julilili42/papers huggingface dataset:
Characteristics of dermatomyositis patients with and without associated malignancy
2021-11-01

Summary Background Dermatomyositis belongs to the rare idiopathic, inflammatory myositis group. A previously postulated link between some cases of dermatomyositis and malignancy has been established in recent years. Criteria suggestive of a malignancy association are still being explored. Patients and Methods We retrospectively analyzed data from 63 patients with dermatomyositis over a period of 15 years. Results The following criteria argue for cancer‐associated dermatomyositis: older age (&gt; 52 years [ P = 0.001], &gt; 65 years [ P = 0.002], ≥ 75 years [ P = 0.002]), shorter time between manifestation and diagnosis of dermatomyositis (malignancy group: 59 days vs. non‐malignancy group: 137 days [ P = 0.022]), typical skin involvement such as Gottron sign ( P = 0.045), centrofacial erythema ( P = 0.036) and typical erythema on the upper arms and forearms ( P = 0.019), oropharyngeal involvement ( P = 0.015) and increased ALT ( P = 0.031). The following criteria argue for non‐cancer‐associated dermatomyositis: younger age (≤ 52 years [ P = 0.001], 40–65 years [ P = 0.045]) and pruritus ( P = 0.026). Conclusions The aforementioned criteria have been documented in the literature, but reported findings are heterogenous concerning the suitability of their markers for malignancy association. Small study populations, few prospective controlled studies, summarization of different forms of myositis and inconsistent use nomenclature contribute to biased results. Our study aims to make an important contribution toward the identification of risk factors in cancer‐associated dermatomyositis.
Removing Inter-Experimental Variability from Functional Data in Systems Neuroscience
2021-11-01

Abstract Integrating data from multiple experiments is common practice in systems neuroscience but it requires inter-experimental variability to be negligible compared to the biological signal of interest. This requirement is rarely fulfilled; systematic changes between experiments can drastically affect the outcome of complex analysis pipelines. Modern machine learning approaches designed to adapt models across multiple data domains offer flexible ways of removing inter-experimental variability where classical statistical methods often fail. While applications of these methods have been mostly limited to single-cell genomics, in this work, we develop a theoretical framework for domain adaptation in systems neuroscience. We implement this in an adversarial optimization scheme that removes inter-experimental variability while preserving the biological signal. We compare our method to previous approaches on a large-scale dataset of two-photon imaging recordings of retinal bipolar cell responses to visual stimuli. This dataset provides a unique benchmark as it contains biological signal from well-defined cell types that is obscured by large inter-experimental variability. In a supervised setting, we compare the generalization performance of cell type classifiers across experiments, which we validate with anatomical cell type distributions from electron microscopy data. In an unsupervised setting, we remove inter-experimental variability from data which can then be fed into arbitrary downstream analyses. In both settings, we find that our method achieves the best trade-off between removing inter-experimental variability and preserving biological signal. Thus, we offer a flexible approach to remove inter-experimental variability and integrate datasets across experiments in systems neuroscience. Code available at https://github.com/eulerlab/rave .
Evaluation of the safety and efficacy of dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women: protocol of a multicentre, two-arm, randomised, placebo-controlled, superiority clinical trial (MAMAH project)
2021-11-01

Introduction Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine–pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin–piperaquine (DHA–PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial’s objective is to determine if monthly 3-day IPTp courses of DHA–PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy. Methods and analysis This is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA–PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria. Ethics and dissemination The protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals. Trial registration number NCT03671109 .
Comparison of Cardiac Output Measurement by Electrical Velocimetry with Echocardiography in Extremely Low Birth Weight Neonates
2021-11-01

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Electrical velocimetry (EV) offers a noninvasive tool for continuous cardiac output (CO) measurements which might facilitate hemodynamic monitoring and targeted therapy in low birth neonates, in whom other methods of CO measurement are not practicably feasible. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This prospective observational study compared simultaneous cardiac output measurements by electrical velocimetry (CO&lt;sub&gt;EV&lt;/sub&gt;) with transthoracic echocardiography (CO&lt;sub&gt;TTE&lt;/sub&gt;) in extremely low birth weight (ELBW) neonates in the neonatal intensive care unit (NICU). Echocardiography was performed by 1 single examiner. Data were analyzed by Bland-Altman analysis and independent-samples analysis of variance. A mean percentage error (MPE) of &amp;#x3c;30% and limits of agreement (LOA) up to ±30% were considered clinically acceptable. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Thirty-eight ELBW neonates were studied and yielded 85 pairs of CO&lt;sub&gt;EV&lt;/sub&gt; and CO&lt;sub&gt;TTE&lt;/sub&gt; measurements. Bland-Altman analysis showed an overall bias (the mean difference) and LOA of −126 and −305 to +52 mL min&lt;sup&gt;−1&lt;/sup&gt;, respectively, and an MPE of 66%. Patients with patent ductus arteriosus had a higher bias with LOA and MPE of −166.8, −370.7 to +37 mL min&lt;sup&gt;−1&lt;/sup&gt;, and 69%, respectively. The overall true precision was 58%. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; This study showed high bias and lack of agreement between EV and TTE for measurement of CO in ELBW infants in NICU, limiting applicability of EV to monitor absolute values.
Three Water Restriction Schedules Used in Rodent Behavioral Tasks Transiently Impair Growth and Differentially Evoke a Stress Hormone Response without Causing Dehydration
2021-11-01

Abstract Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its effects on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone (CORT) in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using postmortem histologic evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Normal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in CORT relative to the control group. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.
Is rushing always faster than strolling? A reaction time study on the processing of sentences containing manner of motion verbs
2021-11-01

In the context of the embodied cognition debate, an effect of motion verb associated speed information has previously been detected using eye-tracking, functional magnetic resonance imaging (fMRI), and reaction times (RT). The latter, for instance, was implemented by Wender and Weber (1982), who observed that participants were faster in detecting motion in sentences associated with fast motion compared to sentences associated with slow motion after having formed mental images of the sentences' content. It remains open whether the reported effects of speed are associated with automatic lexical-semantic retrieval processes or whether they reflect higher top-down cognitive processes. To answer this question, the paradigm by Wender and Weber (1982) was adopted and further elaborated in the present study. In Experiment 1 visualization instructions were eliminated. Additionally, the stimulus material was manipulated in regards to the agent of the described movement (human vs. object motion) in order to determine the representation's modality (visual vs. motoric). In Experiment 2, the task to detect motion was replaced by the task to judge sensicality. The results suggest that the prompt to perform mental imagery is not a precondition for the engagement of modal representations in this speed of motion paradigm and that the involved representations' modality is visual rather than motoric. However, the modal representations' involvement is dependent on the task. They thus do not seem to be part of the invariant semantic representation of manner of motion verbs.
[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline].
2021-11-01

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.
Obscuring digital route-choice information prevents delay-induced congestion
2021-11-01

Although routing applications increasingly affect individual mobility choices, their impact on collective traffic dynamics remains largely unknown. Smart communication technologies provide accurate traffic data for choosing one route over other alternatives; yet, inherent delays undermine the potential usefulness of such information. Here, we introduce and analyze a simple model of collective traffic dynamics, which results from route choice relying on outdated traffic information. We find for sufficiently small information delays that traffic flows are stable against perturbations. However, delays beyond a bifurcation point induce self-organized flow oscillations of increasing amplitude—congestion arises. Providing delayed information averaged over sufficiently long periods of time or, more intriguingly, reducing the number of vehicles adhering to the route recommendations may prevent such delay-induced congestion. We reveal the fundamental mechanisms underlying these phenomena in a minimal two-road model and demonstrate their generality in microscopic, agent-based simulations of a road network system. Our findings provide a way to conceptually understand system-wide traffic dynamics caused by broadly used non-instantaneous routing information and suggest how resulting unintended collective traffic states could be avoided.
Novel models for the prediction of drug–gene interactions
2021-11-02

Mathematical modeling provides an opportunity to investigate complex DGI scenarios and can facilitate the development process of safe and efficient personalized dosing regimens. However, reliable DGI model input data from <i>in vivo</i> and <i>in vitro</i> measurements are crucial. For this, collaboration among pharmacometricians, laboratory scientists and clinicians is important to provide homogeneous datasets and unambiguous model parameters. For a broad adaptation of validated DGI models in clinical practice, interdisciplinary cooperation should be promoted and qualification toolchains must be established.
The formation of (Ni-Co-Sb)-Ag-As ore shoots in hydrothermal galena-sphalerite-fluorite veins
2021-11-02

Abstract Unusual hydrothermal native As-sulfide ± native Ag ± arsenide ± antimonide ± sulfosalt ore shoots and their co-genetic sulfide-fluorite-barite-quartz host veins, which are common in the region and in whole Central Europe, were investigated at three localities in the Schwarzwald, SW Germany, to understand the physico-chemical processes governing the change from a normal (= common) hydrothermal to an exceptional ore shoot regime. Based on fluid inclusions, the formation of the gangue minerals is the result of binary mixing between a NaCl-rich brine and a CaCl 2 -rich brine (both ~ 20 wt% NaCl aq.). This mixing correlation, major and minor fluid composition, formation temperature (~ 150 °C), and δ 34 S signature are identical (within error) in ore shoots and host veins. Thermodynamic modeling indicates that ore shoot formation must have resulted from a change in redox conditions by a local influx of a volumetrically minor reducing agent, probably hydrocarbons. The elemental content and the mineralogy of each ore shoot locality (Ag-As-rich: Münstertal; Ag–Ni-As-rich: Urberg; Ag–Ni-As-Sb-rich: Wieden) reflect the metal content of the binary mixed fluid, while mineral textures, successions, and assemblages are thermodynamically and, regarding sulfur, kinetically controlled. The formation of vein and ore shoot sulfides requires an addition of sulfide, most probably from the sulfide-bearing host rocks, because thermodynamic and kinetic reasons suggest that the two major vein-forming and metal-bearing fluids are not the source of the sulfur. The final ore shoot textures are influenced by later hydrothermal remobilization processes of As and Ag. This results in a number of sulfosalts, mostly proustite-pyrargyrite. Interestingly, the greater thermodynamic stability of Sb-endmember sulfosalts enables them to form even in As-dominated fluid systems.
Expression of glucose transporter‐2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses
2021-11-02

Abstract The retina has the highest relative energy consumption of any tissue, depending on a steady supply of glucose from the bloodstream. Glucose uptake is mediated by specific transporters whose regulation and expression are critical for the pathogenesis of many diseases, including diabetes and diabetic retinopathy. Here, we used immunofluorescence to show that glucose transporter‐2 (GLUT2) is expressed in horizontal cells of the mouse neuroretina in proximity to inner retinal capillaries. To study the function of GLUT2 in the murine retina, we used organotypic retinal explants, cultivated under entirely controlled, serum‐free conditions and exposed them to streptozotocin, a cytotoxic drug transported exclusively by GLUT2. Contrary to our expectations, streptozotocin did not measurably affect horizontal cell viability, while it ablated rod and cone photoreceptors in a concentration‐dependent manner. Staining for poly‐ADP‐ribose (PAR) indicated that the detrimental effect of streptozotocin on photoreceptors may be associated with DNA damage. The negative effect of streptozotocin on the viability of rod photoreceptors was counteracted by co‐administration of either the inhibitor of connexin‐formed hemi‐channels meclofenamic acid or the blocker of clathrin‐mediated endocytosis dynasore. Remarkably, cone photoreceptors were not protected from streptozotocin‐induced degeneration by neither of the two drugs. Overall, these data suggest the existence of a GLUT2‐dependent glucose transport shuttle, from horizontal cells into photoreceptor synapses. Moreover, our study points at different glucose uptake mechanisms in rod and cone photoreceptors. image
A refined approach to the diagnosis of Burkitt lymphoma in a resource‐poor setting
2021-11-02

Burkitt lymphoma (BL) is among the most studied human malignancies. The distinction of BL from other aggressive B-cell lymphomas is important for providing optimal oncological care. In the revised 4th edition of the World Health Organization (WHO) classification, BL is defined as ‘a highly aggressive but curable lymphoma that often presents in extranodal sites or as an acute leukemia. It is composed of monomorphic medium-sized B-cells with basophilic cytoplasm and numerous mitotic figures, usually with a demonstrable MYC gene translocation to an IG locus. The frequency of EBV (Epstein Barr virus) infection varies according to the epidemiological subtype of BL. No single parameter, such as morphologic, genetic analysis or immunophenotyping can be used as the gold standard for diagnosis of BL; a combination of several diagnostic techniques is necessary.
Hexagonal arrays of plasmonic gold nanopyramids on flexible substrates for surface-enhanced Raman scattering
2021-11-02

Abstract Surface-enhanced Raman spectroscopy (SERS) with pyramidal gold nanostructures increases the signal of Raman active analytes, since hotspots form at the edges and tip of a nanopyramid under illumination. 2D hexagonal arrays of pyramidal nanostructures with a quadratic base are fabricated through cost-effective nanosphere lithography and transferred onto elastomeric polydimethylsiloxane. By making use of the {111} crystal plane of a silicon (100) wafer, an inverted pyramidal array is etched, which serves as the complementary negative for the gold nanostructures. Either a continuous gold thin-film with protruding pyramids or separate isolated nanopyramids are produced. Three basic fabrication strategies are presented. The SERS enhancement is verified by Raman mapping of 4-mercaptobenzoic acid (4-MBA) molecules. Fabrication on a flexible substrate paves the way for future applications on curved surfaces or in situ tunable resonances.
TAMI-34. TARGETING CSF1R AND PD1 IN EXPERIMENTAL GLIOMA
2021-11-02

Abstract The treatment of glioblastoma remains a challenge. Novel therapeutic strategies are urgently needed. Targeting the immunosuppressive glioblastoma-associated microenvironment is an interesting approach in this regard. Tumor-associated macrophages represent a distinct population of tumor-infiltrating immune cells with tumor-promoting features. The colony stimulating factor-1/ colony stimulating factor-1 receptor (CSF-1/CSF1R) axis plays an important role for macrophage differentiation and survival inside the tumor microenvironment. We thus aimed at investigating the antiglioma activity of CSF1R inhibition alone or in combination with blockade of programmed death (PD) 1. We detected CSF1R expression in paired tissue samples of primary and corresponding progressive glioblastoma. We investigated anti-CSF1R treatment alone or in combination with anti-PD1 antibodies in the orthotopic syngeneic VM/Dk SMA560 glioma mouse model, evaluated post-treatment effects and assessed treatment-induced cytotoxicity in a coculture model of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) ex vivo. Anti-CSF1R monotherapy increased the latency until the onset of neurological symptoms. Combinations of anti-CSF1R and anti-PD1 antibodies prolonged the latency until the onset of neurological symptoms and led to long-term survivors in vivo. Immunohistochemical analysis of post-treatment SMA-560 glioma revealed a modulation of the microenvironment, including increased T cell infiltration and reduced numbers of tumor-associated macrophages. Furthermore, we observed treatment-induced cytotoxicity of combined anti-CSF1R and anti-PD1 treatment in the PDM/TILs cocultures ex vivo. Taken together, our data indicates that CSF1R is a promising therapeutic target for glioblastoma, potentially in combination with PD1 inhibition.
When Yeast Cells Change their Mind: Cell Cycle “Start” is Reversible under Starvation
2021-11-02

Abstract Eukaryotic cells decide in late G1 whether to commit to another round of genome duplication and division. This point of irreversible cell cycle commitment is a molecular switch termed “Restriction Point” in mammals and “Start” in budding yeast. At Start, yeast cells integrate multiple signals such as pheromones, osmolarity, and nutrients. If sufficient nutrients are lacking, cells will not pass Start. However, how the cells respond to nutrient depletion after they have made the Start decision, remains poorly understood. Here, we analyze by live cell imaging how post-Start yeast cells respond to nutrient depletion. We monitor fluorescently labelled Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re -import Whi5 back into the nucleus. This occurs when cells are faced with starvation up to 20 minutes after Start. In these cells, the positive feedback loop is interrupted, Whi5 re-binds DNA, and CDK activation occurs a second time once nutrients are replenished. Cells which re-import Whi5 also become sensitive to mating pheromone again, and thus behave like pre-Start cells. In summary, we show that upon starvation the commitment decision at Start can be reversed. We therefore propose that in yeast, as has been suggested for mammalian cells, cell cycle commitment is a multi-step process, where irreversibility in face of nutrient signaling is only reached approximately 20 minutes after CDK activation at Start.