Miracle-dz/UniFAR-FTUs huggingface dataset:
Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management

Background: The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Methods: Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Results: Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. Conclusions: There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with topical corticosteroids and without discontinuation of the systemic treatment.
Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response

The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50%) that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1), and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1). Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/), obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.
A simple object-oriented and open-source model for scientific and policy analyses of the global climate system – Hector v1.0

Abstract. Simple climate models play an integral role in the policy and scientific communities. They are used for climate mitigation scenarios within integrated assessment models, complex climate model emulation, and uncertainty analyses. Here we describe Hector v1.0, an open source, object-oriented, simple global climate carbon-cycle model. This model runs essentially instantaneously while still representing the most critical global-scale earth system processes. Hector has a three-part main carbon cycle: a one-pool atmosphere, land, and ocean. The model's terrestrial carbon cycle includes primary production and respiration fluxes, accommodating arbitrary geographic divisions into, e.g., ecological biomes or political units. Hector actively solves the inorganic carbon system in the surface ocean, directly calculating air–sea fluxes of carbon and ocean pH. Hector reproduces the global historical trends of atmospheric [CO2], radiative forcing, and surface temperatures. The model simulates all four Representative Concentration Pathways (RCPs) with equivalent rates of change of key variables over time compared to current observations, MAGICC (a well-known simple climate model), and models from the 5th Coupled Model Intercomparison Project. Hector's flexibility, open-source nature, and modular design will facilitate a broad range of research in various areas.
Old age at diagnosis increases risk of tumor progression in nasopharyngeal cancer

Age at diagnosis has been found to be a prognostic factor of outcomes in various cancers. However, the effect of age at diagnosis on nasopharyngeal cancer (NPC) progression has not been explored. We retrospectively evaluated the relationship between age and disease progression in 3,153 NPC patients who underwent radiotherapy, chemotherapy, or chemoradiotherapy between 2007 and 2009. Patients were randomly assigned to either a testing cohort or a validation cohort by computer-generated random assignment. X-tile plots determined the optimal cut-point of age based on survival status to be ≤61 vs. >61 years. Further correlation analysis showed that age >61 years was significantly correlated with the tumor progression and therapeutic regimen in both testing and validation cohorts (P <0.05). In the present study, we observed that older age (>61 years) was a strong and independent predictor of poor disease-free survival (DFS) and cancer-specific survival (CSS), in both univariate and multivariate analyses. Age was also found to be a significant prognostic predictor as well (P <0.05) when evaluating patients with the same disease stage. ROC analysis confirmed the predictive value of age on NPC-specific survival in both cohorts (P <0.001) and suggested that age may improve the ability to discriminate outcomes in NPCs, especially regarding tumor progression. In conclusion, our study suggests that older age at NPC diagnosis is associated with a higher incidence of tumor progression and cancer-specific mortality. Age is a strong and independent predictor of poor outcomes and may allow for more tailored therapeutic decision-making and individualized patient counseling.
The VLA-COSMOS 3 GHz Large Project: Continuum data and source catalog release

We present the VLA-COSMOS 3 GHz Large Project based on 384 hours of observations with the Karl G. Jansky Very Large Array (VLA) at 3 GHz (10 cm) toward the two square degree Cosmic Evolution Survey (COSMOS) field. The final mosaic reaches a median rms of 2.3 uJy/beam over the two square degrees at an angular resolution of 0.75". To fully account for the spectral shape and resolution variations across the broad (2 GHz) band, we image all data with a multiscale, multifrequency synthesis algorithm. We present a catalog of 10,830 radio sources down to 5 sigma, out of which 67 are combined from multiple components. Comparing the positions of our 3 GHz sources with those from the Very Long Baseline Array (VLBA)-COSMOS survey, we estimate that the astrometry is accurate to 0.01" at the bright end (signal-to-noise ratio, S/N_3GHz > 20). Survival analysis on our data combined with the VLA-COSMOS 1.4~GHz Joint Project catalog yields an expected median radio spectral index of alpha=-0.7. We compute completeness corrections via Monte Carlo simulations to derive the corrected 3 GHz source counts. Our counts are in agreement with previously derived 3 GHz counts based on single-pointing (0.087 square degrees) VLA data. In summary, the VLA-COSMOS 3 GHz Large Project simultaneously provides the largest and deepest radio continuum survey at high (0.75") angular resolution to date, bridging the gap between last-generation and next-generation surveys.
Enhanced linear-array photoacoustic beamforming using modified coherence factor

Abstract. Photoacoustic imaging (PAI) is a promising medical imaging modality providing the spatial resolution of ultrasound imaging and the contrast of optical imaging. For linear-array PAI, a beamformer can be used as the reconstruction algorithm. Delay-and-sum (DAS) is the most prevalent beamforming algorithm in PAI. However, using DAS beamformer leads to low-resolution images as well as high sidelobes due to nondesired contribution of off-axis signals. Coherence factor (CF) is a weighting method in which each pixel of the reconstructed image is weighted, based on the spatial spectrum of the aperture, to mainly improve the contrast. We demonstrate that the numerator of the formula of CF contains a DAS algebra and propose the use of a delay-multiply-and-sum beamformer instead of the available DAS on the numerator. The proposed weighting technique, modified CF (MCF), has been evaluated numerically and experimentally compared to CF. It was shown that MCF leads to lower sidelobes and better detectable targets. The quantitative results of the experiment (using wire targets) show that MCF leads to for about 45% and 40% improvement, in comparison with CF, in the terms of signal-to-noise ratio and full-width-half-maximum, respectively.
Mini-screw Implant or Transpalatal Arch-Mediated Anchorage Reinforcement during Canine Retraction: A Randomized Clinical Trial

Objective To compare mesial movement of upper first molars during maxillary canine retraction using a pre-adjusted edgewise appliance provided by anchorage reinforcement and a transpalatal arch or mini-screw implant. Design Randomized clinical trial. Setting Department of Orthodontics and Dentofacial Orthopedics, Armed Forces Medical College, Pune, India. Subjects and methods From a cohort of subjects requiring the extraction of both upper first premolars and pre-adjusted edgewise appliances to correct their malocclusion, a total of 30 were randomly allocated to receive two different forms of anchorage reinforcement: Group A – receiving mini-screw implant and Group B – receiving a transpalatal arch Group A subjects received titanium mini-screw implants placed at the start of treatment between the maxillary second premolar and maxillary first molar. Maxillary second premolars were secured to the mini-screw implants using of 0·010-inch stainless steel ligature wire. Group B subjects received a custom-made transpalatal arch which was soldered to maxillary first molar bands. Active canine retraction was initiated in both groups on placement of a 0·019×0·025-inch stainless steel archwire using nickel titanium closed coil springs. Outcome measures Mesial movement of the upper first molars as measured on pre- (T1) and post-treatment (T2) lateral skull radiographs. Results The results showed that in Group A the mean mesial movement of the first molars between T1 and T2 was 0·0 mm (SD 0·02; P = 0·90), whereas in Group B there was a mean forward movement of the first maolars of 2·48 mm (SD 0·71; P<0·001). Conclusion In this trial, mini-screw implants placed prior to levelling and aligning were able to provide absolute anchorage during maxillary canine retraction, in contrast to a transpalatal arch.
Viral Specific Factors Contribute to Clinical Respiratory Syncytial Virus Disease Severity Differences in Infants

Background There is a wide range of severity of respiratory syncytial viral (RSV) disease in previously healthy infants. Host factors have been well demonstrated to contribute to disease severity differences. However the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied. Methods Low-passage isolates of RSV collected prospectively from infants with different degrees of RSV disease severity were evaluated in vitro, holding host factors constant, so as to assess whether isolates induced phenotypically different cytokine/chemokine concentrations in a human lung epithelial cell line. Sixty-seven RSV isolates from previously healthy infants (38 hospitalized for acute RSV infection (severe disease) and 29 never requiring hospitalization (mild disease)) were inoculated into A549, lung epithelial cells at precisely controlled, low multiplicity of infection to mimic natural infection. Cultures were evaluated at 48 hours, 60 hours, and 72 hours to evaluate area under the curve (AUC) cytokine/chemokine induction. Results Cells infected with isolates from severely ill infants produced higher mean concentrations of all cytokine/chemokines tested (IL-1α, IL-6, IL-8 and RANTES) at all-time points tested. RSV isolates collected from infants with severe disease induced significantly higher AUCIL-8 and AUCRANTES secretion in infected cultures than mild disease isolates (p=0.028 and p=0.019 respectively). IL-8 and RANTES concentrations were 4 times higher at 48 hours for these severely ill infant isolates. Additionally, 38 isolates were evaluated at all-time points for quantity of virus. RSV concentration significantly correlated with both IL-8 and RANTES at all-time points. Neither cytokine/chemokine concentrations nor RSV concentrations were associated with RSV subgroup. Discussion Infants’ RSV disease severity differences may be due in part to intrinsic viral strain-specific characteristics.
Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells

Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in spatial scope can contribute to the functional diversity of retinal ganglion cell types.
Point-Based POMDP Algorithms: Improved Analysis and Implementation

Existing complexity bounds for point-based POMDP value iteration algorithms focus either on the curse of dimensionality or the curse of history. We derive a new bound that relies on both and uses the concept of discounted reachability; our conclusions may help guide future algorithm design. We also discuss recent improvements to our (point-based) heuristic search value iteration algorithm. Our new implementation calculates tighter initial bounds, avoids solving linear programs, and makes more effective use of sparsity.
Macrolide-inducible resistance to clindamycin and the D-test.

Clindamycin has been used to treat serious infections caused by susceptible Staphylococcus aureus strains in children for more than 30 years. It remains effective for many infections caused by community-acquired methicillin-resistant S. aureus (CAMRSA). Clindamycin also is useful for selected infections caused by pneumococci, group A streptococci, and a number of other microbes. Absorption after oral administration is nearly complete, yielding serum concentrations that approximate those from intravenous (IV) administration. This permits early transition to outpatient management of susceptible infections without the complications of continued IV access. Clindamycin resistance is common among health care-associated MRSA strains. Most CA-MRSA remain susceptible to date, but resistance rates vary by region. Pneumococcal resistance to clindamycin may exceed 30% in some areas of the US, while about 4% of group A streptococcal isolates are resistant. Macrolide-inducible resistance to clindamycin was first recognized in the laboratory in the early 1960s. Clinical isolates resistant to clindamycin were first recognized in 1968. Relapse of S. aureus infection in a rabbit model of endocarditis during clindamycin therapy was observed in the early 1970s. Clinical and bacteriologic relapse in a patient with S. aureus endocarditis during the fourth week of clindamycin therapy after initial improvement was reported in 1976. The initial isolate was susceptible to erythromycin and clindamycin while that from the relapse was resistant to both. This led to abandonment of clindamycin for treatment of endocarditis. The mechanism by which resistance to clindamycin can emerge during therapy, the D-test used to detect it, and the clinical implications are discussed in this review.
Distribution and biomarker of carbon‐14 labeled fullerene C60 ([14C(U)]C60) in pregnant and lactating rats and their offspring after maternal intravenous exposure

A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon‐14 labeled C60 ([14C(U)]C60). Rats were administered [14C(U)]C60 (~0.2 mg [14C(U)]C60 kg–1 body weight) or 5% polyvinylpyrrolidone (PVP)‐saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [14C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [14C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [14C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl‐tRNA biosynthesis. This study demonstrated that [14C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. Copyright © 2015 John Wiley & Sons, Ltd.
Toddlers' Verb Lexicon Diversity and Grammatical Outcomes.

PURPOSE The goals of this study were to quantify longitudinal expectations for verb lexicon growth and to determine whether verb lexicon measures were better predictors of later grammatical outcomes than noun lexicon measures. METHOD Longitudinal parent-report measures from the MacArthur-Bates Communicative Development Inventory (Fenson et al., 2007) from ages 21 to 30 months from an archival database were used to model growth in common noun and verb lexicon size for 45 typically developing toddlers. Communicative Development Inventory growth coefficients and 24-month measures of lexical diversity from spontaneous language samples were used to predict 30-month grammatical outcomes on the Index of Productive Syntax (Scarborough, 1990). RESULTS Average verb growth was characterized by 50.57 verbs at 24 months, with linear growth of 8.29 verbs per month and deceleration overall. Children with small verb lexicons or slow linear growth at 24 months accelerated during this developmental period. Verb lexicon measures were better predictors of grammatical outcomes than noun lexicon measures, accounting for 47.8% of the variance in Index of Productive Syntax scores. Lexical verb diversity in spontaneous speech emerged as the single best predictor. CONCLUSION Measures of verb lexicon size and diversity should be included as part of early language assessment to guide clinical decision making with young children at risk for language impairment.
The Markov blankets of life: autonomy, active inference and the free energy principle

This work addresses the autonomous organization of biological systems. It does so by considering the boundaries of biological systems, from individual cells to Home sapiens, in terms of the presence of Markov blankets under the active inference scheme—a corollary of the free energy principle. A Markov blanket defines the boundaries of a system in a statistical sense. Here we consider how a collective of Markov blankets can self-assemble into a global system that itself has a Markov blanket; thereby providing an illustration of how autonomous systems can be understood as having layers of nested and self-sustaining boundaries. This allows us to show that: (i) any living system is a Markov blanketed system and (ii) the boundaries of such systems need not be co-extensive with the biophysical boundaries of a living organism. In other words, autonomous systems are hierarchically composed of Markov blankets of Markov blankets—all the way down to individual cells, all the way up to you and me, and all the way out to include elements of the local environment.
Treatment of tuberculosis in complex emergencies in developing countries: a scoping review

Almost 172 million people live in complex emergencies globally resulting from political and/or economic instability. The provision and continuity of health care in complex emergencies remain a significant challenge. Health agencies are often hesitant to implement tuberculosis programmes in particular because its treatment requires a longer commitment than most acute diseases. However, not treating tuberculosis promptly increases mortality and untreated tuberculosis further increases the incidence of tuberculosis. Given that complex emergencies are increasing globally, there is an urgent need to analyse the available evidence to improve our understanding of how best to deliver tuberculosis programmes in such settings. Using a scoping review method, we selected and analysed 15 studies on tuberculosis programmes in complex emergencies. We found that despite the challenges, tuberculosis programmes have been successful in complex emergencies. We identified seven cross-cutting factors that were found to be important: service providers and treatment regime, training and supervision, donor support, adherence, leadership and coordination, monitoring and government and community support. In general, programmes showed greater creativity and flexibility to adapt to the local conditions and at times, it also meant diverting from the WHO guidelines. We identify areas of further research including the need to study the effectiveness of programmes that divert from the WHO guidelines and their implication on drug resistance.
On the Bollobás–Eldridge Conjecture for Bipartite Graphs

Let G be a simple graph on n vertices. A conjecture of Bollobás and Eldridge [5] asserts that if $\delta (G)\geq \frac{kn-1}{k+1}$ then G contains any n vertex graph H with Δ(H) = k. We prove a strengthened version of this conjecture for bipartite, bounded degree H, for sufficiently large n. This is the first result on this conjecture for expander graphs of arbitrary (but bounded) degree. An important tool for the proof is a new version of the Blow-Up Lemma.