julilili42/papers huggingface dataset:
Molecular surveillance of the Pfmdr1 N86Y allele among Congolese pregnant women with asymptomatic malaria
2020-05-07

<title>Abstract</title> <bold>Background </bold>Malaria in pregnancy is associated with considerable morbidity and mortality.<bold> </bold>Regular surveillance of artemisinin−based combination therapy tolerance, or molecular makers of resistance, is vital for effective malaria treatment, control and eradication programmes. <italic>Plasmodium falciparum </italic>multiple drug resistance-1 gene (<italic>Pfmdr1</italic>) N86Y mutation is associated with reduced susceptibility to lumefantrine. This study assessed the prevalence of <italic>Pfmdr1</italic> N86Y in Brazzaville, Republic of Congo. <bold>Methods </bold>A total 1001 of <italic>P. falciparum-</italic>infected blood samples obtained from asymptomatic malaria pregnant women having a normal child delivery at the Madibou Integrated Health Centre were analysed. <italic>Pfmdr1</italic> N86Y genotyping was conducted using PCR-restriction fragment length polymorphism. <bold>Results </bold>The wild type <italic>Pfmdr1</italic> N86 allele was predominant (&gt;68 %) in this study, whereas a few isolates carrying the either the mutant allele (<italic>Pfmdr1</italic> 86Y) alone or both alleles (mixed genotype). The dominance of the wildtype allele (<italic>pfmdr1 </italic>N86) indicates the plausible decline <italic>P. falciparum</italic> susceptibility to lumefantrine. <bold>Conclusion </bold>This study gives an update on the prevalence of <italic>Pfmdr1</italic> N86Y alleles in Brazzaville, Republic of Congo. It also raises concern on the imminent emergence of resistance against artemether−lumefantrine in this setting. This study underscores the importance to regular artemether−lumefantrine efficacy monitoring to inform the malaria control programme of the Republic of Congo.
The unusual behavior of the young X-ray pulsar SXP 1062 during the 2019 outburst
2020-05-08

\\nWe present the results of the first dedicated observation of the young X-ray pulsar SXP 1062 in the broad X-ray energy band obtained during its 2019 outburst with the NuSTAR and XMM-Newton observatories. The analysis of the pulse-phase averaged and phase-resolved spectra in the energy band from 0.5 to 70 keV did not reveal any evidence for the presence of a cyclotron line. The spin period of the pulsar was found to have decreased to 979.48 ± 0.06 s implying a ∼10% reduction compared to the last measured period during the monitoring campaign conducted about five years ago, and is puzzling considering that the system apparently has not shown major outbursts ever since. The switch of the pulsar to the spin-up regime supports the common assumption that torques acting on the accreting neutron star are nearly balanced and thus SXP 1062 likely also spins with a period close to the equilibrium value for this system. The current monitoring of the source also revealed a sharp drop in its soft X-ray flux right after the outburst, which is in drastic contrast to the behavior during the previous outburst when the pulsar remained observable for years with only a minor flux decrease after the end of the outburst. This unexpected off state of the source lasted for at most 20 days after which SXP 1062 returned to the level observed during previous campaigns. We discuss this and other findings in context of the modern models of accretion onto strongly magnetized neutron stars.\\n
Functional brain age prediction suggests accelerated aging in preclinical familial Alzheimer’s disease, irrespective of fibrillar amyloid-beta pathology
2020-05-08

Abstract We aimed at developing a model able to predict brain aging from resting state functional connectivity (rs-fMRI) and assessing whether genetic risk/determinants of Alzheimer’s disease (AD) and amyloid (Aβ) pathology contributes to accelerated brain aging. Using data collected in 1340 cognitively unimpaired participants from 18 to 94 years old selected across multi-site cohorts, we showed that chronological age can be predicted across the whole lifespan from topological properties of graphs constructed from rs-fMRI. We subsequently used the difference between the model-predicted age and the chronological age in pre-symptomatic autosomal dominant AD (ADAD) mutation carriers and asymptomatic individuals at risk of sporadic AD and assessed the influence of genetics and Aβ pathology on brain age. Applying our predictive model in the context of preclinical AD revealed that the pre-symptomatic phase of ADAD is characterized by accelerated functional brain aging. This phenomenon is independent from, and might precede, detectable fibrillar Aβ deposition.
Pontine Lesions Impair Visually Guided Eye and Hand Movements
2020-05-08

Summary Although animal research and some rare human case reports suggest that lesions of the dorsal pons yield saccadic and smooth pursuit eye movement deficits, little is known about the functional topology of the human pontine nuclei (PN) and whether limb movements are similarly affected as eye movements. Saccadic as well as SP eye and pointing movements were measured in six patients with lesions in the PN region. Five patients of the six exhibited dysmetric saccades, whilst smooth pursuit gain was reduced in four. Pontine lesions also alter the relationship between amplitude, velocity, and velocity skewness of saccadic eye movements. Limb movement trajectories were more curved in four patients. The results suggest that the lesions impair a general calibration mechanism that uses the parallel fiber-Purkinjecell synapse in the cerebellar cortex to adjust the timing of muscle innervation in visually guided oculomotor as well as limb movement tasks.
Whole brain snapshot CEST at 3T using 3D‐EPI: Aiming for speed, volume, and homogeneity
2020-05-09

Purpose CEST MRI enables imaging of distributions of low‐concentrated metabolites as well as proteins and peptides and their alterations in diseases. CEST examinations often suffer from low spatial resolution, long acquisition times, and concomitant motion artifacts. This work aims to maximize both resolution and volume coverage with a 3D‐EPI snapshot CEST approach at 3T, allowing for fast and robust whole‐brain CEST MRI. Methods Resolution and temporal SNR of 3D‐EPI examinations with nonselective excitation were optimized at a clinical 3T MR scanner in five healthy subjects using a clinical head/neck coil. A CEST presaturation module for low power relayed nuclear Overhauser enhancement and amide proton transfer contrast was applied as an example. The suggested postprocessing included motion correction, dynamic B 0 correction, denoising, and B 1 correction and was compared to an established 3D‐gradient echo‐based sequence. Results CEST examinations were performed at 1.8 mm nominal isotropic resolution in 4.3 s per presaturation offset. In contrast to slab‐selective 3D or multislice approaches, the whole brain was covered. Repeated examinations at three different B 1 values took 13 minutes for 58 presaturation offsets with temporal SNR around 75. The resulting CEST effects revealed significant gray and white matter contrast and were of similar quality across the whole brain. Coefficient of variation across three healthy subjects was below 9%. Conclusion The suggested protocol enables whole brain coverage at 1.8 mm isotropic resolution and fast acquisition of 4.3 s per presaturation offset. For the fitted CEST amplitudes, high reproducibility was proven, increasing the opportunities of quantitative CEST investigations at 3T significantly.
Management of rare movement disorders in Europe: outcome of surveys of the European Reference Network for Rare Neurological Diseases
2020-05-09

Background and purpose The diagnosis of rare movement disorders is difficult and specific management programmes are not well defined. Thus, in order to capture and assess care needs, the European Reference Network for Rare Neurological Diseases has performed an explorative care need survey across all European Union (EU) countries. Methods This is a multicentre, cross‐sectional study. A survey about the management of different rare movement disorders (group 1, dystonia, paroxysmal dyskinesia and neurodegeneration with brain iron accumulation; group 2, ataxias and hereditary spastic paraparesis; group 3, atypical parkinsonism; group 4, choreas) was sent to an expert in each group of disorders from each EU country. Results Some EU countries claimed for an increase of teaching courses. Genetic testing was not readily available in a significant number of countries. Regarding management, patients’ accessibility to tertiary hospitals, to experts and to multidisciplinary teams was unequal between countries and groups of diseases. The availability of therapeutic options, such as botulinum toxin or more invasive treatments like deep brain stimulation, was limited in some countries. Conclusions The management of these conditions in EU countries is unequal. The survey provides evidence that a European care‐focused network that is able to address the unmet rare neurological disease care needs and inequalities is highly warranted.
Mysterious Uškiani - Armenian Gold: The Driving Force for Development in the Bronze Age Caucasus Region?
2020-05-09

The Gegharkunik region on the south eastern edge of Lake Sevan (Armenia) is a part of southern Caucasia uniquely suited to demonstrate the intensive interchange between pre-Christian settlement and gold mining. The enclosed landscape can be seen in this regard as a prehistoric terra incognita due to the wholesale lack of archaeological and archaeometallurgical investigations to date. It has been proven that there was major exploitation of gold from the defined geographical area in antiquity. One of the largest gold mines in Near East is still located there today. The mines position on the Sotk pass, which is the direct connection between southern and eastern Caucasia and thus has a strategic importance for the entire region, is also of significance. Initial approaches revealed outlines of the prehistoric settlement patterns which could be placed in relation to contemporary gold mining in a clearly delineated natural corridor along this superregional communication and trade route. The intention is to implement an intensive holistic-archaeological and archaeometallurgical investigation of the settlement network in the surroundings of the gold mine and an interdisciplinary attempt to imbed these structures in the larger ecological and anthropogenic environment. The existence of placer gold in several local rivers as well as ancient mining traces has already been demonstrated. The findings of placer gold, along with the geochemical fingerprinting of primary and secondary gold sources from this region will make it possible to analyze the origins of golden artefacts found in the wider vicinity of the area. The opportunity to study gold items from numerous Age finds from Armenia allow for an extensive reconstruction of the early use of gold and its importance in ancient Near Eastern cultures.
Bayesian Preference Inference in Dialogue
2020-05-09

An utterance is referentially ambiguous if it has several potential referents. Observing how listeners make choices among those referents can reveal their hidden beliefs and preferences, besides giving hints at their responding processes. We asked subjects to observe how one of the objects is chosen following a possibly ambiguous utterance and to infer which preferences the listener may have had in mind when choosing the particular object. In order to adjust this interaction to a dialogue-like setting, we extended the traditional one-shot reference game to a round of 4-trial games. Moreover, we modeled the process within the Rational Speech Act framework, implementing iterative inference over multiple trials, where posteriors from previous trials carry over to the next trial as priors. The model predicts human inference behavior better than a baseline model as well as better than a non-iterative model. The results imply that, in principle, humans are able to compute Bayesian-like inferences in dialogue, learning about the beliefs and preferences of others in an iterative, cumulative manner.
The Effect of Attention on Fixation Stability During Dynamic Fixation Testing in Stargardt Disease
2020-05-10

Our results suggest that differences in static and dynamic assessment of fixation stability are dependent not only on different test durations but also on the testing protocol of a single fixation target vs fixation target plus simultaneous perimetry testing and provide information on the conduct of fixation testing for clinical trials.
Maternal perinatal depressive symptoms trajectories and impact on toddler behavior – the importance of symptom duration and maternal bonding
2020-05-11

Different onset and timing of maternal depression showed distinct associations with child behavioral problems. The effects of antenatal depression were not mediated by maternal bonding, indicating underlying mechanisms possibly related to fetal programming. Screening of depressive symptoms even during pregnancy would be important in routine care in order to early identify and treat depression.
Whole-Exome Sequencing in NF1-Related West Syndrome Leads to the Identification of KCNC2 as a Novel Candidate Gene for Epilepsy
2020-05-11

Abstract Patients with neurofibromatosis type 1 (NF1) have an increased risk for West syndrome (WS), but the underlying mechanisms linking NF1 and WS are unknown. In contrast to other neurocutaneous syndromes, intracerebral abnormalities explaining the course of infantile spasms (IS) are often absent and the seizure outcome is usually favorable. Several studies have investigated a potential genotype–phenotype correlation between NF1 and seizure susceptibility, but an association was not identified. Therefore, we identified three patients with NF1-related WS (NF1-WS) in a cohort of 51 NF1 patients and performed whole-exome sequencing (WES) to identify genetic modifiers. In two NF1 patients with WS and good seizure outcome, we did not identify variants in epilepsy-related genes. However, in a single patient with NF1-WS and transition to drug-resistant epilepsy, we identified a de novo variant in KCNC2 (c.G499T, p.D167Y) coding for Kv3.2 as a previously undescribed potassium channel to be correlated to epilepsy. Electrophysiological studies of the identified KCNC2 variant demonstrated both a strong loss-of-function effect for the current amplitude and a gain-of-function effect for the channel activation recommending a complex network effect. These results suggest that systematic genetic analysis for potentially secondary genetic etiologies in NF1 patients and severe epilepsy presentations should be done.
Chromatic Pupil Campimetry Reveals Functional Defects in Exudative Age-Related Macular Degeneration with Differences Related to Disease Activity
2020-05-11

With the combination of short recording time, objectiveness of the measurement and gaze-correction for fixation problems, this method presents a suitable complement to the currently used clinical functional tests of the macula.
Summary-statistics-based power analysis: A new and practical method to determine sample size for mixed-effects modelling
2020-05-11

This article proposes a summary-statistics-based power analysis --- a practical method for conducting power analysis for mixed-effects modelling with two-level nested data (for both binary and continuous predictors), complementing the existing formula-based and simulation-based methods. The proposed method bases its logic on conditional equivalence of the summary-statistics approach and mixed-effects modelling, paring back the power analysis for mixed-effects modelling to that for a simpler statistical analysis (e.g., one-sample t test). Accordingly, the proposed method allows us to conduct power analysis for mixed-effects modelling using popular software such as G*Power or the pwr package in R and, with minimum input from relevant prior work (e.g., t value). We provide analytic proof and a series of statistical simulations to show the validity and robustness of the summary-statistics-based power analysis and show illustrative examples with real published work. We also developed a web app (https://koumurayama.shinyapps.io/summary_statistics_based_power/) to facilitate the utility of the proposed method. While the proposed method has limited flexibilities compared to the existing methods in terms of the models and designs that can be appropriately handled, it provides a convenient alternative for applied researchers when there is limited information to conduct power analysis.
Designing a therapeutic SARS-CoV-2 T-cell-inducing vaccine for high-risk patient groups
2020-05-11

Abstract Here, we describe the preliminary results of an experimental vaccination of a self-experimenting healthy volunteer with eight SARS-CoV-2-derived peptides: five predicted to bind to HLA class I molecules (CD8 peptides) and three predicted to bind to HLA-DR molecules (CD4 peptides). The vaccine formulation also included one long and one short CMV-pp65-derived peptide that had previously been administered to the same individual and could thus act as positive controls. It further contained the new adjuvant XS15 and was administered as an emulsion in Montanide as a single subcutaneous (s.c.) injection. Peripheral blood mononuclear cells (PBMCs) isolated from blood drawn on day 36 before vaccination and day 19 after vaccination were assessed using an ex vivo Interferon-γ ELISpot assay. We detected strong vaccine-induced T-cell responses against all four CD4 peptides and against the recall CMV CD8 epitope, but found no immune responses against the five predicted SARS-CoV-2 CD8 peptides. Antibody reactivity against all the SARS-CoV-2 CD4 peptides, as detected using ELISA, was negative or marginal. We interpret these results in terms of the prospects of a therapeutic vaccine to be applied in symptomatic COVID-19 patients. An advantage of this approach is the possibility to assess efficacy or failure within a short time after vaccination.
Fromquicktoquick-to-infinitival: on what is lexeme specific across paradigmatic and syntagmatic distributions
2020-05-11

Adjectives are paradigmatically versatile: they combine with many different items in the same syntactic configuration. They are also syntagmatically versatile: they occur in many different syntactic configurations. Given this versatility, how and to what extent can lexeme-specific preferences and features of the adjectives be identified? With the adjective quick as its starting point, this article answers this question by using corpus data, contrasting the behavior of quick with that of its semantic neighbors. Case study 1 investigates quick 's attributive usage. It is shown that quick in its default usage combines with eventive heads, and that there are clear differences in combinatorial preferences across its semantic neighbors. Case study 2 investigates the quick-to - infinitival construction. Here, direct combination with eventive heads is impossible. It behaves differently from other adj - to - infinitival constructions as well as the competing quickly constructions. Comparison of the availability of this construction for quick 's semantic neighbors, and linking this to the results of study 1, shows a clear connection between paradigmatic and syntagmatic distributions.
Substandard and Falsified Antibiotics and Medicines against Noncommunicable Diseases in Western Cameroon and Northeastern Democratic Republic of Congo
2020-05-12

Falsified and substandard medicines may undermine the progress toward the Sustainable Development Goals. The present study investigated the quality of 13 essential medicines in Cameroon and the Democratic Republic of Congo (DR Congo). Five hundred six medicine samples were collected from the government and faith-based health facilities, private pharmacies, and informal vendors (total 60 facilities). Collected samples were analyzed according to the U.S. Pharmacopeia (USP) for identity, content, and dissolution of their active pharmaceutical ingredients (APIs) and for uniformity of dosage units. Three samples (0.6%) were identified as falsified. Overall, 8.5% of the samples failed USP specifications for the content of the API and 11.7% failed dissolution testing. Medicines from informal vendors showed a higher out-of-specification rate (28.2%) than other types of drug outlets (12.3%; <i>P</i> < 0.0001). All three falsified medicines had been sold by informal vendors. The failure rate of medicines stated to be produced in Europe (5.1%) was lower than that for medicines from Asia (17.7%; <i>P</i> = 0.0049) and Africa (22.2%; <i>P</i> = 0.0042). Medicines against noncommunicable diseases showed a higher failure rate than antibiotics (25.3% versus 12.1%; <i>P</i> = 0.0004). Four hundred fifty-one of the samples were analyzed in Cameroon and the DR Congo with the Global Pharma Health Fund Minilab (thin-layer chromatography and disintegration testing). The three falsified medicines were readily detected in Minilab analysis. However, substandard samples were detected with low sensitivity. A well-enforced ban of medicine sales by informal vendors and increased attention to supplier qualification in the procurement process may reduce the prevalence of substandard and falsified medicines.
Where Does Cumulative Culture Begin? A Plea for a Sociologically Informed Perspective
2020-05-12

Abstract Recent field studies have broadened our view on cultural performances in animals. This has consequences for the concept of cumulative culture. Here, we deconstruct the common individualist and differential approaches to culture. Individualistic approaches to the study of cultural evolution are shown to be problematic, because culture cannot be reduced to factors on the micro level of individual behavior (methodological individualism, “atomism”) but possesses a dynamic that only occurs on the group level and profoundly affects the individuals (“holism”). Naive individuals, as a prerequisite of an atomistic perspective, do not exist. We address the construction of a social approach to (cumulative) culture by introducing an inevitable social embedding of the individual development of social beings. The sociological notion of “habitus” as embodied cultural capital permits us to understand social transmission of behavioral components on a very basic level, resulting in a cumulative effect. Bits of information, movement, handling of material, attitudes, and preferences below distinct functional units are acquired through transfer mechanisms simpler than emulation and imitation such as peering, participation, co-performance, or engagement with a material environment altered by group members. The search for a zero point of cumulative culture becomes as useless as the search for a zero point of culture. Culture is cumulative.
The Changing Global Epidemic of HIV and Ocular Disease
2020-05-12

<b>Purpose</b>: Overview of the evolving epidemiology of human immunodeficiency virus (HIV)-related ocular disease over time. <b>Method</b>: Narrative review. <b>Results</b>: HIV enhances susceptibility to opportunistic eye infections, has direct pathogenic effects, and places patients at risk of immune recovery inflammatory syndromes in previously infected eyes after starting highly-active antiretroviral therapy (HAART). Widespread availability of HAART has resulted in a decrease of infectious ocular conditions such as cytomegalovirus retinitis, toxoplasmic retinitis, squamous cell carcinoma of the conjunctiva, and microvascular retinopathy. However, large coexisting burdens of tuberculosis, herpesvirus infection and syphilis (among others) continue to contribute to the burden of ocular disease, especially in low-resource settings. Growing risks of cataract, retinopathy and retinal nerve fiber thinning can affect patients with chronic HIV on HAART; thought due to chronic inflammation and immune activation. <b>Conclusion</b>: The changing epidemic of ocular disease in HIV-infected patients warrants close monitoring and identification of interventions that can help reduce the imminent burden of disease.