Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet-Rich Plasma Therapy: An Effective Approach for Managing Knee Osteoarthritis

Platelet-rich plasma (PRP) is a promising non-invasive therapeutic intervention for knee osteoarthritis (KOA) that has generated significant interest due to anecdotal accounts of its efficacy, resulting in reduced recovery time in various orthopedic interventions. This systematic review examines the effectiveness of PRP in managing KOA. Specifically, it seeks to determine the extent to which PRP can treat KOA patients effectively, alleviate KOA symptoms, and improve patient outcomes. Additionally, the review aims to identify the optimal concentration and composition of PRP required to achieve therapeutic results in KOA. Furthermore, the review investigates whether PRP can modify the synovial environment structurally and immunologically to improve outcomes in KOA patients. We conducted a comprehensive literature search on PubMed, Orthogate, Clinicaltrials.gov, and Embase of clinical trials investigating PRP treatment in KOA patients in the last five years. The results indicated that PRP is effective in treating KOA patients. Evidence shows that PRP therapy can alleviate pain, enhance joint function, increase range of motion, and improve mobility in KOA patients. PRP was effective in treating KOA when the mean platelet concentration of PRP treatment was 4.83 to 5.91 times higher than the baseline whole blood platelet concentration. However, studies investigating PRP with a mean platelet concentration of 3.48 to 4.04 times higher than baseline failed to demonstrate statistically significant improvements. PRP therapy slowed down KOA progression, which validates its effectiveness in impeding further structural damage and arresting the degenerative impact of the disease. Nonetheless, further investigation is necessary to examine how PRP therapy can modify the progression of the disease. Furthermore, future research should identify the most effective platelet concentration levels that provide optimal symptom relief. There is a need for further research to identify the specific PRP configuration that is most pertinent in a clinical setting, as there is a lack of standardization in PRP manufacturing protocols, including the variety of experimental setups and dosing schedules utilized in different studies.
Accessing Meals on Wheels: A qualitative study exploring the experiences of service users and people who refer them to the service

Abstract Aims This study aimed to explore the perceptions of Meals on Wheels (MoWs) service users (SUs), and people who refer them to MoWs (‘referrers’), with accessing and commencing the service in England, the barriers that might hinder service uptake, and what information would be valued when considering accessing the service. Methods Semistructured interviews were conducted in May–July 2022 with seven SUs and 21 referrers, recruited from four MoWs providers across England. Data were analysed using inductive thematic analysis. Results Participants indicated various pathways into the service, but referrers (family members) were more likely to be the ones enquiring about, and commencing, MoWs for SUs. Once an enquiry about MoWs had been made, the service was perceived as straightforward to set up. However, existing preconceptions and stereotypes were perceived to act as barriers to accessing MoWs. Information that participants deemed important to have available when deciding on whether to access MoWs related to the meals, the specific services provided, the reliability and flexibility of delivery and the cost of services. Conclusion These findings could inform MoWs service providers' public awareness strategies about MoWs, to facilitate referrals to the service for adults with care and support needs. Patient or Public Contribution An advisory group of people with lived experience of MoWs (users of the service and their family referrers) extensively discussed the findings of the research and advised on the implications and future dissemination steps.
KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling

Abstract Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.
Compositional variations in Cu-Ni-PGE sulfides of the Dunka Road Deposit, Duluth Complex, Minnesota; the importance of combined assimilation and magmatic processes

The Dunka Road deposit is one of ten occurences of Cu-Ni sulfides bearing platinum-group elements (PGE) on the northwestern margin of the Duluth Complex, in Minnesota. Mineralization has been linked to contamination of the host troctolitic magma through assimilation of argillaceous rocks from the Virginia Formation. On the basis of texture and composition, the sulfide mineralization is divided into five types: 1) norite-hosted disseminated sulfides, 2) troctolite-hosted disseminated sulfides, 3) PGE-rich disseminated sulfide horizons, 4) pyrrhotite-rich massive sulfides, and 5) chalcopyrite-rich disseminated sulfides. The norite-hosted sulfides exhibit featues suggestive of the magma's substantial contamination, such as high proportions of pyrrhotite and arsenide minerals, and high mean values of S/Se (9,700) and δ34S (ll.2%₀). They are also generally metal-poor, implying that the sulfides interacted with a relatively low volume of silicate melt (i.e., low R factor). The troctolite-hosted sulfides formed at moderate degrees of contamination, as indicated by their intermediate mean values of S/Se (4,600) and δ34S (7.8%₀). The PGE-rich sulfide horizons show little sign of contamination, and have mantle-like mean values of S/Se (2,600) and δ34S (2.1%o). Their very high PGE contents suggest that they formed at elevated R factors. The pyrrhotite-rich massive sulfides and associated chalcopyrite-rich disseminated sulfides have relatively high mean values of S/Se (8,000) and δ34S (10.2%o), indicative of significant contamination. The former are interpreted to represent a cumulate of monosulfide solid-solution (mss), whereas the chalcopyrite-rich sulfides represent the fractionated sulfide liquid. A general increase in the degree of contamination is observed toward the base of the intrusion, associated with a decrease in R factor and metal concentration of the sulfides. This likely results from the introduction of partial melt from the metasedimentary country-rocks, which was cooler than the mafic magma and led to the early crystallization of the sulfide liquid.
Invasive fungal infections in hematologic malignancies: Incidence, management, and antifungal therapy

The incidence of invasive fungal infections (IFIs) has increased in recent years as a result of increasing the incidence of hematologic malignancies (HMs). IFIs, as the opportunistic diseases, are the most important concern in these patients with a high mortality rate. These infections are one of the leading causes of morbidity and mortality in HM patients and an important factor in increasing the costs of patients’ management because of the prolonged hospitalization and the inevitable need to use antifungal agents. Due to the changes in the pattern of organisms causing IFIs, unavailability of effective and safe antifungal drugs, and high rate of drug resistance as well as lack of fast and accurate diagnostic methods, these infections have become a serious and life-threatening problem necessitating effective prevention and treatment strategies using suitable antifungal agents, especially in high-risk patients. The aim of the present study was to review the pathogens causing various types of IFIs, diagnostic methods, and novel prophylactic and therapeutic antifungal regimens in HM patients according to the new published studies and clinical trials.
Genome-wide identi ﬁ cation and expression analysis of the KCS gene family in soybean ( Glycine max ) reveal their potential roles in response to abiotic stress

Very long chain fatty acids (VLCFAs) are fatty acids with chain lengths of 20 or more carbon atoms, which are the building blocks of various lipids that regulate developmental processes and plant stress responses. 3-ketoacyl-CoA synthase encoded by the KCS gene is the key rate-limiting enzyme in VLCFA biosynthesis, but the KCS gene family in soybean ( Glycine max ) has not been adequately studied thus far. In this study, 31 KCS genes (namely GmKCS1 - GmKCS31 ) were identi ﬁ ed in the soybean genome, which are unevenly distributed on 14 chromosomes. These GmKCS genes could be phylogenetically classi ﬁ ed into seven groups. A total of 27 paralogous GmKCS gene pairs were identi ﬁ ed with their Ka/Ks ratios indicating that they had undergone purifying selection during soybean genome expansion. Cis -acting element analysis revealed that GmKCS promoters contained multiple hormone-and stress-responsive elements, indicating that GmKCS gene expression levels may be regulated by various developmental and environmental stimuli. Expression pro ﬁ les derived from RNA-seq data and qRT-PCR experiments indicated that GmKCS genes were diversely expressed in different organs/tissues, and many GmKCS genes were found to be differentially expressed in the leaves under cold, heat, salt, and drought stresses, suggesting their critical role in soybean resistance to abiotic stress. These results provide fundamental information about the soybean KCS genes and will aid in their further functional elucidation and exploitation.
Ambient Aqueous Synthesis of Imine-Linked Covalent Organic Frameworks (COFs) and Fabrication of Freestanding Cellulose Nanofiber@COF Nanopapers

Covalent organic frameworks (COFs) are usually synthesized under solvothermal conditions that require the use of toxic organic solvents, high reaction temperatures, and complicated procedures. Additionally, their insolubility and infusibility present substantial challenges in the processing of COFs. Herein, we report a facile, green approach for the synthesis of imine-linked COFs in an aqueous solution at room temperature. The key behind the synthesis is the regulation of the reaction rate. The preactivation of aldehyde monomers using acetic acid significantly enhances their reactivity in aqueous solutions. Meanwhile, the still somewhat lower imine formation rate and higher imine breaking rates in aqueous solution, in contrast to conventional solvothermal synthesis, allow for the modulation of the reaction equilibrium and the crystallization of the products. As a result, highly crystalline COFs with large surface areas can be formed in relatively high yields in a few minutes. In total, 16 COFs are successfully synthesized from monomers with different molecular sizes, geometries, pendant groups, and core structures, demonstrating the versatility of this approach. Notably, this method works well on the gram scale synthesis of COFs. Furthermore, the aqueous synthesis facilitates the interfacial growth of COF nanolayers on the surface of cellulose nanofibers (CNFs). The resulting CNF@COF hybrid nanofibers can be easily processed into freestanding nanopapers, demonstrating high efficiency in removing trace amounts of antibiotics from wastewater. This study provides a route to the green synthesis and processing of various COFs, paving the way for practical applications in diverse fields.
Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: a cohort study of 14 778 patients from the French health insurance database (SNDS)

Background Sex differences in phenotype presentation, disease trajectory and treatment response in psoriatic arthritis (PsA) have been reported. Nevertheless, whether classes of targeted therapies differentially affect men and women with PsA remains unclear. Objectives To assess the effect of sex on the long-term persistence of each class of targeted therapies in PsA. Methods This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. We included all adults with PsA who were new users of targeted therapies (not in the year before the index date) during 2015–2021 and studied all treatment lines during the study period. Persistence was defined as the time from treatment initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by sex involved multivariate frailty models with conventional synthetic disease-modifying antirheumatic drugs and prednisone as time-dependant variables. Results We included 14 778 patients with PsA who were new users of targeted therapies: 8475 (57%) women (mean age 50±13 years; 15 831 lines), 6303 (43%) men (mean age 51±13 years; 10 488 lines). Overall, 1-year persistence was 52% for women and 62% for men and at 3 years it was 27% and 39%, respectively. After adjustments, persistence was lower for women than men for inhibitors of tumour necrosis factor (TNFi) (adjusted HR (HRa) 1.4, 99% CI 1.3 to 1.5) and interleukin 17 inhibitor (IL17i) (HRa 1.2, 99% CI 1.1 to 1.3) but not IL12/23i (HRa 1.1, 99% CI 0.9 to 1.3), IL23i (HRa 1.1, 99% CI 0.7 to 1.5) or Janus kinase inhibitor (JAKi) (HRa 1.2, 99% CI 0.9 to 1.6). Conclusion The treatment persistence was lower for women than men for TNFi and IL17i but not for IL12/23i, IL23i or JAKi.
Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet‐induced oxidative damage by increasing endogenous antioxidants in HaCaT cells

Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ–tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure.
Short-term and long-term behavioral effects of vaccination mandates

ABSTRACT Current COVID-19 vaccination levels are insufficient to achieve herd immunity. To implement effective interventions toward ending the pandemic, it is essential to understand why people are motivated and willing to receive vaccination. The study aims to evaluate attitudes toward COVID-19 vaccination mandates and the impact of policies on future vaccine uptake and behavior utilizing self-determination theory. We conducted an online survey (n = 569) in the U.S. and Turkey to investigate a relationship between respondents’ psychological needs and their willingness and motivation to receive COVID vaccination. The study examined the possible impact of vaccine mandates on these needs. Autonomy satisfaction was the leading predictor of willingness to receive vaccination (p < .0001). Relatedness satisfaction was the leading predictor of one’s intention to receive vaccination (OR = 3.382; p = .0001). The strongest positive correlation was found between needs frustration and external motivation. A moderate positive correlation was found between competence frustration and introjected motivation. No association was found between vaccine mandates and psychological needs. Need satisfaction, especially autonomy and relatedness, appear to positively influence willingness and intention to receive a vaccination. On the other hand, need frustration, especially autonomy and competence frustration, correlates with external motivation, thereby suggesting a detrimental long-term effect on vaccination behavior. Need satisfaction promotes positive vaccination behavior, while need frustration might adversely affect motivation and willingness to receive vaccination. Strategies promoting autonomous decision-making might be more effective than vaccination enforcement in sustaining positive vaccination behavior.
Geostationary satellite observations of extreme and transient methane emissions from oil and gas infrastructure

Significance Decreasing atmospheric methane emissions is an urgent priority to slow near-term climate change. Satellites have unique capabilities to pinpoint methane sources in support of climate action, but the current observing system is entirely in low-Earth orbit and thus has difficulty identifying and quantifying transient emissions. Here, we demonstrate continuous 5-min monitoring of large methane point sources with the U.S. Geostationary Operational Environmental Satellites (GOES). We apply this to quantify an extreme 3-h methane release from a natural gas pipeline in Durango, Mexico. We detect other large releases lasting less than 1 h from oil and gas infrastructure. Our results demonstrate the potential for continuous monitoring of large methane point sources from geostationary orbit.
Nonstationary extreme flood/rainfall frequency analysis informed by large‐scale oceanic fields for Xidayang Reservoir in North China

Climate is a primary driver for extreme rainfall and flood events. In this paper, the temporally changing flood risk associated with the annual maximum 30‐day rainfall (30‐day AMR) and the annual maximum daily inflow (AMDI) related to the Xidayang Reservoir catchment is analysed from a climatic context. This is the largest catchment in Daqing River Basin in North China and is highly prone to floods related to the East Asian summer monsoon. Two climate factors, the average May‐June‐July sea surface temperature anomalies in areas of the northern Indian Ocean and western Pacific Ocean, are identified. They show a high negative correlation with the AMDI and 30‐day AMR. Bayesian nonstationary models are then developed for the AMDI and 30‐day AMR using the climate predictors identified as covariates. We compared three types of models of AMDI and 30‐day AMR: (1) time‐invariant, (2) linear temporal trend and (3) climate informed, and found that the climate‐informed models exhibit the best performance according to Deviance Information Criterion (DIC) and 90th percentile Bayesian coverage rate for both AMDI and 30‐day AMR. A significant decreasing trend is identified in the AMDI and the 30‐day AMR, which is found to be associated with the climate predictors. Leave one out cross validation (LOOCV) is used to demonstrate that these models have decent skill in predicting year‐to‐year variability in flood risk. This can help to provide flood/rainfall dynamic management measures for reservoirs in Daqing River Basin using information from before the beginning of monsoon season, thus facilitating adaptation to a changing climate.
Characteristics of precipitation extremes in Malaysia associated with El Niño and La Niña events

This study investigates the El Niño‐Southern Oscillation (ENSO)‐related seasonal variations in precipitation extremes based on the observed daily precipitation dataset of 23 meteorological stations in Malaysia, spanning a period of 46 years from 1966 to 2011. The extreme indices were a subset of the Expert Team for Climate Change Detection and Indices (ETCCDI) that covers the duration, frequency and intensity aspects of precipitation extremes. Seasonal composites of ‘El Niño minus neutral’ and ‘La Niña minus neutral’ years of these indices were computed based on El Niño and La Niña occurrences during the period. The results showed that the ENSO‐related variations in precipitation extremes were generally coherent with the variations in total precipitation. Generally, dry (wet) precipitation extremes tended to enhance during El Niño (La Niña); however, this was dependent on season and location. The El Niño and La Niña influences on precipitation extremes were not entirely linear. While the impacts of El Niño and La Niña were generally opposite for most locations and seasons, there were cases where both exerted in‐phase influences. The impacts were also dependent on the intensity of the event itself. While the El Niño impacts were generally coherent across different intensities, La Niña can have entirely different impacts among different categories. During December–January–February (DJF), strong (moderate) La Niña caused a significant decrease (increase) in wet precipitation extremes over the Peninsular Malaysia. This was related to the broadening (narrowing and westward displacement) of the anomalous cyclonic circulation over the western north Pacific during strong (moderate) La Niña. Hence, the likelihood for widespread flooding over the east coast of the Peninsular Malaysia during DJF increases during moderate but not during strong La Niña events.
Hypoxia-inducible factor 1 alpha protein increases without changes in mRNA during acute hypoxic exposure of the Gulf killifish, Fundulus grandis

ABSTRACT The hypoxia inducible factor 1 (HIF1) is a central regulator of the molecular responses of animals to low oxygen. While the hypoxia-responsiveness of HIF1 is generally attributed to the stabilization of the alpha protein subunit (HIF1α) at low oxygen, several studies on fish report increased tissue levels of HIF1A mRNA during hypoxia, suggesting transcriptional regulation. In the current study, HIF1α protein and HIF1A mRNA were determined in parallel in tissues of Gulf killifish, Fundulus grandis, exposed to short-term hypoxia (24 h at 1 mg O2 l−1). HIF1α protein was higher in brain, ovary, and skeletal muscle from fish exposed to hypoxia compared with normoxic controls by 6 h, and it remained elevated in brain and ovary at 24 h. In contrast, HIF1A mRNA levels were unaffected by hypoxia in any tissue. Moreover, HIF1α protein and HIF1A mRNA levels in the same tissues were not correlated with one another during either normoxia or hypoxia. Hence, an increase in HIF1α protein does not depend upon an increase in HIF1A mRNA during acute exposure to low oxygen in this species. The results support the widely accepted mechanism of post-translational protein stabilization, rather than new transcription, during the initial response of fish to hypoxia.
In Search of the True Gypsy: From Enlightenment to Final Solution

CHOICE - "This is a book sure to elicit continued controversy and should be part of every Gypsy collection, but it will be of limited interest to nonspecialists". Patterns of Prejudice, Vol 34, No 1 "Willem"s work is a very important and welcome addition. " Holocaust and Genocide Studies "Willem"s study will become a milestone in the history of research on the Gypsies, because it, in excellent fashion, makes this very history its theme.