–numerical associations: Comparison of four stimulation sites
2024-02-01

Abstract Neuromodulation with transcranial direct current stimulation (tDCS) is an increasingly popular research tool to experimentally manipulate cortical areas and probe their causal involvements in behavior, but its replicability and regional specificity are not clear. This registered report investigated cathodal tDCS effects on spatial–numerical associations (i.e., the SNARC effect), the numerical distance effect (NDE), and inhibitory control (i.e., stop‐signal reaction time; SSRT). Healthy adults ( N = 160) were randomly assigned to one of five groups to receive sham tDCS or 1 mA cathodal tDCS to one of four stimulation sites (left/right prefrontal cortex [PFC], left/right posterior parietal cortex) with extracephalic return. We replicated that cathodal tDCS over the left PFC reduced the SNARC effect compared to sham tDCS and to tDCS over the left parietal cortex. However, neither NDE nor SSRT were modulated in the main analyses. Post hoc contrasts and exploratory analyses showed that cathodal tDCS over the right PFC had a time‐dependent effect by delayed practice‐related improvements in SSRT. Math anxiety moderated changes in the NDE in the groups receiving tDCS to the right parietal cortex. With few exceptions, the replicability and regional specificity of tDCS effects on behavior were weak and partially moderated by individual differences. Future research needs to characterize the parameter settings for effective neuromodulation.
The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients
2024-02-01

Abstract CYP3A4 activity shows considerable interindividual variability. Although studies indicate 60%–80% is heritable, common single nucleotide variants (SNVs) in CYP3A4 together only explain ~10%. Transcriptional factors, such as the testis‐specific Y‐encoded‐like proteins (TSPYLs) family, have been reported to regulate the expression of CYP enzymes including CYP3A4 in vitro. Here, we investigated the effect of genetic variants in TSPYL on CYP3A4 activity using data from a clinical study and a human liver bank. Five SNVs (rs3828743, rs10223646, rs6909133, rs1204807, and rs1204811) in TSPYL were selected because of a reported effect on CYP3A4 expression in vitro or suggested clinical effect. For the clinical study, whole blood concentrations, clinical data, and DNA were available from 295 kidney transplant recipients participating in the prospective MECANO study. A multivariate pharmacokinetic model adjusted for body weight, steroid treatment, and CYP3A4 genotype was used to assess the effect of the genetic variants on cyclosporine clearance. In multivariate analysis, homozygous carriers of rs3828743 had a 18% lower cyclosporin clearance compared to the wild‐type and heterozygous patients (28.72 vs. 35.03 L/h, p = 0.018) indicating a lower CYP3A4 activity and an opposite direction of effect compared to the previously reported increased CYP3A4 expression. To validate, we tested associations between rs3828743 and CYP3A4 mRNA and protein expression as well as enzyme activity with data from a liver bank ( n = 150). No association with any of these end points was observed. In conclusion, the totality of evidence is not in support of a significant role for TSPYL SNV rs3828743 in explaining variability in CYP3A4 activity.
Magnitude of Urine Albumin and KIM-1 Changes Can be Used to Differentiate Glomerular Injury From Tubular Injury in Rats
2024-02-01

Emerging urinary kidney safety biomarkers have been evaluated in recent years and have been shown to be superior to the serum parameters blood urea nitrogen (BUN) and creatinine (sCr) for monitoring kidney injury in the proximal tubule. However, their potential application in differentiating the location of the initial kidney injury (eg, glomerulus vs tubule) has not been fully explored. Here, we assessed the performance of two algorithms that were constructed using either an empirical or a mathematical model to predict the site of kidney injury using a data set consisting of 22 rat kidney toxicity studies with known urine biomarker and histopathologic outcomes. Two kidney safety biomarkers used in both models, kidney injury molecule 1 (KIM-1) and albumin (ALB), were the best performers to differentiate glomerular injury from tubular injury. The performance of algorithms using these two biomarkers against the gold standard of kidney histopathologic examination showed high sensitivity in differentiating the location of the kidney damage to either the glomerulus or the proximal tubules. These data support the exploration of such an approach for use in clinical settings, leveraging urinary biomarker data to aid in the diagnosis of either glomerular or tubular injury where histopathologic assessments are not conducted.
Somatic gene delivery for flexiblein vivomodeling of high-risk sarcoma
2024-02-01

ABSTRACT A particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle wildtype mice. This optimized sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities, including Synovial Sarcoma (SS), fusion-positive and fusion-negative Rhabdomyosarcoma (RMS), Alveolar Soft Part Sarcoma (ASPS), Undifferentiated Pleomorphic Sarcoma (UPS) and Infantile Fibrosarcoma (IFS). Comprehensive molecular profiling and cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets. Syngeneic allografting enabled reliable preservation and scalability of Sarcoma-EPO-GEMMs for treatment trials, such as B7-H3-directed CAR-T cell therapy in an immunocompetent background.
Genome-guided purification of high amounts of the siderophore ornibactin and detection of potentially novel burkholdine derivatives produced by Burkholderia catarinensis 89T
2024-02-01

Abstract Aim The increased availability of genome sequences has enabled the development of valuable tools for the prediction and identification of bacterial natural products. Burkholderia catarinensis 89T produces siderophores and an unknown potent antifungal metabolite. The aim of this work was to identify and purify natural products of B. catarinensis 89T through a genome-guided approach. Materials and methods The analysis of B. catarinensis 89T genome revealed 16 clusters putatively related to secondary metabolism and antibiotics production. Of particular note was the identification of a nonribosomal peptide synthetase (NRPS) cluster related to the production of the siderophore ornibactin, a hybrid NRPS-polyketide synthase Type 1 cluster for the production of the antifungal glycolipopeptide burkholdine, and a gene cluster encoding homoserine lactones (HSL), probably involved in the regulation of both metabolites. We were able to purify high amounts of the ornibactin derivatives D/C6 and F/C8, while also detecting the derivative B/C4 in mass spectrometry investigations. A group of metabolites with molecular masses ranging from 1188 to 1272 Da could be detected in MS experiments, which we postulate to be new burkholdine analogs produced by B. catarinensis. The comparison of B. catarinensis BGCs with other Bcc members corroborates the hypothesis that this bacterium could produce new derivatives of these metabolites. Moreover, the quorum sensing metabolites C6-HSL, C8-HSL, and 3OH-C8-HSL were observed in LC-MS/MS analysis. Conclusion The new species B. catarinensis is a potential source of new bioactive secondary metabolites. Our results highlight the importance of genome-guided purification and identification of metabolites of biotechnological importance.
Binding of response-independent task rules
2024-02-01

Abstract Binding theories claim that features of an episode are bound to each other and can be retrieved once these features are re-encountered. Binding effects have been shown in task-switching studies with a strong focus on bindings of observable features such as responses. In this study, we aimed to investigate whether task rules, translating stimulus information into motor output can be bound and subsequently retrieved even if they act independently from specific response codes. To address this question, we utilized a task-switching paradigm with varying visual context features. Unlike previous studies, tasks in the present study did not differ in their response options, and sequential response repetitions were eliminated by design. In three experiments, we observed larger task-switch costs on trials repeating the context of the previous trial than on context-change trials. According to binding accounts, this suggests that response-independent task rules adopted in the previous trial became bound to the context feature and were retrieved upon re-encountering the context feature in the current trial. The results of this study generalize previous findings indicating that binding processes can include response-independent control to task-switching situations.
Nonlinear black hole scalarization in multi-scalar Gauss-Bonnet gravity
2024-02-01

Abstract A process called nonlinear scalarization was recently demonstrated to exist for black holes in scalar-Gauss-Bonnet gravity. Contrary to the standard spontaneous scalarization, the nonlinear scalarization is a process which allows for a Schwarzschild black hole and a scalarized black hole, both linearly stable, to coexist. We extend the search for black holes with nonlinear scalarization in the case of multi-scalar Gauss-Bonnet gravity – a class of theories which allow for hairy compact objects with vanishing scalar charge, hence, there are no constraints from the binary pulsar observations. We demonstrate numerically the existence of such black hole solutions with nonlinear scalarization in the multi-scalar Gauss-Bonnet theories with exponential coupling function which is of fourth leading order in the scalar field.
Long-term recurrence-free survival following pancreatic surgery with HIPEC treatment for locally advanced pancreatic adenocarcinoma
2024-02-01

More than 5 years previous to this report, a female patient in her 60s underwent oncological left-sided pancreatic resection and adrenalectomy including splenectomy for locally advanced pancreatic adenocarcinoma (PDAC), recommended by a multidisciplinary tumour board (MDT). Additionally, she was treated with gemcitabine-containing hyperthermic intraperitoneal chemotherapy (HIPEC) for 60 minutes in the framework of a clinical trial (PanHIPEC), aiming to determine the safety and feasibility (not efficacy) of this approach. Following the postoperative MDT recommendation, she subsequently received adjuvant chemotherapy consisting of six cycles of gemcitabine and cisplatin for a histopathologically confirmed PDAC of the pancreatic tail with infiltration of the left-sided adrenal gland (pT3, pN1 (3/16), cM0, L0, V0, Pn1, R0, G2). Five years and five months after pancreatic surgery and HIPEC, the patient has no signs of tumour recurrence as determined by follow-up examination including CT scan and CA19-9 tumour marker serology.
Colorimetric surface lipid quantification in Drosophila
2024-02-01

Abstract Insects are covered with free neutral cuticular hydrocarbons (CHC) that may be linear, branched, and unsaturated and vary in their chain length. The CHC composition is species‐specific and contributes to the adaptation of the animal to its ecological niche. Commonly, CHCs contribute substantially to the inward and outward barrier function of the cuticle and serve pheromonal communication. They are generally determined by gas‐chromatography, a time‐consuming method requiring detailed expertize, but it is not available in many laboratories. Here, we report on the establishment of a colorimetric method allowing semi‐quantitative determination of unsaturated CHCs in Drosophila flies. This method is based on the in vitro reaction of vanillin with double bounds in lipid molecules in an acidic solution to generate a reddish color. We found a robust correlation between gas chromatographic and vanillin‐colorimetric data on unsaturated CHCs amounts in single flies. As the role of unsaturated CHCs in the performance of insects in their environment is only partly understood, we think that this novel method would allow fast and broad analyses of this type of CHCs in insects both in the field and in laboratories and thereby contribute to a substantial improvement in the investigation of this matter.
A shade-responsive microProtein in the ArabidopsisATHB2gene regulates elongation growth and root development
2024-02-01

Abstract The ability of plants to thrive under suboptimal light conditions, such as shade, is crucial for their overall survival and reproductive success. Here, we show that Arabidopsis seedlings produce a large number of alternative transcripts when exposed to shade. Notably, one of the identified transcript candidates, which was upregulated in shade conditions, was found to be an alternative transcript of the ATHB2 gene. ATHB2 belongs to the HD-ZIPII class of transcription factors and is a well-established regulator of the shade avoidance response. The function of the alternative transcript and the small leucine zipper protein encoded by it, ATHB2miP, was investigated. We found that ATHB2miP is primarily expressed in the shoot meristem and interacts with full-length ATHB2 protein to inhibit its activity through a negative feedback mechanism. Deletion of the genomic region encoding the leucine zipper domain of the ATHB2 gene using CRISPR, resulted in plants exhibiting altered shade avoidance responses and root development. We show that the leucine zipper domain is required for dimerising and localising to nuclear photobodies. There is a significant overlap in deregulated genes between plants ectopically expressing ATHB2miP and athb2 mutant plants. The analysis of gene ontology and clustering revealed that the most affected processes are auxin synthesis and signaling, root development, and iron homeostasis. Shade growth experiments at different iron concentrations revealed a role for ATHB2 in regulating iron uptake and showed that iron availability affects shade growth in an ATHB2 -dependent manner. This study identifies ATHB2miP as a novel regulator of shade avoidance responses in Arabidopsis, highlighting the intricate transcriptional regulation underlying these processes.
Wilhelm Wundt: His bumpy start in science at the University of Tübingen.
2024-02-01

In 1851, Wilhelm Wundt embarked on his university journey at the University of Tübingen, initially enrolling as a medical student. This article draws from Wundt's autobiography and supplementary sources to illuminate the motivations behind his choice of Tübingen, shedding light on how this pivotal phase influenced both his scientific trajectory and his personal development. It offers insights into Wundt's perspectives on university and city life in Tübingen, providing a nuanced understanding of his formative years. Wundt's nonlinear entry into the realm of science serves as a source of reassurance and inspiration for contemporary psychology students facing similar initial challenges in their academic pursuits. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Signal shapes in multiwire proportional chamber-based TPCs
2024-02-01

Abstract A large-volume Time Projection Chamber (TPC) is the main tracking and particle identification (PID) detector of the ALICE experiment at the CERN LHC. PID in the TPC is performed via specific energy-loss measurements (d E /d x ), which are derived from the average pulse-height distribution of ionization generated by charged-particle tracks traversing the TPC volume. During Runs 1 and 2, until 2018, the gas amplification stage was based on multiwire proportional chambers (MWPC). Signals from the MWPC show characteristic long negative tails after an initial positive peak due to the long ion drift times in the MWPC amplification region. This so-called ion tail can lead to a significant amplitude loss in subsequently measured signals, especially in the high-multiplicity environment of high-energy Pb-Pb collisions, which results in a degradation of the d E /d x resolution. A detailed study of the signal shapes measured with the ALICE TPC with the Ne-CO 2 (90-10) and Ar-CO 2 (90-10) gas mixtures is presented, and the results are compared with three-dimensional Garfield simulations. The impact of the ion tail on the PID performance is studied employing the ALICE simulation framework and the feasibility of an offline correction procedure to account for the ion tail is demonstrated.
Cerebral venous sinus thrombosis and thrombocytopenia after adenovirus infection due to heparin-independent anti-PF4 antibodies
2024-02-01

Introduction Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease that primarily affects adults. However, its occurrence in paediatric patients presents unique challenges. This paper discusses a paediatric case of severe CVST and thrombocytopenia following adenovirus infection, resembling vaccine-induced immune thrombotic thrombocytopenia (VITT). The aim of this study is to serologically characterize antibodies against platelet factor 4 (PF4)/heparin detected in the serum of patients and to investigate their ability to induce thrombosis ex vivo.
In vitro generated megakaryocytes for the detection of human platelet antigen-specific alloantibodies
2024-02-01

Introduction Serologic characterization of anti-human platelet antigen (HPA) alloantibodies is crucial in fetal neonatal alloimmune thrombocytopenia (FNAIT). The monoclonal antibody immobilization of platelet antigens (MAIPA) assay is accepted as the gold standard test for the detection of platelet antibodies, however, it requires fresh platelets from HPA-genotyped donors, which is challenging for some labs. Megakaryocytes express HPA epitopes and offer an alternative source for detecting anti-HPA antibodies. The objective of this study was to assess the efficacy of a novel assay called monoclonal antibody immobilization of megakaryocyte antigens (MAIMA) for detecting anti-HPA antibodies.
Prevalence of Anti-PF4/Heparin Antibodies After Second COVID-19 Vaccination in Healthcare Workers
2024-02-01

Introduction Anti-platelet factor 4 (PF4) antibodies have been identified as the cause of vaccine-induced immune thrombotic thrombocytopenia following adenoviral vector-based COVID-19 vaccines. Previous studies have primarily focused on determining the frequency of anti-PF4 antibodies shortly after the first COVID-19 vaccination, leaving the rates of anti-PF4 antibody positivity after second vaccinations largely unknown.
Heterozygous RUNX1-gene deletion in a patient with mild thrombocytopenia and a platelet granule secretion defect
2024-02-01

Introduction Inherited platelet disorders (IPD) are a heterogynous group of disorders affecting platelet number and function. Next generation sequencing (NGS) has been an important tool to analyze genetic alterations in multiple genes. However, platelet function analysis performed with light transmission aggregometry (LTA), flow cytometry, and microscopy are important to identify patients with an IDP and to characterize the platelet phenotype. We investigated a young girl, who presented with multiple hematoma and mild thrombocytopenia (Plt. 109 G/L). Case history revealed that a few of her mother ́s relatives had suffered from leukemia as adults.
Platelet factor 4 mediates procoagulant platelet and increased thrombus formation in vaccine-induced thrombotic thrombocytopenia via SYK signaling pathway
2024-02-01

Introduction Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but life-threatening prothrombotic syndrome observed in individuals following vaccination with vector-based SARS-CoV-2 (ChAdOx1 CoV-19) vaccine. Laboratory findings indicate that VITT is caused by antibodies (Abs) that recognize specific heparin-independent epitopes on the endogenous chemokine platelet factor 4 (PF4) which results in the initiation of a multicellular driven prothrombotic condition and onset of thrombosis at unusual sites. Despite PF4 has been identified as the primary target of anti-PF4 VITT patient antibodies, a deeper understanding regarding the mechanisms of anti-PF4 VITT Ab-mediated prothrombotic conditions is missing. In this study we investigate the regulatory and mechanistic role of PF4 in anti-PF4 VITT Ab-induced procoagulant platelet (PLT) and thrombus formation ex vivo.
Cold stored platelets –investigations of thrombus formation in a microfluidic system
2024-02-01

Introduction Platelet concentrates (PCs) are used to treat or prevent bleeding in patients with impaired platelet function or after injury. Cold storage was shown to better preserve platelet function, over the current standard – room temperature (RT) storage in vitro. Our aim is to establish an ex vivo model to evaluate the contribution of PCs in thrombus formation and to investigate the effect of different storage conditions on platelet functions.
Blood viscoelastic testing could support the management of patients with hemophilia A
2024-02-01

Introduction Measurement of Factor VIII activity is decisive for the bleeding management of patients with hemophilia A in emergency situations. However, in most laboratories the determination of factor VIII activity takes several hours and is not available as an emergency parameter especially during holidays and weekends. Thrombelastography is a point-of-care method that provides data on different coagulation parameters in whole blood samples. It is well established so that the coagulation system can be monitored in emergency situations using this easy to use method. It gives a rapid overview of all phases of coagulation and fibrinolysis. Most results are available within a few minutes. In this paper, we report on the use of thrombelastography in the management of patients with hemophilia.
Dysregulations of fibrinolysis system can be detected in frozen plasma samples using thrombelastography
2024-02-01

Introduction Thrombelastography (TE) is a standard lab test which measures coagulation parameters in whole blood samples in real time [1] [2]. The method serves as a useful point-of-care test to diagnose and manage patients with coagulation disorders [3]. The advantage of TE is the rapid overview of all phases of coagulation and fibrinolysis [4]. However, this method is limited by the need for immediate testing and difficulty in dissecting the exact mechanism of the dysregulation.
Therapeutic influence of ACKR3/CXCR7 in inducing Anticoagulant Acylcarnitines: implications for Deep Vein Thrombosis and Coronary Artery Disease
2024-02-01

Introduction Pharmacological targeting of the chemokine receptor ACKR3/CXCR7 regulates arterial thrombosis, platelet reactivity and thrombo-inflammatory response following myocardial infarction, those induced by immunothrombotic IgGs, and in coronary artery disease (CAD) patients ex vivo. CXCR7 agonist triggers the generation of anti-platelet lipid 12-HETrE which ligates the prostacyclin receptor and induces the platelet inhibitory cAMP dependent signaling cascade. Current investigation explores the antithrombotic and anticoagulatory implications of targeting CXCR7.