julilili42/papers huggingface dataset:
Prevalence, intensity and associated risk factors of soil-transmitted helminth infections among individuals living in Bata district, Equatorial Guinea
2023-05-17

Background Soil transmitted Helminths (STH) infections remain a public health concern worldwide, particularly in tropical and subtropical areas where these diseases are highly endemic. Knowing the prevalence and risk factors of the disease is crucial for efficient STH control strategies in endemic areas. The scarcity of epidemiological data on STH for Equatorial Guinea has motivated the decision to perform the present study. Methods A cluster-based cross-sectional study was carried out in Bata district from November 2020 to January 2021. Stool samples were collected for the diagnostic of STH infections using Kato-Katz technique. Descriptive statistics was performed for determination of STH prevalence and intensity, while logistic regression models were used to assess the risk factors associated with STH infections. Results A total of 340 participants were included in the study with a mean age of 24 years (SD = 23.7) and 1.2 female-to-male sex-ratio. The overall prevalence of any STH was 60% (95%CI: 55–65). The most prevalent species were Ascaris lumbricoides (43%, 95%CI: 37–48) and Trichuris trichiura (40%, 95%CI: 35–46). Intensity of infection were mainly light to moderate. A trend of association was observed between age and any STH infection (overall p-value = 0.07), with a significant difference observed between children aged 5–14 years as compared to those aged 1–4 (aOR 2.12; 95%CI: 1.02–4.43, p-value = 0.04), while locality was significantly associated with STH infection (overall p-value &lt;0.001) with a higher odds observed for peri-urban area as compared to urban area (aOR 4.57; 95%CI: 2.27–9.60, p-value &lt;0.001). Conclusion Bata district is a high STH transmission area, where school-aged children and peri-urban areas are associated with a higher risk of any STH infection. This situation calls for a full implementation of the WHO recommendations for STH control; mass drug administration of anthelminthic twice a year to the whole population with great attention to school age children, and prioritizing peri-urban areas where safe water, improve sanitation, and hygiene education should be implemented to achieve a better control.
Genetic and Clinical Profile of Retinopathies Due to Disease-Causing Variants in Leber Congenital Amaurosis (LCA)-Associated Genes in a Large German Cohort
2023-05-17

To report the spectrum of Leber congenital amaurosis (LCA) associated genes in a large German cohort and to delineate their associated phenotype. Local databases were screened for patients with a clinical diagnosis of LCA and for patients with disease-causing variants in known LCA-associated genes independent of their clinical diagnosis. Patients with a mere clinical diagnosis were invited for genetic testing. Genomic DNA was either analyzed in a diagnostic-genetic or research setup using various capture panels for syndromic and non-syndromic IRD (inherited retinal dystrophy) genes. Clinical data was obtained mainly retrospectively. Patients with genetic and phenotypic information were eventually included. Descriptive statistical data analysis was performed. A total of 105 patients (53 female, 52 male, age 3–76 years at the time of data collection) with disease-causing variants in 16 LCA-associated genes were included. The genetic spectrum displayed variants in the following genes: CEP290 (21%), CRB1 (21%), RPE65 (14%), RDH12 (13%), AIPL1 (6%), TULP1 (6%), and IQCB1 (5%), and few cases harbored pathogenic variants in LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5, and RD3 (altogether accounting for 14%). The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen (cone-rod dystrophy, 5%; congenital stationary night blindness, 2%). Among LCA patients, 50% were caused by variants in CEP290 (29%) and RPE65 (21%), whereas variants in other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, and RDH12 7%, and sporadically LRAT, NMNAT1, CRX, RD3, and RPGRIP1). In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, concentric narrowing of the visual field, and extinguished electroretinograms. However, there were also exceptional cases with best corrected visual acuity as high as 0.8 (Snellen), well-preserved visual fields, and preserved photoreceptors in spectral domain optical coherence tomography. Phenotypic variability was seen between and within genetic subgroups. The study we are presenting pertains to a considerable LCA group, furnishing valuable comprehension of the genetic and phenotypic spectrum. This knowledge holds significance for impending gene therapeutic trials. In this German cohort, CEP290 and CRB1 are the most frequently mutated genes. However, LCA is genetically highly heterogeneous and exhibits clinical variability, showing overlap with other IRDs. For any therapeutic gene intervention, the disease-causing genotype is the primary criterion for treatment access, but the clinical diagnosis, state of the retina, number of to be treated target cells, and the time point of treatment will be crucial.
The Origin of Ultramafic Complexes with Melilitolites and Carbonatites: A Petrological Comparison of the Gardiner (E Greenland) and Kovdor (Russia) Intrusions
2023-05-17

Abstract In many alkaline complexes, large amounts of ultramafic rocks occur together with carbonatites, melilitolites and other alkaline silicate rocks. There is an ongoing debate if and how these contrasting lithologies were formed by differentiation of a common, mantle-derived silicate magma or rather by metasomatic processes between carbonatite and country rocks. In order to find petrological evidence for one or the other, two key examples, the Gardiner (E Greenland) and Kovdor (Russia) complexes are compared in this study. Despite their similar tectonic setting and succession of rock types, they show significant differences in the texture and mineral composition of ultramafic rocks. Ultramafic rocks from Kovdor include calcite- and biotite-rich dunites and pyroxenites without typical cumulate textures. They consist of Ni-poor forsterite, Cr-poor diopside and Ni-Cr-poor spinel and are possibly metasomatic reaction products between mantle-derived carbonatite melts and silicic host rocks. Similar ultramafic rocks are associated with carbonatites e. g. at Palabora (South Africa), Afrikanda (Russia), and Salitre (Brazil). In contrast, the ultramafic rocks from Gardiner show well-preserved cumulate textures and consist of Ni-rich forsterite, Cr-rich diopside as well as Cr-Ni-Ti-rich spinel and also contain F-Cl-rich apatite. They record an increase in aSiO2 from dunite to pyroxenite at similar fO2 (ΔFMQ ~ +1.2, with FMQ = fayalite-magnetite-quartz buffer), indicating that these rocks represent cumulates of an evolving, moderately oxidized mafic melt derived from a Ti-rich mantle source, similar to other rocks of the North Atlantic igneous province. In contrast to systems like Kovdor where carbonatite metasomatism is likely dominant, Ti-rich parental silicate magmas can abundantly crystallize Ti phases, as recorded by massive perovskite cumulates in Gardiner melilitolites. This can effectively scavenge HFSE from the magmatic system early in its evolution and likely explains HFSE-barren carbonatites at Gardiner, while those from Kovdor are highly HFSE-enriched. In summary, the results of our study provide strong textural and mineral chemical evidence that ultramafic rocks in alkaline complexes can be of both cumulate and metasomatic origin; the specific type has an important bearing on their HFSE enrichment and on the types of ores present in such complexes.
Fano Resonances in Plasmonic Ring‐Disc‐Pair Systems
2023-05-17

Fano resonances in plasmonic nanostructures, generated by the spectral interference between a broad resonance or continuum and a narrow resonance, have attracted significant interest in recent literature. Herein, by introducing a nanodisc next to a nanoring via electron beam lithography, a set of Fano resonances for such a ring‐disc‐pair (RDP) hybrid is confirmed through coupling between the dipolar disc mode and different multipolar bonding ring modes. Furthermore, the influence of the RDP's geometric dimensions on the dark‐field scattering spectra is experimentally studied, indicating that the contrast ratio of Fano resonances can be improved by optimizing the ring/disc sizes and narrowing the gap in accordance with previous studies. The disc size can also control the spectral locations of these Fano peaks ranging from the visible to the near‐infrared regime. In addition, by comparing the Fano resonances among a series of ring/split‐ring/rod structures with varying curvatures coupled to a neighboring disc in simulations, it is demonstrated that the RDP presents stronger sensitivity for the same gap distance and shows high‐quality Fano resonances compared with more common disc‐inside‐ring cavities in literature.
Exploring the Effects of Scanpath Feature Engineering for Supervised Image Classification Models
2023-05-17

Image classification models are becoming a popular method of analysis for scanpath classification. To implement these models, gaze data must first be reconfigured into a 2D image. However, this step gets relatively little attention in the literature as focus is mostly placed on model configuration. As standard model architectures have become more accessible to the wider eye-tracking community, we highlight the importance of carefully choosing feature representations within scanpath images as they may heavily affect classification accuracy. To illustrate this point, we create thirteen sets of scanpath designs incorporating different eye-tracking feature representations from data recorded during a task-based viewing experiment. We evaluate each scanpath design by passing the sets of images through a standard pre-trained deep learning model as well as a SVM image classifier. Results from our primary experiment show an average accuracy improvement of 25 percentage points between the best-performing set and one baseline set.
Publishing protocols as a new PI
2023-05-17

Effie Bastounis recently started a lab at the University of Tübingen that studies how physical forces guide the interactions of host cells with bacterial pathogens. Former STAR Protocols Lead editor Shawnna Buttery discussed with Effie her experience publishing research at Cell Press journals and how that led to her publishing in STAR Protocols. Effie also shared her thoughts on the usefulness of protocols journals and the importance of protocols to a new PI. For more information on the protocols related to this backstory, please refer to Muenkel et al.<sup>1</sup> and Bastounis et al.<sup>2</sup>.
USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer
2023-05-18

Abstract SREBP2 is a master regulator of the mevalonate pathway (MVP), a biosynthetic process that drives the synthesis of dolichol, heme A, ubiquinone and cholesterol and also provides substrates for protein prenylation. Here, we identify SREBP2 as a novel substrate for USP28, a deubiquitinating enzyme that is frequently upregulated in squamous cancers. Our results show that silencing of USP28 reduces expression of MVP enzymes and lowers metabolic flux into this pathway. We also show that USP28 binds to mature SREBP2, leading to its deubiquitination and stabilisation. USP28 depletion rendered cancer cells highly sensitive to MVP inhibition by statins, which was rescued by the addition of geranyl-geranyl pyrophosphate. Analysis of human tissue microarrays revealed elevated expression of USP28, SREBP2 and MVP enzymes in lung squamous cell carcinoma (LSCC) compared to lung adenocarcinoma (LADC). Moreover, CRISPR/Cas-mediated deletion of SREBP2 selectively attenuated tumour growth in a KRas/p53/LKB1 mutant mouse model of lung cancer. Finally, we demonstrate that statins synergise with a dual USP28/25 inhibitor to reduce viability of SCC cells. Our findings suggest that combinatorial targeting of MVP and USP28 could be a therapeutic strategy for the treatment of squamous cell carcinomas.
Alignment of magnetic sensing and clinical magnetomyography
2023-05-18

Neuromuscular diseases are a prevalent cause of prolonged and severe suffering for patients, and with the global population aging, it is increasingly becoming a pressing concern. To assess muscle activity in NMDs, clinicians and researchers typically use electromyography (EMG), which can be either non-invasive using surface EMG, or invasive through needle EMG. Surface EMG signals have a low spatial resolution, and while the needle EMG provides a higher resolution, it can be painful for the patients, with an additional risk of infection. The pain associated with the needle EMG can pose a risk for certain patient groups, such as children. For example, children with spinal muscular atrophy (type of NMD) require regular monitoring of treatment efficacy through needle EMG; however, due to the pain caused by the procedure, clinicians often rely on a clinical assessment rather than needle EMG. Magnetomyography (MMG), the magnetic counterpart of the EMG, measures muscle activity non-invasively using magnetic signals. With super-resolution capabilities, MMG has the potential to improve spatial resolution and, in the meantime, address the limitations of EMG. This article discusses the challenges in developing magnetic sensors for MMG, including sensor design and technology advancements that allow for more specific recordings, targeting of individual motor units, and reduction of magnetic noise. In addition, we cover the motor unit behavior and activation pattern, an overview of magnetic sensing technologies, and evaluations of wearable, non-invasive magnetic sensors for MMG.
Doubly Constrained C-terminal of Roc (COR) Domain-Derived Peptides Inhibit Leucine-Rich Repeat Kinase 2 (LRRK2) Dimerization
2023-05-18

Missense mutations along the leucine-rich repeat kinase 2 (LRRK2) protein are a major contributor to Parkinson's Disease (PD), the second most commonly occurring neurodegenerative disorder worldwide. We recently reported the development of allosteric constrained peptide inhibitors that target and downregulate LRRK2 activity through disruption of LRRK2 dimerization. In this study, we designed doubly constrained peptides with the objective of inhibiting C-terminal of Roc (COR)-COR mediated dimerization at the LRRK2 dimer interface. We show that the doubly constrained peptides are cell-permeant, bind wild-type and pathogenic LRRK2, inhibit LRRK2 dimerization and kinase activity, and inhibit LRRK2-mediated neuronal apoptosis, and in contrast to ATP-competitive LRRK2 kinase inhibitors, they do not induce the mislocalization of LRRK2 to skein-like structures in cells. This work highlights the significance of COR-mediated dimerization in LRRK2 activity while also highlighting the use of doubly constrained peptides to stabilize discrete secondary structural folds within a peptide sequence.
Peritoneal regression grading score (PRGS): first evidence for independent predictive and prognostic significance
2023-05-18

Abstract Objectives The peritoneal regression grading score (PRGS) is a four-tied pathologic score measuring tumor regression in biopsies from patients with peritoneal metastasis (PM) receiving chemotherapy. Methods This retrospective analysis of a prospective registry (NCT03210298) analyses 97 patients with isolated PM under palliative chemotherapy. We examined the predictive value of the initial PRGS for overall survival (OS) and the prognostic value of PRGS in repeated peritoneal biopsies. Results The 36 (37.1 %) patients with an initial mean PRGS≤2 had a longer median OS (12.1 months, CI 95 % 7.8–16.4) vs. 8.0 months (CI 95 % 5.1–10.8 months) in 61 (62.9 %) patients with PRGS≥3 (p=0.02) After stratification, the initial PRGS was an independent predictor of OS (Cox-regression, p&lt;0.05). Out of 62 patients receiving≥two chemotherapy cycles, 42 (67.7 %) had a histological response (defined as a lower or stable mean PRGS in successive therapy cycles), and 20 (32.3 %) progressed (defined as an increasing mean PRGS). PRGS response was associated with a longer median OS (14.6 months, CI 5–95 % 6.0–23.2) vs. 6.9 (CI 5–95 % 0.0–15.9) months. PRGS response was prognostic in the univariate analysis (p=0.017). Thus, PRGS had both a predictive and prognostic significance in patients with isolated PM receiving palliative chemotherapy in this patient cohort. Conclusions This is the first evidence for the independent predictive and prognostic significance of PRGS in PM. These encouraging results need validation in an adequately powered, prospective study.
Heart Rate Variability and Perceived Stress in Teacher Training: Facing the Reality Shock With Mindfulness?
2023-05-18

Background The beginning of the career of teachers is a demanding phase. In the combined roles of teacher and trainee, and in the shift from academic to practical learning, trainee teachers have to acquire competencies in teaching as well as coping with stress. In this phase, the phenomenon of “reality shock” is widely observed. Objective A mindfulness training was developed to support teacher trainees during their first year. This intervention study investigated perceived and physiological stress at teachers’ career start and the stress reducing effects of the mindfulness training in this phase. Methods In a quasi-experimental design, 19 out of 42 participants from this sample underwent mindfulness-based stress reduction training and a wait-list control group (N = 23) underwent a compact course after post measurements. We measured physiological stress parameters and perceived stress at 3 different time points. Heart rate signals were acquired in ambulatory assessment sequences, including teaching, rest periods, and cognitive tasks. The data were analyzed in linear mixed-effects models. Results We found high physiological stress in the very beginning of teacher training, which attenuated over time. The mindfulness intervention only led to a greater reduction in heart rate ( d = .53 to .74) in situations where the intervention group had shown higher heart rate levels initially, but not in heart rate variability. However, the mindfulness group significantly reduced ( d = .63) their perceived stress and maintained ( d = .55) this improvement, while the control group maintained a highly elevated perceived stress level throughout. Conclusion The mindfulness training could reduce subjective stress, which otherwise seems to be a long-lasting aspect of beginning teachers’ “reality shock”. Indications of a superior reduction of physiological stress in demanding situations were weak, while generally, undue physiological stress seems to be a temporary phenomenon in the initial phase of teacher induction.
Accelerating Transformer Inference for Translation via Parallel Decoding
2023-05-18

Autoregressive decoding limits the efficiency of transformers for Machine Translation (MT). The community proposed specific network architectures and learning-based methods to solve this issue, which are expensive and require changes to the MT model, trading inference speed at the cost of the translation quality. In this paper, we propose to address the problem from the point of view of decoding algorithms, as a less explored but rather compelling direction. We propose to reframe the standard greedy autoregressive decoding of MT with a parallel formulation leveraging Jacobi and Gauss-Seidel fixed-point iteration methods for fast inference. This formulation allows to speed up existing models without training or modifications while retaining translation quality. We present three parallel decoding algorithms and test them on different languages and models showing how the parallelization introduces a speedup up to 38% w.r.t. the standard autoregressive decoding and nearly 2x when scaling the method on parallel resources. Finally, we introduce a decoding dependency graph visualizer (DDGviz) that let us see how the model has learned the conditional dependence between tokens and inspect the decoding procedure.
Selective Inhibitors of Janus Kinase 3 Modify Responses to Lipopolysaccharides by Increasing the Interleukin-10-to-Tumor Necrosis Factor α Ratio
2023-05-18

Janus kinase (JAK) inhibitors act at low doses (<i>e.g</i>., tofacitinib, 0.2-0.4 μmol/kg bid) in clinical use, suggesting an efficient underlying mode of action. We hypothesized that their effectiveness is due to their ability to raise the ratio of IL-10 to TNFα. Unlike other JAK isoforms, JAK3 is expressed mainly in hematopoietic cells and is essential for immune function. We used JAK3 selective inhibitors with preferential distribution to immune cells. Inhibition of JAK3 in human leukocytes reduced TNFα and IL-6 but maintained levels of IL-10, while pan-JAK inhibitors increased TNFα, IL-6, and IL-10. JAK1 is required for IL-10 receptor signaling, which suggests that, at exposure above the IC<sub>50</sub> (55 nM for tofacitinib on JAK1), there is less feedback control of TNFα levels. This leads to self-limiting effects of JAK1 inhibitors and could place an upper limit on appropriate doses. <i>In vivo</i>, treating mice with JAK3 inhibitors before LPS administration decreased plasma TNFα and increased IL-10 above vehicle levels, suggesting that JAK3 inhibition may limit TNFα release by increasing IL-10 while leaving the IL-10 receptor functional. This mechanism should have general utility in controlling autoimmune diseases and can be conveniently observed by measuring the ratio of IL-10 to TNFα. In summary, our targeted, "leukotropic" inhibitors more effectively increased IL-10/TNFα ratios than unselective control compounds and could, therefore, be ideal for autoimmune therapy.
Implementing Remote Patient Monitoring for Patients During Systemic Cancer Therapy
2023-05-18

Mobile monitoring of outpatients during cancer therapy becomes possible through technological advancements. This study leveraged a new remote patient monitoring app for in-between systemic therapy sessions. Patients’ evaluation showed that the handling is feasible. Clinical implementation must consider an adaptive development cycle for reliable operations.
Cross-Registry Benchmarking of Data Quality: Lessons Learned
2023-05-18

Feedback of data quality measures to study sites is an established procedure in the management of registries. Comparisons of data quality between registries as a whole are missing. We implemented a cross-registry benchmarking of data quality within the field of health services research for six projects. Five (2020) and six (2021) quality indicators were selected from a national recommendation. The calculation of the indicators was adjusted to the registries’ specific settings. Nineteen (2020) and 29 results (2021) could be included in the yearly quality report. Seventy-four per cent (2020) and 79% (2021) of the results did not include the threshold in their 95%-confidence-limits. The benchmarking revealed several starting points for a weak-point analysis through a comparison of results with a predefined threshold as well as through comparisons among each other. In the future, a cross-registry benchmarking might be part of services provided through a health services research infrastructure.
Modeling Clinical Guidelines for an Epilepsy-CDSS: The EDiTh Project
2023-05-18

The knowledge transformation process involves the guideline for the diagnosis and therapy of epilepsy to an executable and computable knowledge base that serves as the basis for a decision-support system. We present a transparent knowledge representation model which facilitates technical implementation and verification. Knowledge is represented in a plain table, used in the frontend code of the software where simple reasoning is performed. The simple structure is sufficient and comprehensible also for non-technical persons (i.e., clinicians).