Miracle-dz/UniFAR-FTUs huggingface dataset:
Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review

Over the years, chondroitin sulfate (CS) has been used as a slow-acting drug for the treatment of osteoarthritis, for the reduction of pain and improvement of function, and for its disease-modifying properties by limiting cartilage volume loss and joint space narrowing progression. However, there have been inconsistencies in published trials regarding clinical efficacy, with reports of a lack of significant effects compared to placebo. The therapeutic effects of chondroitin sulfate may depend on many variables, such as the source of origin, purity, and contamination with by-products. Another source of confusion may be related to the fact that CS is commonly combined with glucosamine, which makes it challenging to isolate the specific contribution of chondroitin to the therapeutic outcome. This is aggravated by the fact that CS supplements, used in many countries, are not regulated, and labels wrongly claim high levels of purity. Many of these inferior CS products may have been used in clinical trials, which may have had limited but significant results. This has led to recent recommendations to opt for higher-purity pharmacologic-grade CS for the treatment of OA. This article aims to provide an up-to-date view of the current literature regarding the biological effects and efficacy of CS and discusses the quality of available chondroitin sulfate supplements and the current direction in CS investigation. This review concludes that pharmacologic-grade CS supplements may have clinically significant benefits when properly standardized; however, high-quality evidence from properly designed clinical trials is still needed to draw definitive conclusions about clinical efficacy in osteoarthritis.
Optimization for Realistic Real-Time Rendering Method for Subsurface Scattering

Monte Carlo photon tracking is used to render translucent materials such as marble, milk, skin, etc. The technique encompasses excessive amount of subsurface scattering that is computationally expensive. Faster approaches are based on approximate models derived from observed results. While such models are efficient, they tend to miss some translucency effects in the rendered results. We present an improved approximation model for real-time rendering of materials based upon computational graphs. Excellent results are obtained improving upon the previous studies.
Modeling Wind Energy Using Copula

In most studies related to wind energy, the quantity of the air density is considered constant, but actually, we know that it is variable and depending on others natural factors. We present a new procedure to estimate the wind density power energy by simulating the components of the air density. The procedure uses the copula theory and demonstrates that the estimated power energy is higher if the air density is not constant.
Oxidative Stress and Inflammatory Biomarkers in People with Methamphetamine Use Disorder

Objective This study aimed to investigate the blood serum levels of biomarkers specifying oxidative stress status and systemic inflammation between people using methamphetamine (METH) and the control group (CG). Serum thiol/disulfide balance and ischemia-modified albumin levels were studied to determine oxidative stress, and serum interleukin-6 (IL-6) levels and complete blood count (CBC) were to assess inflammation. Methods Fifty patients with METH use disorder (MUD) and 36 CG participants were included in the study. Two tubes of venous blood samples were taken to measure oxidative stress, serum thiol/disulfide balance, ischemia-modified albumin, and IL-6 levels between groups. The correlation of parameters measuring oxidative stress and inflammation between groups with sociodemographic data was investigated. Results In this study, serum total thiol, free thiol levels, disulfide/native thiol percentage ratios, and serum ischemia-modified albumin levels of the patients were statistically significantly higher than the healthy controls. No difference was observed between the groups in serum disulfide levels and serum IL-6 levels. Considering the regression analysis, only the duration of substance use was a statistically significant factor in explaining serum IL-6 levels. The parameters showing inflammation in the CBC were significantly higher in the patients than in the CG. Conclusion CBC can be used to evaluate systemic inflammation in patients with MUD. Parameters measuring thiol/disulfide homeostasis and ischemia-modified albumin can be, also, used to assess oxidative stress.
Peptide mixed phosphonates for covalent complex formation with thioesterases in nonribosomal peptide synthetases

Natural macrocyclic peptides derived from microorganisms are medicinal resources that are important for the development of new therapeutic agents. Most of these molecules are biosynthesized by a nonribosomal peptide synthetase (NRPS). The thioesterase (TE) domain in NRPS is responsible for the macrocyclization of mature linear peptide thioesters in a final biosynthetic step. NRPS‐TEs can cyclize synthetic linear peptide analogs and can be utilized as biocatalysts for the preparation of natural product derivatives. Although the structures and enzymatic activities of TEs have been investigated, the substrate recognition and substrate‐TE interaction during the macrocyclization step are still unknown. To understand the TE‐mediated macrocyclization, here we report the development of a substrate‐based analog with mixed phosphonate warheads, which can react irreversibly with the Ser residue at the active site of TE. We have demonstrated that the tyrocidine A linear peptide (TLP) with a p‐nitrophenyl phosphonate (PNP) enables efficient complex formation with tyrocidine synthetase C (TycC)‐TE containing tyrocidine synthetase.
Development of a Family-Centered Communication Tool for Kidney Health in Premature Infants: Qualitative Focus Group Study Using Human-Centered Design Methodology

Background Premature infants are at increased risk of kidney-related complications, including acute kidney injury (AKI) and chronic kidney disease (CKD). The risk of CKD in prematurely born infants is underrecognized by health care teams and caregivers. Understanding how to communicate the risk of CKD to caregivers is essential for longitudinal clinical follow-up and adherence. Objective This study aimed to determine family caregiver attitudes toward kidney health and risk communication during a neonatal intensive care admission. We also sought to understand caregiver preferences for the communication of information surrounding the risk of CKD in premature infants. Methods We augmented standard qualitative group sessions with human-centered design methods to assess parent preferences and clinician perspectives. Caregivers recruited had a prematurely born child who spent time in the neonatal intensive care unit at Riley Hospital for Children in Indianapolis, Indiana, and experienced AKI or another kidney complication, which put them at risk for future CKD. We used a variety of specific design methods in these sessions, including card sorting, projective methods, experience mapping, and constructive methods. Results A total of 7 clinicians and 8 caregivers participated in 3 group sessions. Caregivers and clinicians readily acknowledged barriers to and drivers of long-term kidney monitoring as well as opportunities for communication of the risk of long-term kidney disease. Caregivers’ primary concerns were for both the type and depth of information conveyed as well as the time at which it was communicated. Participants emphasized the importance of collaboration between the hospital care team and the primary care provider. Participant input was synthesized into several prototype concepts and, ultimately, into a rough prototype of a website and an informational flyer. Conclusions Caregivers of premature infants are open to communication about kidney health during their neonatal admission. The next phase of this work will translate caregivers’ preferences into family-centered communication tools and test their efficacy in the neonatal intensive care unit.
Advancements in a FRET Biosensor for Live-Cell Fluorescence-Lifetime High-Throughput Screening of Alpha-Synuclein

There is a critical need for small molecules capable of rescuing pathophysiological phenotypes induced by alpha-synuclein (aSyn) misfolding and oligomerization. Building upon our previous aSyn cellular fluorescence lifetime (FLT)-Förster resonance energy transfer (FRET) biosensors, we have developed an inducible cell model incorporating the red-shifted mCyRFP1/mMaroon1 (OFP/MFP) FRET pair. This new aSyn FRET biosensor improves the signal-to-noise ratio, reduces nonspecific background FRET, and results in a 4-fold increase (transient transfection) and 2-fold increase (stable, inducible cell lines) in FRET signal relative to our previous GFP/RFP aSyn biosensors. The inducible system institutes greater temporal control and scalability, allowing for fine-tuning of biosensor expression and minimizes cellular cytotoxicity due to overexpression of aSyn. Using these inducible aSyn-OFP/MFP biosensors, we screened the Selleck library of 2684 commercially available, FDA-approved compounds and identified proanthocyanidins and casanthranol as novel hits. Secondary assays validated the ability of these compounds to modulate aSyn FLT-FRET. Functional assays probing cellular cytotoxicity and aSyn fibrillization demonstrated their capability to inhibit seeded aSyn fibrillization. Proanthocyanidins completely rescued aSyn fibril-induced cellular toxicity with EC50 of 200 nM and casanthranol supported a 85.5% rescue with a projected EC50 of 34.2 μM. Furthermore, proanthocyanidins provide a valuable tool compound to validate our aSyn biosensor performance in future high-throughput screening campaigns of industrial-scale (million-compound) chemical libraries.
Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy

Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. ABSTRACT Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. Analyses of serial clinical isolates of any Candida species are uncommon and often analyze a limited number of samples collected over months of antifungal therapy with multiple drug classes, limiting the ability to understand relationships between drug classes and specific mutations. Here, we performed comparative genomic and phenotypic analysis of 20 serial C. lusitaniae bloodstream isolates collected daily from an individual patient treated with micafungin monotherapy during a single 11-day hospital admission. We identified isolates with decreased micafungin susceptibility 4 days after initiation of antifungal therapy and a single isolate with increased cross-resistance to micafungin and fluconazole, despite no history of azole therapy in this patient. Only 14 unique single nucleotide polymorphisms (SNPs) were identified between all 20 samples, including three different FKS1 alleles among isolates with decreased micafungin susceptibility and an ERG3 missense mutation found only in the isolate with increased cross-resistance to both micafungin and fluconazole. This is the first clinical evidence of an ERG3 mutation in C. lusitaniae that occurred during echinocandin monotherapy and is associated with cross-resistance to multiple drug classes. Overall, the evolution of multidrug resistance in C. lusitaniae is rapid and can emerge during treatment with only first-line antifungal therapy.
Emotion category-modulated interpretation bias in perceiving ambiguous facial expressions

In contrast to prototypical facial expressions, we show less perceptual tolerance in perceiving vague expressions by demonstrating an interpretation bias, such as more frequent perception of anger or happiness when categorizing ambiguous expressions of angry and happy faces that are morphed in different proportions and displayed under high- or low-quality conditions. However, it remains unclear whether this interpretation bias is specific to emotion categories or reflects a general negativity versus positivity bias and whether the degree of this bias is affected by the valence or category of two morphed expressions. These questions were examined in two eye-tracking experiments by systematically manipulating expression ambiguity and image quality in fear- and sad-happiness faces (Experiment 1) and by directly comparing anger-, fear-, sadness-, and disgust-happiness expressions (Experiment 2). We found that increasing expression ambiguity and degrading image quality induced a general negativity versus positivity bias in expression categorization. The degree of negativity bias, the associated reaction time and face-viewing gaze allocation were further manipulated by different expression combinations. It seems that although we show a viewing condition-dependent bias in interpreting vague facial expressions that display valence-contradicting expressive cues, it appears that the perception of these ambiguous expressions is guided by a categorical process similar to that involved in perceiving prototypical expressions.
Sur les périodes des intégrales doubles et sur une classe d'équations différentielles linéaires

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The Plasmodium Lactate/H+ Transporter PfFNT Is Essential and Druggable In Vivo

Malaria parasites in the blood stage express a single transmembrane transport protein for the release of the glycolytic end product l-lactate/H+ from the cell. This transporter is a member of the strictly microbial formate-nitrite transporter (FNT) family and a novel putative drug target. ABSTRACT Malaria parasites in the blood stage express a single transmembrane transport protein for the release of the glycolytic end product l-lactate/H+ from the cell. This transporter is a member of the strictly microbial formate-nitrite transporter (FNT) family and a novel putative drug target. Small, drug-like FNT inhibitors potently block lactate transport and kill Plasmodium falciparum parasites in culture. The protein structure of Plasmodium falciparum FNT (PfFNT) in complex with the inhibitor has been resolved and confirms its previously predicted binding site and its mode of action as a substrate analog. Here, we investigated the mutational plasticity and essentiality of the PfFNT target on a genetic level, and established its in vivo druggability using mouse malaria models. We found that, besides a previously identified PfFNT G107S resistance mutation, selection of parasites at 3 × IC50 (50% inhibitory concentration) gave rise to two new point mutations affecting inhibitor binding: G21E and V196L. Conditional knockout and mutation of the PfFNT gene showed essentiality in the blood stage, whereas no phenotypic defects in sexual development were observed. PfFNT inhibitors mainly targeted the trophozoite stage and exhibited high potency in P. berghei- and P. falciparum-infected mice. Their in vivo activity profiles were comparable to that of artesunate, demonstrating strong potential for the further development of PfFNT inhibitors as novel antimalarials.
Pathogenesis of Common Ocular Diseases: Emerging Trends in Extracellular Matrix Remodeling

ABSTRACT The prevalence of visual impairments in human societies is worrying due to retinopathy complications of several chronic diseases such as diabetes, cardiovascular diseases, and many more that are on the rise worldwide. Since the proper function of this organ plays a pivotal role in people’s quality of life, identifying factors affecting the development/exacerbation of ocular diseases is of particular interest among ophthalmology researchers. The extracellular matrix (ECM) is a reticular, three-dimensional (3D) structure that determines the shape and dimensions of tissues in the body. The ECM remodeling/hemostasis is a critical process in both physiological and pathological conditions. It consists of ECM deposition, degradation, and decrease/increase in the ECM components. However, disregulation of this process and an imbalance between the synthesis and degradation of ECM components are associated with many pathological situations, including ocular disorders. Despite the impact of ECM alterations on the development of ocular diseases, there is not much research conducted in this regard. Therefore, a better understanding in this regard, can pave the way toward discovering plausible strategies to either prevent or treat eye disorders. In this review, we will discuss the importance of ECM changes as a sentimental factor in various ocular diseases based on the research done up to now. Graphical abstract
Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?

Objective Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods Participants (n = 148) with bipolar depression were randomised to (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (＋4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications

Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG).
Sex differences in skeletal muscle fiber types: A meta‐analysis

Biopsies have been acquired from living men and women to determine proportions of Type I (slow‐twitch) and II (fast‐twitch) skeletal muscle fibers since the 1970s. Sex differences have been assumed but the literature has not been submitted to meta‐analysis. Here, the aim was to generate effect sizes of sex differences in muscle fiber cross‐sectional areas, distribution percentages, and area percentages. Data from 2875 men and 2452 women, who participated in 110 studies, were analyzed. Myofibrillar adenosine triphosphatase histochemistry was used in 71.8% of studies to classify fibers as Type I, II, IIA, and/or IIX; immunohistochemistry, immunofluorescence, or sodium dodecyl sulfate‐polyacrylamide gel electrophoresis were used in 35.4% of studies to similarly classify myosin heavy chain (MHC) isoform content. Most studies involved biopsies from vastus lateralis (79.1%) in healthy individuals (92.7%) between 18 and 59 years old (80.9%). Men exhibited greater cross‐sectional areas for all fiber types (g = 0.40–1.68); greater distribution percentages for Type II, MHC II, IIA, IIX fibers (g = 0.26–0.34); greater area percentages for Type II, IIA, MHC IIA, IIX fibers (g = 0.39–0.93); greater Type II/I and Type IIA/I fiber area ratios (g = 0.63, 0.94). Women exhibited greater Type I and MHC I distribution percentages (g = −0.13, −0.44); greater Type I and MHC I area percentages (g = −0.53, −0.69); greater Type I/II fiber area ratios (g = −1.24). These data, which represent the largest repository of comparative muscle fiber type data from living men and women, can inform discussions about biological sex and its impact on pathologies and sports performance (e.g., explaining sex differences in muscle strength and muscle endurance).
A Study of the HWRF Analysis and Forecast Impact of Realistically Simulated CYGNSS Observations Assimilated as Scalar Wind Speeds and as VAM Wind Vectors

In preparation for the launch of the NASA Cyclone Global Navigation Satellite System (CYGNSS), a variety of observing system simulation experiments (OSSEs) were conducted to develop, tune, and assess methods of assimilating these novel observations of ocean surface winds. From a highly detailed and realistic hurricane nature run (NR), CYGNSS winds were simulated with error characteristics that are expected to occur in reality. The OSSE system makes use of NOAA’s HWRF Model and GSI data assimilation system in a configuration that was operational in 2012. CYGNSS winds were assimilated as scalar wind speeds and as wind vectors determined by a variational analysis method (VAM). Both forms of wind information had positive impacts on the short-term HWRF forecasts, as shown by key storm and domain metrics. Data assimilation cycle intervals of 1, 3, and 6 h were tested, and the 3-h impacts were consistently best. One-day forecasts from CYGNSS VAM vector winds were the most dynamically consistent with the NR. The OSSEs have a number of limitations; the most noteworthy is that this is a case study, and static background error covariances were used.