Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex and country differences in gout: cross-country comparison between Sweden and the UK

Objective Compare characteristics, sex differences, and management of gout in Sweden and the UK. Method The results from two separate primary care gout surveys from Sweden and the UK were compared. Participants aged ≥18 years with gout were sent a questionnaire asking about lifestyle, gout characteristics, uratelowering therapy (ULT), comorbidities, disability, and disease impact. For sex comparison, participants were pooled across countries. Results In total, 784 (80% male) participants from Sweden and 500 (87% male) from the UK were included. Swedish patients were significantly older at gout onset, mean (SD) age 72 (12) versus 63 (13) years, (p<0.0001), with more comorbidities, and more frequent use of ULT (48% vs 35%, p=0.0005, age-adjusted). Use of alcohol and diuretics was significantly more common among UK patients, who also reported a higher number of gout flares, mean (SD) 2.2 (1.7) versus 1.6 (3.6), (p=0.003) age-adjusted. Females with gout were older at gout onset, mean (SD) age 67 (13) versus 56 (15), (p<0.0001), more often obese, and reported higher use of diuretics. Furthermore, females reported greater impact of gout, more pain and physical limitations, whereas no sex differences were seen in ULT or flares. Conclusions In the UK, gout was more frequently associated with modifiable risk factors. People with gout in Sweden were more commonly taking ULT and had lower frequency of gout flares and impact of gout. Females with gout more commonly took diuretics, had higher body mass index, and reported greater physical disability, which should be considered when managing gout in women.
Non‐erythropoiesis stimulating agent, non‐iron therapies for the management of anemia: A scoping review

Anemia contributes substantially to the global burden of disease, affecting approximately one third of the population. Anemia is associated with an array of poor outcomes, and—when coupled with other comorbidities—increased mortality.2–13 Chronic disease and inflammation retard normal pathways of iron metabolism, leading to iron sequestration and suppression of marrow function. Inflammation induces pro-inflammatory cytokines and mediators which upregulate the iron transport regulatory protein, hepcidin. Hepcidin expression downregulates the iron transport protein ferroportin and thus limits iron egress from cells, leading to restricted uptake and reticuloendothelial sequestration of iron. While iron deficiency remains the leading cause of anemia worldwide, amongst hospitalized patients the anemia of chronic disease is a common cause of anemia. Both iron deficiency and inflammation contribute to anemia in the peri-operative population, with anemia conferring a heightened risk of complications, readmission, and mortality.3,5,10,16–18 Given the burden of anemia amongst hospitalized and surgical patients, there has been considerable research interest in the treatment of anemia as a modifiable risk factor to reduce perioperative complications. Trials of intravenous iron and erythropoietin (EPO) as part of surgical Patient Blood Management programs have had mixed results.19–24 Furthermore, both iron supplementation and EPO are associated with economic costs and adverse effects which may limit their clinical utility. Increased understanding of the pathophysiology of anemia and inflammation have yielded new therapeutic targets, some of which have translated to promising novel drug treatments in pre-clinical and early clinical trials.27–34 Prominent amongst this group are the prolyl hydroxylase inhibitors, a class of agents which stabilize the transcription factor for EPO induction. These agents have demonstrated efficacy in treating anemia in patients with chronic kidney disease.29,31–34 The etiology of anemia in surgical patients is complex, involving both inflammation and blood loss; hence,
Data encryption scheme with extended arithmetic coding

In this work, we extend arithmetic coding and present a data encryption scheme that achieves data compression and data security at the same time. This scheme is based on a chaotic dynamics, which makes use of the fact that the decoding process of arithmetic coding scheme can be considered as the repetition of Bernoulli shift map. Data encryption is achieved by controlling the piecewise linear maps by a secret key in three kinds of approach: (i) perturbation method, (ii) switching method, and (iii) source extension method. Experimental results show that the obtained arithmetic codes for a message are randomly distributed on the mapping domain [0,1) by using different keys without seriously deteriorating the compression ratio, and the transition of the orbits in the domain [0,1) is similar to the chaotic dynamics.
Intra-individual variation of sperm DNA fragmentation in the Human ejaculate

Abstract This retrospective study assessed the biological intra-individual variability of the percentage of sperm with DNA damage (SDF) observed in subsequent ejaculates of the same individual. Variation in SDF was analyzed using the Mean Signed Difference (MSD) statistic based on 131 individuals, comprising 333 ejaculates. Either two, three or four ejaculates were collected from each individual. With this cohort of individuals two main questions were addressed; (1) does the number of ejaculates analyzed influence the variability in the level of SDF associated with each individual? and (2) is the variability observed in SDF similar when individuals are ranked according to their level of SDF? Results showed that the variation observed in mean SDF was not different when 2, 3 or 4 ejaculates were analyzed; consequently, we suggest that the assessment of SDF based on two ejaculates is likely to be representative of the mean SDF expected for the individual. In parallel, it was determined that the variation in SDF increased as SDF increased; in individuals presenting with an SDF value of lower than 30% (potentially fertile), only 5% possessed levels of MSD that could be considered as variable as that presented by individuals presenting with a recurrent high SDF. Finally, we showed that a single assessment of SDF in individuals with medium SDF (20-30%) was less likely to be predictive of the SDF value in the next ejaculate, and therefore, less informative of the patient’s SDF status.
Prospective Randomized Trial of Biologic Augmentation With Bone Marrow Aspirate Concentrate in Patients Undergoing Arthroscopic Rotator Cuff Repair

Background: Although initial studies have demonstrated that concentrated bone marrow aspirate (cBMA) injections promote rotator cuff repair (RCR) healing, there are no randomized prospective studies investigating clinical efficacy. Hypothesis/Purpose: To compare outcomes after arthroscopic RCR (aRCR) with and without cBMA augmentation. It was hypothesized that cBMA augmentation would result in statistically significant improvements in clinical outcomes and rotator cuff structural integrity. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients indicated for aRCR of isolated 1- to 3-cm supraspinatus tendon tears were randomized to receive adjunctive cBMA injection or sham incision. Bone marrow was aspirated from the iliac crest, concentrated using a commercially available system, and injected at the aRCR site after repair. Patients were assessed preoperatively and serially until 2 years postoperatively via the following functional indices: American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test, 12-Item Short Form Health Survey, and Veterans RAND 12-Item Health Survey. Magnetic resonance imaging (MRI) was performed at 1 year to assess rotator cuff structural integrity according to Sugaya classification. Treatment failure was defined as decreased 1- or 2-year ASES or SANE scores as compared with preoperative baseline, the need for revision RCR, or conversion to total shoulder arthroplasty. Results: An overall 91 patients were enrolled (control, n = 45; cBMA, n = 46): 82 (90%) completed 2-year clinical follow-up and 75 (82%) completed 1-year MRI. Functional indices significantly improved in both groups by 6 months and were sustained at 1 and 2 years (all P < .05). The control group showed significantly greater evidence of rotator cuff retear according to Sugaya classification on 1-year MRI (57% vs 18%; P < .001). Treatment failed for 7 patients in each group (control, 16%; cBMA, 15%). Conclusion: cBMA-augmented aRCR of isolated supraspinatus tendon tears may result in a structurally superior repair but largely fails to significantly improve treatment failure rates and patient-reported clinical outcomes when compared with aRCR alone. Additional study is warranted to investigate the long-term benefits of improved repair quality on clinical outcomes and repair failure rates. Registration: NCT02484950 (ClinicalTrials.gov identifier).
Patient‐centered outcomes in the POLO study of active maintenance olaparib for germline BRCA‐mutated metastatic pancreatic cancer

The phase 3 POLO study demonstrated a significant progression‐free survival (PFS) benefit and preserved health‐related quality of life (HRQOL) for active maintenance treatment with olaparib vs placebo in patients with metastatic pancreatic cancer and a germline BRCA mutation. Here, we present a post hoc analysis of the patient‐centered outcomes: time without significant symptoms of disease progression or toxicity (TWiST) and quality‐adjusted TWiST (Q‐TWiST).
Speciation Underpinned by Unexpected Molecular Diversity in the Mycorrhizal Fungal Genus Pisolithus

Abstract The mutualistic ectomycorrhizal (ECM) fungal genus Pisolithus comprises 19 species defined to date which colonize the roots of >50 hosts worldwide suggesting that substantial genomic and functional evolution occurred during speciation. To better understand this intra-genus variation, we undertook a comparative multi-omic study of nine Pisolithus species sampled from North America, South America, Asia, and Australasia. We found that there was a small core set of genes common to all species (13%), and that these genes were more likely to be significantly regulated during symbiosis with a host than accessory or species-specific genes. Thus, the genetic “toolbox” foundational to the symbiotic lifestyle in this genus is small. Transposable elements were located significantly closer to gene classes including effector-like small secreted proteins (SSPs). Poorly conserved SSPs were more likely to be induced by symbiosis, suggesting that they may be a class of protein that tune host specificity. The Pisolithus gene repertoire is characterized by divergent CAZyme profiles when compared with other fungi, both symbiotic and saprotrophic. This was driven by differences in enzymes associated with symbiotic sugar processing, although metabolomic analysis suggest that neither copy number nor expression of these genes is sufficient to predict sugar capture from a host plant or its metabolism in fungal hyphae. Our results demonstrate that intra-genus genomic and functional diversity within ECM fungi is greater than previously thought, underlining the importance of continued comparative studies within the fungal tree of life to refine our focus on pathways and evolutionary processes foundational to this symbiotic lifestyle.
Some new algorithms for recursive estimation in constant, linear, discrete-time systems

Certain recently developed fast algorithms for recursive estimation in constant continuous-time linear systems are extended to discrete-time systems. The main feature is the replacement of the Riccati-type difference equation that is generally used for such problems by another set of difference equations that we call of Chandrasekhar-type. The total number of operations in the new algorithm is in general less than with the Riccati-equation based Kalman filter, with significant reductions being obtained in several important special cases. The algorithms are derived via a factorization of increments of the Riccati equation variable, a method that can be extended to nonsymmetric Riccati equations as well.
Understanding of H mode pedestal characteristics using the multimachine pedestal database

With use of a multimachine pedestal database, essential issues for each regime of ELM types are investigated. They include (i) understanding and prediction of pedestal pressure during type I ELMs, a reference operation mode of a future tokamak reactor; (ii) identification of the operation regime of type II ELMs, which have small ELM amplitude with good confinement characteristics; (iii) identification of the upper stability boundary of type III ELMs for access to the higher confinement regimes with type I or II ELMs; (iv) understanding the relation between core confinement and pedestal temperature in conjunction with the confinement degradation in high density discharges. Both scaling and model based approaches for expressing pedestal pressure are shown to roughly scale the experimental data well and could be used to make initial predictions for a future reactor. q and delta are identified as important parameters for obtaining the type II ELM regime. A theoretical model of type III ELMs is shown to reproduce the upper stability boundary reasonably well. It is shown that there exists some critical pedestal temperature below which the core confinement starts to degrade. It is also shown that it is possible to obtain improved pedestal conditions for good confinement in high density discharges by increasing the plasma triangularity.
The role of neurofilament transport in the radial growth of myelinated axons

The cross-sectional area of myelinated axons increases greatly during postnatal development in mammals and is an important influence on axonal conduction velocity. This radial growth is driven primarily by an accumulation of neurofilaments, which are cytoskeletal polymers that serve a space-filling function in axons. Neurofilaments are assembled in the neuronal cell body and transported into axons along microtubule tracks. The maturation of myelinated axons is accompanied by an increase in neurofilament gene expression and a decrease in neurofilament transport velocity, but the relative contributions of these processes to the radial growth are not known. Here, we address this question by computational modeling of the radial growth of myelinated motor axons during postnatal development in rats. We show that a single model can explain the radial growth of these axons in a manner consistent with published data on axon caliber, neurofilament and microtubule densities, and neurofilament transport kinetics in vivo. We find that the increase in the cross-sectional area of these axons is driven primarily by an increase in the influx of neurofilaments at early times and by a slowing of neurofilament transport at later times. We show that the slowing can be explained by a decline in the microtubule density.
Where are the medical countermeasures against the ARS and DEARE? A current topic relative to an animal model research platform, radiation exposure context, the acute and delayed effects of acute exposure, and the FDA animal rule

Abstract Purpose A question echoed by the National Biodefense Science Board (NBSB) in 2010, remains a reasonable question in 2023; ‘Where are the Countermeasures? ’. A critical path for development of medical countermeasures (MCM) against acute, radiation-induced organ-specific injury within the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE) requires the recognition of problems and solutions inherent in the path to FDA approval under the Animal Rule. Keep Rule number one in mind, It’s not easy. Considerations The current topic herein is focused on defining the nonhuman primate model(s) for efficient MCM development relative to consideration of prompt and delayed exposure in the context of the nuclear scenario. The rhesus macaque is a predictive model for human exposure of partial-body irradiation with marginal bone marrow sparing that allows definition of the multiple organ injury in the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE). The continued definition of natural history is required to delineate an associative or causal interaction within the concurrent multi-organ injury characteristic of the ARS and DEARE. A more efficient development of organ specific MCM for both pre-exposure and post-exposure prophylaxis to include acute radiation-induced combined injury requires closing critical gaps in knowledge and urgent support to rectify the national shortage of nonhuman primates. The rhesus macaque is a validated, predictive model of the human response to prompt and delayed radiation exposure, medical management and MCM treatment. A rational approach to further development of the cynomolgus macaque as a comparable model is urgently required for continued development of MCM for FDA approval. Conclusion It is imperative to examine the key variables relative to animal model development and validation, The pharmacokinetics, pharmacodynamics and exposure profiles, of candidate MCM relative to route, administration schedule and optimal efficacy define the fully effective dose. The conduct of adequate and well-controlled pivotal efficacy studies as well as safety and toxicity studies support approval under the FDA Animal Rule and label definition for human use.
Polysaccharide II Surface Anchoring, the Achilles’ Heel of Clostridioides difficile

Cell wall glycopolymers (CWGPs) in Gram-positive bacteria have been reported to be involved in several bacterial processes. CWGP anchoring to peptidoglycan is important for growth and virulence. ABSTRACT Cell wall glycopolymers (CWPGs) in Gram-positive bacteria have been reported to be involved in several bacterial processes. These polymers, pillars for proteins and S-layer, are essential for the bacterial surface setup, could be essential for growth, and, in pathogens, participate most often in virulence. CWGPs are covalently anchored to peptidoglycan by proteins that belong to the LytR-CpsA-PSr (LCP) family. This anchoring, important for growth, was reported as essential for some bacteria such as Bacillus subtilis, but the reason why CWGP anchoring is essential remains unknown. We studied LcpA and LcpB of Clostridioides difficile and showed that they have a redundant activity. To delete both lcp genes, we set up the first conditional-lethal mutant method in C. difficile and showed that polysaccharide II (PSII) anchoring at the bacterial surface is essential for C. difficile survival. In the conditional-lethal mutant, C. difficile morphology was impaired, suggesting that peptidoglycan synthesis was affected. Because Lcp proteins are transferring CWPGs from the C55-undecaprenyl phosphate (also needed in the peptidoglycan synthesis process), we assumed that there was competition between PSII and peptidoglycan synthesis pathways. We confirmed that UDP-MurNAc-pentapeptide precursor was accumulated, showing that peptidoglycan synthesis was blocked. Our results provide an explanation for the essentiality of PSII anchoring in C. difficile and suggest that the essentiality of the anchoring of CWPGs in other bacteria can also be explained by the blocking of peptidoglycan synthesis. To conclude, our results suggest that Lcps are potential new targets to combat C. difficile infection. IMPORTANCE Cell wall glycopolymers (CWGPs) in Gram-positive bacteria have been reported to be involved in several bacterial processes. CWGP anchoring to peptidoglycan is important for growth and virulence. We set up the first conditional-lethal mutant method in Clostridioides difficile to study LcpA and LcpB involved in the anchoring of CWPGs to peptidoglycan. This study offers new tools to reveal the role of essential genes in C. difficile. LcpA and LcpB activity was shown to be essential, suggesting that they are potential new targets to combat C. difficile infection. In this study, we also showed that there is competition between the polysaccharide II synthesis pathway and peptidoglycan synthesis that probably exists in other Gram-positive bacteria. A better understanding of these mechanisms allows us to define the Lcp proteins as a therapeutic target for potential design of novel antibiotics against pathogenic Gram-positive bacteria.
3D bioprinted autologous bone particle scaffolds for cranioplasty promote bone regeneration with both implanted and native BMSCs

Although autologous bone (AB) grafting is considered to be the gold standard for cranioplasty, unresolved problems remain, such as surgical-site infections and bone flap absorption. In this study, an AB scaffold was constructed via three-dimensional (3D) bedside-bioprinting technology and used for cranioplasty. To simulate the skull structure, a polycaprolactone shell was designed as an external lamina, and 3D-printed AB and a bone marrow-derived mesenchymal stem cell (BMSC) hydrogel was used to mimic cancellous bone for bone regeneration. Our in vitro results showed that the scaffold exhibited excellent cellular affinity and promoted osteogenic differentiation of BMSCs in both two-dimensional and 3D culture systems. The scaffold was implanted in beagle dog cranial defects for up to 9 months, and the scaffold promoted new bone and osteoid formation. Further in vivo studies indicated that transplanted BMSCs differentiated into vascular endothelium, cartilage, and bone tissues, whereas native BMSCs were recruited into the defect. The results of this study provide a method for bedside bioprinting of a cranioplasty scaffold for bone regeneration, which opens up another window for clinical applications of 3D printing in the future.
Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: A secondary analysis of a randomized single‐blind placebo‐controlled study

To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon‐like peptide‐1 (GLP‐1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux‐en‐Y gastric bypass (RYGB).
Iron accumulation and axonal damage of cerebellum in idiopathic cervical dystonia

Postmortem brain study indicated that cerebellar Purkinje cell (PC) loss might be a pathological finding in patients with inherited and idiopathic cervical dystonia (ICD). The analysis of conventional magnetic resonance imaging brain scans failed to yield support for this finding. Previous studies have identified that iron overload can be the consequence of neuron death. The objectives of this study were to investigate iron distribution and demonstrate changes in axons in the cerebellum, providing evidence for PC loss in patients with ICD.