julilili42/papers huggingface dataset:
A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies
2022-05-16

Abstract Objectives To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses. Methods We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures. Results Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies. Conclusions In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.
Paleoclimatic and paleoenvironmental reconstructions based on the small vertebrates from the Middle Paleolithic of Hohle Fels Cave, SW Germany
2022-05-16

Abstract In this paper, we analyse the fish and small mammal assemblages from the Middle Paleolithic horizons of Hohle Fels Cave to reconstruct the paleoclimatic and paleoenvironmental conditions faced by the Neanderthal groups who occupied the site. The fish assemblage indicates that the freshwater ecosystem around this site was characterized by a pre-mountain river system with the presence of permanent, oxygen-rich, and cold running waters. The results of the Habitat Weighting Method and the Bioclimatic Model applied to the small mammal assemblage, coupled with the new dates obtained for the Archaeological Horizon (AH) IX, allow us to identify two different climatic phases. One phase (AH X-XII) is more temperate possibly corresponding to the end of Marine Isotope Stage (MIS) 5; the other (AH VI-IX) is colder and more arid corresponding to the end of MIS 4 through the beginning of MIS 3. Open environments with a relatively stable forest component dominated the landscape during this part of the Middle Paleolithic. These two climatic phases appear to correspond to different levels of occupational intensity by Neanderthals, with higher occupational intensity during mild climatic periods and lower intensity during cold, arid periods. Our climatic reconstruction and recent absolute dating, together with the recovery of a complete leaf point near the top of AH X, have important implications for the cultural stratigraphy and cultural chronology of the region. Archaeologist have traditionally viewed leaf points as key artefacts of the Blattspitzengruppe , a cultural complex attributed to the end of Middle Paleolithic; however, this stratigraphic, climatic, and chronological context indicates the need to revise this interpretation.
MR-double-zero – Proof-of-concept for a framework to autonomously discover MRI contrasts
2022-05-16

New MR contrasts for mapping a given target can be discovered by derivative-free optimization of parametrized sequences that are directly executed on a real MRI scanner. This is demonstrated by 're-discovery' of a chemical exchange weighted sequence. The proposed method is considered to be a paradigm shift towards autonomous, model-free and target-driven sequence design.
Classification of Patient Portals Described in Evaluation Studies Using the TOPCOP Taxonomy
2022-05-16

Many patient portals have been introduced and evaluated in recent years. The results of evaluation studies are difficult to compare, however, as the evaluated patient portal is often not clearly or only incompletely described in the publication. This problem is common to evaluations in health informatics. We evaluated the completeness of descriptions of patient portals in 15 exemplary evaluation publications using the TOPCOP taxonomy. Our results show that core functionalities such as portal design, patient communication, educational features, or system notifications were quite clearly described in all 15 evaluation studies. Other descriptions, such as web accessibility or data management, were often not provided. We conclude that taxonomies such as TOPCOP should be used and even required for describing interventions in evaluation papers.
Autosomal dominant and sporadic late onset Alzheimer's disease share a commonin vivopathophysiology
2022-05-17

Abstract The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of ‘sporadic’ late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer’s Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct.
Population Genetics and Signatures of Selection in Early Neolithic European Farmers
2022-05-17

Abstract Human expansion in the course of the Neolithic transition in western Eurasia has been one of the major topics in ancient DNA research in the last 10 years. Multiple studies have shown that the spread of agriculture and animal husbandry from the Near East across Europe was accompanied by large-scale human expansions. Moreover, changes in subsistence and migration associated with the Neolithic transition have been hypothesized to involve genetic adaptation. Here, we present high quality genome-wide data from the Linear Pottery Culture site Derenburg-Meerenstieg II (DER) (N = 32 individuals) in Central Germany. Population genetic analyses show that the DER individuals carried predominantly Anatolian Neolithic-like ancestry and a very limited degree of local hunter-gatherer admixture, similar to other early European farmers. Increasing the Linear Pottery culture cohort size to ∼100 individuals allowed us to perform various frequency- and haplotype-based analyses to investigate signatures of selection associated with changes following the adoption of the Neolithic lifestyle. In addition, we developed a new method called Admixture-informed Maximum-likelihood Estimation for Selection Scans that allowed us test for selection signatures in an admixture-aware fashion. Focusing on the intersection of results from these selection scans, we identified various loci associated with immune function (JAK1, HLA-DQB1) and metabolism (LMF1, LEPR, SORBS1), as well as skin color (SLC24A5, CD82) and folate synthesis (MTHFR, NBPF3). Our findings shed light on the evolutionary pressures, such as infectious disease and changing diet, that were faced by the early farmers of Western Eurasia.
First experiences of integrating computational thinking into a blended learning in‐service training program for STEM teachers
2022-05-17

Abstract Over the last two decades, computational thinking (CT) has gained importance in discussions about competencies that students require to deal with complex problems in a world shaped by digitalization. Therefore, schools and teachers should integrate CT into their instructional practices. Particularly, the STEM (Science, Technology, Engineering, and Mathematics) subjects are seen as a meaningful context for embedding CT. Yet, there are only a few professional development programs that address STEM teachers and how to integrate CT. Thus, in our study, we redesigned an in‐service teacher training program. The redesigned program was offered in a blended‐learning format, consisting of alternating digital and face‐to‐face phases. As part of the digital phases, an interactive online self‐learning module on CT was introduced to foster transdisciplinary competencies in the field of STEM to solve complex problems. To identify the perceptions and development of the participants of the training program and the online module on CT a within‐subject design was used with a questionnaire survey, conducted with a pre‐post‐follow‐up design. The first results of the ongoing survey indicate high satisfaction with both the program itself and the online CT module. At the beginning of the program, about two‐thirds of the participating teachers were completely unfamiliar with the term CT, nevertheless, interest in the new topic was high. It was shown the program was able to create initial awareness of the meaning and importance of CT. In addition, teachers who have engaged with CT during the intervention seem to use CT‐related practices more often in the classroom afterward.
What have we learned from genome-wide association studies (GWAS) in Parkinson's disease?
2022-05-17

After fifteen years of genome-wide association studies (GWAS) in Parkinson's disease (PD), what have we learned? Addressing this question will help catalogue the progress made towards elucidating disease mechanisms, improving the clinical utility of the identified loci, and envisioning how we can harness the strides to develop translational GWAS strategies. Here we review the advances of PD GWAS made to date while critically addressing the challenges and opportunities for next-generation GWAS. Thus, deciphering the missing heritability in underrepresented populations is currently at the reach of hand for a truly comprehensive understanding of the genetics of PD across the different ethnicities. Moreover, state-of-the-art GWAS designs hold a true potential for enhancing the clinical applicability of genetic findings, for instance, by improving disease prediction (PD risk and progression). Lastly, advanced PD GWAS findings, alone or in combination with clinical and environmental parameters, are expected to have the capacity for defining patient enriched cohorts stratified by genetic risk profiles and readily available for neuroprotective clinical trials. Overall, envisioning future strategies for advanced GWAS is currently timely and can be instrumental in providing novel genetic readouts essential for a true clinical translatability of PD genetic findings.
Screening and Whole Genome Sequencing of SARS-CoV-2 Circulating During the First Three Waves of the COVID-19 Pandemic in Libreville and the Haut-Ogooué Province in Gabon
2022-05-17

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 viral dynamics in Africa have been less documented than on other continents. In Gabon, a Central African country, a total number of 37,511 cases of COVID-19 and 281 deaths have been reported as of December 8, 2021. After the first COVID-19 case was reported on March 12, 2020, in the capital Libreville, the country experienced two successive waves. The first one, occurred in March 2020 to August 2020, and the second one in January 2021 to May 2021. The third wave began in September 2021 and ended in November 2021. In order to reduce the data gap regarding the dynamics of SARS-CoV-2 in Central Africa, we performed a retrospective genotyping study using 1,006 samples collected from COVID-19 patients in Gabon from 2020 to 2021. Using SARS-CoV-2 variant screening by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and whole genome sequencing (WGS), we genotyped 809 SARS-CoV-2 samples through qRT-PCR and identified to generated 291 new genomes. It allowed us to describe specific mutations and changes in the SARS-CoV-2 variants in Gabon. The qRT-PCR screening of 809 positive samples from March 2020 to September 2021 showed that 119 SARS-CoV-2 samples (14.7%) were classified as VOC Alpha (Pangolin lineage B.1.1.7), one (0.1%) was a VOC Beta (B.1.351), and 198 (24.5 %) were VOC Delta (B.1.617.2), while 491 samples (60.7%) remained negative for the variants sought. The B1.1 variant was predominant during the first wave while the VOC Alpha dominated the second wave. The B1.617.2 Delta variant is currently the dominant variant of the third wave. Similarly, the analysis of the 291 genome sequences indicated that the dominant variant during the first wave was lineage B.1.1, while the dominant variants of the second wave were lineages B.1.1.7 (50.6%) and B.1.1.318 (36.4%). The third wave started with the circulation of the Delta variant (B.1.617). Finally, we compared these results to the SARS-CoV-2 sequences reported in other African, European, American and Asian countries. Sequences of Gabonese SARS-CoV-2 strains presented the highest similarities with those of France, Belgium and neighboring countries of Central Africa, as well as West Africa.
The wastewater micropollutant carbamazepine in insectivorous birds—an exposure estimate
2022-05-17

Abstract Insects with aquatic life stages can transfer sediment and water pollutants to terrestrial ecosystems, which has been described for metals, polyaromatic hydrocarbons, and polychlorinated chemicals. However, knowledge of the transfer of aquatic micropollutants released by wastewater treatment plants is scarce despite some preliminary studies on their occurrence in riparian spiders. In our study, we address a major analytical gap focusing on the transfer of the micropollutant carbamazepine from the larvae to the adult midges of Chironomus riparius using an optimized QuEChERS extraction method and HPLC–MS/MS applicable to both life stages down to the level of about three individuals. We show that the uptake of carbamazepine by larvae is concentration-dependent and reduces the emergence rate. Importantly, the body burden remained constant in adult midges. Using this information, we estimated the daily exposure of insectivorous tree swallows as terrestrial predators to carbamazepine using the energy demand of the predator and the energy content of the prey. Assuming environmentally relevant water concentrations of about 1 μg/L, the daily dose per kilogram of body weight for tree swallows was estimated to be 0.5 μg/kg/day. At places of high water contamination of 10 μg/L, the exposure may reach 5 μg/kg/day for this micropollutant of medium polarity. Considering body burden changes upon metamorphosis, this study fills the missing link between aquatic contamination and exposure in terrestrial habitats showing that wastewater pollutants can impact birds’ life. Clearly, further analytical methods for biota analysis in both habitats are urgently required to improve risk assessment. Graphical abstract
Bottom-up memorial landscapes between social protest and top-down tourist destination: the case of Chicano Park in San Diego (California) – an analysis based on Ralf Dahrendorf’s conflict theory
2022-05-17

In an empirical study based on a landscape biographical approach, the processes of constructing memorial landscapes are traced and analysed for tourism-related communications of top-down marketing as well as framed in terms of conflict theory with regard to their productivity and their generating of life chances.
Double‐row dipole/loop combined array for human whole brain imaging at 7 T
2022-05-17

Important issues in designing radiofrequency (RF) coils for human head imaging at ultra‐high field (UHF; ≥7 T) are the inhomogeneity and longitudinal coverage (along the magnet axis) of the transmit (Tx) RF field. Both the homogeneity and coverage produced by Tx volume coils can be improved by means of three‐dimensional (3D) RF shimming, which requires the use of multirow Tx‐arrays. In addition, according to recent findings of the ultimate intrinsic signal‐to‐noise ratio (UISNR) theory, the loop‐only receive (Rx) arrays do not provide optimal SNR near the brain center at UHF. The latter can be obtained by combining complementary conductive structures carrying different current patterns (e.g., loops and dipole antennas). In this work, we developed, constructed, and evaluated a novel 32‐element hybrid array design for human head imaging at 7 T. The array consists of 16 transceiver loops placed in two rows circumscribing the head and 16 folded‐end Rx‐only dipoles positioned in the centers of loops. By placing all elements in a single layer, we increased RF power deposition into the tissue and, thus, preserved the Tx‐efficiency. Using this hybrid design also simplifies the coil structure by minimizing the total number of array elements. The array demonstrated whole brain coverage, 3D RF shimming capability, and high SNR. It provided ~15% higher SNR near the brain center and, depending on the RF shim mode, from 20% to 40% higher Tx‐efficiency than a common commercial head array coil.
Bringing shape into focus: Assessing differences between blades and bladelets and their technological significance in 3D form
2022-05-17

Laminar technologies have been adopted by Paleolithic foragers to produce a variate range of stone implements. Archaeologists have been capable of reconstructing the different reduction procedures involved in the production of laminar stone tools, often underlying a separation between the bigger blanks (i.e., blades) and smaller bladelets. However, these two blank types are in most cases poorly defined because their classification typically relies on arbitrary size thresholds that do not consider blank shape, which is a fundamental component of tool production and function. In this study, we investigate whether traditional classifications of blades and bladelets are meaningful in terms of morphology. For this purpose, we employ a three-dimensional geometric morphometric approach on a large sample of complete blanks retrieved from one of the earliest industries assigned to modern humans in southern Europe: the Protoaurignacian. We rely on a cutting edge protocol for acquiring virtual 3D meshes of stone tools using micro-computed tomography, which enables to scan large datasets of small-sized lithics. Our findings highlight distinct morphological tendencies across blank types that are in part triggered by the technological variability of the Protoaurignacian, including a shape component that significantly correlates with the three-dimensional size of the artifacts. Furthermore, we demonstrate the merits of combining 3D size and shape variables by running a discriminant function analysis that successfully classifies most artifacts into blades or bladelets. Overall, our results demonstrate that virtual analysis of stone tool form (both size and shape) can elucidate unknown aspects of lithic technology and its implications for human behavior in the past.
Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering
2022-05-17

The equilibrium between scaffold degradation and neotissue formation, is highly essential for in situ tissue engineering. Herein, biodegradable grafts function as temporal roadmap to guide regeneration. The ability to monitor and understand the dynamics of degradation and tissue deposition in in situ cardiovascular graft materials is therefore of great value to accelerate the implementation of safe and sustainable tissue-engineered vascular grafts (TEVGs) as a substitute for conventional prosthetic grafts. In this study, we investigated the potential of Raman microspectroscopy and Raman imaging to monitor degradation kinetics of supramolecular polymers, which are employed as degradable scaffolds in in situ tissue engineering. Raman imaging was applied on in vitro degraded polymers, investigating two different polymer materials, subjected to oxidative and enzymatically-induced degradation. Furthermore, the method was transferred to analyze in vivo degradation of tissue-engineered carotid grafts after 6 and 12 months in a sheep model. Multivariate data analysis allowed to trace degradation and to compare the data from in vitro and in vivo degradation, indicating similar molecular observations in spectral signatures between implants and oxidative in vitro degradation. In vivo degradation appeared to be dominated by oxidative pathways. Furthermore, information on collagen deposition and composition could simultaneously be obtained from the same image scans. Our results demonstrate the sensitivity of Raman microspectroscopy to determine degradation stages and the assigned molecular changes non-destructively, encouraging future exploration of this techniques for time-resolved quality assessment of in situ tissue engineering processes.
Proteins released into the plant apoplast by the obligate parasitic protist Albugo selectively repress phyllosphere-associated bacteria
2022-05-17

Biotic and abiotic interactions shape natural microbial communities. The mechanisms behind microbe-microbe interactions, particularly those protein-based, are not well understood. We hypothesize that secreted proteins are a powerful and highly specific toolset to shape and defend plant niches. We have studied Albugo candida , an obligate plant parasite from the protist Oomycota phylum, for its potential to modulate the growth of bacteria through secretion of proteins into the apoplast. Amplicon sequencing and network analysis of Albugo -infected and uninfected samples revealed an abundance of negative correlations between Albugo and other phyllosphere microbes. Analysis of the apoplastic proteome of Albugo colonized leaves combined with machine-learning predictors enabled the selection of candidates for heterologous expression and study of their inhibitory activity. We found that three of the candidate proteins show selective antimicrobial activity on gram-positive bacteria isolated from Arabidopsis thaliana and that these inhibited bacteria are important for the stability of the community structure. We could ascribe the antibacterial activity of the candidates to intrinsically disordered regions and positively correlate it with net charge. This is the first report of protist proteins with antimicrobial activity under apoplastic conditions that therefore are potential biocontrol tools for targeted manipulations of the microbiome.