Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice

Significance Light pervasively affects physiology and behavior, especially the sleep–wake cycle (SWc), which is generated by clock signaling in the suprachiasmatic nuclei (SCN). Light synchronizes this clock and additionally exerts direct (circadian-independent) acute effects on sleep. However, it has never been clarified whether longer photic exposure, as experienced daily, might exert long-term sustained direct light effects (SDLE). Recording sleep in mice lacking a functional clock and/or the retinal photopigment melanopsin, we uncovered that circadian-driven input and SDLE equally contribute to SWc. SDLE were primarily mediated through melanopsin, with half relayed through SCN, redefining the latter’s role. Modeling allowed SWc prediction under simulated jet lags, further demonstrating SDLE as an important mechanism to consider when managing health consequences of light exposure. Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep–wake disturbances. The nychthemeral sleep–wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light–dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light–dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/-) or SCN lesioning and/or melanopsin-based phototransduction (Opn4−/−), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light–dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.
A computational reproducibility study of PLOS ONE articles featuring longitudinal data analyses

Computational reproducibility is a corner stone for sound and credible research. Especially in complex statistical analyses—such as the analysis of longitudinal data—reproducing results is far from simple, especially if no source code is available. In this work we aimed to reproduce analyses of longitudinal data of 11 articles published in PLOS ONE. Inclusion criteria were the availability of data and author consent. We investigated the types of methods and software used and whether we were able to reproduce the data analysis using open source software. Most articles provided overview tables and simple visualisations. Generalised Estimating Equations (GEEs) were the most popular statistical models among the selected articles. Only one article used open source software and only one published part of the analysis code. Replication was difficult in most cases and required reverse engineering of results or contacting the authors. For three articles we were not able to reproduce the results, for another two only parts of them. For all but two articles we had to contact the authors to be able to reproduce the results. Our main learning is that reproducing papers is difficult if no code is supplied and leads to a high burden for those conducting the reproductions. Open data policies in journals are good, but to truly boost reproducibility we suggest adding open code policies.
Infection of Arabidopsis by cucumber mosaic virus triggers jasmonate‐dependent resistance to aphids that relies partly on the pattern‐triggered immunity factor BAK1

Abstract Many aphid‐vectored viruses are transmitted nonpersistently via transient attachment of virus particles to aphid mouthparts and are most effectively acquired or transmitted during brief stylet punctures of epidermal cells. In Arabidopsis thaliana, the aphid‐transmitted virus cucumber mosaic virus (CMV) induces feeding deterrence against the polyphagous aphid Myzus persicae. This form of resistance inhibits prolonged phloem feeding but promotes virus acquisition by aphids because it encourages probing of plant epidermal cells. When aphids are confined on CMV‐infected plants, feeding deterrence reduces their growth and reproduction. We found that CMV‐induced inhibition of growth as well as CMV‐induced inhibition of reproduction of M. persicae are dependent upon jasmonate‐mediated signalling. BRASSINOSTEROID INSENSITIVE1‐ASSOCIATED KINASE1 (BAK1) is a co‐receptor enabling detection of microbe‐associated molecular patterns and induction of pattern‐triggered immunity (PTI). In plants carrying the mutant bak1‐5 allele, CMV induced inhibition of M. persicae reproduction but not inhibition of aphid growth. We conclude that in wildtype plants CMV induces two mechanisms that diminish performance of M. persicae: a jasmonate‐dependent and PTI‐dependent mechanism that inhibits aphid growth, and a jasmonate‐dependent, PTI‐independent mechanism that inhibits reproduction. The growth of two crucifer specialist aphids, Lipaphis erysimi and Brevicoryne brassicae, was not affected when confined on CMV‐infected A. thaliana. However, B. brassicae reproduction was inhibited on CMV‐infected plants. This suggests that in A. thaliana CMV‐induced resistance to aphids, which is thought to incentivize virus vectoring, has greater effects on polyphagous than on crucifer specialist aphids.
Neonatal presentation of genetic epilepsies: Early differentiation from acute provoked seizures

Although most seizures in neonates are due to acute brain injury, some represent the first sign of neonatal onset genetic epilepsies. Delay in recognition and lack of expert assessment of neonates with epilepsy may result in worse developmental outcomes. As in older children and adults, seizure semiology in neonates is an essential determinant in diagnosis. We aimed to establish whether seizure type at presentation in neonates can suggest a genetic etiology.
Stewardship of global collective behavior

Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a “crisis discipline” just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
Performance of the FREND™ COVID-19 IgG/IgM Duo point-of-care test for SARS-CoV-2 antibody detection

ABSTRACT Purpose In the context of the current COVID-19 pandemic, multiple serological assays for the detection of severe acute respiratory syndrome 2 (SARS-CoV-2) immune response are currently being developed. This study compares the FRENDTM COVID-19 IgG/IgM Duo (NanoEntec) a point of care (POCT) assay with the automated Elecsys anti-SARS-CoV-2 electrochemiluminescent assay (Roche Diagnostics). Methods Serum samples (n = 81) from PCR-confirmed SARS-CoV-2 positive patients at different time points after the onset of symptoms were analyzed with both assays. An additional 24 serum samples with cross reactivity potential were also included. Results The sensitivity of the COVID-19 IgG/IgM Duo assay was higher as compared to the Elecsys anti-SARS-CoV-2 assay, especially when using the combined IgM/IgG result in samples analyzed within 6 days after the onset of symptoms (46.2% vs. 15.4%). The sensitivity of both assays increased with increasing time interval after the onset of symptoms and reached 100% for the COVID-19 IgG/IgM Duo assay in samples taken 14 days or more after symptom onset. Specificity of the COVID-19 IgG/IgM Duo assay was 95.8% for IgM, 91.7% for IgG and 87.5% for the combination of both. Conclusion This study shows that the sensitivity of both assays was highly dependent on the time interval between the onset of the COVID-19 symptoms and serum sampling. Furthermore, rapid serological testing for SARS-CoV-2 antibodies by means of the FRENDTM COVID-19 IgG/IgM Duo POCT assay showed a comparable diagnostic performance as the reference automated immunoassay.
Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions

Background The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound–guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. Methods We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. Results The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16–5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02–5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26–129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64–80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. Conclusion RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.
Amaryllidaceae Alkaloid Cherylline Inhibits the Replication of Dengue and Zika Viruses

Dengue fever, caused by dengue virus (DENV) is the most prevalent arthropod-borne viral disease and is endemic in many tropical and subtropical parts of the world, with an increasing incidence in temperate regions. The closely related flavivirus Zika virus (ZIKV) can be transmitted vertically in utero and causes congenital Zika syndrome and other birth defects. ABSTRACT Dengue fever, caused by dengue virus (DENV), is the most prevalent arthropod-borne viral disease and is endemic in many tropical and subtropical parts of the world, with an increasing incidence in temperate regions. The closely related flavivirus Zika virus (ZIKV) can be transmitted vertically in utero and causes congenital Zika syndrome and other birth defects. In adults, ZIKV is associated with Guillain-Barré syndrome. There are no approved antiviral therapies against either virus. Effective antiviral compounds are urgently needed. Amaryllidaceae alkaloids (AAs) are a specific class of nitrogen-containing compounds produced by plants of the Amaryllidaceae family with numerous biological activities. Recently, the AA lycorine was shown to present strong antiflaviviral properties. Previously, we demonstrated that Crinum jagus contained lycorine and several alkaloids of the cherylline, crinine, and galanthamine types with unknown antiviral potential. In this study, we explored their biological activities. We show that C. jagus crude alkaloid extract inhibited DENV infection. Among the purified AAs, cherylline efficiently inhibited both DENV (50% effective concentration [EC50], 8.8 μM) and ZIKV replication (EC50, 20.3 μM) but had no effect on HIV-1 infection. Time-of-drug-addition and -removal experiments identified a postentry step as the one targeted by cherylline. Consistently, using subgenomic replicons and replication-defective genomes, we demonstrate that cherylline specifically hinders the viral RNA synthesis step but not viral translation. In conclusion, AAs are an underestimated source of antiflavivirus compounds, including the effective inhibitor cherylline, which could be optimized for new therapeutic approaches.
Limited evidence for a positive relationship between hybridization and diversification across seed plant families

Hybridization has experimental and observational ties to evolutionary processes and outcomes such as adaptation, speciation, and radiation. Although it has been hypothesized that hybridization and diversification are positively correlated, this idea remains largely untested empirically, and hybridization can also potentially reduce diversity. Here, we use a hybridization database on 170 seed plant families, life history information, and a time‐calibrated phylogeny to test for phylogenetically‐corrected associations between hybridization and diversification rates, while also taking into account life‐history traits that may be correlated with both processes. We use three methods to estimate diversification rates and two metrics of hybridization. Although hybridization explains only a small amount of overall variation in diversification rates, we show that diversification and hybridization are sometimes positively correlated, although the effect sizes are very small. Moreover, the relationship remains detectable when incorporating the correlations between diversification and two other life history characteristics, perenniality and woodiness. We discuss potential mechanisms for this association under four different scenarios: hybridization may drive diversification, diversification may drive hybridization, both hybridization and diversification may jointly be driven by other factors, or, as an alternative, that there is in fact no relationship between the two. We suggest future studies to disentangle the causal structure.
Fatal Human Infection with Evidence of Intrahost Variation of Eastern Equine Encephalitis Virus, Alabama, USA, 2019

Eastern equine encephalitis virus (EEEV) is an arbovirus in the family Togaviridae, genus Alphavirus, found in North America and associated with freshwater/hardwood swamps in the Atlantic, Gulf Coast, and Great Lakes regions. EEEV disease in humans is rare but causes substantial illness and death. To investigate the molecular epidemiology and microevolution of EEEV from a fatal case in Alabama, USA, in 2019, we used next-generation sequencing of serum and cerebrospinal fluid (CSF). Phylogenetic inference indicated that the infecting strain may be closely related to isolates from Florida detected during 2010–2014, suggesting potential seeding from Florida. EEEV detected in serum displayed a higher degree of variability with more single-nucleotide variants than that detected in the CSF. These data refine our knowledge of EEEV molecular epidemiologic dynamics in the Gulf Coast region and demonstrate potential quasispecies bottlenecking within the central nervous system of a human host.
Prevalence and phenotype associations of complement factor I mutations in geographic atrophy

Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age‐related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease‐causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross‐sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype‐phenotype study was performed. Four hundred and sixty‐eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 μg/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.
Percutaneous Endoscopic Gastrostomy in Children: An Update to the ESPGHAN Position Paper

ABSTRACT Background: The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper from 2015 on percutaneous endoscopic gastrostomy (PEG) required updating in the light of recent clinical knowledge and data published in medical journals since 2014. Methods: A systematic review of medical literature from 2014 to 2020 was carried out. Consensus on the content of the manuscript, including recommendations, was achieved by the authors through electronic and virtual means. The expert opinion of the authors is also expressed in the manuscript when there was a lack of good scientific evidence regarding PEGs in children in the literature. Results: The authors recommend that the indication for a PEG be individualized, and that the decision for PEG insertion is arrived at by a multidisciplinary team (MDT) having considered all appropriate circumstances. Well timed enteral nutrition is optimal to treat faltering growth to avoid complications of malnutrition and body composition. Timing, device choice and method of insertion is dependent on the local expertise and after due consideration with the MDT and family. Major complications such as inadvertent bowel perforation should be avoided by attention to good technique and by ensuring the appropriate experience of the operating team. Feeding can be initiated as early as 3 hours after tube placement in a stable child with iso-osmolar feeds of standard polymeric formula. Low-profile devices can be inserted initially using the single-stage procedure or after 2–3 months by replacing a standard PEG tube, in those requiring longer-term feeding. Having had a period of non-use and reliance upon oral intake for growth and weight gain—typically 8–12 weeks—a PEG may then safely be removed after due consultation. In the event of non-closure of the fistula the most successful method for closing it, to date, has been a surgical procedure, but the Over-The-Scope-Clip (OTSC) has recently been used with considerable success in this scenario. Conclusions: A multidisciplinary approach is mandatory for the best possible treatment of children with PEGs. Morbidity and mortality are minimized through team decisions on indications for insertion, adequate planning and preparation before the procedure, subsequent monitoring of patients, timing of the change to low-profile devices, management of any complications, and optimal timing of removal of the PEG.
Nomogram for predicting mandatory ICU admission after gastrectomy for gastric cancer.

BACKGROUND This study aimed to identify risk factors that were associated with mandatory intensive care unit (ICU) admission after gastrectomy for gastric cancer. We then employed these risk factors to construct and validate a nomogram for predicting mandatory ICU admission after gastrectomy, which may identify those who require ICU indeed and improve ICU utilization. METHODS A number of 999 gastric cancer patients undergoing gastrectomy from January 2010 to June 2019 were included in the retrospective study. Forty-three patients were classified into mandatory ICU admission groups, and the remaining 956 patients were allocated into the no need for ICU admission group. The candidate variables, including patient demographic characteristics, preoperative laboratory tests and surgical variables, were compared between the two groups. We then carried out univariate and multivariate logistic regression analyses to find out risk factors for mandatory ICU admission. In order to develop the predictive model, we used Akaike information criterion (AIC) to select risk factors via a step-down backward process from the multivariate regression model. RESULTS A number of risk factors for mandatory ICU admission were identified and subsequently used to build the nomogram: age [odds ratio (OR), 1.03; 95% CI, 1.00-1.07; P=0.031], ASA status (III-IV vs. I- II: OR,1.74; 95% CI, 0.88-3.46; P=0.114), tumor size (OR, 1.28; 95% CI, 1.08-1.51; P=0.004), estimated blood loss (OR, 1.001; 95% CI, 1.000-1.001; P=0.082) as well as intraoperative transfusion (Yes vs. No: OR, 3.82; 95% CI, 1.87-7.82; P<0.001). C-index of the nomogram was 0.800, indicating good discrimination. Both Calibration curve and Hosmer-Lemeshow goodness-of-fit tests (P=0.128) showed that there was a high degree of agreement between the prediction and actual outcome. CONCLUSIONS A nomogram to predict mandatory ICU admission after gastrectomy for gastric cancer was constructed and validated. Clinicians could apply this predictive model to improve usage of limited ICU resources effectively.