julilili42/papers huggingface dataset:
How to alleviate cardiac injury from electric shocks at the cellular level
2022-12-22

Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, but their utility against cardiac injury from cardiopulmonary resuscitation (CPR) remains to be established. We studied the time course of cell killing, mechanisms of cell death, and protection with P188 in AC16 human cardiomyocytes exposed to micro- or nanosecond pulsed electric field (μsPEF and nsPEF) shocks. A 3D printer was customized with an electrode holder to precisely position electrodes orthogonal to a cell monolayer in a nanofiber multiwell plate. Trains of nsPEF shocks (200, 300-ns pulses at 1.74 kV) or μsPEF shocks (20, 100-μs pulses at 300 V) produced a non-uniform electric field enabling efficient measurements of the lethal effect in a wide range of the electric field strength. Cell viability and caspase 3/7 expression were measured by fluorescent microscopy 2–24 h after the treatment. nsPEF shocks caused little or no caspase 3/7 activation; most of the lethally injured cells were permeable to propidium dye already at 2 h after the exposure. In contrast, μsPEF shocks caused strong activation of caspase 3/7 at 2 h and the number of dead cells grew up to 24 h, indicating the prevalence of the apoptotic death pathway. P188 at 0.2–1% reduced cell death, suggesting its potential utility in vivo to alleviate electric injury from defibrillation.
The 100-monthSwiftcatalogue of supergiant fast X–ray transients
2022-12-22

Supergiant fast X-ray transients (SFXTs) are high mass X-ray binaries (HMXBs) displaying X-ray outbursts that can reach peak luminosities up to 10 38 erg s −1 and spend most of their lives in more quiescent states with luminosities as low as 10 32 −10 33 erg s −1 . During the quiescent states, less luminous flares are also frequently observed with luminosities of 10 34 −10 35 erg s −1 . The main goal of the comprehensive and uniform analysis of the SFXT Swift triggers presented in this paper is to provide tools to predict whether a transient that has no known X-ray counterpart may be an SFXT candidate. These tools can be exploited for the development of future missions exploring the variable X-ray sky through large field-of-view instruments. We examined all available data on outbursts of SFXTs that triggered the Swift /Burst Alert Telescope (BAT) collected between 2005 August 30 and 2014 December 31, in particular those for which broad-band data, including the Swift /X-ray Telescope (XRT) data, are also available. This work complements and extends our previous catalogue of SFXT flares detected by BAT from 2005 February 12 to 2013 May 31, since we now include the additional BAT triggers recorded until the end of 2014 (i.e. beyond the formal first 100 months of the Swift mission). Due to a change in the mission’s observational strategy, virtually no SFXT triggers obtained a broad-band response after 2014. We processed all BAT and XRT data uniformly by using the Swift Burst Analyser to produce spectral evolution dependent flux light curves for each outburst in the sample. The BAT data allowed us to infer useful diagnostics to set SFXT triggers apart from the general γ -ray burst population, showing that SFXTs uniquely give rise to image triggers and are simultaneously very long, faint, and ‘soft’ hard-X-ray transients. We find that the BAT data alone can discriminate very well the SFXTs from other classes of fast transients, such as anomalous X-ray pulsars and soft gamma repeaters. On the contrary, the XRT data collected around the time of the BAT triggers are shown to be decisive for distinguishing SFXTs from, for instance, accreting millisecond X-ray pulsars and jetted tidal disruption events. The XRT observations of 35 (out of 52 in total) SFXT BAT triggers show that in the soft X-ray energy band, SFXTs display a decay in flux from the peak of the outburst of at least three orders of magnitude within a day and rarely undergo large re-brightening episodes, favouring in most cases a rapid decay down to the quiescent level within three to five days (at most).
Lithic Standardization and Behavioral Complexity in the Middle Stone Age – A Case Study From Sibhudu, South Africa
2022-12-22

The concept of standardization has been applied in archaeological research as a proxy measure for cognitive and behavioral complexity since the late nineteenth century. Here we evaluate these issues in the context of the Middle Stone Age (MSA) examining microlithic technology and laminar blanks and their corresponding core reduction and tool assemblages from the Howiesons Poort (HP) and Sibhudan from Sibhudu (South Africa). We find both standardization and variability among different techno-typological components of these technocomplexes. Similar degrees of standardization characterize the metrics of the bladelet assemblages in the Sibhudan and the backed pieces in the HP, but they remain much more variable than products from craft specialists. We argue for a careful interpretation of standardization in lithic technology taking into account factors like raw material, technological redundancy, site use patterns, functionality and tool biographies. Standardization in lithic tools per se is not an ideal proxy measure for behavioral complexity.
‘Just another world’: an interpretive biography of the cultural transition of two West African footballers in Germany
2022-12-22

This paper explored the cultural and career transition experiences of two elite West African footballers in Germany using the approach of interpretive biography. By analysing data collected through semi-structured interviews, the players’ narratives revealed a range of experiences emerging at different temporal points or life domains. The experiences included the psychosocial states of pre-transition, the challenges associated with language and weather, the increased demands of professionalism, the challenge of adapting to a new environment and routines of daily life, the superficiality of relationships and the attendant loneliness. It however, advanced literature by demonstrating how an African footballer in Europe may locate self and progress career within the European football economy and how a high-status African migrant athlete may use his social position to characterise self in a certain manner so as to exercise the right to belong.
Two cases of severe vitamin D3 intoxication treated with therapeutic plasma exchange and high cut-off hemodialysis
2022-12-22

Abstract We report on a 53-year-old female patient and a 33-year-old male patient presenting with life-threatening hypercalcemic crisis caused by self-induced vitamin-D intoxication. Both patients took high doses of vitamin D 3 supplements, cumulatively up to 2,500,000–10,000,000 I.U. over several months. Accordingly, serum 25-OH-vitamin D concentrations were increased to 663 and 1289 nmol/L (reference 50–175 nmol/L), respectively. As forced diuresis and bisphosphonates failed to correct recurrent hypercalcemia, we hypothesized that add-on extracorporeal treatments might help overcome the refractory situation. Considering the binding of vitamin D 3 metabolites to vitamin D-binding protein (VDBP, 59 kDa), we started extracorporeal treatments involving total plasma exchange with replacement by human albumin and by fresh frozen plasma, online hemodiafiltration and high cut-off hemodialysis. We found that in the former case, total plasma exchange with albumin and fresh frozen plasma and high cut-off hemodialysis lowered both 25-OH-vitamin D 3 and 1,25-OH-vitamin D 3, whereas in the latter case total plasma exchange with albumin was found to more effectively remove vitamin D metabolites compared to high cut-off hemodialysis. In contrast, the amount of total plasma calcium removed by high cut-off hemodialysis was higher compared to total plasma exchange with albumin. During follow up, patients 1 and 2 achieved almost normal total plasma calcium and vitamin D concentrations after 355 and 109 days, respectively. These two cases suggest that extracorporeal treatments with high cut-off hemodialysis and total plasma exchange with albumin may be considered as add-on treatment in refractory cases of vitamin D 3 -induced hypercalcemia to lower plasma 25-OH-vitamin D 3 concentrations.
Comparing Top-Down Proteoform Identification: Deconvolution, PrSM Overlap, and PTM Detection
2022-12-22

Generating top-down tandem mass spectra (MS/MS) for complex mixtures of proteoforms has become possible through improvements in fractionation, on-line separation, dissociation, and mass analysis. The algorithms to match MS/MS to sequences have undergone a parallel evolution, with both spectral alignment and peak matching being paired with diverse methods for scoring proteoform-spectral matches (PrSMs). This study assesses state-of-the-art algorithms for top-down identification through three distinct challenges. The first is identifying a large yield of PrSMs while controlling false discovery rate (FDR) in identifying thousands of proteoforms from complex cell lysates via four software workflows: ProSight Proteome Discoverer, TopPIC, Informed Proteomics, and pTop. The second is the deconvolution of data from both Thermo Orbitrap-class and Bruker maXis Q-TOF instruments to produce consistent precursor charge and mass determinations while generating fragment mass lists to optimize identification. The third attempts to detect diverse post-translational modifications (PTMs) in proteoforms from bovine milk and human ovarian tissue. The data demonstrate that existing software suites produce admirable sensitivity, in some cases identifying a third of collected MS/MS with FDR controlled below 2%; the overlap in these PrSMs, however, illustrates real value in searching data with multiple search engines. Differences among identification workflows seem to result from each search algorithm incorporating its own deconvolution algorithm. By transmitting deconvolution data from multiple deconvolution routes (Thermo Xtract, Bruker Auto MSn, Mascot Distiller, TopFD, and FLASHDeconv) to the downstream TopPIC search algorithm, we were able to detect common causes of deconvolution disagreement. The detection of PTMs was very inconsistent among search algorithms, with some workflows suggesting as little as 1% of PrSMs from bovine milk were singly-phosphorylated while other workflows found that 18% of PrSMs were singly-phosphorylated. Taken together, these results make a strong argument for top-down researchers to adopt a standard practice of analyzing each MS/MS experiment with at least two different search engines.
Higher sediment redistribution rates related to burrowing animals than previously assumed as revealed by time-of-flight-based monitoring
2022-12-22

Abstract. Burrowing animals influence surface microtopography and hillslope sediment redistribution, but changes often remain undetected due to a lack of automated high-resolution field monitoring techniques. In this study, we present a new approach to quantify microtopographic variations and surface changes caused by burrowing animals and rainfall-driven erosional processes applied to remote field plots in arid and Mediterranean climate regions in Chile. We compared the mass balance of redistributed sediment between burrow and burrow-embedded area, quantified the cumulative sediment redistribution caused by animals and rainfall, and upscaled the results to a hillslope scale. The newly developed instrument, a time-of-flight camera, showed a very good detection accuracy. The animal-caused cumulative sediment excavation was 14.6 cm3 cm−2 yr−1 in the Mediterranean climate zone and 16.4 cm3 cm−2 yr−1 in the arid climate zone. The rainfall-related cumulative sediment erosion within burrows was higher (10.4 cm3 cm−2 yr−1) in the Mediterranean climate zone than the arid climate zone (1.4 cm3 cm−2 yr−1). Daily sediment redistribution during rainfall within burrow areas was up to 350 %(40 %) higher in the Mediterranean (arid) zone compared to burrow-embedded areas and much higher than previously reported in studies that were not based on continuous microtopographic monitoring. A total of 38 % of the sediment eroding from burrows accumulated within the burrow entrance, while 62 % was incorporated into hillslope sediment flux, which exceeds previous estimations 2-fold. On average, animals burrowed between 1.2–2.3 times a month, and the burrowing intensity increased after rainfall. This revealed a newly detected feedback mechanism between rainfall, erosion, and animal burrowing activity, likely leading to an underestimation of animal-triggered hillslope sediment flux in wetter climates. Our findings hence show that the rate of sediment redistribution due to animal burrowing is dependent on climate and that animal burrowing plays a larger than previously expected role in hillslope sediment redistribution. Subsequently, animal burrowing activity should be incorporated into soil erosion and landscape evolution models that rely on soil processes but do not yet include animal-induced surface processes on microtopographical scales in their algorithms.
Let’s stay in touch: Frequency (but not mode) of interaction between leaders and followers predicts better leadership outcomes
2022-12-22

Successful leadership requires leaders to make their followers aware of expectations regarding the goals to achieve, norms to follow, and task responsibilities to take over. This awareness is often achieved through leader-follower communication. In times of economic globalization and digitalization, however, leader-follower communication has become both more digitalized (virtual, rather than face-to-face) and less frequent, making successful leader-follower-communication more challenging. The current research tested in four studies (three preregistered) whether digitalization and frequency of interaction predict task-related leadership success. In one cross-sectional (Study 1, N = 200), one longitudinal (Study 2, N = 305), and one quasi-experimental study (Study 3, N = 178), as predicted, a higher frequency (but not a lower level of digitalization) of leader-follower interactions predicted better task-related leadership outcomes (i.e., stronger goal clarity, norm clarity, and task responsibility among followers). Via mediation and a causal chain approach, Study 3 and Study 4 ( N = 261) further targeted the mechanism; results showed that the relationship between (higher) interaction frequency and these outcomes is due to followers perceiving more opportunities to share work-related information with the leaders. These results improve our understanding of contextual factors contributing to leadership success in collaborations across hierarchies. They highlight that it is not the digitalization but rather the frequency of interacting with their leader that predicts whether followers gain clarity about the relevant goals and norms to follow and the task responsibilities to assume.
Higher Frequencies of T-Cells Expressing NK-Cell Markers and Chemokine Receptors in Parkinson’s Disease
2022-12-22

Immune cells are thought to be involved in a destructive cycle of sterile cerebral inflammatory responses in neurodegenerative diseases such as Parkinson’s Disease (PD). Despite their peripheral origin, immune cells may enter the CNS due to impaired blood–brain barrier function and may potentially contribute to neuronal damage. Hence, specific characteristics of peripherally activated immune cells could help in understanding neurodegeneration in PD and could potentially serve as accessible disease markers. To investigate immune cell activation status, the expression of receptors for cell surface molecules CD161, NKG2A, NKG2C and NKG2D as well as chemokine receptors CCR6, CXCR2, CXCR3 and CCR5 associated with neurodegenerative diseases was investigated. The frequencies of peripheral CD8+ T-cells expressing the inhibitory and activating receptors NKG2A and NKG2C, and the activating receptor NKG2D were higher in PD patients than in healthy matched controls. The frequencies of NKG2C+CD8− cells were also higher, whereas the frequencies of CD161+ cells were not significantly different. Of the chemokine receptor-expressing cells, only the proportion of CD4−CD56+CCR5+ T-cells was higher in PD patients than in the controls. These observations support the hypothesis that an imbalance in the activation state of T-cells plays a role in the pathological processes of PD and suggest that peripheral blood immune cell phenotypes could be specific early markers for inflammation in PD.
CUX1-related neurodevelopmental disorder: Deep insights into phenotype-genotype spectrum and underlying pathology
2022-12-22

Abstract Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1 +/− mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished cases). A Cux1 +/− mouse model was used to analyze CUX1 expression in the brain and evaluate susceptibility to epilepsy. We describe 34 patients with 26 different null and four missense variants. The leading symptoms were mild to moderate delayed speech and motor development, and intellectual disability. In Cux1 +/− mice, we found delayed growth, histologically normal brains, and increased susceptibility to seizures. In Cux1 +/− brains, the expression of Cux1 transcripts was half of WT animals. Expression of CUX1 proteins was also reduced, although in early postnatal animals significantly more than in adults. In summary, disease-causing CUX1 variants result in a non-syndromic phenotype of developmental delay and intellectual disability. In some patients, this phenotype ameliorates with age, resulting in a clinical catch-up and normal IQ in adulthood. Furthermore, the balance of CUX1 isoform expression in the brain during development appears to be important for this favorable clinical course.
Anxiety associated with perceived uncontrollable stress enhances expectations of environmental volatility and impairs reward learning.
2022-12-22

Unavoidable stress elicits perceived lack of controllability and learned helplessness, which is a risk-factor for depression. Stress, anxiety, and depression can all alter reward learning. In a preregistered study during the first-wave of the COVID-19 pandemic, we used self-reported measures of depression, anxiety, uncontrollable stress, and COVID-19 risk from 427 online participants to predict performance in a three-armed-bandit probabilistic reward learning task. As hypothesised, uncontrollable stress predicted impaired learning of optimal choices. Uncontrollable stress also predicted a greater proportion of probabilistic errors following negative feedback for correct choices, which reflected interpretation of ambiguous negative feedback as a change in task reward contingencies. Moreover, this effect of uncontrollable stress on probabilistic errors was mediated by state anxiety. A parameter from the best-fitting hidden Markov model that estimates expected beliefs that the identity of the optimal choice will shift across images, mediated effects of state anxiety on probabilistic errors and learning deficits. Our findings show that following uncontrollable stress, anxiety promotes an overly volatile representation of the reward structure of uncertain environments, impairing reward attainment, which is a potential path to anhedonia in depression.
Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction
2022-12-22

Abstract Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remain largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD. Therefore, we performed a transcriptome study of SAD and ELA using RNA sequencing. Analyzing differential gene expression, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD whilst no significant differences in expression were identified with respect to ELA. The most significantly expressed gene was MAPK3 being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analyses ( WGCNA ) identified only modules significantly associated with ELA, not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3) revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD. In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.
Attentive Variational Information Bottleneck for TCR–peptide interaction prediction
2022-12-23

Abstract Motivation We present a multi-sequence generalization of Variational Information Bottleneck and call the resulting model Attentive Variational Information Bottleneck (AVIB). Our AVIB model leverages multi-head self-attention to implicitly approximate a posterior distribution over latent encodings conditioned on multiple input sequences. We apply AVIB to a fundamental immuno-oncology problem: predicting the interactions between T-cell receptors (TCRs) and peptides. Results Experimental results on various datasets show that AVIB significantly outperforms state-of-the-art methods for TCR–peptide interaction prediction. Additionally, we show that the latent posterior distribution learned by AVIB is particularly effective for the unsupervised detection of out-of-distribution amino acid sequences. Availability and implementation The code and the data used for this study are publicly available at: https://github.com/nec-research/vibtcr. Supplementary information Supplementary data are available at Bioinformatics online.