julilili42/papers huggingface dataset:
Intraoperative monitoring of cerebrovascular autoregulation in infants and toddlers receiving major elective surgery to determine the individually optimal blood pressure – a pilot study
2023-02-14

Introduction Inducing general anesthesia (GA) in children can considerably affect blood pressure, and the rate of severe critical events owing to this remains high. Cerebrovascular autoregulation (CAR) protects the brain against blood-flow-related injury. Impaired CAR may contribute to the risk of cerebral hypoxic–ischemic or hyperemic injury. However, blood pressure limits of autoregulation (LAR) in infants and children are unclear. Materials and methods In this pilot study CAR was monitored prospectively in 20 patients aged &amp;lt;4 years receiving elective surgery under GA. Cardiac- or neurosurgical procedures were excluded. The possibility of calculating the CAR index hemoglobin volume index (HVx), by correlating near-infrared-spectroscopy (NIRS)-derived relative cerebral tissue hemoglobin and invasive mean arterial blood pressure (MAP) was determined. Optimal MAP (MAPopt), LAR, and the proportion of time with a MAP outside LAR were determined. Results The mean patient age was 14 ± 10 months. MAPopt could be determined in 19 of 20 patients, with an average of 62 ± 12 mmHg. The required time for a first MAPopt depended on the extent of spontaneous MAP fluctuations. The actual MAP was outside the LAR in 30% ± 24% of the measuring time. MAPopt significantly differed among patients with similar demographics. The CAR range averaged 19 ± 6 mmHg. Using weight-adjusted blood pressure recommendations or regional cerebral tissue saturation, only a fraction of the phases with inadequate MAP could be identified. Conclusion Non-invasive CAR monitoring using NIRS-derived HVx in infants, toddlers, and children receiving elective surgery under GA was reliable and provided robust data in this pilot study. Using a CAR-driven approach, individual MAPopt could be determined intraoperatively. The intensity of blood pressure fluctuations influences the initial measuring time. MAPopt may differ considerably from recommendations in the literature, and the MAP range within LAR in children may be smaller than that in adults. The necessity of manual artifact elimination represents a limitation. Larger prospective and multicenter cohort studies are necessary to confirm the feasibility of CAR-driven MAP management in children receiving major surgery under GA and to enable an interventional trial design using MAPopt as a target.
Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder
2023-02-14

<title>Abstract</title> Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P&lt;����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
Suspicious cities: An analysis of the securitisation of urban everyday life in London and Brussels
2023-02-14

This article engages with the material-discursive ways in which urban everyday life in London and Brussels has transformed under the impression of (counter)terrorism and demonstrates how human and non-human bodies are entangled in this process. Following Barad’s understanding of posthumanist performativity, I conceptualise urban everyday life as an entanglement of intra-acting sites, objects, and people. My historiographic analysis of everyday life in London and Brussels shows how both metropoles have incrementally adopted a culture of pre-emptive security because more and more human and non-human bodies are increasingly assigned with material-discursive suspiciousness, while simultaneously more and more human and non-human bodies are charged with looking out for suspiciousness. As the notion of entanglement reveals how everyone and everything that intra-acts in urban everyday life is also to some extent accountable for its securitisation, my findings imply ultimately an ethical responsibility to counter the securitisation of everyday life in European metropoles which I argue constitutes a process of urban segregation.
Mulching time of forest meadows influences insect diversity
2023-02-14

Abstract The diversity in meadows is affected by numerous aspects, such as the amount and type of fertilisation and the timing and frequency of cutting. The effects of mowing on the diversity of plants and insects have been studied in detail. However, the effect of mulching (vegetation is cut, shredded, and left in place, instead of being removed) on insects in small forest meadows has received limited scrutiny to date. In this study, we examined how different mulching times influenced insect diversity of forest meadows. We sampled insect larvae and observed flower‐visiting insects at 24 sites in the Northern Black Forest in south‐west Germany. We applied four treatments with six replicates each: (i) mulching in June, (ii) mulching in September, (iii) mulching in June and September, and (iv) no mulching as a control. The overall larval community was dominated by Symphyta (45%, Hymenoptera) and Lepidoptera (44%). The flower‐visiting insect community was dominated by Syrphidae (80%, Diptera). The insect larvae were negatively influenced by all mulching treatments. The abundance and species richness of flower visitors was reduced by mulching in June only and by mulching in both June and September. Summary: Given that meadow management is required for conserving grassland diversity our results indicate that for insect larvae other mulching methods, than those we tested, such as mulching with an arthropod‐friendly mulching machine, strip‐mulching, or delayed mulching may help this crucial stage of insect development. For insect flower visitors mulching in September is beneficial.
The genetic architecture of human cerebellar morphology supports a key role for the cerebellum in human evolution and psychopathology
2023-02-14

Abstract The functional domain of the cerebellum has expanded beyond motor control to also include cognitive and affective functions. In line with this notion, cerebellar volume has increased over recent primate evolution, and cerebellar alterations have been linked to heritable mental disorders. To map the genetic architecture of human cerebellar morphology, we here studied a large imaging genetics sample from the UK Biobank (n discovery = 27,302; n replication: 11,264) with state-of-the art neuroimaging and biostatistics tools. Multivariate GWAS on regional cerebellar MRI features yielded 351 significant genetic loci (228 novel, 94% replicated). Lead SNPs showed positive enrichment for relatively recent genetic mutations over the last 20-40k years (i.e., overlapping the Upper Paleolithic, a period characterized by rapid cultural evolution), while gene level analyses revealed enrichment for human-specific evolution over the last ∼6-8 million years. Finally, we observed genetic overlap with major mental disorders, supporting cerebellar involvement in psychopathology. Teaser Genome-wide analysis of cerebellar morphology reveals links to recent human evolution and psychopathology
Genetic analysis ofVCPvariants in a Turkish dementia cohort
2023-02-14

Abstract Valosin-containing protein ( VCP ) mutations are causative for multisystem proteinopathy, a disease characterized by variable phenotypes including inclusion body myopathy, Paget’s disease of bone, and frontotemporal dementia. More recent reports identified VCP variants as the cause of other neurodegenerative diseases, such as Parkinson’s disease and vacuolar tauopathy. We screened a Turkish dementia cohort for VCP variants in order to assess their role as the cause of disease in this population. One hundred and forty six Turkish dementia patients were examined clinically and were analyzed for VCP coding variants using whole-exome sequencing. Familial samples were collected and analyzed in order to test for segregation of candidate variants. We identified a heterozygous missense VCP p.Ile216Met variant segregating with disease in a family where the proband was diagnosed with prodromal dementia with Lewy bodies. Our report potentially extends the spectrum of phenotypes attributed to VCP mutations to include prodromal dementia with Lewy bodies.
Structural elements that enable specificity for mutant EGFR kinase domains with next-generation small-molecule inhibitors.
2023-02-14

Specificity for a desired enzyme target is an essential property of small-molecule inhibitors. Molecules targeting oncogenic driver mutations in the epidermal growth factor receptor (EGFR) kinase domain have had a considerable clinical impact due to their selective binding to cancer-causing mutants compared to wild type. Despite the availability of clinically approved drugs for cancers driven by EGFR mutants, persistent challenges in drug resistance in the past decades have led to newer generations of drugs with divergent chemical structures. The present clinical complications are mainly due to acquired resistance to third-generation inhibitors by the acquisition of the C797S mutation. Diverse fourth-generation candidates and tool compounds with C797S selectivity have emerged and their structural characterization has allowed for understanding of the molecular factors that allow for EGFR mutant selective binding. Here, we have reviewed all known structurally-characterized EGFR TKIs targeting clinically-relevant mutations to identify consistent binding mode features that enable C797S inhibition. Newer generation EGFR inhibitors exhibit consistent and previously underutilized hydrogen bonding interactions with the conserved K745 and D855 residue side chains. We also consider binding modes and hydrogen bonding interactions of inhibitors targeting the classical ATP and the more unique allosteric sites.
Front Cover: When Two Become One: Conformational Changes in FXR/RXR Heterodimers Bound to Steroidal Antagonists (ChemMedChem 4/2023)
2023-02-14

The Front Cover features the farnesoid X receptor (FXR) which is a nuclear receptor with a role in regulating bile acid synthesis and cholesterol homeostasis. This work studies the ligand-mediated FXR activation and heterodimerization using microsecond timescale molecular dynamics simulations. Recently reported FXR antagonists and well stablished agonists were investigated. Changes in the heterodimerization interface induced by antagonists prevent recruitment of co-regulatory elements. These results provide insights into their conformational changes and show what happens when two nuclear receptors become one system. More information can be found in the Research Article by Alejandro Díaz-Holguín, Azam Rashidian, Thales Kronenberger et al.
Collective atom-cavity coupling and nonlinear dynamics with atoms with multilevel ground states
2023-02-15

We investigate experimentally and theoretically the collective coupling between atoms with multilevel ground-state manifolds and an optical cavity mode. In our setup the cavity field optically pumps populations among the ground states. The ensuing dynamics can be conveniently described by means of an effective dynamical atom-cavity coupling strength that depends on the occupation of the individual states and their coupling strengths with the cavity mode. This leads to a dynamical backaction of the atomic populations on the atom-cavity coupling strength which results in a nonexponential relaxation dynamics. We experimentally observe this effect with laser-cooled 87Rb atoms, for which we monitor the collective normal-mode splitting in real time. Our results show that the multilevel structure of electronic ground states can significantly alter the relaxation behavior in atom-cavity settings as compared to ensembles of two-level atoms.
Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial
2023-02-15

Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p &lt; 0.001, hazard ratio 0.53, 95%CI 0.36–0.78, p &lt; 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p &lt; 0.05, hazard ratio 0.18, 95%CI 0.05–0.62, p &lt; 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4–78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.
Ancient DNA of narrow-headed vole reveal common features of the Late Pleistocene population dynamics in cold-adapted small mammals
2023-02-15

The narrow-headed vole, collared lemming and common vole were the most abundant small mammal species across the Eurasian Late Pleistocene steppe-tundra environment. Previous ancient DNA studies of the collared lemming and common vole have revealed dynamic population histories shaped by climatic fluctuations. To investigate the extent to which species with similar adaptations share common evolutionary histories, we generated a dataset comprised the mitochondrial genomes of 139 ancient and 6 modern narrow-headed voles from several sites across Europe and northwestern Asia covering approximately the last 100 thousand years (kyr). We inferred Bayesian time-aware phylogenies using 11 radiocarbon-dated samples to calibrate the molecular clock. Divergence of the main mtDNA lineages across the three species occurred during marine isotope stages (MIS) 7 and MIS 5, suggesting a common response of species adapted to open habitat during interglacials. We identified several time-structured mtDNA lineages in European narrow-headed vole, suggesting lineage turnover. The timing of some of these turnovers was synchronous across the three species, allowing us to identify the main drivers of the Late Pleistocene dynamics of steppe- and cold-adapted species.
Rationalizing Aggregate Structures with Orbital Contributions to the Exchange‐Repulsion Energy**
2023-02-15

Abstract It is shown that repulsive interactions have a crucial influence on the structure of prototypical non‐covalently bonded systems. To explain this, we propose a molecular orbital‐based model for the exchange‐repulsion contribution to the total interaction energy. As a central result, our model shows that energetically preferred aggregate structures frequently exhibit reduced exchange repulsion, which can be deduced from the nodal structure of certain occupied orbitals. This is used to explain key features of the intermolecular potentials of the Cl 2 ‐He, benzene‐benzene, and benzene‐hexafluorobenzene aggregates, which are not correctly reproduced by commonly applied electrostatic models.
Four-year follow-up on fatigue and sleep quality of a three-armed partly randomized controlled study in breast cancer survivors with cancer-related fatigue
2023-02-15

Abstract Cancer-related fatigue (CRF) is a frequent long-term symptom in non-metastasized breast cancer patients (BC). This 4-year follow-up intended to compare the long-term effects of a 10-week multimodal therapy (MT: sleep education, psychoeducation, eurythmy- and painting therapy) and combination therapy [CT: MT plus aerobic training (AT)] to AT-control. BC-patients were randomized or allocated by preference to three arms in a comprehensive cohort study. Primary outcome was a composite score including Pittsburgh Sleep Quality Index (PSQI) and Cancer Fatigue Scale (CFS-D), captured at baseline, after 10 weeks of intervention (T1), 6 months later (T2), and after 4 years (T3). We exploratively tested for superiority of MT and CT versus AT after 4 years (T3) based on the statistical model of the main analysis. Of 126 (65 randomized) BC-patients included, 105 started treatments and 79 were re-assessed for long-term effects (T3). MT and CT were superior over AT after 4 years regarding PSQI/CFS-D and PSQI sum-score, respectively (all p &lt; 0.05), but not for CFS-D. The multimodal and combination treatment for breast cancer patients with CRF indicates sustainable long-term superiority over aerobic training for the outcomes sleep quality and combined sleep quality/fatigue. A confirmative randomized controlled trial is warranted.
Student diversity and e‐exam acceptance in higher education
2023-02-15

Abstract Background The use of e‐exams in higher education is increasing. However, the role of student diversity in the acceptance of e‐exams is an under‐researched topic. In the current study, we considered student diversity in terms of three sociodemographic characteristics (age, gender, and second language) and three dispositional student characteristics (computer anxiety, test anxiety, and technology openness). Objectives The main objective of this study was to investigate the relationship between student diversity and acceptance of e‐exams. Methods Our research combined cross‐sectional analyses ( N = 1639) with data from a natural experiment on the introduction of e‐exams versus the established paper‐pencil exams ( N = 626) and used both self‐report and institutional data. Sociodemographic and dispositional characteristics were indirectly related to pre‐exam acceptance via expectancy variables from the Technology Acceptance Model framework. Results and Conclusions Comparisons of post‐exam acceptance showed that practical experience with the e‐exam led to a significant increase in e‐exam acceptance, and that students with low openness toward technology particularly benefited from this effect. Students' exam performance (i.e., grades) was unrelated to the exam format or their pre‐exam acceptance of the e‐exam format, and this was true across students' sociodemographic and dispositional characteristics. Takeaway Student diversity plays a role in e‐exam acceptance, but its influence is mitigated by first‐hand experience with e‐exams. The practical implications for higher education institutions aiming to implement e‐exams are discussed.
A Residual Marker of Cognitive Reserve Is Associated with Resting-State Intrinsic Functional Connectivity Along the Alzheimer’s Disease Continuum
2023-02-15

Background: Cognitive reserve (CR) explains inter-individual differences in the impact of the neurodegenerative burden on cognitive functioning. A residual model was proposed to estimate CR more accurately than previous measures. However, associations between residual CR markers (CRM) and functional connectivity (FC) remain unexplored. Objective: To explore the associations between the CRM and intrinsic network connectivity (INC) in resting-state networks along the neuropathological-continuum of Alzheimer’s disease (ADN). Methods: Three hundred eighteen participants from the DELCODE cohort were stratified using cerebrospinal fluid biomarkers according to the A(myloid-β)/T(au)/N(eurodegeneration) classification. CRM was calculated utilizing residuals obtained from a multilinear regression model predicting cognition from markers of disease burden. Using an independent component analysis in resting-state fMRI data, we measured INC of resting-state networks, i.e., default mode network (DMN), frontoparietal network (FPN), salience network (SAL), and dorsal attention network. The associations of INC with a composite memory score and CRM and the associations of CRM with the seed-to-voxel functional connectivity of memory-related were tested in general linear models. Results: CRM was positively associated with INC in the DMN in the entire cohort. The A+T+N+ group revealed an anti-correlation between the SAL and the DMN. Furthermore, CRM was positively associated with anti-correlation between memory-related regions in FPN and DMN in ADN and A+T/N+. Conclusion: Our results provide evidence that INC is associated with CRM in ADN defined as participants with amyloid pathology with or without cognitive symptoms, suggesting that the neural correlates of CR are mirrored in network FC in resting-state.
Reliability of Data Collected via Ecological Momentary Assessment on the Example of FeverApp Registry
2023-02-15

The FeverApp registry is an ambulant ecological momentary assessment (EMA) model registry focusing on research of fever in children. Verification of EMA reliability is a challenge, due to absence of other source data. To ensure the reliability of EMA data, 973 families were invited to reassess their documentation in a survey. The survey contained questions (a) regarding the number of children, (b) genuineness of entries, (c) completeness of submitted fever episodes, (d) medication, (e) usefulness and further usage of the app. Of those invited, 438 families (45% response rate) participated in the survey. Of these, 363 (83%) families have registered all their children, 208 families have one child. The majority (n = 325, 74.2%) of families stated that they only made genuine entries in the app. Agreement between survey and app for fever episodes is 90% (Cohen’s κ = 0.75 [0.66, 0.82]). Medication shows 73.7% agreement, κ = 0.49 [0.42; 0.54]. The majority (n = 245, 55.9%) consider the app as an additional benefit and 87.3% would like to use it further. Email surveys are a possible approach to evaluate EMA based registry data. The possible observation units (children and fever episodes) show an adequate reliability. With this approach, surveys of further samples and variables could help to improve the quality of EMA based registries.