Miracle-dz/UniFAR-FTUs huggingface dataset:
Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels

Melatonin is one of the most used pharmacologic treatments for sleep problems in autism spectrum disorder, though its relationship with circadian and sleep parameters is still not well stablished. A naturalistic study was conducted in children with autism spectrum disorder, previously drug-naïve, before and after treatment with immediate-release melatonin. Circadian rhythms and sleep parameters were studied using an ambulatory circadian-monitoring device, and saliva samples were collected enabling determination of dim light melatonin onset. Twenty-six children with autism spectrum disorder (age 10.50 ± 2.91) were included. Immediate-release melatonin modified circadian rhythm as indicated by wrist skin temperature, showing an increase at night. A positive correlation was found between time of peak melatonin and sleep efficiency improvement values. Sleep-onset latency and efficiency improved with immediate-release melatonin. Immediate-release melatonin could be an effective treatment to improve sleep onset and restore a typical pattern of wrist temperature, which appears to be lost in autism spectrum disorder.
The auditory stimulus reduced the visual inhibition of return: Evidence from psychophysiological interaction analysis

Visual inhibition of return (IOR) is a mechanism for preventing attention from returning to previously examined spatial locations. Previous studies have found that auditory stimuli presented simultaneously with a visual target can reduce or even eliminate the visual IOR. However, the mechanism responsible for decreased visual IOR accompanied by auditory stimuli is unclear. Using functional magnetic resonance imaging, we aimed to investigate how auditory stimuli reduce visual IOR. Behaviorally, we found that the visual IOR accompanying auditory stimuli was significant but smaller than the visual IOR. Neurally, only in the validly cued trials, the superior temporal gyrus showed increased neural coupling with the intraparietal sulcus, presupplementary motor area, and some other areas in audiovisual conditions compared with visual conditions. These results suggest that the reduction in visual IOR by the simultaneous auditory stimuli may be due to a dual mechanism: rescuing the suppressed visual salience and facilitating response initiation. Our results support crossmodal interactions can occur across multiple neural levels and cognitive processing stages. This study provides a new perspective for understanding attention‐orienting networks and response initiation based on crossmodal information.
Kidney clearance of fibroblast growth factor-23 in humans

Purpose of review Recent studies have shed light on factors influencing FGF23 regulation in terms of its production and cleavage. However, less is known about FGF23 elimination from circulation. The kidney's role in FGF23 elimination will be the focus of this review. Recent findings Marked abnormalities in FGF23 physiology have been observed in persons with reduced kidney function compared with healthy persons and raise the question of whether the kidney may be directly regulating FGF23 concentrations. FGF23 concentrations rise dramatically after onset of acute kidney injury and early chronic kidney disease and are associated with poor clinical outcomes. New studies leveraging measurements of FGF23 in the aorta and renal veins concurrently demonstrate that the human kidney efficiently extracts both intact and C-terminal FGF23 from the circulation independent of kidney function and catabolize the hormone. Additionally, the kidney's reduction of PTH predicts the amount it will reduce both C-terminal and intact FGF23. Summary The human kidney removes both intact FGF23 and its C-terminal fragments. FGF23 catabolism within the kidney may be influenced by PTH concentrations, and other factors. Future studies to understand regulation of these hormones and the kidney's role in this interplay are timely.
Using Mice to Model Human Osteoarthritis: Age, Biologic Sex, and Pain Matter

Osteoarthritis (OA), by far the most common form of arthritis worldwide, affects over 500 million adults (1) and has been noted in most mammalian species examined. The structural changes of OA, including cartilage loss, subchondral bone thickening, osteo-phyte formation, and synovial hypertrophy/in ﬂ ammation, accompanied by pain and loss of function, appear to be similar across species. Despite increasing knowledge of OA pathobiology gleaned from studies in humans and animal models, we still lack an intervention proven to modulate structural progression, which has contributed to a rising proportion of patients with OA requiring joint replacement (2). Likewise, the options for pain relief are limited, leaving many patients frustrated with their condition. Rodents, including mice and rats, are commonly used in preclinical studies because they are readily available in suf ﬁ cient numbers, more affordable than larger species, grow rapidly
Comparison Solutions Between Lie Group Method and Numerical Solution of (RK4) for Riccati Differential Equation

This paper introduced Lie group method as a analytical method and then compared to RK4 and Euler forward method as a numerical method. In this paper the general Riccati equation is solved by symmetry group. Numerical comparisons between exact solution, Lie symmetry group and RK4 on these equations are given. In particular, some examples will be considered and the global error computed numerically.
Understanding Virus Structure and Dynamics through Molecular Simulations

Viral outbreaks remain a serious threat to human and animal populations and motivate the continued development of antiviral drugs and vaccines, which in turn benefits from a detailed understanding of both viral structure and dynamics. While great strides have been made in characterizing these systems experimentally, molecular simulations have proven to be an essential, complementary approach. In this work, we review the contributions of molecular simulations to the understanding of viral structure, functional dynamics, and processes related to the viral life cycle. Approaches ranging from coarse-grained to all-atom representations are discussed, including current efforts at modeling complete viral systems. Overall, this review demonstrates that computational virology plays an essential role in understanding these systems.
Approved and investigational fluorescent optical imaging agents for disease detection in surgery

Fluorescent optical imaging is becoming an increasingly attractive imaging tool that physicians can utilise as it can detect previously ‘unseen’ changes in tissue at a cellular level that are consistent with disease. This is possible using a range of fluorescently labelled imaging agents that, once excited by specific wavelengths of light, can illuminate damaged and diseased tissues. For surgeons, such agents can permit dynamic, intraoperative imaging providing a real-time guide as they resect diseased tissue.
Current Pharmaceutical Biotechnology

Background: Psoriatic arthritis (PsA) is a musculoskeletal disease that adversely affects physical mobility and quality of life. It is challenging to manage because of the heterogeneous nature of the symptoms and the current treatment options. Purpose: To explore the patient and rheumatologist perspectives of PsA to help improve understanding of the disease experience and improve disease management. Methods: A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and rheumatologists and patients with psoriasis or PsA was conducted. Questionnaire data were collected from 31 dermatologists, 34 rheumatologists, 90 patients with psoriasis, and 98 patients with PsA and analysed using descriptive statistics. Here, data from rheumatologists and patients with PsA are presented. Results: The results revealed similarities and differences in the rheumatologist and patient perspectives of PsA. Rheumatologists and patients agreed on the impact that PsA had on patients’ quality of life and that more education was needed. However, they differed on several aspects of disease management. Rheumatologists estimated the time to diagnosis as four times shorter than what patients experienced. Patients accepted their diagnosis more than rheumatologists perceived them to; rheumatologists perceived patients to be worried or fearful. Patients perceived joint pain as their most severe symptom, in contrast to rheumatologists, who presumed skin appearance was the most severe symptom. Reported input into PsA treatment goals differed significantly. More than half of the rheumatologists reported equal patient-physician input into goal development as opposed to <10% of patients reporting the same. Almost half of patients reported no input into the development of their treatment goals. Conclusion: The management of PsA could benefit from enhanced screening and re-evaluation of what PsA outcomes have the most value to patients and rheumatologists. A multidisciplinary approach is recommended with increased patient involvement in disease management and individualized treatment options. A R T I C L E H I S T O R Y Received: August 26, 2022 Revised: February 13, 2023 Accepted: March 20, 2023 DOI: 10.2174/1573397119666230516162221
Immune checkpoint inhibitors: maximizing benefit whilst minimizing toxicity

ABSTRACT Introduction The advent of immunotherapy has revolutionized the treatment of cancer; anti-tumor efficacy has been observed with immune checkpoint inhibitors (ICI) in ~20 different cancer types with durable responses in some cases. However, the risk of toxicity in the form of immune-related adverse events (irAE) partially counterbalances these benefits, and there are no FDA-approved biomarkers to categorize patients by likelihood of response or risk of irAEs. Areas covered We conducted a thorough review of the literature of clinical studies regarding ICI and their toxicities. In this review, we synthesize the current body of literature about ICI treatment and irAE by summarizing the classes and uses of ICI, how to identify patients at risk for irAE, present the current understanding of irAE development, describe ongoing research into biomarkers of irAE, examine opportunities for irAE prevention, described management of steroid refractory irAE, and highlight future directions for development of prevention and management strategies. Expert opinion While ongoing biomarker studies are promising, it is unlikely that there will be a ‘one-size-fits-all’ approach to categorizing irAE risk. In contrast, improved management and irAE prophylaxis are potentially in reach, and ongoing trials will help elucidate best practices.
Knockout of protein phosphatase 1 in Leishmania major reveals its role during RNA polymerase II transcription termination

Abstract The genomes of kinetoplastids are organized into polycistronic transcription units that are flanked by a modified DNA base (base J, beta-D-glucosyl-hydroxymethyluracil). Previous work established a role of base J in promoting RNA polymerase II (Pol II) termination in Leishmania major and Trypanosoma brucei. We recently identified a PJW/PP1 complex in Leishmania containing a J-binding protein (JBP3), PP1 phosphatase 1, PP1 interactive-regulatory protein (PNUTS) and Wdr82. Analyses suggested the complex regulates transcription termination by recruitment to termination sites via JBP3-base J interactions and dephosphorylation of proteins, including Pol II, by PP1. However, we never addressed the role of PP1, the sole catalytic component, in Pol II transcription termination. We now demonstrate that deletion of the PP1 component of the PJW/PP1 complex in L. major, PP1-8e, leads to readthrough transcription at the 3’-end of polycistronic gene arrays. We show PP1-8e has in vitro phosphatase activity that is lost upon mutation of a key catalytic residue and associates with PNUTS via the conserved RVxF motif. Additionally, purified PJW complex with associated PP1-8e, but not complex lacking PP1-8e, led to dephosphorylation of Pol II, suggesting a direct role of PNUTS/PP1 holoenzymes in regulating transcription termination via dephosphorylating Pol II in the nucleus.
Placental weight and its relationship with the birth weight of term infants and body mass index of the mothers

Objective Placental pathology is a well-known cause of perinatal and neonatal mortality and morbidity, and may correlate with placental growth, which can be assessed indirectly by anthropometric placental measurements. The aim of this cross-sectional study was to investigate mean placental weight and its relationship with birthweight and maternal body mass index (BMI). Methods Fresh (not formalin fixed) consecutively delivered placentae of term newborns (37–42 weeks), collected between February 2022 and August 2022, and the mothers and newborns, were included. Mean placental weight, birthweight and maternal BMI were calculated. Pearson’s correlation coefficient, linear regression, and one-way analysis of variance were used to analyse continuous and categorical data. Results Out of 390 samples, 211 placentae (with 211 newborns and mothers) were included in this study after exclusion criteria were applied. Mean placental weight was 494.45 ± 110.39 g, and mean term birth weight/placental weight ratio was 6.21 ± 1.21 (range, 3.35–11.62 g). Placental weight was positively correlated with birthweight and maternal BMI, but not with newborn sex. Linear regression effect estimation of placental weight on birthweight revealed a medium correlation (R2 = 0.212; formula, 1.4553 × X + 2246.7, where X is placental weight [g]). Conclusion Placental weight was revealed to positively correlate with birthweight and maternal BMI.
Five-year outcomes of tricuspid valve repair versus replacement; a propensity score-matched analysis

Background Tricuspid valve repair (TVr) is the recommended approach for managing tricuspid regurgitation; however, there is a concern about the long-term durability of the repair. Therefore, this study aimed to compare the long-term outcomes of TVr versus tricuspid valve replacement (TVR) in a matched cohort of patients. Methods This study included 1161 patients who underwent tricuspid valve (TV) surgery from 2009 to 2020. Patients were grouped according to the procedure into two groups: patients who underwent TVr (n = 1020) and patients who underwent TVR (n = 159). The propensity score identified 135 matched pairs. Results Renal replacement therapy and bleeding were significantly higher in the TVR group compared to the TVr group both before and after matching. Thirty-day mortality occurred in 38 (3.79%) patients in TVr group versus 3 (1.89%) in the TVR group (P ≤ 0.001) but was not significant after matching. After matching, TV reintervention (hazard ratio (HR): 21.44 (95% CI: 2.17–211.95); P = 0.009) and heart failure rehospitalization (HR: 1.89 (95% CI: 1.13–3.16); P = 0.015) were significantly higher in the TVR group. There was no difference in mortality in the matched cohort (HR: 1.63 (95% CI: 0.72–3.70); P = 0.25). Conclusions TVr was associated with lower renal impairment, reintervention, and heart failure rehospitalization than replacement. TVr remains the preferred approach whenever feasible.
Anti-IL17 treatment in childhood chronic rheumatic diseases

ABSTRACT Introduction Interleukin-17 (IL-17) is a family of cytokines that plays a key role in several rheumatic diseases in both adults and children. In the last few years, several drugs targeting IL-17 have been developed. Areas covered We present a review on the current state of the art regarding the use of anti-IL17 in childhood chronic rheumatic diseases. To date, the available evidence is limited and mainly focuses on juvenile idiopathic arthritis (JIA) and a specific autoinflammatory disease called deficiency of IL-36 receptor antagonist (DITRA). Recently, a randomized controlled trial resulted in the approval of secukinumab (an anti-IL17 monoclonal antibody) for JIA, due to its demonstrated efficacy and safety. Promising and potential uses of anti-IL17 in Behçet’s syndrome and synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome have also been described. Expert opinion Increasing knowledge about the pathogenetic mechanisms underlying rheumatic diseases is leading to an improvement in the care of several chronic autoimmune diseases. In this scenario, anti-IL17 therapies (such as secukinumab and ixekizumab) might be an optimal choice. Recent data on the use of secukinumab in juvenile spondyloarthropathies can be a starting point for future treatment strategies in other pediatric rheumatic diseases, such as Behçet’s syndrome and the chronic non-bacterial osteomyelitis disease spectrum, particularly SAPHO syndrome.
A Mapping Review of Netnography in Nursing

People use the Web to seek health-related information and to discuss health issues with peers. Netnography, a qualitative research methodology, has gained the attention of researchers interested in people’s health and health issues. However, no previous reviews have accounted for how netnography is used in nursing research. The purpose of this mapping review was to generate a map of netnographic research in nursing. The search was conducted in PubMed, Academic Search Elite, the Cumulative Index to Nursing and Allied Health Literature, Medline, PsycINFO, Scopus, and Web of Science. Data were extracted from 53 original articles. The results show an increasing trend in published netnographies over time; 34% of the total sample was published in 2021. Of the total, 28% originated from Sweden, and 81% had used a covert approach. In studies in which the researchers used more participatory designs, the time spent on online forums ranged between 4 weeks and 20 months. Informed consent is found to be an issue in netnographic studies. We discuss the fact that nursing researchers have used netnography to address a wide range of research topics of concern and interest, from self-care support in an online forum for older adults to nursing students’ perspectives on effective pedagogy. In line with the digital transformation in society in general, we discuss the fact that netnography as a research methodology offers great opportunities for nurse researchers to monitor new spaces and places that presuppose online methodological knowledge.
Prediction of Thermoacoustic Limit Cycles during Premixed Combustion using the Modified Galerkin Approach

The present work extends the Generalized Instability Model, which solves the pressure wave equation via the modified Galerkin method, to include nonlinear heat release models in the form of Flame Describing Functions as well as acoustic losses at the boundaries. These extensions are required for limit cycle prediction in premixed combustors. The governing equations are presented in detail followed by the implementation of two Flame Describing Functions obtained experimentally from a bluff body burner and a swirl stabilized burner. For both test cases, multiple operating points are analyzed, with the model predicting correctly the stability in all cases. Good correspondence between modeled and measured limit cycle amplitudes for the unstable modes is also obtained. However, a parametric study shows that the predicted limit cycle amplitude has a strong dependence on the heat release model and on the acoustic losses present in the system. This indicates that both the energy gain due the combustion process and the acoustic losses through the boundaries need to be determined accurately for limit cycle prediction.
Is the quality of evidence in health technology assessment deteriorating over time? A case study on cancer drugs in Australia

Abstract Objective This study aimed to assess whether there have been changes in the quality of clinical evidence submitted for government subsidy decisions on cancer medicines over the past 15 years. Methods We reviewed public summary documents (PSDs) reporting on subsidy decisions made by the Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to July 2020. Information was extracted on the study design, directness of comparison, sample size, and risk of bias (RoB). Changes in the quality of evidence were assessed using regression analysis. Results Overall, 214 PSDs were included in the analysis. Thirty-seven percent lacked direct comparative evidence. Thirteen percent presented observational or single-arm studies as the basis for decisions. Among PSDs presenting indirect comparisons, 78 percent reported transitivity issues. Nearly half (41 percent) of PSDs reporting on medicines supported by head-to-head studies noted there was a moderate/high/unclear RoB. PSDs reporting concerns with RoB increased by a third over the past 7 years, even after adjusting for disease rarity and trial data maturity (OR 1.30, 95% CI: 0.99, 1.70). No time trends were observed regarding the directness of clinical evidence, study design, transitivity issues, or sample size during any of the analyzed periods. Conclusion Our findings indicate that the clinical evidence supplied to inform funding decisions for cancer medicines is often of poor quality and has been deteriorating over time. This is concerning as it introduces greater uncertainty in decision making. This is particularly important as the evidence supplied to the PBAC is often the same as that supplied to other global decision-making bodies.
Scoping review of outpatient health services utilization among women

Abstract Background: Health services utilization, as one of the mechanisms of the health system, guarantees a healthy life and improves well-being for everyone. Aims: The aim of this study was to identify factors affecting the use of outpatient health services among women. Methods/designs: This scoping review examined the studies related to outpatient health services utilization (OHSU) and its determinants among women. This review was conducted on English language studies published between 2010 and 2023 (All searches were conducted on 20 January 2023). Studies available in databases such as Web of Science, MEDLINE (PubMed), Scopus, Wiley library, Proquest, and Google Scholar were searched manually. Selected keywords and their equivalents were used to search for related articles in each database. Results: A total of 18 795 articles were identified, of which 37 met the inclusion criteria. Findings showed that age, marital status, level of education, employment status, income level, socioeconomic status, rape experience, health insurance, health status, ethnicity, living in rural areas, quality of services, area of residence, having a purpose in life and access to health services affect OHSU among women. Conclusions: The results of the present review showed that in order to achieve the universal goals of health services coverage and health service utilization, it is necessary for countries to provide insurance coverage to the maximum number of people. Also, policies should change in favor of the elderly, poor and low-income, low-educated, rural, ethnic minority, and chronically ill women and provide them with free preventive health services.