Miracle-dz/UniFAR-FTUs huggingface dataset:
Sigma-1 receptor-regulated efferocytosis by infiltrating circulating macrophages/microglial cells protects against neuronal impairments and promotes functional recovery in cerebral ischemic stroke

Background: Efferocytosis of apoptotic neurons by macrophages is essential for the resolution of inflammation and for neuronal protection from secondary damage. It is known that alteration of the Sigma-1 receptor (Sig-1R) is involved in the pathological development of some neurological diseases, including ischemic stroke. The present study aimed to investigate whether and how Sig-1R regulates the phagocytic activity of macrophages/microglia and its significance in neuroprotection and neurological function in stroke. Methods: The roles of Sig-1R in the efferocytosis activity of microglia/macrophages using bone marrow-derived macrophages (BMDMs) or using Sig-1R knockout mice subjected to transient middle artery occlusion (tMCAO)-induced stroke were investigated. The molecular mechanism of Sig-1R in the regulation of efferocytosis was also explored. Adoptive transfer of Sig-1R intact macrophages to recipient Sig-1R knockout mice with tMCAO was developed to observe its effect on apoptotic neuron clearance and stroke outcomes. Results: Depletion of Sig-1R greatly impaired the phagocytic activity of macrophages/microglia, accordingly with worsened brain damage and neurological defects in Sig-1R knockout mice subjected to tMCAO. Adoptive transfer of Sig-1R intact bone marrow-derived macrophages (BMDMs) to Sig-1R knockout mice restored the clearance activity of dead/dying neurons, reduced infarct area and neuroinflammation, and improved long-term functional recovery after cerebral ischemia. Mechanistically, Sig-1R-mediated efferocytosis was dependent on Rac1 activation in macrophages, and a few key sites of Rac1 in its binding pocket responsible for the interaction with Sig-1R were identified. Conclusion: Our data provide the first evidence of the pivotal role of Sig-1R in macrophage/microglia-mediated efferocytosis and elucidate a novel mechanism for the neuroprotection of Sig-1R in ischemic stroke.
Is Halving Maintenance of Voriconazole Safe and Efficient in Patients Suffering from Invasive Fungal Infections with Serious Hepatic Dysfunction?

Background There is a wide debate about the efficacy and safety of voriconazole in patients with impaired hepatic function at Child-Pugh C level. Objective The purpose of this study was to investigate the safety and efficacy between the two groups treated with different dosages of voriconazole (400mg/day vs 200mg/day) in the treatment of invasive fungal infections (IFIs) in patients with hepatic dysfunction. Methods A retrospective study enrolling patients with hepatic dysfunction receiving intravenous voriconazole for IFIs from January 1st, 2017, to December 30th, 2021 was conducted. Patients were enrolled in the 400mg per day dose group and 200mg per day dose group. In patients with the same degree of hepatic impairment, factors affecting prognosis were screened and differences in steady-state blood trough concentrations (Cmin) of voriconazole, positive G/GM tests and adverse effects (AEs) were compared between the two groups described above. Results In total, 308 patients with IFIs were enrolled. For Child-Pugh C class, patients receiving the halved maintenance dose had a lower Cmin and AEs rate but higher recovered rate compared to those receiving maintenance dose, and significant predictors of recovery were dosage (OR, 5.131; 95% CI, 1.599–16.464; p = 0.006) and diabetes (OR, 0.111; 95% CI, 0.020–0.597; p = 0.010). For patients of Child-Pugh A & B class, chronic liver disease (OR, 0.334; 95% CI, 0.159–0.704; p = 0.004) was a prognosis-related factor. Conclusion Halving maintenance dose ensure the efficacy and safety of voriconazole in patients suffering from invasive fungal infections with serious hepatic dysfunction.
Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody

Introduction Antibody formation in transfusion-dependent thalassemia is associated with chronic hemolysis and repeated transfusions. Hemolysis produces heme, which mediates B-cell differentiation into plasma cells and produces antibodies influenced by interleukin-21 (IL-21). Objective This study aimed to compare IL-21 levels, plasma cell percentage, and red blood cell antibodies between positive and negative allo-autoantibody thalassemia before and after hemin administration. Materials and Methods This research employed a quasi-experimental nonequivalent control group pre-test and post-test design performed from April to November 2021 at Soetomo Academic Hospital in Surabaya, Indonesia. Heparinized blood samples of 5 mL and 4 mL and EDTA blood samples of 3 mL were taken from positive (29 patients) and negative (28 patients) allo-autoantibody thalassemia participants. Hemin 20 µM was added to 5 mL of heparinized blood, incubated for 2 hours, prepared into peripheral blood mononuclear cells (PBMCs), and cultured for 3 days. The percentage of plasma cells (CD38+CD184+) of cultured and uncultured PBMCs was measured by BD FACSCalibur Flow Cytometer. IL-21 levels of plasma and supernatants were measured with Sandwich Enzyme-Linked Immunosorbent Assay by Elabscience. Red blood cell antibodies were detected by QWALYS 3 E.M. Technology. Autoantibodies were determined by the Grifols gel tube method. Results IL-21 levels were significantly different in the positive and negative allo-autoantibody thalassemia groups after hemin administration. The percentage of plasma cells in the positive allo-autoantibody group increased significantly after the administration of hemin. The percentage of plasma cells between thalassemia groups was not significantly different before the hemin administration but increased significantly after it. Red blood cell antibodies after the administration of hemin were significantly different in the negative allo-autoantibody group but not significantly different in the positive allo-autoantibody group. Conclusion Hemin administration affected IL-21 levels, plasma cell percentage, and antibody formation in positive and negative allo-auto antibody thalassemia.
3D convective Cahn--Hilliard equation

We consider the initial boundary value problem for the 3D convective Cahn - Hilliard equation with periodic boundary conditions. This gives rise to a continuous dynamical system on $\dot L^2(\Omega)$. Absorbing balls in $\dot L^2(\Omega), \dot H_{per}^1(\Omega)$ and $\dot H_{per}^2(\Omega)$ are shown to exist. Combining with the compactness property of the solution semigroup we conclude the existence of the global attractor. Restricting the dynamical system on the absorbing ball in $\dot H_{per}^2(\Omega)$ and using the general framework in Eden et. all. [5] the existence of an exponential attractor is guaranteed. This approach also gives an explicit upper estimate of the dimension of the exponential attractor, albeit of the global attractor.
Synergistic Antibacterial Potential of Greenly Synthesized Silver Nanoparticles with Fosfomycin Against Some Nosocomial Bacterial Pathogens

Introduction A considerable number of morbidities and fatalities occur worldwide as a result of the multidrug resistant microorganisms that cause a high prevalence of nosocomial bacterial infections. Hence, the current investigation was conducted to evaluate the antibacterial potency of green fabricated silver nanoparticles (AgNPs) against four different nosocomial pathogens. Methods The flower extract of Hibiscus sabdariffa mediated green fabrication of AgNPs and their physicochemical features were scrutinized using different techniques. Antimicrobial activity of the biogenic AgNPs and their synergistic patterns with fosfomycin antibiotic were evaluated using disk diffusion assay. Results and Discussion UV spectral analysis affirmed the successful formation of AgNPs through the detection of broad absorption band at 395 and 524 nm, indicating the surface plasmon resonance of the biofabricated AgNPs. In this setting, the biofabricated AgNPs demonstrated average particle size of 58.682 nm according to transmission electron microscope (TEM) micrographs. The detected hydrodynamic diameter was higher than that noticed by TEM analysis, recording 72.30 nm in diameter and this could be attributed to the action of capping agents, which was confirmed by Fourier Transform Infrared (FT-IR) analysis. Disk diffusion assay indicated the antibacterial potency of biogenic AgNPs (50 μg/disk) against Enterobacter cloacae, Methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli strains with relative inhibition zone diameters of 12.82 ± 0.36 mm, 14.54 ± 0.15 mm, 18.35 ± 0.24 mm and 21.69 ± 0.12 mm, respectively. In addition, E. coli was found to be the most susceptible strain to the biogenic AgNPs. However, the highest synergistic pattern of AgNPs-fosfomycin combination was detected against K. pneumonia strain recording relative synergistic percentage of 64.22%. In conclusion, the detected synergistic efficiency of AgNPs and the antibiotic fosfomycin highlight the potential for utilizing this combination in the biofabrication of effective antibacterial agents against nosocomial pathogens.
Cost-Effectiveness of Empagliflozin in Combination with Standard Care versus Standard Care Only in the Treatment of Heart Failure Patients in Finland

Purpose Sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin has recently been shown to improve the outcomes of heart failure (HF) patients regardless of patient’s left ventricular ejection fraction by reducing the combined risk of cardiovascular death or hospitalization for worsening HF. The aim of this study was to assess the cost-effectiveness of adding empagliflozin to the standard care (SC) in comparison to SC only in the treatment of HF in Finland. Patients and Methods The assessment was performed in the cost-utility framework using two Markov cohort state-transition models, one for HF with reduced ejection fraction (HFrEF) and one for HF with preserved ejection fraction (HFpEF). The models have been primarily developed based on the EMPEROR-Reduced and EMPEROR-Preserved trials which informed the modelled patient characteristics, efficacy of treatments in terms of associated risks for heart failure hospitalizations, cardiovascular (CV) and non-CV death, treatment related adverse events (AE), and state- and event-specific health-related quality of life weights (EQ-5D). Direct health care costs were estimated from Finnish published references. Cost-effectiveness was assessed from health care payer perspective based on incremental cost-effectiveness ratio (ICER; cost per quality adjusted life-year [QALY] gained) and probability of cost-effectiveness (at willingness-to-pay [WTP] of 35,000 euros/QALY). The ICER was reported as the weighted (HFrEF, 43.5%; HFpEF, 56.5%) average result of the two models. Results Empagliflozin + SC treatment increased the average quality-adjusted life-expectancy, and treatment costs of HF patients by 0.15 QALYs and 1,594 euros, respectively, when compared to SC. An additional QALY with empagliflozin was thus gained at a cost of 10,621 euros. The probability of empagliflozin + SC being cost-effective compared to placebo + SC was 77.6% and 83.5% with WTP of 35,000 and 100,000 euros/QALY, respectively. Conclusion Empagliflozin is a cost-effective treatment for patients with HF in the Finnish health care setting.
Sleep Disturbance in Musculoskeletal Conditions: Impact of a Digital Care Program

Background Musculoskeletal (MSK) pain is highly prevalent worldwide, resulting in significant disability, and comorbid sleep disturbances. Digital therapy for MSK pain can provide significant improvements in care access, alongside pain and disability reductions. However, studies on the effect of such programs on sleep are lacking. Purpose To evaluate the impact on pain-related sleep impairment after a 12-week remote multimodal digital care program (DCP) for MSK conditions. Patients and Methods This is an ad-hoc analysis of a decentralized single-arm study into engagement and clinical outcomes after a DCP for MSK rehabilitation. Patients were stratified by baseline sleep disturbance, based on sleep questions in the questionnaires: Oswestry Disability Index, Neck Disability Index, and the Quick Disabilities of the Arm, Shoulder and Hand questionnaire. Additional outcomes were pain, Generalized Anxiety Disorder 7-item scale, Patient Health 9-item questionnaire, Work Productivity, and Activity Impairment, and program engagement. Results At baseline, 5749 patients reported sleep disturbance (78.0% of eligible patients). These reported significantly worse clinical outcomes at baseline than patients without sleep disturbance (all p<0.001). Patients with comorbid sleep disturbance showed improvements in sleep, with a significant proportion reporting full recovery at program completion: 56% of patients with upper limb conditions (including 10% of patients with severe sleep disturbance at baseline), and 24% with spine conditions. These patients also reported significant improvements in all clinical outcomes at program completion. Engagement and satisfaction were high, and also higher than in patients without sleep impairment. Conclusion This is the first study of its kind investigating the effect of a completely remote DCP for MSK pain on sleep. Patients reporting comorbid sleep disturbance had significant improvement in sleep, alongside pain, mental health and work productivity at program completion. The results suggest that a DCP for MSK pain can improve sleep disturbances in patients with upper limb and spine conditions.
Local structures of III-V diluted magnetic semiconductors Ga 1 − x Mn x As studied using extended x-ray-absorption fine structure

Local structures around Mn in ${\mathrm{Ga}}_{1\ensuremath{-}x}{\mathrm{Mn}}_{x}\mathrm{As}$ ($x=0.005$ and 0.074) films have been studied using Mn $K$-edge extended x-ray-absorption fine structure. In the ${\mathrm{Ga}}_{1\ensuremath{-}x}{\mathrm{Mn}}_{x}\mathrm{As}$ films, Mn atoms are substituted into the Ga sites in the zinc-blende-type GaAs lattice. The Mn-As bond length (2.49\char21{}2.50 \AA{}) in ${\mathrm{Ga}}_{1\ensuremath{-}x}{\mathrm{Mn}}_{x}\mathrm{As}$ is 2\char21{}3 % larger than the Ga-As bond length (2.44 \AA{}) in bulk GaAs. The longer Mn-As bonds cause local disorder in the GaAs lattice, the degree of which increases with the Mn composition.
High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

Background Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC. Methods Kaplan–Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC. Results DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC. Conclusion This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.
Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies

Acute myeloid leukemia (AML) arising from myeloproliferative neoplasms (MPNs) represents a small subtype of secondary AML (sAML). This entity is well known to be associated with poor responses to available treatment options and dismal outcomes. To date, there are no standardized treatment options and there has been very little therapeutic advancement in recent years. This is a stark contrast to other subsets of AML for which there have been significant advances in therapeutic approaches, especially for patients with targetable mutations. We aim to focus our review on the incidence, risk factors for leukemogenesis, pathogenesis, molecular landscape, and emerging therapeutic options in post-myeloproliferative neoplasm acute myeloid leukemia (post-MPN AML).
In-Hospital Emergency Treatment Delay Among Chinese Patients with Acute Ischaemic Stroke: Relation to Hospital Arrivals and Implications for Triage Pathways

Introduction Timely access to emergency treatment during in-hospital care phase is critical for managing the onset of acute ischaemic stroke (AIS), particularly in developing countries. We aimed to explore in-hospital emergency treatment delay and the relation of door-to-needle (DTN) time to ambulance arrivals vs walk-in arrivals. Methods Data were collected from 1276 Chinese AIS patients admitted to a general, tertiary-level hospital for intravenous thrombolysis. Information on patients’ characteristics and time taken during in-hospital emergency treatment was retrieved from the hospital registry data and medical records. Ambulance arrival was defined as being transported by emergency ambulance services, while walk-in arrival was defined as arriving at hospital by regular vehicle. In-hospital emergency treatment delay occurred when the DTN time exceeded 60 minutes. We performed multivariable logistic regression analysis to explore the association between hospital arrivals (by ambulance vs by walk-in) and treatment delay after adjustment for age, sex, education, marital status, residence, medical insurance, number of symptoms, clinical severity and survival outcome. Results Over half (53.76%) of patients aged over 60 years. Around one-fifth (20.61%) of patients admitted to hospital through emergency ambulance services, while their counterparts arrived by regular vehicle. Overall, the median time taken from the hospital door to treatment initiation was 86.0 minutes. Patients arrived by ambulance (adjusted odds ratio [aOR] = 1.744, 95% confidence interval [CI] = 1.185–2.566, p = 0.005), had higher socio-economic status (aOR = 1.821, 95% CI = 1.251–2.650; p = 0.002), or paid out-of-pocket (aOR = 2.323, 95% CI = 1.764–3.060; p < 0.001) had an increased likelihood of in-hospital emergency treatment delays. Conclusion In-hospital emergency treatment delay is common in China, and occurs throughout the entire emergency treatment journey. Having a triage pathway involving hospital arrival by ambulance seems to be more likely to experience in-hospital emergency treatment delay. Further efforts to improve triage pathways may require qualitative evidence on provider- and institutional-level factors associated with in-hospital emergency treatment delay.
Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care. We found that vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways. To determine the specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology and pain transmission during OA progression, we studied intra-articular (IA) injections of VEGF ligands into murine knee joints. Only VEGF ligands specific for the activation of VEGFR1, but not VEGFR2, induced allodynia within 30 min. Interventions in OA by inhibitors of VEGFRs were done in vivo using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.
Incidence and Pattern of Neuro-Ophthalmological Disorders Presenting to Vitreoretinal Clinics in Bhutan: A 3-Year National Study

Purpose To inform national health policy, we quantified the pattern of neuro-ophthalmological disorders (NODs) presenting to the national vitreoretinal clinics in Bhutan. Study Design Retrospective cross-sectional study. Methods We reviewed all new NODs patients over three years. Demographic data, presenting complaints, treatment history, systemic diseases, diagnostic procedures, and diagnoses were quantified. Logistic regression examined the odds of factors linked to more common NODs. Results Of 226 patients, the majority were males (54.0%), farmers (60.2%), and urbanites (55.8%). Loss of vision was the most common presenting complaint (57.9%), followed by head or orbital trauma (19.5%). The best corrected visual acuity (BCVA) of 216 eyes (47.8%) was ≤6/60. Hypertension was the most common systemic disease (16.4%), followed by diabetes (3.5%), and intracranial space-occupying lesions (3.5%). Neuroimaging (37.6%) was the most common diagnostic test performed, followed by visual field testings (VFTs) (22.9%). With a NOD incidence of 7.8% p.a. (226/2913), optic atrophy (OA) was diagnosed in 134 patients (59.3%). Other common NODs were optic neuritis (15.5%), papilloedema (9.3%), and traumatic optic neuropathy (8.4%). Female gender increased the odds for glaucomatous OA by 2.65× (p = 0.044), and age by 1.09× per year (p < 0.001). Being female increased the odds of optic neuritis by 2.57× (p = 0.03). Conclusion Over half of the NODs were OA, which could be curable with timely treatment. Improved treatment of glaucoma and non-communicable diseases would reduce the risk of NODs-induced visual loss in Bhutan. The need for improved neuro-ophthalmological assessment and a coordinated multidisciplinary approach to NODs are the highest priorities.
Dynamics of a cantilever beam attached to a moving base

The behavior of a cantilever beam built into a rigid body that is performing a specified motion of rotation and translation is studied with two objectives in mind. First, because the subject is of interest in connection with spacecraft antennae, helicopter rotor blades, robot arms, and other systems that perform complex motions, we create an algorithm that can be used to predict the behavior of the beam when the base undergoes general three-dimensional motions. Effects such as centrifugal stiffening and vibrations induced by Coriolis forces are accommodated automatically, rather than with the aid of ad hoc provisions. The second objective is to draw attention to fundamental flaws in certain multibody computer programs currently under development or already in use. To this end, we construct a second simulation algorithm, one that embodies the procedure apparently employed in the programs in question, and then compare simulation results produced by computer programs based on the two algorithms. Conflicts between the two approaches that thus come to light are discussed in detail.