Miracle-dz/UniFAR-FTUs huggingface dataset:
A validated liquid chromatography/tandem mass spectrometry method for the analysis of efavirenz in 0.2 mg hair samples from human immunodeficiency virus infected patients.

RATIONALE Drug levels in hair provide a longer window of detection, compared to plasma drug levels, and therefore hair analysis has the advantage of assessing adherence over a longer period of time. No methods for the analysis of antiretroviral drugs in hair currently exist in South Africa, and worldwide there is only one validated method for the determination of efavirenz in hair that has been published. METHODS Efavirenz was extracted from 0.2 mg of hair through a simultaneous pulverization and extraction step. Separation was achieved on an Agilent Poroshell C18 column using an isocratic elution with a total run time of 3 min. A triple quadrupole mass spectrometer set to electrospray ionization in positive multiple reaction monitoring mode was used for detection. The method was validated over the concentration range 0.625-40 ng/mg. RESULTS Using ten times less hair than in a previously published method, the lower limit of quantitation was validated at 0.625 ng/mg. The interday and intraday assay precision, expressed as the percentage coefficient of variation (CV), for spiked calibration standards and quality control samples was lower than 7% and accuracy ranged from 97 to 110%. For quality controls prepared from authentic hair the CV was less than 12%. The extraction efficiency for authentic quality control samples was determined to be 83% after repeated extractions of the same samples. CONCLUSIONS This paper reports the first quantitative method for the determination of efavirenz in hair to be developed in South Africa. The validated method allowed for the successful monitoring of efavirenz in hair collected from HIV-infected patients as part of a clinical study.
Stochastic model-based minimization of weakly convex functions

We consider an algorithm that successively samples and minimizes stochastic models of the objective function. We show that under weak-convexity and Lipschitz conditions, the algorithm drives the expected norm of the gradient of the Moreau envelope to zero at the rate $O(k^{-1/4})$. Our result yields new complexity guarantees for the stochastic proximal point algorithm on weakly convex problems and for the stochastic prox-linear algorithm for minimizing compositions of convex functions with smooth maps. Moreover, our result also recovers the recently obtained complexity estimate for the stochastic proximal subgradient method on weakly convex problems.
Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins.

FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display peptidyl-prolyl isomerase activities and act as coreceptors for immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs can enhance infectivity. However, developing druglike ligands for FKBPs or Mips has proven difficult, and many FKBPs and Mips still lack biologically useful ligands. To explore the scope and potential of C5-substituted [4.3. 1]-aza-bicyclic sulfonamides as a broadly applicable class of FKBP inhibitors, we developed a new synthesis method for the bicyclic core scaffold and used it to prepare an FKBP- and Mip-focused library. This allowed us to perform a systematic structure-activity-relationship analysis across key human FKBPs and microbial Mips, yielding highly improved inhibitors for all the FKBPs studied. A cocrystal structure confirmed the molecular-binding mode of the core structure and explained the affinity gained as a result of the preferred substituents. The best FKBP and Mip ligands showed promising antimalarial, antileginonellal, and antichlamydial properties in cellular models of infectivity, suggesting that substituted [4.3. 1]-aza-bicyclic sulfonamides could be a novel class of anti-infectives.
Spatial Assortment of Mixed Propagules Explains the Acceleration of Range Expansion

Range expansion of spreading organisms has been found to follow three types: (i) linear expansion with a constant rate of spread; (ii) bi-phase expansion with a faster linear expansion following a slower linear expansion; and (iii) accelerating expansion with a continuously increasing rate of spread. To date, no overarching formula exists that can be applied to all three types of range expansion. We investigated how propagule pressure, i.e., the initial number of individuals and their composition in terms of dispersal ability, affects the spread of a population. A system of integrodifference equations was then used to model the spatiotemporal dynamics of the population. We studied the dynamics of dispersal ability as well as the instantaneous and asymptotic rate of spread. We found that individuals with different dispersal abilities were spatially sorted with the stronger dispersers situated at the expanding range front, causing the velocity of expansion to accelerate. The instantaneous rate of spread was found to be fully determined by the growth and dispersal abilities of the population at the advancing edge of the invasion. We derived a formula for the asymptotic rate of spread under different scenarios of propagule pressure. The results suggest that data collected from the core of the invasion may underestimate the spreading rate of the population. Aside from better managing of invasive species, the derived formula could conceivably also be applied to conservation management of relocated, endangered or extra-limital species.
Genome Evolution and Nitrogen Fixation in Bacterial Ectosymbionts of a Protist Inhabiting Wood-Feeding Cockroaches

ABSTRACT By combining genomics and isotope imaging analysis using high-resolution secondary ion mass spectrometry (NanoSIMS), we examined the function and evolution of Bacteroidales ectosymbionts of the protist Barbulanympha from the hindguts of the wood-eating cockroach Cryptocercus punctulatus. In particular, we investigated the structure of ectosymbiont genomes, which, in contrast to those of endosymbionts, has been little studied to date, and tested the hypothesis that these ectosymbionts fix nitrogen. Unlike with most obligate endosymbionts, genome reduction has not played a major role in the evolution of the Barbulanympha ectosymbionts. Instead, interaction with the external environment has remained important for this symbiont as genes for synthesis of transporters, outer membrane proteins, lipopolysaccharides, and lipoproteins have been retained. The ectosymbiont genome carried two complete operons for nitrogen fixation, a urea transporter, and a urease, indicating the availability of nitrogen as a driving force behind the symbiosis. NanoSIMS analysis of C. punctulatus hindgut symbionts exposed in vivo to 15N2 supports the hypothesis that Barbulanympha ectosymbionts are capable of nitrogen fixation. This genomic and in vivo functional investigation of protist ectosymbionts highlights the diversity of evolutionary forces and trajectories that shape symbiotic interactions. IMPORTANCE The ecological and evolutionary importance of symbioses is increasingly clear, but the overall diversity of symbiotic interactions remains poorly explored. In this study, we investigated the evolution and nitrogen fixation capabilities of ectosymbionts attached to the protist Barbulanympha from the hindgut of the wood-eating cockroach Cryptocercus punctulatus. In addressing genome evolution of protist ectosymbionts, our data suggest that the ecological pressures influencing the evolution of extracellular symbionts clearly differ from intracellular symbionts and organelles. Using NanoSIMS analysis, we also obtained direct imaging evidence of a specific hindgut microbe playing a role in nitrogen fixation. These results demonstrate the power of combining NanoSIMS and genomics tools for investigating the biology of uncultivable microbes. This investigation paves the way for a more precise understanding of microbial interactions in the hindguts of wood-eating insects and further exploration of the diversity and ecological significance of symbiosis between microbes.
The Spectral Diversity of Resting-State Fluctuations in the Human Brain

In order to assess whole-brain resting-state fluctuations at a wide range of frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a multiband EPI sequence with a low TR (354 ms) and compared to 20 resting-state datasets from standard, high-TR (1800 ms) EPI scans. The spatial distribution of fluctuations in various frequency ranges are analyzed along with the spectra of the time-series in voxels from different regions of interest. Functional connectivity specific to different frequency ranges (<0.1 Hz; 0.1–0.25 Hz; 0.25–0.75 Hz; 0.75–1.4 Hz) was computed for both the low-TR and (for the two lower-frequency ranges) the high-TR datasets using bandpass filters. In the low-TR data, cortical regions exhibited highest contribution of low-frequency fluctuations and the most marked low-frequency peak in the spectrum, while the time courses in subcortical grey matter regions as well as the insula were strongly contaminated by high-frequency signals. White matter and CSF regions had highest contribution of high-frequency fluctuations and a mostly flat power spectrum. In the high-TR data, the basic patterns of the low-TR data can be recognized, but the high-frequency proportions of the signal fluctuations are folded into the low frequency range, thus obfuscating the low-frequency dynamics. Regions with higher proportion of high-frequency oscillations in the low-TR data showed flatter power spectra in the high-TR data due to aliasing of the high-frequency signal components, leading to loss of specificity in the signal from these regions in high-TR data. Functional connectivity analyses showed that there are correlations between resting-state signal fluctuations of distant brain regions even at high frequencies, which can be measured using low-TR fMRI. On the other hand, in the high-TR data, loss of specificity of measured fluctuations leads to lower sensitivity in detecting functional connectivity. This underlines the advantages of low-TR EPI sequences for resting-state and potentially also task-related fMRI experiments.
Carbon isotope evidence for a northern source of deep water in the glacial western North Atlantic

Significance Understanding glacial ocean circulation is tied to understanding heat transport in the North Atlantic, growth and maintenance of ice sheets, and atmospheric CO2 content. The proxy data are sparse, but, for decades, it has been thought that the North Atlantic did not produce deep water during the Last Glacial Maximum, unlike today. New C isotope results from a core at 5 km in the western North Atlantic indicate a young, glacial deep water may have been formed in the surface Labrador Sea by freezing and brine rejection. These data call for a revised circulation scheme where southern source water centered at 4.2 km would have been sandwiched between glacial North Atlantic intermediate water and the new dense bottom water. The prevailing view of western Atlantic hydrography during the Last Glacial Maximum (LGM) calls for transport and intermixing of deep southern and intermediate northern end members. However, δ13C and Δ14C results on foraminifera from a sediment core at 5.0 km in the northern subtropics show that there may have also been a northern source of relatively young, very dense, nutrient-depleted water during the LGM (18 ky to 21 ky ago). These results, when integrated with data from other western North Atlantic locations, indicate that the ocean was poorly ventilated at 4.2 km, with better ventilation above and below that depth. If this is a signal of water mass source and not nutrient storage, it would indicate that a previously unrecognized deep water end member originated along the western margin of the Labrador Sea, analogous to dense water formation today around Antarctica and in the Okhotsk Sea.
CT-guided radiofrequency ablation of spinal osteoblastoma: treatment and long-term follow-up

Abstract Objective: Osteoblastoma (OB) is a painful, rare, benign bone tumour usually observed in young populations, and this condition involves the spine in up to one-third of cases. We sought to focus on the minimally invasive treatment of spinal OB with radiofrequency ablation (RFA) under computed tomography (CT) guidance. When performed near the spinal cord, surgery can lead to instability of the spine, sometimes requiring additional interventions to stabilise the segments involved, and can cause the precocious onset of arthrosis or other degenerative diseases. The results were evaluated both clinically and with the aid of diagnostic imaging techniques during a 5-year follow-up study. Materials and methods: Eleven patients affected by spinal OB were treated in a single session with biopsy and CT-guided RFA. Pre- and post-evaluations of the patients were performed both clinically and with CT and magnetic resonance imaging (MRI). Results: Complete success in terms of pain relief was achieved in all patients. Additional treatments were not required in any patients. There were no complications. During follow-up, neither complications nor pathological findings related to the treatment were observed. Conclusions: Our experience demonstrates that RFA for spinal OB is safe and effective. One of the main advantages of this technique is represented by its lower grade of invasiveness compared with that for potentially hazardous surgical manoeuvres.
Physico-chemical characteristics of wheat distillers dried grain with solubles sourced from a Saskatchewan ethanol plant.

The proximate composition and the effect of moisture content on particle size and particle distribution, bulk and particle densities, color, flow properties, compression characteristics, moisture sorption behavior, and frictional properties of plant-sourced wheat distillers dried grains with solubles (DDGS) were assessed. Proximate composition significantly differed between samples obtained from two production batches. Protein content of wheat DDGS was higher while its fat content was lower compared to published corn DDGS values. Most of the physical properties were significantly affected by moisture content. Under the Carr classification system, plant-sourced wheat DDGS was considered as fairly flowable and floodable and may require measures to assure flow and prevent flushing. The Kawakita-Ludde and Guggenheim, Anderson and De Boer (GAB) models adequately described its compression characteristics and moisture sorption behavior, respectively.
Selective right atrial cardioneuroablation in functional atrioventricular block.

We read the article with a great interest by Rivorola et al. 1 published recently in Europace Journal entitled ‘Selective atrial vagal denervation guided by spectral mapping to treat advanced atrioventricular block’. In this case report, the authors have reported the consequence of cardioneuroablation procedure in a 38-year-old male with vagally mediated atrioventricular (AV) block during sleep. They targeted the endocardial regions with spectral characteristics of endocardial vagal …
Characterization of Thermally Evaporated In2S3 Films for Solar Cell Application

Indium sulphide (In2S3) is one of the best alternatives for CdS as a buffer layer in CuInGaSe2-based thin film heterojunction solar cells. In this work, In2S3 films were prepared by thermal evaporation of In2S3 powder onto glass substrates at different temperatures that vary from 200°C to 300°C. The as-grown films were characterized using appropriate techniques to evaluate the chemical and physical properties. The X-ray diffraction analysis revealed that all the films were polycrystalline in nature with a strong (109) plane as the preferred orientation and consisted of tetragonal and cubic phases. The crystallite size and the lattice parameters are calculated. The scanning electron micrographs indicated smooth surface with fine grains. The optical analysis revealed a high optical transmittance for the layers with a direct optical band gap that varied in the range of 1.8–2.2 eV.
ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.
Efficient approximation algorithms for the Hamming center problem

The Hamming center problem for a set S of k binary strings, each of length n, is to find a binary string fl of length n that minimizes the maximum Hamming distance between p and any string in S. Its decision version is known to be NP-complete [2]. We provide several approximation algorithms for the Hamming center problem. Our main result is a randomized ($ + E)approximation algorithm running in polynomial time if the Hamming radius of S is at least superlogarithmic in k. Furthermore, we show how to find in polynomial time a set B of O(log k) strings of length n such that for each string in S there is at least one string in B within Hamming distance not exceeding the radius of S.
Osthole Enhances Osteogenesis in Osteoblasts by Elevating Transcription Factor Osterix via cAMP/CREB Signaling In Vitro and In Vivo

Anabolic anti-osteoporotic agents are desirable for treatment and prevention of osteoporosis and fragility fractures. Osthole is a coumarin derivative extracted from the medicinal herbs Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim.f. Osthole has been reported with osteogenic and anti-osteoporotic properties, whereas the underlying mechanism of its benefit still remains unclear. The objective of the present study was to investigate the osteopromotive action of osthole on mouse osteoblastic MC3T3-E1 cells and on mouse femoral fracture repair, and to explore the interaction between osthole-induced osteopromotive effect and cyclic adenosine monophosphate (cAMP) elevating effect. Osthole treatment promoted osteogenesis in osteoblasts by enhancing alkaline phosphatase (ALP) activity and mineralization. Oral gavage of osthole enhanced fracture repair and increased bone strength. Mechanistic study showed osthole triggered the cAMP/CREB pathway through the elevation of the intracellular cAMP level and activation of the phosphorylation of the cAMP response element-binding protein (CREB). Blockage of cAMP/CREB downstream signals with protein kinase A (PKA) inhibitor KT5720 partially suppressed osthole-mediated osteogenesis by inhibiting the elevation of transcription factor, osterix. In conclusion, osthole shows osteopromotive effect on osteoblasts in vitro and in vivo. Osthole-mediated osteogenesis is related to activation of the cAMP/CREB signaling pathway and downstream osterix expression.
Anti-bacterial Effects of Polymethylmethacrylate with In situ Generated Silver Nanoparticles on Primary Colonizers of Human Dental Plaque and Cariogenic Bacteria

Aims: Polymethylmethacrylates (PMMAs) remain the most popular material for use in orthodontics, particularly in developing countries, because of their low cost and ease of use. Biofilm formation of cariogenic bacteria on these surfaces may contribute to tooth decay, gingivitis, and periodontitis. Nanoparticle-sized silver (NanoAg) inhibits the growth of microorganisms, but anticariogenic effects of NanoAg in situ in PMMA (NanoAg-ISOriginal Research Article Annual Research & Review in Biology, 4(10): 1587-1601, 2014 1588 PMMA) in orthodontics have not been explored. Therefore, the primary purpose of the current study was to evaluate the antimicrobial activity of NanoAg-IS-PMMA against primary colonizers of human dental plaque and cariogenic bacteria in planktonic and biofilm cultures, grown as mono-species biofilms and mixed-species biofilms. Study Design: In vitro. Place and Duration of Study: Department of Medical Microbiology, Department of Orthodontics, Pediatrics Infectious Disease Research Center; Tehran, Iran. August, 2012– May, 2013. Methodology: Chemical-cure orthodontic resin was used to synthesize NanoAg-IS-PMMA using silver benzoate. Antibacterial effects of NanoAg-IS-PMMA were assessed against Streptococcus sobrinus, S. sanguinis, S. mitis, and Actinomyces naeslundii as well as cocultures of the four species by inhibition of bacterial adherence and growth inhibition of planktonic and biofilm bacterial cells on NanoAg-IS-PMMA. Results: NanoAg-IS-PMMA reduced bacterial adhesion by 36.2%–88.1%, depending on the bacterial type. Planktonic cultures of the microorganisms exposed to NanoAg-ISPMMA showed a significant decrease (99.99%) in a time-dependent manner, over 28 days. Exposure to NanoAg-IS-PMMA inhibited biofilm formation of all test bacteria and their cocultures by 77.6%–99.96%, compared to PMMA. In addition, NanoAg-IS-PMMA retained some inhibitory effects for the third generation of biofilm formation. Conclusion: Our data supports the finding that NanoAg-IS-PMMA effectively inhibited adherence of primary colonizers of human dental plaque and cariogenic bacteria to NanoAg-IS-PMMA surfaces, in addition to rendering strong anticariogenic effects in the planktonic and subsequent mono-species biofilms and mixed-species biofilms formation. This demonstrated that NanoAg-IS-PMMA has the potential to minimize colonization of cariogenic bacteria and biofilm formation on orthodontic appliances.
Retention and adherence: global challenges for the long-term care of adolescents and young adults living with HIV

Purpose of review Adolescents living with HIV are the only age group with increasing HIV mortality at a time of global scale-up of access to antiretroviral therapy (ART). As a ‘treat all’ strategy is implemented worldwide, it is critically important to optimize retention and adherence for this vulnerable group. Recent findings Adolescents and young adults living with HIV have poorer outcomes when compared with adults at each stage of the HIV care cascade, irrespective of income setting. Rates of viral suppression are lowest for adolescents living with HIV, and adherence to ART remains an enormous challenge. High-quality studies of interventions to improve linkage to, and retention in, care on suppressive ART are starkly lacking for adolescents and young adults living with HIV across the globe. However, examples of good practice are beginning to emerge but require large-scale implementation studies with outcome data disaggregated by age, route of infection, and income setting, and include young pregnant women and key populations groups. Summary There is an urgent need for evidence-based interventions addressing gaps in the adolescent HIV care cascade, including supporting retention in care and adherence to ART.