Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting

Significance Antibiotic combination therapy is a promising strategy to combat the rising problem of resistance. However, developing such strategies is hindered by the lack of an experimental system that allows testing of strategies in a realistic epidemiological context. We present an approach to test the effects of different treatment strategies in vitro in order to narrow the gap between computational and clinical studies. Using a laboratory automation system, we approximate the epidemiological population dynamics expected in a hospital setting using experimentally evolving bacterial populations. We show that as long as there is no influx of double resistance into the system, combination therapy outperforms all other tested strategies, even at concentrations lower than those used for monotherapy. The rapid rise of antibiotic resistance, combined with the increasing cost and difficulties to develop new antibiotics, calls for treatment strategies that enable more sustainable antibiotic use. The development of such strategies, however, is impeded by the lack of suitable experimental approaches that allow testing their effects under realistic epidemiological conditions. Here, we present an approach to compare the effect of alternative multidrug treatment strategies in vitro using a robotic liquid-handling platform. We use this framework to study resistance evolution and spread implementing epidemiological population dynamics for treatment, transmission, and patient admission and discharge, as may be observed in hospitals. We perform massively parallel experimental evolution over up to 40 d and complement this with a computational model to infer the underlying population-dynamical parameters. We find that in our study, combination therapy outperforms monotherapies, as well as cycling and mixing, in minimizing resistance evolution and maximizing uninfecteds, as long as there is no influx of double resistance into the focal treated community.
Determination of phosphorus distribution in the silicon dioxide/silicon layer system by secondary ion mass spectrometry

A measurement technique for quantitative distribution analysis of phosphorus in the layer system SiO/sub 2//Si was developed. Oxygen primary ions and an increased oxygen pressure (5 x 10/sup -5/ mbar) in the sample chamber were used for elimination of the matrix effect. Precise adjustment of the mass spectrometer during depth profiling with high mass resolution was controlled by a computer routine. Charging effects were compensated by flooding of the sample with electrons, optimized biasing of the accelerating potential of the secondary ions, and normalization to a reference signal. A detection limit of 1 x 10/sup 16/ atoms x cm/sup -3/ and an accuracy of +/- 30% were obtained. The improved measurement technique was used for determination of segregation coefficients, which are used as input parameters for process modeling in metal oxide semiconductor transistor production.
DeepIII: Predicting Isoform-Isoform Interactions by Deep Neural Networks and Data Fusion

Alternative splicing enables a gene translating into different isoforms and into the corresponding proteoforms, which actually accomplish various biological functions of a living body. Isoform-isoform interactions (IIIs) provide a higher resolution interactome to explore the cellular processes and disease mechanisms than the canonically studied protein-protein interactions (PPIs), which are often recorded at the coarse gene level. The knowledge of IIIs is critical to map pathways, understand protein complexity and functional diversity, but the known IIIs are very scanty. In this paper, we propose a deep learning based method called DeepIII to systematically predict genome-wide IIIs by integrating diverse data sources, including RNA-seq datasets of different human tissues, exon array data, domain-domain interactions (DDIs) of proteins, nucleotide sequences and amino acid sequences. Particularly, DeepIII fuses these data to learn the representation of isoform pairs with a four-layer deep neural networks, and then performs binary classification on the learnt representation to achieve the prediction of IIIs. Experimental results show that DeepIII achieves a superior prediction performance to the state-of-the-art solutions and the III network constructed by DeepIII gives more accurate isoform function prediction. Case studies further confirm that DeepIII can differentiate the individual interaction partners of different isoforms spliced from the same gene. The code and datasets of DeepIII are available at http://mlda.swu. edu.cn/codes.php? name=DeepIII.
Metamizole-Induced Type I Kounis Syndrome.

Kounis syndrome (KS) is defined as acute coronary syndrome (ACS) triggered by mast cell and platelet activation in the setting of allergic or anaphylactic insults. KS is a unique and complex cause of ACS and many cases may be missed due to its highly variable clinical manifestations. In this report, we present a case of KS type I triggered by metamizole in the absence of a previous history of allergy to this drug. Following the administration of metamizole, the patient developed generalized acute urticaria, chest pain and diaphoresis. Electrocardiography (ECG) showed ST-segment elevation suggestive of myocardial infarction complicated by ventricular tachycardia. No coronary disease was observed on coronary angiography. The cardiac manifestations of KS may be life-threatening, and so it is important to appropriately recognize and treat this condition. LEARNING POINTS Kounis syndrome (KS) diagnosis requires a high index of suspicion and should be considered in patients who present with acute coronary syndrome (ACS) soon after the administration of a new medication or possible allergic stimulus.Treatment should be administered carefully, since some drugs used to treat the cardiac manifestations of KS can worsen the allergic reaction.The prognosis is generally good with appropriate treatment, but some complications may occur, such as malignant arrhythmia.
A review of the BCG vaccine and other approaches toward tuberculosis eradication

ABSTRACT Despite aggressive eradication efforts, Tuberculosis (TB) remains a global health burden, one that disproportionally affects poorer, less developed nations. The only vaccine approved for TB, the Bacillus of Calmette and Guérin (BCG) vaccine remains controversial because it’s stated efficacy has been cited as anywhere from 0 to 80%. Nevertheless, there have been exciting discoveries about the mechanism of action of the BCG vaccine that suggests it has a role in immunization schedules today. We review recent data suggesting the vaccine imparts protection against both tuberculosis and non-tuberculosis pathogens via a newly discovered immune system called trained immunity. BCG’s efficacy also appears to be tied to its affect on granulocytes at the epigenetic and hematopoietic stem cell levels, which we discuss in this article at length. We also write about how the different strains of the BCG vaccine elicit different immune responses, suggesting that certain BCG strains are more immunogenic than others. Finally, our review delves into how the current vaccine is being reformulated to be more efficacious, and track the development of the next generation vaccines against TB.
Use of Brentuximab Vedotin in a Non-HIV Patient with Primary Effusion Lymphoma.

Primary effusion lymphoma is a rare and aggressive large B-cell lymphoma presenting as malignant effusion with poor prognosis. Although it is more prevalent among HIV patients, it has also been described in non-HIV immunocompromised individuals. Given its rarity, there are no large randomized trials regarding the best therapeutic option. The choice of therapy is based on retrospective studies, case reports and preclinical data. We present the case of a non-HIV patient with relapsed disease after treatment with CHOP who was then successfully treated with brentuximab vedotin, achieving complete remission. LEARNING POINTS Primary effusion lymphoma is a rare entity in non-HIV patients, so there are no clinical trials regarding therapeutic options or management decisions.Targeted therapy with brentuximab vedotin has been used in other CD30 positive malignancies and in HIV-related primary effusion lymphoma with good outcomes.We present the case of a non-HIV patient with primary effusion lymphoma who was successfully treated with brentuximab vedotin, which highlights the potential role of a new therapeutic approach in this subgroup of patients.
Prevalence and longitudinal correlates of recent exposure to fentanyl among HIV-positive people who use unregulated drugs during a community-wide overdose crisis

ABSTRACT The United States and Canada are experiencing an opioid overdose crisis driven largely by exposure to fentanyl (a potent synthetic opioid), with little known about fentanyl exposure among HIV-positive people who use unregulated drugs (PWUD). We sought to estimate the prevalence and correlates of fentanyl exposure among a community-recruited sample derived from a prospective cohort study of HIV-positive PWUD in Vancouver, Canada. Generalized linear mixed-effects analyses were used to identify longitudinal factors associated with a fentanyl-positive urine drug screen test. Between June 2016-November 2017, 456 participants were recruited and contributed 1007 observations. At baseline, 96% of participants were ART-exposed, 72% had an HIV viral load (VL) <50 copies/mL and 21% had a fentanyl-positive test. Longitudinally, fentanyl-positive tests were characterized by: younger participant age (Adjusted Odds Ratio [AOR] = 0.45), recent non-fatal overdose (AOR = 2.30), engagement in opioid agonist therapy (AOR = 1.91), and at least daily heroin injection (AOR = 11.27). CD4+ cell count was negatively associated with fentanyl urine positivity (AOR = 0.92) (all p < 0.05). We identified several risk factors for overdose linked to fentanyl exposure among this sample, although no link with HIV treatment engagement or detectable HIV VL. Innovative strategies are needed to reduce the harmful effects of the contaminated unregulated drug supply experienced by PWUD.
Obstructive Sleep Apnea Treatment and Dementia Risk in Older Adults.

STUDY OBJECTIVES To examine associations between PAP therapy, adherence and incident diagnoses of Alzheimer's disease (AD), mild cognitive impairment (MCI), and dementia not-otherwise-specified (DNOS) in older adults. METHODS This retrospective study utilized Medicare 5% fee-for-service claims data of 53,321 beneficiaries, aged 65+, with an OSA diagnosis prior to 2011. Study participants were evaluated using ICD-9 codes for neurocognitive syndromes [AD(n=1,057), DNOS(n=378), and MCI(n=443)] that were newly-identified between 2011-2013. PAP treatment was defined as presence of ≥1 durable medical equipment (HCPCS) code for PAP supplies. PAP adherence was defined as ≥2 HCPCS codes for PAP equipment, separated by≥1 month. Logistic regression models, adjusted for demographic and health characteristics, were used to estimate associations between PAP treatment or adherence and new AD, DNOS, and MCI diagnoses. RESULTS In this sample of Medicare beneficiaries with OSA, 59% were men, 90% were non-Hispanic whites and 62% were younger than 75y. The majority (78%) of beneficiaries with OSA were prescribed PAP (treated), and 74% showed evidence of adherent PAP use. In adjusted models, PAP treatment was associated with lower odds of incident diagnoses of AD and DNOS (OR=0.78, 95% CI:0.69-0.89; and OR=0.69, 95% CI:0.55-0.85). Lower odds of MCI, approaching statistical significance, were also observed among PAP users (OR=0.82, 95% CI:0.66-1.02). PAP adherence was associated with lower odds of incident diagnoses of AD (OR=0.65, 95% CI:0.56-0.76). CONCLUSIONS PAP treatment and adherence are independently associated with lower odds of incident AD diagnoses in older adults. Results suggest that treatment of OSA may reduce risk of subsequent dementia.
Effect of age of the laying hen on the composition of the egg

abstract 1. All eggs laid by a group of 16 light‐body‐weight hens during the laying year were weighed and divided into yolk, albumen and shell and the wet and dry weights of the components determined. 2. After an initial period of about 2 months, the weights of egg, water, wet albumen, wet and dry yolk increased with age, whereas those of dry albumen and wet and dry shell remained constant. Dry shell per square centimetre surface area decreased with age but water per square centimetre surface area remained constant.
Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease

Over-accumulation of oxalate in humans may lead to nephrolithiasis and nephrocalcinosis. Humans lack endogenous oxalate degradation pathways (ODP), but intestinal microbes can degrade oxalate using multiple ODPs and protect against its absorption. The exact oxalate-degrading taxa in the human microbiota and their ODP have not been described. We leverage multi-omics data (>3000 samples from >1000 subjects) to show that the human microbiota primarily uses the type II ODP, rather than type I. Furthermore, among the diverse ODP-encoding microbes, an oxalate autotroph, Oxalobacter formigenes, dominates this function transcriptionally. Patients with inflammatory bowel disease (IBD) frequently suffer from disrupted oxalate homeostasis and calcium oxalate nephrolithiasis. We show that the enteric oxalate level is elevated in IBD patients, with highest levels in Crohn’s disease (CD) patients with both ileal and colonic involvement consistent with known nephrolithiasis risk. We show that the microbiota ODP expression is reduced in IBD patients, which may contribute to the disrupted oxalate homeostasis. The specific changes in ODP expression by several important taxa suggest that they play distinct roles in IBD-induced nephrolithiasis risk. Lastly, we colonize mice that are maintained in the gnotobiotic facility with O. formigenes, using either a laboratory isolate or an isolate we cultured from human stools, and observed a significant reduction in host fecal and urine oxalate levels, supporting our in silico prediction of the importance of the microbiome, particularly O. formigenes in host oxalate homeostasis.
Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

Animals have evolved light-sensitive G protein–coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins. Using genomic data from over 400 mammalian species from 22 orders, unique patterns of evolution for each mammalian opsins were identified, including photoisomerases, RGR-opsin (RGR) and peropsin (RRH), as well as atypical opsins, encephalopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5). The results demonstrate that OPN5 and rhodopsin show extreme conservation across all mammalian lineages. The cone opsins, SWS1 and LWS, and the nonvisual opsins, OPN3 and RRH, demonstrate a moderate degree of sequence conservation relative to other opsins, with some instances of lineage-specific gene loss. Finally, the photoisomerase, RGR, and the best-studied atypical opsin, OPN4, have high sequence diversity within mammals. These conservation patterns are maintained in human populations. Importantly, all mammalian opsins retain key amino acid residues important for conjugation to retinal-based chromophores, permitting light sensitivity. These patterns of evolution are discussed along with known functions of each atypical opsin, such as in circadian or metabolic physiology, to provide insight into the observed patterns of evolutionary constraint.
Neurobiology of Avoidant/Restrictive Food Intake Disorder in Youth With Overweight/Obesity Versus Healthy Weight

ABSTRACT Objective Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight. Method Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger. Results Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [−45.09, −3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB. Conclusions Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.
The role of kinematic properties in multiple object tracking

People commonly track objects moving in complex natural displays and their performance in the multiple object tracking paradigm has been used to study such visual attention for more than three decades. Given the theoretical and practical importance of object tracking, it is critical to understand how people solve the correspondence problem to track objects; however, it remains unclear what information people use to achieve this feat. In particular, although people can track multiple moving objects based on their positions, there is ambiguity about whether people can track objects via higher order kinematic information, such as velocity. We designed a paradigm in which position was rendered uninformative to directly examine whether people could use higher order kinematic information to track multiple objects. We find that people can track via velocity, but not acceleration, even though observers can reliably detect the acceleration cue that they cannot use for tracking. Furthermore, we show a capacity constraint on using higher order kinematic information—people perform worse when required to use velocity to resolve correspondence for multiple object pairs simultaneously. Together, our results suggest that, although people can use higher order kinematic information for object tracking, precise higher order kinematic information is not freely available from the early visual system.
Bio-Guided Study on Melastoma malabathricum Linn Leaves and Elucidation of its Biological Activities

The present study aimed to isolate and identify constituents with antibacterial activity from the Methanol extract of Melastoma malabathricum leaves (MMML) through bioassay guided fractionation. Furthermore, the study scoped to evaluate the cytotoxic effects of M. malabathricum leaves fractions for possible protective effect of antoxidative constituents present in the fractions. The MMML extract was fractionated by Vacuum Liquid Chromatography (VLC) to afford M. malabathricum leaves fractions (ML1-ML6) of increasing polarities. Antibacterial activity of plant extract, six fractions and two bioactive constituents against Staphylococcus aureus reference strain, methicillin-resistant Staphylococcus aureus reference strain (MRSA), eleven clinical MRSA isolates, three clinical Pseudomonas aeruginosa isolates and P. aeruginosa reference strain was evaluated using Minimum Inhibitory Concentration (MIC). The bioactive constituents responsible for antibacterial activity of MMML, fractions were detected by direct TLC-bioautography. The data obtained from MIC assay showed that ML5 effectively inhibited growth of all test bacterial pathogens. Direct TLC-bioautography revealed that ML5 had the highest number of antibacterial compounds. Following bioassay-guided fractionation, Kaempferol-3-O-(2", 6"-di-O-p-trans-coumaroyl)-β-glucopyranoside and Kaempferol were isolated from ML5. The structures of bioactive compounds were elucidated using Nuclear Magnetic Resonance (NMR) spectroscopy from 1HNMR and 13CNMR. In addition, the cytotoxic effect of M. malabathricum leaves fractions (ML1-ML6) revealed that ML5 had the highest Cytotoxicity Concentration (CC50) at 0.75 mg mL-1, an observation traceable to the presence of flavonoids constituents with antioxidant properties. Therefore, the results clearly indicate that MMML, fractions and bioactive constituents have profound antibacterial activity. Furthermore, antioxidative compounds from ML5 fraction exert their effects by enhancing the level of CC50.
Risk of Cancer Following an Ischemic Stroke in the Canadian Longitudinal Study on Aging

ABSTRACT: Background: Stroke survivors may be at higher risk of incident cancer, although the magnitude and the period at risk remain unclear. We conducted a retrospective cohort study to compare the risk of cancer in stroke survivors to that of the general population. Methods: The Canadian Longitudinal Study on Aging is a large population-based cohort of individuals aged 45–85 years when recruited (2011–2015). We used data from the comprehensive subgroup (n = 30,097) to build a retrospective cohort with individual exact matching for age (1:4 ratio). We used Cox proportional hazards models to estimate hazard ratios of new cancer diagnosis with and without a prior stroke. Results: We respectively included 920 and 3,680 individuals in the stroke and non-stroke groups. We observed a higher incidence of cancer in the first year after stroke that declined afterward (p-value = 0.030). The hazard of new cancer diagnosis after stroke was significantly increased (hazard ratio: 2.36; 95% CI: 1.21, 4.61; p-value = 0.012) as compared to age-matched non-stroke participants after adjustments. The most frequent primary cancers in the first year after stroke were prostate (n = 8, 57.1%) and melanoma (n = 2, 14.3%). Conclusions: The hazard of new cancer diagnosis in the first year after an ischemic stroke is about 2.4 times higher as compared to age-matched individuals without stroke after adjustments. Surveillance bias may explain a portion of post-stroke cancer diagnoses although a selection bias of healthier participants likely led to an underestimation of post-stroke cancer risk. Prospective studies are needed to confirm the potentially pressing need to screen for post-stroke cancer.
Cu(I)/Cu(III) catalytic cycle involved in Ullmann-type cross-coupling reactions

Abstract Copper-catalyzed cross-coupling reactions for C–heteroatom bond formation have attracted numerous research groups in the past 15 years aiming at finding more efficient methodologies under milder conditions. The use of auxiliary ligands has tremendously improved Ullmann-type couplings although a general methodology for different heteroatom-nucleophiles is still lacking. Mechanistic insights are seen as a clue for designing new effective, broad-scope and general methodologies. In this review we describe the widely discussed mechanistic options for this reaction and the use of model compounds to unravel key mechanistic aspects for copper-catalyzed C–heteroatom transformations. Stable aryl-Cu(III) species in model systems are shown to be reliable active catalysts in the coupling of a broad nucleophile scope such as phenols, amides, sulfides, selenides, phosphites, halides and also activated methylene susbtrates for carbon–carbon couplings.