Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual responses to a single oral dose of albendazole indicate reduced efficacy against soil-transmitted helminths in an area with high drug pressure

Background Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment. Methodology/Principal findings We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People’s Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites. Conclusions/Significance We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB. Trial registration The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018.
Influence of hydrotrope on solubility and bioavailability of curcumin: its complex formation and solid-state characterization

Abstract In this study, meglumine (Meg) and arginine (Arg), acting as the hydrotrope, were used to form the stable curcumin (Cur)-hydrotrope complexes, respectively. Based on the single factor experiment optimization, the Cur-Meg/or Cur-Arg complex was prepared and then characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The results showed that Cur-Meg/Arg complexes bound together by hydrogen bonds/or ionic bonds were successfully prepared and the amorphous state of Cur appeared in their complexes. Compared with the Cur-Meg complex, Cur-Arg had better stability in stress testing. Cur-Meg/Arg complexes had a faster drug release rate in vitro and the area-under-curve (AUC) of Cur-Meg/Arg solutions in rats were at least 6.3-fold larger than that of the Cur suspensions. These findings suggest that hydrotropy combined with solid dispersion technique is a simple and effective way to improve the bioavailability of Cur. HIGHLIGHTS The optimal Cur-Meg/or Cur-Arg complex powder was prepared and characterized. The Cur release rate in vitro was significantly improved. The bioavailability can be improved when using Cur-Meg/or Cur-Arg complex. A simple and effective way to improve the bioavailability of Cur.
A FZD7-specific Antibody–Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models

Although WNT signaling is frequently dysregulated in solid tumors, drugging this pathway has been challenging due to off-tumor effects. Current clinical pan-WNT inhibitors are nonspecific and lead to adverse effects, highlighting the urgent need for more specific WNT pathway–targeting strategies. We identified elevated expression of the WNT receptor Frizzled class receptor 7 (FZD7) in multiple solid cancers in The Cancer Genome Atlas, particularly in the mesenchymal and proliferative subtypes of ovarian serous cystadenocarcinoma, which correlate with poorer median patient survival. Moreover, we observed increased FZD7 protein expression in ovarian tumors compared with normal ovarian tissue, indicating that FZD7 may be a tumor-specific antigen. We therefore developed a novel antibody–drug conjugate, septuximab vedotin (F7-ADC), which is composed of a chimeric human–mouse antibody to human FZD7 conjugated to the microtubule-inhibiting drug monomethyl auristatin E (MMAE). F7-ADC selectively binds human FZD7, potently kills ovarian cancer cells in vitro, and induces regression of ovarian tumor xenografts in murine models. To evaluate F7-ADC toxicity in vivo, we generated mice harboring a modified Fzd7 gene where the resulting Fzd7 protein is reactive with the human-targeting F7-ADC. F7-ADC treatment of these mice did not induce acute toxicities, indicating a potentially favorable safety profile in patients. Overall, our data suggest that the antibody–drug conjugate approach may be a powerful strategy to combat FZD7-expressing ovarian cancers in the clinic.
Valsartan nano‐filaments alter mitochondrial energetics and promote faster healing in diabetic rat wounds

Chronic wounds are a common and debilitating condition associated with aging populations that impact more than 6.5 million patients in the United States. We have previously demonstrated the efficacy of daily topical 1% valsartan in treating wounds in diabetic mouse and pig models. Despite these promising results, there remains a need to develop an extended‐release formulation that would reduce patient burden by decreasing the frequency of daily applications. Here, we used nanotechnology to self‐assemble valsartan amphiphiles into a filamentous structure (val‐filaments) that would serve as a scaffold in wound beds and allow for steady, localised and tunable release of valsartan amphiphiles over 24 days. Two topical treatments of this peptide‐based hydrogel on full‐thickness wounds in Zucker Diabetic Fatty rats resulted in faster rates of wound closure. By day 23, all val‐filament treated wounds were completely closed, as compared to one wound closed in the placebo group. Mechanistically, we observed enrichment of proteins involved in cell adhesion and energetics pathways, downregulation of Tgf‐β signalling pathway mediators (pSmad2, pSmad3 and Smad4) and increased mitochondrial metabolic pathway intermediates. This study demonstrates the successful synthesis of a sustained‐release valsartan filament hydrogel, its impact on mitochondrial energetics and efficacy in treating diabetic wounds.
Perceptions and experiences of engaging in physical activity following coronary artery bypass graft surgery

ABSTRACT Background Engagement in physical activity (PA) during the recovery period following coronary artery bypass graft (CABG) surgery improves physical and health-related quality-of-life outcomes. Objective To explore people’s perceptions and experiences of engaging in PA during the first three months following CABG surgery. Methods A mixed methods study design was utilized. Quantitative data were collected via accelerometer activity capture and standardized questionnaires. Qualitative data were collected via semi-structured interviews at weeks 1, 3, 6 and 12 post-hospital discharge. Interviews were analyzed using inductive thematic analysis. Results Two overarching themes described the overall experience of engaging in PA: 1) “Navigating a difficult and unfamiliar road to recovery” and 2) “Still cautious but becoming more confident and able. ” These themes described the impact over time that various physical (i.e., fatigue, pain, medical complications, and physical deconditioning), psychological (i.e., fear, confidence, uncertainty, and motivation), and environmental (support) factors had on PA engagement, as well as the relationships between these factors. Conclusion The findings provided insight into the physical, psychological, and environmental factors that impacted participants’ PA engagement following CABG surgery. This knowledge may benefit health professionals to optimize preparation and support for adults to engage in PA post-hospital discharge following CABG surgery.
Multiple Congenital Ocular Anomalies in a silver coat Missouri Fox Trotter stallion

Abstract This is the first description of Multiple Congenital Ocular Anomalies (MCOA) in a silver coat Missouri Fox Trotter determined to be heterozygous for the Silver PMEL17 missense mutation associated with MCOA and a silver coat in other breeds. The stallion was treated for meningoencephalitis and bilateral uveitis of unknown origin. A complete ophthalmic examination and ocular ultrasonography were performed. As an incidental finding, the patient exhibited bilateral cystic lesions restricted to the temporal anterior uvea consistent with the Cyst phenotype and was genotyped heterozygous for the Silver mutation. Additionally, 4 other non-silver colored Missouri Fox Trotters were genotyped homozygous for the wild-type allele. Screening for PMEL17 mutation in Missouri Fox Trotters accompanied by ophthalmic phenotype characterization is recommended to determine the allelic frequency and facilitate informed breeding decisions since the silver coat color is particularly popular.
Expression of miRNAs derived from plasma exosomes in patients with intestinal Behçet's syndrome.

OBJECTIVES MicroRNAs (miRNAs) derived from plasma exosomes are potential diagnostic biomarkers. However, little is known about the expression of miRNAs derived from plasma exosomes in patients with intestinal Behçet's syndrome (BS). This study aimed to explore the difference of miRNAs derived from plasma exosomes between intestinal BS patients and healthy people, and further identify potential biomarkers that predict the disease activity of intestinal BS. METHODS A total of 43 intestinal BS patients and 23 healthy volunteers were enrolled, among whom 23 were active intestinal BS and 20 were stable intestinal BS. The miRNAs expression profiles of plasma exosomes in 3 active intestinal BS patients and 3 healthy volunteers were determined using next-generation high throughput sequencing. Additionally, significantly differentially expressed miRNAs were further analysed by quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort of 60 subjects. RESULTS From the sequencing analysis, 15 miRNAs were identified to be differently expressed (p<0.05). Of these, 13 miRNAs were up-regulated, and 2 were down-regulated in intestinal BS patients compared with healthy volunteers. Furthermore, qRT-PCR analysis confirmed that miR-141-3p was down-regulated and miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p were up-regulated in intestinal BS patients' plasma exosomes. Additionally, the level of miR-141-3p was negatively correlated with disease activity indicators of intestinal BS, while miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p was positively correlated with disease activity indicators of intestinal BS. CONCLUSIONS Circulating miR-141-3p, miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p derived from plasma exosomes may serve as biomarkers of disease activity in intestinal BS.
A Chimeric TGA Repressor Slows Down Fruit Maturation and Ripening in Tomato.

The bZIP transcription factor (TF) SlTGA2.2 was previously highlighted as a possible hub in a network regulating fruit growth and transition to ripening (maturation phase). It belongs to a clade of transcription factors well known for their involvement in the regulation of the salicylic acid (SA) - dependent systemic acquired resistance (SAR). To investigate if this TGA TF plays a role in tomato fruit growth and maturation, we took advantage of the fruit-specific SlPPC2 promoter (PPC2pro) to target the expression of a SlTGA2.2-SRDX chimeric repressor in a developmental window restricted to early fruit growth and maturation. Here, we show that this SlTGA2.2-SRDX repressor alters early fruit development and metabolism, including chloroplast number and structure, considerably extends the time necessary to reach the mature green stage and slows down fruit ripening. RNAseq and plant hormone analyses reveal that PPC2pro:SlTGA2.2-SRDX fruits are maintained in an immature stage as long as PPC2pro is active, through early modifications of plant hormonal signalling and down-regulation of MADS-RIN and NAC-NOR ripening regulators. Once PPC2pro becomes inactive and therefore SlTGA2.2-SRDX expression is reduced, ripening can proceed, albeit at a slower pace than normal. Altogether, this work emphasizes the developmental continuum between fruit growth, maturation and ripening and provides a useful tool to alter and study the molecular bases of tomato fruit transition to ripening.
Examining associations between concussion history, subjectively experienced memory problems, and general health factors in older men

Abstract Objective Examine associations between subjective memory complaints (SMCs), concussion history, and cognitive, psychological, and physical health in older men from the general population. Method Participants were 504 men aged 50–79 who were recruited using an online labor market. Participants completed a survey assessing demographics, medication history, concussion history, recent memory problems, and additional aspects of recent cognitive, mental, and physical health. Results Men with a lifetime history of ≥3 concussions also reported a lifetime history of being prescribed medication for anxiety (46.8%), depression (43.5%), chronic pain (79.0%), and high blood pressure (66.1%). When asked about symptoms experienced over the past year and the past week, they endorsed higher rates of cognitive and mental health problems, migraines, and difficulties with sleep and fatigue. The multivariable logistic regression model for predicting mild or greater memory problems was significant, χ2(8) = 168.97, p < . 001. In unadjusted analyses, significant predictors, in order of magnitude (strongest to weakest), were fatigue (odds ratio [OR] = 3.21), back or neck pain (OR = 2.28), migraines (OR = 2.11), anxiety (OR = 2.07), depression (OR = 2.04), difficulty sleeping (OR = 1.98), and concussion history (OR = 1.49). In the multivariable model, only back or neck pain (OR = 1.51, p = .004) and fatigue (OR = 1.99, p = .004) were significant predictors. Conclusions A personal history of multiple concussions was associated with perceived memory problems, but to a lesser degree than fatigue, back or neck pain, and migraines.
Facile decoration of two-dimensional Ti3C2T x nanoplates with CuS nanoparticles via a facile in situ synthesis strategy at room temperature for superhigh specific capacitance of supercapacitors

Although supercapacitors have attracted more and more attention owing to their fast charging speed and high power density, their wide applications have still been limited by their low energy density. In this study, a new CuS-nanoparticle-decorated Ti3C2T x electrode material is fabricated via a facile in situ synthesis strategy at room temperature. CuS nanoparticles, generated from the in situ reaction of Cu (NO3)2·3H2O with Na2S·9H2O, are anchored between the Ti3C2T x interlayers through electrostatic interaction. This type of structural construction is found capable of not only reducing the surface oxidation of Ti3C2T x , but also preventing the accumulation of CuS nanoparticles by the template effect of Ti3C2T x nanoplates. As a result, the CuS/Ti3C2T x nanohybrid delivers a maximum specific capacitance of 911 F g−1 at 1 A g−1 and a good cycling stability. A symmetric supercapacitor fabricated using the CuS/Ti3C2T x nanohybrid as the electrode material exhibits an energy density of 43.56 W h kg−1 with a power density of 475 W kg−1. Consequently, this work provides a new perspective of microstructural design for the preparation of electrode materials with superhigh specific capacitance through an easy and low-cost in situ-reaction method at room temperature.
Theoretical model study of adsorbed antimalarial-graphene dimers: doping effects, photophysical parameters, intermolecular interactions, edge adsorption, and SERS

Abstract Future diagnostics and therapy applications are in part riding on the discovery and implementation of new optical techniques and strategies (which often derive from dyads) for example, prediction of features in surface-enhanced Raman spectroscopy requires the study of chromophore-chromophore interactions involve intermolecular forces, drug delivery, and photo mechanisms which are of great interest. New matches between chromophore systems (i.e. FRET), and π-delocalized surfaces are important to study. We explore low-molecular weight drug molecules and their interaction with the reporter material/surface of graphene. Bonding, charge transfer and orbital interactions for 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole (megazol or AMIT) on graphene were carried out. The graphene model substrate was monotonically/monatomically substituted (doped) with one neutral heteroatom (N/O/S/B) in place of one carbon center; chemical adsorption of AMIT is due to charge transfer from doped graphene to AMIT (DFT). Our AMIT-nanocluster studies show that the nanoclusters will act as a sensor component for the detection of drugs due to SERS. Our findings identified that the greater the energy of the charge transfer, the stronger the calculated chemical adsorption. Additionally, charge transfer is highest for the N-doped systems and least for pristine graphene, resulting in a stronger adsorption energy for N-doped graphene. Mulliken charge analysis of structures confirms enhancement found in QD-AMIT systems. Communicated by Ramaswamy H. Sarma
Autoantibodies against the envelope proteins of endogenous retroviruses K102 and K108 in patients with systemic lupus erythematosus correlate with active disease.

OBJECTIVES To determine if patients with systemic lupus erythematosus (SLE), a disease characterised by elevated type I interferons reminiscent of anti-viral immunity, have expression of human endogenous retrovirus K (HERV-K) proviruses capable of producing envelope (Env) protein, as well as associated autoantibodies against the Env protein. METHODS ELISAs were conducted with recombinant Env protein and sera from SLE patients with active (n=60) or inactive (n=49) disease, healthy controls (n=47), other rheumatic disorders (n=59), as well as plasma from paediatric lupus patients with active (n=30) or inactive (n=30) disease, and 17 healthy children. Antibody reactivity was evaluated for correlations with clinical and laboratory parameters of the patients. Expression of HERV-K transcripts were profiled in SLE leukocytes by RNA-Seq. RESULTS Both adult and paediatric SLE patients had autoantibodies against HERV-K Env with higher titres than healthy controls or patients with Sjögren's syndrome, small- or large-vessel vasculitis, or psoriatic arthritis. Transcripts from only two HERV-K loci capable of producing Env, HERV-K102 and -K108, were detected among the 10 expressed loci in SLE patients. CONCLUSIONS Our data reveal that HERV-K proviruses are expressed in SLE and that the HERV-K-encoded Env protein elicits an immune response in patients, particularly during active disease.
Patient prioritization and management during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic affected the healthcare system in a major way generally. Healthcare re-organization of resources and manpower, establishing management protocols and specific patients’ pathways are all evolving with the continuously changing situation. Neuro-vascular management and its re-organization are part of these global measures to cope with this pandemic in a way to establish less risky patients’ pathways, help in patients’ triage, protecting the staff by introducing training and applying safety measures and to manage neuro-vascular emergencies and elective activity. We here describe the situation of the pandemic affecting neuro-vascular interventions and propose our recommendations for patients’ triage, resources management and organization, remote solutions and preparations for any future waves.
Factors associated with pediatric vaccine hesitancy of parents: a cross-sectional study in Turkey

ABSTRACT Aim: This study aims to determine the prevalence and associated factors of vaccine hesitancy in females with children aged 12 months to 6 years who receive service from the antenatal class of a tertiary hospital in Turkey. Method: The study group includes 370 parents receiving service from a tertiary hospital. The data collection tools of the study were a descriptive data form and the Parent Attitudes about Childhood Vaccines survey.The data were analyzed using chi-square analysis and logistic regression analysis. Results: In our study, the prevalence of vaccine hesitancy was determined as 13.8% and vaccine refusal prevalence as 4.8%. In univariate analysis, vaccine hesitancy was found to be significantly higher in mothers with a university education, who got pregnant with treatment, who were not trained about pediatric vaccines in the antenatal follow-up, who followed anti-vaccine groups on social media, and who did not use vitamin D and iron supplements regularly or never used for their child. Vaccine hesitancy was significantly higher in parents who stated that their information sources of vaccines were not scientific, who were worried about vaccine ingredients (aluminum, mercury, pig gelatine) and who used alternative medicine practices (p < .05). In multivariate analysis, the risk of vaccine hesitancy increases 3.05 times in pregnancies with treatment, 3.74 times in those who did not use vitamin D or iron preparations, 3.01 times in those who followed anti-vaccine groups on social media,2.93 times in parents who were worried about the vaccine ingredients. Conclusion: Our findings suggest that the prevalence of vaccine hesitancy and risk factors should be monitored closely in the following years.
Mist chemical vapor deposition of crystalline MoS2 atomic layer films using sequential mist supply mode and its application in field-effect transistors

Molybdenum disulfide (MoS2) mono/bilayer have been systematically investigated using atmospheric-pressure mist chemical vapor deposition (mist CVD) from (NH4)2MoS4 dissolved in N-methyl-2-pyrrolidone as a precursor. Film deposition was performed by alternating MoS2 mist storage within a closed chamber and mist exhaust, i.e. sequential mist supply mode at different furnace temperatures, storage times of precursor, and repetition cycles of mist supply on thermally grown SiO2 (th-SiO2) and mist-CVD grown Al1−x Ti x O y (ATO) layers coated on p+-Si substrates. The average size of the MoS2 flake and their number of stack layers could be controlled by tuning the deposition parameters combined with substrate pretreatment. Field-effect transistors with MoS2 atomic mono/bilayer as a channel layer exhibited mobility up to 31–40 (43–55) cm2 V−1 s−1 with a threshold voltage of −1.6 (−0.5) V, subthreshold slope of 0.8 (0.11) V dec.−1, and on/off ratio of 3.2 × 104 (3.6 × 105) on th-SiO2 (ATO) layers as gate dielectric layers without mechanical exfoliation. These findings imply that mist CVD is available for the synthesis of metal transition metal dichalcogenide and metal oxide layers as channel and gate dielectric layers, respectively.