julilili42/papers huggingface dataset:
Mode effect: An issue of perspective? Writing mode differences in a spelling assessment in German children with and without developmental dyslexia
2021-02-21

Digital technology has an increasing influence on writing processes. In this context, the question arises whether changes in writing mode (i.e., handwriting vs. computer‐keyboard typing) also require changes in writing assessments. However, data directly comparing writing mode influences in children with and without developmental writing deficits are scarce. This study investigated the influence of writing mode in German‐speaking, typically developing children and children with developmental dyslexia (DD) from two different levels. Results showed on a general level that writing mode influenced overall spelling accuracy , writing time , and self‐corrections comparably in children with and without DD. On a rule‐specific level, outcomes for writing time and self‐corrections substantiated these findings. However, as regards spelling accuracy , a mode effect was only apparent for capitalization, whereas other spelling rules were resistant to writing mode influences. Present findings suggest that a mode effect is present only for typing specific aspects (e.g., capitalization) rather than reflecting a general influence on orthographic principles (e.g., grapheme–phoneme assignment, morphologic principles). These mode‐specific aspects seem to comparably affect the writing performance of typically developing children and children with DD. We recommend writing assessments to consider that different writing modes may influence individual spelling rules differently.
Error-driven learning of communication systems in biological life forms
2021-02-21

Life forms on Earth use a vast array of methods of communication, within which there is a wide range of complexity and adaptivity. As far as is currently known, the systems most capable of adapting to new input and new communicative needs are human languages. This seems to result from the high degree of reliance on learning, relative to genetic encoding, in human linguistic systems. We propose that the relative contribution of learning versus genetic encoding will have a similar effects on complexity and adaptivity in extraterrestrial communication systems. We discuss this issue from the perspective of discriminative learning, a learning theory that has accounted for many learning effects in animals, including in human language. We investigate two aspects of the human communicative signal that are likely to differ in extraterrestrial life forms compared to human speech - atmospheric effects and biological effects - and how variation in these characteristics on other planets might impact the signal. Our analyses show that even subtle differences in these attributes have a substantial impact on signal properties.
A Novel SNCA A30G Mutation Causes Familial Parkinsonʼs Disease
2021-02-22

ABSTRACT Background The SNCA gene encoding α‐synuclein (αSyn) is the first gene identified to cause autosomal‐dominant Parkinsonʼs disease (PD). Objective We report the identification of a novel heterozygous A30G mutation of the SNCA gene in familial PD and describe clinical features of affected patients, genetic findings, and functional consequences. Methods Whole exome sequencing was performed in the discovery family proband. Restriction digestion with Bbvl was used to screen SNCA A30G in two validation cohorts. The Greek cohort included 177 familial PD probands, 109 sporadic PD cases, and 377 neurologically healthy controls. The German cohort included 136 familial PD probands, 380 sporadic PD cases, and 116 neurologically healthy controls. We also conducted haplotype analysis using 13 common single nucleotide variants around A30G to determine the possibility of a founder effect for A30G. We then used biophysical methods to characterize A30G αSyn. Results We identified a novel SNCA A30G (GRCh37, Chr4:90756730, c.89 C&gt;G) mutation that co‐segregated with the disease in five affected individuals of three Greek families and was absent from controls. A founder effect was strongly suggested by haplotype analysis. The A30G mutation had a local effect on the intrinsically disordered structure of αSyn, slightly perturbed membrane binding, and promoted fibril formation. Conclusion Based on the identification of A30G co‐segregating with the disease in three families, the absence of the mutation in controls and population databases, and the observed functional effects, we propose SNCA A30G as a novel causative mutation for familial PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Abrasion regimes in fluvial bedrock incision
2021-02-22

Abstract River incision into bedrock drives landscape evolution and couples surface changes to climate and tectonics in uplands. Mechanistic bedrock erosion modeling has focused on plucking—the hydraulic removal of large loosened rock fragments—and on abrasion—the slower fracturing-driven removal of rock due to impacts of transported sediment—which produces sand- or silt-sized fragments at the mineral grain scale (i.e., wear). An abrasion subregime (macro-abrasion) has been hypothesized to exist under high impact energies typical of cobble or boulder transport in mountain rivers, in which larger bedrock fragments can be generated. We conducted dry impact abrasion experiments across a wide range of impact energies and found that gravel-sized fragments were generated when the impact energy divided by squared impactor diameter exceeded 1 kJ/m2. However, the total abraded volume followed the same kinetic-energy scaling regardless of fragment size, holding over 13 orders of magnitude in impact energy and supporting a general abrasion law. Application to natural bedrock rivers shows that many of them likely can generate large fragments, especially in steep mountain streams and during large floods, transporting boulders in excess of 0.6 m diameter. In this regime, even single impacts can cause changes in riverbed topography that may drive morphodynamic feedbacks.
Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis
2021-02-22

Intronic hexanucleotide repeat expansions (HREs) in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis, a devastating, incurable motoneuron (MN) disease. The mechanism by which HREs trigger pathogenesis remains elusive. The discovery of repeat-associated non-ATG (RAN) translation of dipeptide repeat proteins (DPRs) from HREs along with reduced exonic C9ORF72 expression suggests gain of toxic functions (GOFs) through DPRs versus loss of C9ORF72 functions (LOFs). Through multiparametric high-content (HC) live profiling in spinal MNs from induced pluripotent stem cells and comparison to mutant FUS and TDP43, we show that HRE C9ORF72 caused a distinct, later spatiotemporal appearance of mainly proximal axonal organelle motility deficits concomitant to augmented DNA double-strand breaks (DSBs), RNA foci, DPRs, and apoptosis. We show that both GOFs and LOFs were necessary to yield the overall C9ORF72 pathology. Increased RNA foci and DPRs concurred with onset of axon trafficking defects, DSBs, and cell death, although DSB induction itself did not phenocopy C9ORF72 mutants. Interestingly, the majority of LOF-specific DEGs were shared with HRE-mediated GOF DEGs. Finally, C9ORF72 LOF was sufficient—albeit to a smaller extent—to induce premature distal axonal trafficking deficits and increased DSBs.
Predominance of HBV Genotype B and HDV Genotype 1 in Vietnamese Patients with Chronic Hepatitis
2021-02-22

Hepatitis delta virus (HDV) coinfection will additionally aggravate the hepatitis B virus (HBV) burden in the coming decades, with an increase in HBV-related liver diseases. Between 2018 and 2019, a total of 205 HBV patients clinically characterized as chronic hepatitis B (CHB; n = 115), liver cirrhosis (LC; n = 21), and hepatocellular carcinoma (HCC; n = 69) were recruited. HBV surface antigen (HBsAg), antibodies against surface antigens (anti-HBs), and core antigens (anti-HBc) were determined by ELISA. The presence of hepatitis B viral DNA and hepatitis delta RNA was determined. Distinct HBV and HDV genotypes were phylogenetically reconstructed and vaccine escape mutations in the “a” determinant region of HBV were elucidated. All HBV patients were HbsAg positive, with 99% (n = 204) and 7% (n = 15) of them being positive for anti-HBc and anti-HBs, respectively. Anti-HBs positivity was higher among HCC (15%; n = 9) compared to CHB patients. The HBV-B genotype was predominant (65%; n = 134), followed by HBV-C (31%; n = 64), HBV-D, and HBV-G (3%; n = 7). HCC was observed frequently among young individuals with HBV-C genotypes. A low frequency (2%; n = 4) of vaccine escape mutations was observed. HBV-HDV coinfection was observed in 16% (n = 33) of patients with the predominant occurrence of the HDV-1 genotype. A significant association of genotypes with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels was observed in HBV monoinfections. The prevalence of the HDV-1 genotype is high in Vietnam. No correlation was observed between HDV-HBV coinfections and disease progression when compared to HBV monoinfections.
Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors
2021-02-23

Abstract Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects. Patients and Methods: The study comprised of dose escalation and dose expansion cohorts. BAY1436032 tablets were orally administered twice daily on a continuous basis in subjects with mIDH1 solid tumors. Results: In dose escalation, 29 subjects with various tumor types were administered BAY1436032 across five doses (150–1,500 mg twice daily). BAY1432032 exhibited a relatively short half-life. Most evaluable subjects experienced target inhibition as indicated by a median maximal reduction of plasma R-2-hydroxyglutarate levels of 76%. BAY1436032 was well tolerated and an MTD was not identified. A dose of 1,500 mg twice daily was selected for dose expansion, where 52 subjects were treated in cohorts representing four different tumor types [lower grade glioma (LGG), glioblastoma, intrahepatic cholangiocarcinoma, and a basket cohort of other tumor types]. The best clinical outcomes were in subjects with LGG (n = 35), with an objective response rate of 11% (one complete response and three partial responses) and stable disease in 43%. As of August 2020, four of these subjects were in treatment for &amp;gt;2 years and still ongoing. Objective responses were observed only in LGG. Conclusions: BAY1436032 was well tolerated and showed evidence of target inhibition and durable objective responses in a small subset of subjects with LGG.
Targeted Profiling of Short-, Medium-, and Long-Chain Fatty Acyl-Coenzyme As in Biological Samples by Phosphate Methylation Coupled to Liquid Chromatography–Tandem Mass Spectrometry
2021-02-23

Fatty acyl-coenzyme As (acyl-CoAs) are of central importance in lipid metabolism pathways. Short-chain acyl-CoAs are usually part of metabolomics, and medium- to (very) long-chain acyl-CoAs are focus of lipidomics studies. However, owing to the specific complex and amphiphilic nature contributed by fatty acyl chains and hydrophilic CoA moiety, lipidomic analysis of acyl-CoAs is still challenging, especially in terms of sample preparation and chromatographic coverage. In this work, we propose a derivatization strategy of acyl-CoAs based on phosphate methylation. After derivatization, full coverage (from free CoA to C25:0-CoA) and good peak shape in liquid chromatography were achieved. At the same time, analyte loss due to the high affinity of phosphate groups to glass and metallic surfaces was resolved, which is beneficial for routine analysis in large-scale lipidomics studies. A sample preparation method based on mixed-mode SPE was developed to optimize extraction recoveries and allow optimal integration of the derivatization process in the analytical workflow. LC-MS/MS was performed with targeted data acquisition by SRM transitions, which were constructed based on similar fragmentation rules observed for all methylated acyl-CoAs. To achieve accurate quantification, uniformly <sup>13</sup>C-labeled metabolite extract from yeast cells was taken as internal standards. Odd-chain and stable isotope-labeled acyl-CoAs were used as surrogate calibrants in the same matrix. LOQs were between 16.9 nM (short-chain acyl-CoAs) and 4.2 nM (very-long-chain acyl-CoAs). This method was validated in cultured cells and was applied in HeLa cells and human platelets of coronary artery disease patients. It revealed distinct acyl-CoA profiles in HeLa cells and platelets. The results showed that this method can effectively detect acyl-CoAs in biological samples. Considering their central importance in many <i>de novo</i> lipid biosynthesis and remodeling processes, this targeted method offers a valid foundation for future lipidomics analysis of acyl-CoA profiles in biological samples, particularly those concerning metabolic syndrome.
Intensive olive production at Levantine sites. New data from Fadous-Kfarabida and Khirbet-ez Zeraqon
2021-02-23

During the third millennium BCE, the Levant experienced an increase in social complexity, visible in the emergence of urban forms and centralised institutions. Specialised agricultural production, particularly of olives, has long been considered a key factor in this transformation. This paper uses charcoal and seed analysis of remains from the Early Bronze Age II-III sites of Tell Fadous-Kfarabida in Lebanon and Khirbet-ez Zeraqon in Jordan, alongside a comparative analysis of published data, to investigate this phenomenon. Olive was an important crop at both sites but Khirbet-ez Zeraqon is situated within a more arid inland location, away from the natural distribution of wild olive, whereas Tell Fadous-Kfarabida had a much lusher vegetation, and was within the distribution of wild olive. While important, olive was possibly not the major crop in terms of macro-nutrient supply in Khirbet-ez Zeraqon but it played a more dominant role in Fadous-Kfarabida. The measurements of the olive stones from both sites show a high variance compared to other sites. At Khirbet-ez Zeraqon this may have been due to specialization by using several cultivars and/or applying irrigation and/or fluctuations in rainfall. At Fadous-Kfarabida morphological wild olives were possibly included in the production as well, which may relate to the development of new olive strains and a likely higher engagement in experimentation. Although an overall linear trend of increasing mean olive stone length, occasionally described as “domestication syndrome”, can be detected for the southern Levant between 7 and 2 kyr BP, the Early Bronze Age measurement data from Fadous-Kfarabida and Khirbet-ez Zeraqon are outside the confidence band of the regression line and indicate that higher variability in some sites can blur a straightforward recognition of the “domestication syndrome”. There seem to have been varied local practices in cultivation and domestication in the Early Bronze Age Levant.
Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations.
2021-02-23

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm affecting typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological examination is required for diagnosis. The mainstay of treatment is a complete surgical resection. Inoperable and/or metastatic PBL may become amenable to complete, delayed surgery after neo-adjuvant chemotherapy. This manuscript presents the internationally consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network – European Registry) project.
Antigen production and development of an indirect ELISA based on the nucleocapsid protein to detect human SARS-CoV-2 seroconversion
2021-02-23

Abstract Serological assays are important tools to identify previous exposure to SARS-CoV-2, helping to track COVID-19 cases and determine the level of humoral response to SARS-CoV-2 infections and/or immunization to future vaccines. Here the SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to homogeneity and high yield using a single chromatography step. The purified SARS-CoV-2 nucleocapsid protein was used to develop an indirect enzyme-linked immunosorbent assay for the identification of human SARS-CoV-2 seroconverts. The assay sensitivity and specificity were determined analyzing sera from 140 PCR-confirmed COVID-19 cases and 210 pre-pandemic controls. The assay operated with 90% sensitivity and 98% specificity; identical accuracies were obtained in head-to-head comparison with a commercial ELISA kit. Antigen coated plates were stable for up to 3 months at 4°C). The ELISA method described is ready to mass production and will be an additional toll to track COVID-19 cases.
Analysis of retinal detachment after post-operative endophthalmitis treated with 23G Pars Plana Vitrectomy
2021-02-23

Abstract Background To evaluate the rate, risk factors, functional outcome and prognosis in eyes with retinal detachment after post-operative endophthalmitis treated with 23G pars plana vitrectomy. Methods Electronic patient files from 2009 until 2018 were screened for the presence of an endophthalmitis. Included were 116 eyes of 116 patients. This population was evaluated for the rate of retinal detachment after 23G Pars Plana Vitrectomy for endophthalmitis following cataract surgery or intravitreal injection. The main outcome measures are retinal detachment and visual acuity. Results Reason for endophthalmitis was previous cataract surgery in 78 patients and following intravitreal injection in 38 patients. First clinical evidence of endophthalmitis was present in median 5 days after the triggering surgery. Twenty-five eyes (21.55%) developed a retinal detachment in average 25 days after endophthalmitis. RD is significantly associated with preoperative visual acuity (p = 0.001). Conclusions Modern 23G vitrectomy technique seems not to lower the rate of retinal detachment after vitrectomy for endophthalmitis. And we also emphasize the prognostic role of preoperative visual acuity in RD development of the endophthalmitis treated with 23G pars plana vitrectomy.
Acute Arthritis of the&nbsp;Temporomandibular&nbsp;Joint due to Lyme&nbsp;Disease:&nbsp;A Case Report and&nbsp;Literature&nbsp;Review
2021-02-23

Abstract Lyme disease is the most frequent tick-borne infectious disease in Europe. It often presents with a wide variety of symptoms. For this reason, affection of the temporomandibular joint (TMJ) caused by Lyme disease (LD) can be misdiagnosed as a common temporomandibular disorder (TMD). The purpose of this case report of a 25-year old woman presenting to the Departments of Orthodontics and Maxillofacial Surgery with extensive symptoms of Temporomandibular Disorder is to illustrate the delayed diagnosis of Lyme disease, which was only made after extensive therapy of the temporomandibular joint. The specialist literature only reports a few cases of patients suffering from Lyme disease with TMJ manifestations. This case report and the relevant literature review aim to emphasize the importance of accurate request of medical history and differential diagnosis of acute TMJ arthritis and arthralgia. Early interdisciplinary diagnosis of Lyme disease and early antibiotic therapy are essential to avoid misdiagnosis and unnecessary, sometimes invasive, therapies.
An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples
2021-02-24

<ns3:p>MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 <ns3:italic>Plasmodium falciparum</ns3:italic> samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.</ns3:p>
Optimising care pathways for adult anorexia nervosa. What is the evidence to guide the provision of high‐quality, cost‐effective services?
2021-02-24

Abstract The aim of this paper is to consider how changes in service planning and delivery might improve the care pathways for adult anorexia nervosa. Although anorexia nervosa has a long history in Europe, its framing as a mental disorder is quite recent. The changing forms and increasing epidemiology of eating disorders has led to the expansion of specialised services. Although some services provide care over the entire clinical course, more often services are divided into those that care for children and adolescents or adults. The transition needs to be carefully managed as currently these services may have a different ethos and expectations. Services for adults have a broad range of diversity (diagnostic subtype, medical severity, comorbidity, stage of illness and psychosocial functioning) all of which impacts on prognosis. A tailored, approach to treatment planning could optimise the pathway. Facilitating early help seeking and rapid diagnosis in primary care and reducing specialised services waiting lists for assessment and treatment could be a form of secondary prevention. The use of precision models and /or continuous outcome monitoring might reduce the third of patients who require more intensive care by applying augmentation strategies. Finally, gains from intensive care might be sustained by relapse prevention interventions and community support to bridge the transition home. Together these measures might reduce the proportion of patients (currently a third) with ill health for over 20 years. For this group rehabilitation strategies may improve functioning until new treatment emerge.
A Single‐Pot Template Reaction Towards a Manganese‐Based T1 Contrast Agent
2021-02-24

Abstract Manganese‐based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium‐based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single‐pot template synthetic strategy to develop a MnCA, MnL Me , and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b =21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA ( K a =4.2×10 3 M −1 ). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half‐life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent.