Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Antibiotic Concentrations in the Vicinity of Antibiotic-Producing Bacteria at the Micron Scale

It is generally assumed that a natural function of antibiotics is to provide their producers with a competitive advantage. If this were the case, sensitive organisms in proximity to producers would be exposed to inhibitory concentrations. ABSTRACT It is generally thought that antibiotics confer upon the producing bacteria the ability to inhibit or kill neighboring microorganisms, thereby providing the producer with a significant competitive advantage. Were this to be the case, the concentrations of emitted antibiotics in the vicinity of producing bacteria might be expected to fall within the ranges of MICs that are documented for a number of bacteria. Furthermore, antibiotic concentrations that bacteria are punctually or chronically exposed to in environments harboring antibiotic-producing bacteria might fall within the range of minimum selective concentrations (MSCs) that confer a fitness advantage to bacteria carrying acquired antibiotic resistance genes. There are, to our knowledge, no available in situ measured antibiotic concentrations in the biofilm environments that bacteria typically live in. The objective of the present study was to use a modeling approach to estimate the antibiotic concentrations that might accumulate in the vicinity of bacteria that are producing an antibiotic. Fick’s law was used to model antibiotic diffusion using a series of key assumptions. The concentrations of antibiotics within a few microns of single producing cells could not reach MSC (8 to 16 μg/L) or MIC (500 μg/L) values, whereas the concentrations around aggregates of a thousand cells could reach these concentrations. The model outputs suggest that single cells could not produce an antibiotic at a rate sufficient to achieve a bioactive concentration in the vicinity, whereas a group of cells, each producing the antibiotic, could do so. IMPORTANCE It is generally assumed that a natural function of antibiotics is to provide their producers with a competitive advantage. If this were the case, sensitive organisms in proximity to producers would be exposed to inhibitory concentrations. The widespread detection of antibiotic resistance genes in pristine environments suggests that bacteria are indeed exposed to inhibitory antibiotic concentrations in the natural world. Here, a model using Fick’s law was used to estimate potential antibiotic concentrations in the space surrounding producing cells at the micron scale. Key assumptions were that per-cell production rates drawn from the pharmaceutical manufacturing industry are applicable in situ, that production rates were constant, and that produced antibiotics are stable. The model outputs indicate that antibiotic concentrations in proximity to aggregates of a thousand cells can indeed be in the minimum inhibitory or minimum selective concentration range.
First order correction for arbitrary anisotropic profiles by implementation of integral equation analysis

An extension of the semianalytical method for the analysis of the first order vector correction of arbitrary isotropic profiles to the analysis of the first order vector correction for arbitrary circular and noncircular anisotropic profiles in optical waveguides is presented. The results presented are only for anisotropic profiles possessing purely diagonal permittivity tensors and, in contrast to conventional purely numerical methods, no approximations in the analysis of the first order correction for arbitrary anisotropic profiles are implemented. The method of analysis is shown to possess extremely high accuracy ( >
On a quick multiplication in normal bases of finite fields

We estimate the complexity of transition from normal bases to standard ones and discuss the related problems of effective realization of arithmetic operations in finite fields of high dimensionality. The work was supported by the Russian Foundation for Basic Research, grant 99–01–01175, the Program of support of leading scientific schools, grant 00–15–96103, the Program ‘Universities of Russia,’ and by the Federal program ‘Integration,’ joint project A0110.
Inhibition of invasive plant Mikania micrantha rapid growth by host-specific rust (Puccinia spegazzinii)

Abstract Mikania micrantha Kunth is a fast-growing global invasive weed species that causes severe damage to natural ecosystems and very large economic losses of forest and crop production. Although Puccinia spegazzinii can effectively inhibit the growth of M. micrantha and is used as a biological control strain in many countries, the mechanism of inhibiting the growth of M. micrantha is not clear. Here, we used a combination of phenotypic, enzyme activity, transcriptomic, and metabolomic approaches to study the response of M. micrantha after infection by P. spegazzinii. In the early stages of rust infection, jasmonic acid (JA), jasmonoyl-isoleucine (JA-Ile), and salicylic acid (SA) levels in infected leaves were significantly lower than those in uninfected leaves. In teliospore initial and developed stages of P. spegazzinii, JA and JA-Ile levels substantially increased by more than 6 times, which resulted in a significant decrease in the accumulation of defense hormone SA in infected leaves of M. micrantha. The contents of plant growth-promoting hormones were significantly reduced in the infected plants as a result of substantial downregulation of the expression of key genes related to hormone biosynthesis. Furthermore, rust infection led to high levels of reactive oxygen species in chloroplasts and the destruction of chlorophyll structure, which also led to decreased photosynthetic gene expression, net photosynthetic rate, activity of Rubisco, and levels of important organic acids in the Calvin cycle. We hypothesized that after P. spegazzinii infection, JA or JA-Ile accumulation not only inhibited SA levels to promote rust infection and development, but also impeded the rapid growth of M. micrantha by affecting plant growth hormones, carbon, and nitrogen metabolic pathways.
Correlating two continuous variables subject to detection limits in the context of mixture distributions

Summary. In individuals who are infected with human immunodeficiency virus (HIV), distributions of quantitative HIV ribonucleic acid measurements may be highly left censored with an extra spike below the limit of detection LD of the assay. A two‐component mixture model with the lower component entirely supported on [0, LD] is recommended to model the extra spike in univariate analysis better. Let LD1 and LD2 be the limits of detection for the two HIV viral load measurements. When estimating the correlation coefficient between two different measures of viral load obtained from each of a sample of patients, a bivariate Gaussian mixture model is recommended to model the extra spike on [0, LD1] and [0, LD2] better when the proportion below LD is incompatible with the left‐hand tail of a bivariate Gaussian distribution. When the proportion of both variables falling below LD is very large, the parameters of the lower component may not be estimable since almost all observations from the lower component are falling below LD. A partial solution is to assume that the lower component's entire support is on [0, LD1]×[0, LD2]. Maximum likelihood is used to estimate the parameters of the lower and higher components. To evaluate whether there is a lower component, we apply a Monte Carlo approach to assess the p‐value of the likelihood ratio test and two information criteria: a bootstrap‐based information criterion and a cross‐validation‐based information criterion. We provide simulation results to evaluate the performance and compare it with two ad hoc estimators and a single‐component bivariate Gaussian likelihood estimator. These methods are applied to the data from a cohort study of HIV‐infected men in Rio de Janeiro, Brazil, and the data from the Women's Interagency HIV oral study. These results emphasize the need for caution when estimating correlation coefficients from data with a large proportion of non‐detectable values when the proportion below LD is incompatible with the left‐hand tail of a bivariate Gaussian distribution.
Genetic rescue remains underused for aiding recovery of federally listed vertebrates in the United States

Abstract Restoring gene flow among fragmented populations is discussed as a potentially powerful management strategy that could reduce inbreeding depression and cause genetic rescue. Yet, examples of assisted migration for genetic rescue remain sparse in conservation, prompting several outspoken calls for its increased use in genetic management of fragmented populations. We set out to evaluate the extent to which this strategy is underused and to determine how many imperiled species would realistically stand to benefit from genetic rescue, focusing on federally threatened or endangered vertebrate species in the United States. We developed a “genetic rescue suitability index (GR index)” based on concerns about small population problems relative to risks associated with outbreeding depression and surveyed the literature for 222 species. We found that two-thirds of these species were good candidates for consideration of assisted migration for the purpose of genetic rescue according to our suitability index. Good candidate species spanned all taxonomic groups and geographic regions, though species with more missing data tended to score lower on the suitability index. While we do not recommend a prescriptive interpretation of our GR index, we used it here to establish that assisted migration for genetic rescue is an underused strategy. For example, we found in total, “genetic rescue” was only mentioned in 11 recovery plans and has only been implemented in 3 of the species we surveyed. A potential way forward for implementation of this strategy is incorporating genetic rescue as a priority in USFWS recovery documentation. In general, our results suggest that although not appropriate for all imperiled species, many more species stand to benefit from a conservation strategy of assisted migration for genetic rescue than those for which it has previously been considered or implemented.
An innovative virtual reality training tool for the pre-hospital treatment of cranialmaxillofacial trauma

Abstract Virtual reality (VR) surgery using the High Technology Computer Corporation Very Immersive Virtual Experience professional 2(HTC VIVE Pro2) suite is a multi-sensory, holistic surgical training experience. A multimedia combination including videos and three-dimensional interaction in VR has been developed to enable trainees to experience a realistic battlefield environment. The innovation allows trainees to interact with the individual components of the cranialmaxillofacial(CMF) anatomy and apply surgical instruments while watching close-up stereoscopic three-dimensional videos of the surgery. In this study, a novel training tool for the pre-hospital treatment of CMF trauma based on immersive virtual reality (iVR) was developed and validated. Twenty-five CMF surgeons evaluated the application for face and content validity. Using a structured assessment process, the surgeons commented on the content of the developed training tool, its realism and usability and the applicability of VR surgery for CMF trauma rescue simulation training. The results confirmed the applicability of VR for delivering training in the pre-hospital treatment of CMF trauma. Modifications were suggested to improve the user experience and interactions with the surgical instruments. This training tool is ready for testing with surgical trainees.
Development of CRISPR/Cas12b-Based Multiple Cross Displacement Amplification Technique for the Detection of Mycobacterium tuberculosis Complex in Clinical Settings

The Mycobacterium tuberculosis complex pathogen is a crucial infectious agent of tuberculosis. Hence, improving the capability of MTC detection is one of the most urgently required strategies for preventing and controlling TB. ABSTRACT Tuberculosis (TB) is a chronic infectious disease with high mortality caused by the Mycobacterium tuberculosis complex (MTC). Its clinical symptoms include a prolonged cough with mucus, pleuritic chest pain, hemoptysis, etc., and predominant complications such as tuberculous meningitis and pleural effusion. Thus, developing rapid, ultrasensitive, and highly specific detection techniques plays an important role in controlling TB. Here, we devised CRISPR/CRISPR-associated 12b nuclease (CRISPR/Cas12b)-based multiple cross displacement amplification technique (CRISPR-MCDA) targeting the IS6110 sequence and used it to detect MTC pathogens. A newly engineered protospacer adjacent motif (PAM) site (TTTC) was modified in the linker region of the CP1 primer. In the CRISPR-MCDA system, the exponentially amplified MCDA amplicons with the PAM sites can guide the Cas12b/gRNA complex to quickly and accurately recognize its target regions, which successfully activates the CRISPR/Cas12b effector and enables ultrafast trans-cleavage of single-stranded DNA reporter molecules. The limit of detection of the CRISPR-MCDA assay was 5 fg/μL of genomic DNA extracted from the MTB reference strain H37Rv. The CRISPR-MCDA assay successfully detected all examined MTC strains and there was no cross-reaction with non-MTC pathogens, confirming that its specificity is 100%. The entire detection process can be completed within 70 min using real-time fluorescence analysis. Moreover, visualization detection (under UV light) was also designed to verify the results, eliminating the use of specialized instruments. In conclusion, the CRISPR-MCDA assay established in this report can be used as a valuable detection technique for MTC infection. IMPORTANCE The Mycobacterium tuberculosis complex pathogen is a crucial infectious agent of tuberculosis. Hence, improving the capability of MTC detection is one of the most urgently required strategies for preventing and controlling TB. In this report, we successfully developed and implemented CRISPR/Cas12b-based multiple cross displacement amplification targeting the IS6110 sequence to detect MTC pathogens. These results demonstrated that the CRISPR-MCDA assay developed in this study was a rapid, ultrasensitive, highly specific, and readily available method which can be used as a valuable diagnostic tool for MTC infection in clinical settings.
Understanding Barriers and Facilitators of Breast and Cervical Cancer Screening among Singapore Women: A Qualitative Approach

Objective: The uptake of breast and cervical cancer screening services among women in Singapore remains inadequate. Little is known about how gender norms influence women’s decision to undergo these screening services in a multi-ethnic Asian context. This research aimed to explore how gender-based qualitative factors influence women’s decision to screen. Methods: Qualitative data were collected using semi-structured interviews from 40 racially diverse women aged 25 and above who had visited polyclinics for their chronic disease management. Women were recruited using a purposive maximum variation sampling strategy to ensure representation of their views from the three major ethnic groups and based on inclusion criteria. Interviews were conducted either face-to-face or via telephone call. Interviews were audiotaped and lasted 30 minutes on average. Interviews were conducted until data saturation was reached. The data was transcribed and analysed thematically. Results: Gender norms and gender non-concordance with the healthcare professionals did not inhibit women from undergoing breast and cervical cancer screening services to a large extent. Women were empowered and had a central role in decision-making for screening services. Healthcare initiatives such as subsidies and mobile health applications facilitated the uptake of breast and cervical cancer screening services but can be improved further. Some of the barriers reported by Malay Muslims were not dissimilar to previous qualitative studies with women in this ethnic and religious group. Conclusion: Gender socialisation, empowerment, and healthcare initiatives did not inhibit our study participants’ decision to undergo breast and cervical cancer screening services. However, new initiatives and strengthening of the existing healthcare initiatives are needed to overcome any remnants of gender-related nuances and convert non-doers into doers.
Formononetin Inhibits Microglial Inflammatory Response and Contributes to Spinal Cord Injury Repair by Targeting the EGFR/MAPK Pathway

ABSTRACT Zhenbao Pill contains many Chinese herbal medicinal ingredients and has been proven to have therapeutic effects on the repair of spinal cord injury (SCI). This study attempts to investigate the role of formononetin (FMN), an ingredient of Zhenbao Pill, in regulating neuroinflammation after SCI and the underlying mechanism. Primary microglia isolated from the spinal cord of newborn rats and human microglial clone 3 (HMC3) cells were stimulated with IL-1β followed by FMN incubation. The cell viability and inflammatory cytokine levels were detected. The target of FMN was predicted and screened using databases. By silencing or overexpression of epidermal growth factor receptor (EGFR), the anti-neuroinflammatory effect of FMN was assessed in vitro. In vivo, FMN was intraperitoneally injected into rats after SCI followed by the neurological function and histopathology examination. The isolated microglia were in high purity, and the different concentrations of FMN incubation had no toxic effects on primary microglia and HMC3 cells. FMN reduced the inflammatory cytokine levels (TNF-α and IL-6) in a concentration-dependent manner. EGFR silencing or FMN incubation decreased p-EGFR and p-p38 levels and down-regulated inflammatory cytokine levels in IL-1β-stimulated cells or supernatants. Nevertheless, the effects of FMN on microglial inflammation were reversed by EGFR overexpression. In vivo, FMN treatment improved the neuromotor function, repaired tissue injury, and inhibited EGFR/p38MAPK phosphorylation. Formononetin inhibits microglial inflammatory response and contributes to SCI repair via the EGFR/p38MAPK signaling pathway.
The impact of performance‐based financing within local health systems: Evidence from Mozambique

Abstract Most evidence on Performance Based Financing (PBF) in low‐income settings has focused on services delivered by providers in targeted health administrations, with limited understanding of how effects on health and care vary within them. We evaluated the population effects of a program implemented in two provinces in Mozambique, focusing on child, maternal and HIV/AIDS care and knowledge. We used a difference‐in‐difference estimation strategy applied to data on mothers from the Demographic Health Surveys, linked to information on their closest health facility. The impact of PBF was limited. HIV testing during antenatal care increased, particularly for women who were wealthier, more educated, or residing in Gaza Province. Knowledge about transmission of HIV from mother‐to‐child, and its prevention, increased, particularly for women who were less wealthy, less educated, or residing in Nampula Province. Exploiting the roll‐out by facility, we found that the effects were concentrated on less wealthy and less educated women, whose closest facility was in the referral network of a PBF facility. Results suggest that HIV testing and knowledge promotion increased in the whole district, as a strategy to boost referral for highly incentivized HIV services delivered in PBF facilities. However, demand‐side constraints may prevent the use of those services.
Novel magnetic resonance KTRANS measurement of blood-brain barrier permeability correlated with covert HE

Background: Using dynamic contrast-enhanced (DCE) MR perfusion and MR spectroscopy this study aimed to characterize the blood-brain barrier permeability and metabolite changes in patients with cirrhosis and without covert HE. Methods: Covert HE was defined using psychometric HE score (PHES). The participants were stratified into 3 groups: cirrhosis with covert HE (CHE) (PHES<-4); cirrhosis without HE (NHE) (PHES≥-4); and healthy controls (HC). Dynamic contrast-enhanced MRI and MRS were performed to assess KTRANS, a metric derivative of blood-brain barrier disruption, and metabolite parameters. Statistical analysis was performed using IBM SPSS (v25). Results: A total of 40 participants (mean age 63 y; male 71%) were recruited as follows: CHE (n=17); NHE (n=13); and HC (n=10). The KTRANS measurement in the frontoparietal cortex demonstrated increased blood-brain barrier permeability, where KTRANS was 0.01±0.02 versus 0.005±0.005 versus 0.004±0.002 in CHE, NHE, and HC patients, respectively (p = 0.032 comparing all 3 groups). Relative to HC with a value of 0.28, the parietal glutamine/creatine (Gln/Cr) ratio was significantly higher in both CHE 1.12 mmoL (p < 0.001); and NHE 0.49 (p = 0.04). Lower PHES scores correlated with higher glutamine/Cr (Gln/Cr) (r=-0.6; p < 0.001) and lower myo-inositol/Cr (mI/Cr) (r=0.6; p < 0.001) and lower choline/Cr (Cho/Cr) (r=0.47; p = 0.004). Conclusion: The dynamic contrast-enhanced MRI KTRANS measurement revealed increased blood-brain barrier permeability in the frontoparietal cortex. The MRS identified a specific metabolite signature with increased glutamine, reduced myo-inositol, and choline, which correlated with CHE in this region. The MRS changes were identifiable in the NHE cohort.
Analytical performance evaluation of Lumipulse® SARS‐CoV‐2 antigen assay in 392 asymptomatic patients

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is one of the current public health care challenges. The main strategy adopted to prevent the spread of infection is the rapid identification of COVID‐19‐positive subjects. The aim of this study was to compare the performance of Lumipulse® antigen immunoassay with the real‐time RT‐PCR, the gold standard for the diagnosis of SARS‐CoV‐2 infection, in a strictly selected asymptomatic population.