julilili42/papers huggingface dataset:
Simultaneous Identification of Functional Antigen-Specific CD8+ and CD4+ Cells after In Vitro Expansion Using Elongated Peptides
2022-10-31

Elongated peptides (EPs), containing possibly one or multiple epitope/s, are increasingly used for the screening of antigen-specific CD8+ and CD4+ cell responses. Here, we present an in vitro protocol that allows the amplification of antigen-specific cells and the subsequent functional analysis of both T cell types using EPs. Known viral-derived epitopes were elongated to 20 mer EPs on the N-, C-, and both termini for HLA class I binders, or on the N- and C- termini for HLA class II binders. With EP stimulation only, the percentage of responding CD8+ T cells was dependent on the elongation site of the EP, whereas CD4+ T cell responses were completely lost in 22% of the tests performed ex vivo. A short-term amplification step plus the addition of a TLR3 agonist (Poly-ICLC) together with an increased EP concentration improved markedly the detection of CD8+ and CD4+ T cell reactivities.
Informing mHealth and Web-Based Eating Disorder Interventions: Combining Lived Experience Perspectives With Design Thinking Approaches
2022-10-31

Background App-based interventions designed to prevent and treat eating disorders have considerable potential to overcome known barriers to treatment seeking. Existing apps have shown efficacy in terms of symptom reduction; however, uptake and retention issues are common. To ensure that apps meet the needs and preferences of those for whom they were designed, it is critical to understand the lived experience of potential users and involve them in the process of design, development, and delivery. However, few app-based interventions are pretested on and co-designed with end users before randomized controlled trials. Objective To address the issue, this study used a highly novel design thinking approach to provide the context and a lived experience perspective of the end user, thus allowing for a deeper level of understanding. Methods In total, 7 young women (mean age 25.83, SD 5.34, range 21-33 years) who self-identified as having a history of body image issues or eating disorders were recruited. Participants were interviewed about their lived experience of body image and eating disorders and reported their needs and preferences for app-based eating disorder interventions. Traditional (thematic analysis) and novel (empathy mapping; visually depicting and empathizing with the user’s personal experience) analyses were performed, providing a lived experience perspective of eating disorders and identifying the needs and preferences of this population in relation to app-based interventions for eating disorders. Key challenges and opportunities for app-based eating disorder interventions were also identified. Results Findings highlighted the importance of understanding and identifying problematic eating disorder symptoms for the user, helpful practices for recovery that identify personal values and goals, the role of social support in facilitating hope, and aspects of usability to promote continued engagement and recovery. Conclusions Practical guidance and recommendations are described for those developing app-based eating disorder interventions. These findings have the potential to inform practices to enhance participant uptake and retention in the context of app-based interventions for this population.
Counterfactual curiosity: motivated thinking about what might have been
2022-10-31

Counterfactual information, information about what might have been, forms the content of counterfactual thoughts and emotions like regret and relief. Recent research suggests that human adults and children, as well as rhesus monkeys, demonstrate ‘counterfactual curiosity’: they are motivated to seek out counterfactual information after making decisions. Based on contemporary theories of curiosity and information seeking and a broad range of empirical literature, we suggest multiple heterogeneous psychological processes that contribute to people's motivation for counterfactual information. This includes processes that are identified in the curiosity literature more generally—the potential use of counterfactual information for adaptive decision making (its long-term instrumental value) and the drive to reduce uncertainty. Additionally, we suggest that counterfactual information may be particularly alluring because of its role in causal reasoning; its relationship with prediction and decision making; and its potential to fulfil emotion regulation and self-serving goals. Some future directions have been suggested, including investigating the role of individual differences in counterfactual curiosity on learning and wellbeing. This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.
The influence of reward in the Simon task: Differences and similarities to the Stroop and Eriksen flanker tasks
2022-10-31

Abstract Previous studies have suggested that performance-contingent reward can modulate cognitive control by biasing irrelevant location-response associations in the Simon task. However, the influence of reward in the case of irrelevant words (Stroop task) or irrelevant flankers (Eriksen Flanker task) remains unclear. Across two preregistered experiments, the present study investigated the influence of reward on conflict processing with different types of distractors. Conflict effects on mean reaction time (RT) were reduced in the Simon task (Experiments 1 and 2) when incongruent versus congruent trials were rewarded, and this modulating effect of reward on conflict processing was also observed in the Eriksen flanker task (Experiment 2), but not in the Stroop task (Experiment 1). We propose that cognitive control adjustments to distractor-specific reward contingencies can be generalized across distractor types producing both perceptual-related (Flanker task) and motor-related (Simon task) conflict, but, if any, to a limited degree when distractors produce additional higher-level task conflict (Stroop task). In addition, distributional RT analyses (delta plots) revealed that rewarded distractor-response associations modulate cognitive control not only via biasing the strength (Simon and Eriksen tasks) but also the time-course of suppressing distractor processing (Eriksen task). Overall, the present study dissociated distractor-general and distractor-specific effects of reward on cognitive control.
The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15
2022-10-31

Abstract In the field of hereditary spastic paraplegia (HSP), progress in molecular diagnostics needs to be translated into robust phenotyping studies to understand genetic and phenotypic heterogeneity and to support interventional trials. ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26, SPG15) is a rare, early-onset complex HSP, characterized by progressive spasticity and a variety of other neurological symptoms. While prior reports, often in populations with high rates of consanguinity, have established a general phenotype, there is a lack of systematic investigations and a limited understanding of age-dependent manifestation of symptoms. Here we delineate the clinical, neuroimaging and molecular features of 44 individuals from 36 families, the largest cohort assembled to date. Median age at last follow-up was 23.8 years covering a wide age range (11–61 years). While symptom onset often occurred in early childhood [median: 24 months, interquartile range (IQR) = 24], a molecular diagnosis was reached at a median age of 18.8 years (IQR = 8), indicating significant diagnostic delay. We demonstrate that most patients present with motor and/or speech delay or learning disabilities. Importantly, these developmental symptoms preceded the onset of motor symptoms by several years. Progressive spasticity in the lower extremities, the hallmark feature of HSP-ZFYVE26, typically presents in adolescence and involves the distal lower limbs before progressing proximally. Spasticity in the upper extremities was seen in 64%. We found a high prevalence of extrapyramidal movement disorders including cerebellar ataxia (64%) and dystonia (11%). Parkinsonism (16%) was present in a subset and showed no sustained response to levodopa. Cognitive decline and neurogenic bladder dysfunction progressed over time in most patients. A systematic analysis of brain MRI features revealed a common diagnostic signature consisting of thinning of the anterior corpus callosum, signal changes of the anterior forceps and non-specific cortical and cerebellar atrophy. The molecular spectrum included 45 distinct variants, distributed across the protein structure without mutational hotspots. Spastic Paraplegia Rating Scale scores, SPATAX Disability Scores and the Four Stage Functional Mobility Score showed moderate strength in representing the proportion of variation between disease duration and motor dysfunction. Plasma neurofilament light chain levels were significantly elevated in all patients (Mann–Whitney U-test, P &amp;lt; 0.0001) and were correlated inversely with age (Spearman’s rank correlation coefficient r = −0.65, P = 0.01). In summary, our systematic cross-sectional analysis of HSP-ZFYVE26 patients across a wide age-range, delineates core clinical, neuroimaging and molecular features and identifies markers of disease severity. These results raise awareness to this rare disease, facilitate an early diagnosis and create clinical trial readiness.
Non-invasive brain-spine interface: Continuous control of trans-spinal magnetic stimulation using EEG
2022-10-31

Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery in patients with motor disorders. Brain-machine interfaces exploit this neuromodulatory strategy and could be used for restoring voluntary control of lower limbs. In this work, we propose a non-invasive brain-spine interface (BSI) that processes electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS), as an approach for lower-limb neurorehabilitation. This novel platform allows to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. We tested this closed-loop system in 10 healthy participants using different stimulation conditions. This BSI efficiently removed stimulation artifacts from EEG regardless of ts-MS intensity used, allowing continuous monitoring of cortical activity and real-time closed-loop control of ts-MS. Our BSI induced afferent and efferent evoked responses, being this activation ts-MS intensity-dependent. We demonstrated the feasibility, safety and usability of this non-invasive BSI. The presented system represents a novel non-invasive means of brain-controlled neuromodulation and opens the door towards its integration as a therapeutic tool for lower-limb rehabilitation.
The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells
2022-10-31

Neurons critically depend on regulated RNA localization and tight control of spatiotemporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause hereditary spastic paraplegia, an autosomal recessive disease leading to predominant degeneration of the long axons of central motoneurons. In this study, we aimed to gain insight into the molecular function of KIF1C and understand how KIF1C dysfunction contributes to motoneuron degeneration. We used affinity proteomics in neuronally differentiated neuroblastoma cells (SH-SY5Y) to identify the protein complex associated with KIF1C in neuronal cells; candidate interactions were then validated by immunoprecipitation, and mislocalization of putative KIF1C cargoes was studied by immunostainings. We found KIF1C to interact with all core components of the exon junction complex (EJC); expression of mutant KIF1C in neuronal cells leads to loss of the typical localization distally in neurites. Instead, EJC core components accumulate in the pericentrosomal region, here colocalizing with mutant KIF1C. These findings suggest KIF1C as a neuronal transporter of the EJC. Interestingly, the binding of KIF1C to the EJC is RNA-mediated, as treatment with RNase prior to immunoprecipitation almost completely abolishes the interaction. Silica-based solid-phase extraction of UV-cross-linked RNA–protein complexes furthermore supports direct interaction of KIF1C with RNA, as recently also demonstrated for kinesin heavy chain. Taken together, our findings are consistent with a model where KIF1C transports mRNA in an EJC-bound and therefore transcriptionally silenced state along neurites, thus providing the missing link between the EJC and mRNA localization in neurons.
Children’s spatial language skills predict their verbal number skills: A longitudinal study
2022-10-31

The process of number symbolization is assumed to be critically influenced by the acquisition of so-called verbal number skills (e.g., verbally reciting the number chain and naming Arabic numerals). For the acquisition of these verbal number skills, verbal and visuospatial skills are discussed as contributing factors. In this context, children’s verbal number skills have been found to be associated with their concurrent spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind). In a longitudinal study with three measurement times (T1, T2, T3) at an interval of about 6 months, we evaluated the predictive role of preschool children’s (mean age at T1: 3 years and 10 months) spatial language skills for the acquisition of verbal number skills. Children’s spatial language skills at T2 significantly predicted their verbal number skills at T3, when controlling for influences of important covariates such as vocabulary knowledge. In addition, further analyses replicated previous results indicating that children’s spatial language skills at T2 were associated with their verbal number skills at T2. Exploratory analyses further revealed that children’s verbal number skills at T1 predict their spatial language at T2. Results suggests that better spatial language skills at the age of 4 years facilitate the future acquisition of verbal number skills.
Recurrence Score® Result Impacts Treatment Decisions in Hormone Receptor-Positive, HER2-Negative Patients with Early Breast Cancer in a Real-World Setting—Results of the IRMA Trial
2022-10-31

Background: Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DX® test were developed to reduce over- and undertreatment. The IRMA trial analyzed the impact of Recurrence Score® (RS) assessment on adjuvant treatment recommendations. Materials and methods: The RS result was assessed in patients with HR+/HER2− unilateral eBC with 0–3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women’s Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result. Results: In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially. Summary: Using the RS result to guide adjuvant treatment decisions in HR+/HER2− breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.
Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations
2022-10-31

Abstract Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
Effectiveness of antimalarial drug combinations in treating concomitant urogenital schistosomiasis in malaria patients in Lambaréné, Gabon: A non-randomised event-monitoring study
2022-10-31

Background Urogenital schistosomiasis is prevalent in many malaria endemic regions of sub-Saharan Africa and can lead to long-term health consequences if untreated. Antimalarial drugs used to treat uncomplicated malaria have shown to exert some activity against Schistosoma haematobium . Here, we explore the efficacy on concomitant urogenital schistosomiasis of first-line recommended artemisinin-based combination therapies (ACTs) and investigational second-generation ACTs when administered for the treatment of uncomplicated malaria in Gabon. Methods Microscopic determination of urogenital schistosomiasis was performed from urine samples collected from patients with confirmed uncomplicated malaria. Egg excretion reduction rate and cure rate were determined at 4-weeks and 6-weeks post-treatment with either artesunate-pyronaridine, artemether-lumefantrine, artesunate-amodiaquine or artefenomel-ferroquine. Results Fifty-two (16%) out of 322 malaria patients were co-infected with urogenital schistosomiasis and were treated with antimalarial drug combinations. Schistosoma haematobium egg excretion rates showed a median reduction of 100% (interquartile range (IQR), 17% to 100%) and 65% (IQR, -133% to 100%) at 4-weeks and 6-weeks post-treatment, respectively, in the artesunate-pyronaridine group (n = 20) compared to 35% (IQR, −250% to 70%) and 65% (IQR, -65% to 79%) in the artemether-lumefantrine group (n = 18). Artesunate-amodiaquine (n = 2) and artefenomel-ferroquine combination (n = 3) were not able to reduce the rate of eggs excreted in this limited number of patients. In addition, cure rates were 56% and 37% at 4- and 6-weeks post-treatment, respectively, with artesunate-pyronaridine and no cases of cure were observed for the other antimalarial combinations. Conclusions Antimalarial treatments with artesunate-pyronaridine and artemether-lumefantrine reduced the excretion of S . haematobium eggs, comforting the hypothesis that antimalarial drugs could play a role in the control of schistosomiasis. Trial Registration This trial is registered with clinicaltrials.gov, under the Identifier NCT04264130 .
Endometriosis in Patients with Mayer-Rokitansky-Küster-Hauser-Syndrome—Histological Evaluation of Uterus Remnants and Peritoneal Lesions and Comparison to Samples from Endometriosis Patients without Mullerian Anomaly
2022-10-31

Congenital Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a Mullerian-duct anomaly that is characterized by agenesis of the uterus and upper part of the vagina. Uterus remnants of varying sizes can often be found. Although a functional uterus is missing, the existence of endometriosis in this patient group has been described in the literature; however, a histopathological comparison of the characteristics of the endometrium within the uterus remnants versus endometriotic peritoneal lesions in the same patient is lacking. Moreover, the characteristics of endometriotic tissue in patients with MRKH syndrome have not been correlated with those of patients with endometriosis without Mullerian anomaly. Patients who underwent laparoscopic neovagina creation with the removal of uterus remnants and possible resection of endometriotic lesions between 2010 and 2022 at the Department of Women’s health of the University of Tuebingen were included in our study. Uterine remnants and endometriotic tissue were evaluated via histopathology and immunohistochemistry and were compared to endometriotic samples from patients without Mullerian anomaly. Endometriosis was detected in nine MRKH patients; in four patients, endometrial remnants could be sufficiently compared to endometriotic lesions. All samples exhibited increased expression of hormonal receptors. In two patients, Ki67 proliferation index was significantly increased in peritoneal endometriotic lesions compared with the endometrium of the remnants. In contrast, endometrium and endometriotic lesions of endometriosis patients did not exhibit any differences in the Ki67 proliferation index. Our results demonstrate distinctive immunohistochemical variability between uterine remnants and endometriotic lesions in patients with MRKH syndrome compared with patients with endometriosis, indicating a possible explanation model of the yet-unknown etiology of endometriosis. For confirmation, investigation of a broader patient collective is necessary.