Miracle-dz/UniFAR-FTUs huggingface dataset:
A study of the acute neurological side effects in hospitalized psychiatric patients receiving neuroleptic drug treatment.

Neuroleptic drugs are essential in the treatment of schizophrenia and many other psychiatric disorders. These drugs do however cause a wide range of side effects which can be very distressing to patients. In particular the acute neurological side effects of parkinsonism, akathisia and dystonia, which are termed extrapyramidal syndromes, can be a limiting factor in the use of these drugs (Weiden et al 1987). Fort Napier Hospital is a large psychiatric referral hospital and the majority of patients admitted require neuroleptic drug treatment. Extrapyramidal side effects are regularly seen amongst these patients. This study was designed to discover the incidence of parkinsonism, akathisia and dystonia amongst patients treated with neuroleptic drugs and what specific factors were responsible for these side effects. Relevent literature on this topic was reviewed and comparable studies done in America, Europe and South Africa are discussed. The study sample consisted of one hundred patients who were examined regularly over a two week period for signs of parkinsonism, akathisia, or dystonia which were rated quantitatively according to specific rating scales. Patient and drug variables were then analysed to assess what factors were responsible for these side effects. The incidence of drug-induced parkinsonism was 29%, akathisia 35% and dystonia 20%. Combinations of these three syndromes were observed resulting in an overall incidence of 47%. High potency drugs such as haloperidol and trifluoperazine were responsible for a large percentage of all the side effects, while of the low potency drugs, thioridazine produced less side effects than chlorpromazine. Oral drugs combined with
Dynamic Chirality in the Mechanism of Action of Allosteric CD36 Modulators of Macrophage-Driven Inflammation.

Dynamic chirality influences numerous processes in nature from protein folding to catalysis. Azapeptides are peptidomimetics possessing semicarbazide residues that can interconvert between sp2 and sp3 hybridization, resulting in stereo-dynamic interconversions of pseudo-R and -S-configurations by way of a planar intermediate. Cyclic azapeptides have shown unprecedented binding affinity to the Cluster of Differentiation 36 receptor (CD36) and ability to mitigate macrophage-driven inflammation by modulation of the Toll-like receptor 2/6 pathway. A novel approach to synthesize cyclic peptides via A3-macrocyclization has been used to make R- and S-configuration controls to study the relevance of semicarbazide hybridization for modulator activity. NMR spectroscopic analysis of potent cyclic azapeptide CD36 modulators (e.g., 1 and 2) and related cyclic peptides demonstrated that binding affinity correlated with conformational rigidity, and a hybridization preference for sp2 > S- > R-sp3 semicarbazide nitrogen configuration. Evidence of the active conformation and the relevance for dynamic chirality serve as insight for creating cyclic (aza)peptide CD36 modulators to curb inflammation.
Effects of long-term aerobic training and detraining on functional capacity and quality of life in hemodialysis patients: A pilot study

Although previous studies have shown the benefits of exercise training in hemodialysis patients, little is known about the effects of long-term of exercise program on these patients. We investigated the effects and the safety of long-term aerobic training and the effects of detraining on functional capacity and quality of life in hemodialysis patients. Ten patients were allocated to two groups: training and detraining. The training group completed at least 30 months of aerobic training, and the detraining group completed at least 20 months and then discontinued the training for at least 10 months. The outcomes were analyzed at baseline, after 3 months of aerobic training and at the 30-month follow-up. The training and detraining groups performed 37 (5.5) and 24 (3.0) months of aerobic training, respectively. The detraining group discontinued the training for 11.0 (2.0) months. After 3 months of aerobic training, six-minute walking test distance increased significantly in both groups (training group = 569 (287.8) vs 635.5 (277.0) m, p = 0.04; detraining group = 454.5 (72.3) vs 515.0 (91.8) m, p = 0.04). There was no significant difference in the six-minute walking test distance in the training group (576.5 (182.5), p > 0.05) and a significant decrease (436.2 (89.6) m, p = 0.04) in the detraining group at the follow-up compared to the third month of aerobic training. No significant difference was observed in quality of life during the study. No complications were found during the protocol of the exercise. These results suggest that long-term aerobic training is safe and can maintain functional capacity in hemodialysis patients. In contrast, detraining can result in loss of functional capacity in these patients.
Concentrations of Aerosol Numbers and Airborne Bacteria, and Temperature and Relative Humidity, and Their Interrelationships in a Tie-Stall Dairy Barn

Simple Summary Aerosol particles are important elements of atmospheric pollution. Livestock barns are some of the most crucial anthropogenic sources of generation and emission of aerosol particles to the surrounding environment. Along with environmental pollution, these particles can cause numerous diseases in humans and animals. Besides causing diseases, these particles are said to have a significant role in the transmission of infectious diseases. Microorganisms that bind to aerosol particles are known as bioaerosols, which ultimately spread diseases in and between farms. Environmental factors such as temperatures (temp.) and relative humidity (RH) may have significant effects on aerosol particles and airborne bacteria. The present study was undertaken to find out which factors have more significant effects on the regulation of aerosol particles and airborne bacteria in the dairy environment. In the present study, we found that temperatures have profound effects on the regulation of aerosol numbers and various airborne bacteria. This temperature-dependent emission inventory of aerosol particles and various airborne bacteria will play a crucial factor in the mitigation of aerosol particles and various airborne bacteria in the dairy environment. Abstract Aerosol particles and airborne microorganisms are crucial factors of indoor air quality. The purpose of the present study was to evaluate the interrelationships among aerosol numbers, various types of airborne bacteria, temperature, and relative humidity (RH) to decide which parameters have more significant relationships among them. The concentrations of aerosol numbers, airborne total aerobic bacteria, Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) in the indoor air, as well as indoor and outdoor temperatures and RH, were assessed each week for a total of 20 days in a tie-stall dairy barn during the summer season in Tochigi, Japan. The mean concentrations of the fine aerosol numbers (0.3–2.0 µm) were greater than the mean concentrations of coarse aerosol numbers (5.0–10.0 µm). Among the airborne total aerobic bacteria, the mean concentration of airborne S. aureus was higher compared with airborne E. coli. More significant positive associations were found between outdoor environmental temperatures and aerosol numbers rather than indoor temperatures and aerosol numbers. All three types of airborne bacteria were associated with both outdoor and indoor environmental temperatures. These findings are crucial in the mitigation of aerosol numbers and airborne bacteria in the indoor air of dairy barns.
Carbon intermediate boosted Fe–ZIF derived α–Fe2O3 as a high-performance negative electrode for supercapacitors

Earth-abundant Fe2O3 is a promising material for the negative electrode of supercapacitors by virtue of its wide potential windows. However, the unsatisfactory electrical conductivity and poor ionic diffusion rate within Fe2O3 results in degraded electrochemical performance. In this work, to address these issues, we demonstrate an easy method to synthesize Fe-based zeolitic imidazolate framework (Fe–ZIF) derived α–Fe2O3@C with remarkable supercapacitive properties. The as-obtained α–Fe2O3@C electrode, with the particular benefit of dispersed distribution of carbon, enabling fast electrochemical response, presents a prospective specific capacitance of 161 Fg−1 at a current density of 1 Ag−1. Furthermore, by using the α–Fe2O3@C architecture as the negative electrode, we fabricated a supercapacitor with Na0.5MnO2 as the positive electrode. Our supercapacitor shows a high energy density of 25 Whkg−1, while the corresponding power density is 2400 Wkg−1 at a current density of 2 Ag−1.
Network Modeling Approaches and Applications to Unravelling Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition of the liver encompassing a range of pathologies including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Research into this disease is imperative due to its rapid growth in prevalence, economic burden, and current lack of FDA approved therapies. NAFLD involves a highly complex etiology that calls for multi-tissue multi-omics network approaches to uncover the pathogenic genes and processes, diagnostic biomarkers, and potential therapeutic strategies. In this review, we first present a basic overview of disease pathogenesis, risk factors, and remaining knowledge gaps, followed by discussions of the need and concepts of multi-tissue multi-omics approaches, various network methodologies and application examples in NAFLD research. We highlight the findings that have been uncovered thus far including novel biomarkers, genes, and biological pathways involved in different stages of NAFLD, molecular connections between NAFLD and its comorbidities, mechanisms underpinning sex differences, and druggable targets. Lastly, we outline the future directions of implementing network approaches to further improve our understanding of NAFLD in order to guide diagnosis and therapeutics.
Efficacy of a povidone‐iodine foam dressing (Betafoam) on diabetic foot ulcer

This study aimed to assess the efficacy of a new povidone‐iodine (PVP‐I) foam dressing (Betafoam) vs foam dressing (Medifoam) for the management of diabetic foot ulcers. This study was conducted between March 2016 and September 2017 at 10 sites in Korea. A total of 71 patients (aged ≥19 years) with type 1/2 diabetes and early‐phase diabetic foot ulcers (Wagener classification grade 1/2) were randomised to treatment with PVP‐I foam dressing or foam dressing for 8 weeks. Wound healing, wound infection, patient satisfaction, and adverse events (AEs) were assessed. The PVP‐I foam and foam dressing groups were comparable in the proportion of patients with complete wound healing within 8 weeks (44.4% vs 42.3%, P = .9191), mean (±SD) number of days to complete healing (31.00 ± 15.07 vs 33.27 ± 12.60 days; P = .6541), and infection rates (11.1% vs 11.4%; P = 1.0000). Median satisfaction score (scored from 0 to 10) at the final visit was also comparable between groups (10 vs 9, P = .2889). There was no significant difference in AE incidence (27.8% vs 17.1%, P = .2836), and none of the reported AEs had a causal relationship with the dressings. The results of this study suggest that PVP‐I foam dressing has wound‐healing efficacy comparable with foam dressing, with no notable safety concerns. This study was funded by Mundipharma Korea Ltd and registered at ClinicalTrials.gov (identifier NCT02732886).
Effects of endothelin (G8002A) gene polymorphism on serum endothelin levels in Turkish coronary artery disease patients

Objectives: The purpose of this study, is to investigate whether endothelin-1 (END-1) polymorphisms are associated with serum endothelin levels and coronary artery disease (CAD) in Turkish population. Methods: We investigated the effect of G8002A polymorphisms in intron 4 of the END-1 gene on serum END-1 levels in 57 coronary artery disease (CAD) individuals and 32 controls. PCR (Polymerase Chain Reaction), RFLP (Restriction Fragment Length Polymorphism), and agarose gel electrophoresis techniques were used to determine the END-1 G8002A genotypes. Serum END-1levels were determined by enzyme-linked immunoassay. Results: Distribution of END-1 genotypes (AA, GG, AG) in patients with CAD are: 9 (15.8%), 21 (36.8%), 27 (47.4%), and in control subjects: 1 (3.1%), 18 (56.3%), 13 (40.6%) respectively. Patients with END-1 A alleles (AA+AG) had higher serum END-1 levels than patients with GG genotypes (3.41+0.34 pg/ml vs 3.20+0.29 pg/ml, p<0.01). Conclusion: The present study demonstrates that the END-1 A alleles may be responsible with high serum END-1 levels and predisposition of coronary artery disease in Turkish patients.
Asian Sand Dust Upregulates IL-6 and IL-8 via ROS, JNK, ERK, and CREB Signaling in Human Nasal Fibroblasts

Background Asian sand dust (ASD) profoundly affects respiratory health by inducing inflammation and causing upper airway inflammatory diseases. Interleukin (IL)-6 and IL-8 are pro-inflammatory mediators that are involved in upper airway inflammatory diseases. However, the effect of ASD on the production of IL-6 and IL-8 in nasal fibroblasts has not been adequately studied. We investigated the effect of ASD on the induction of pro-inflammatory mediators and its underlying mechanisms in nasal fibroblasts. Methods Real-time cytotoxicity assays were used to determine the effect of ASD on the viability of fibroblasts. Enzyme-linked immunosorbent assays and real-time polymerase chain reactions were performed to determine whether ASD induced the expression of IL-6 and IL-8. Reactive oxygen species (ROS) were quantified using 2, 7-dichlorofluorescein-diacetate and MitoSOX Red. Induction of IL-6 and IL-8 signal transduction pathways by ASD was confirmed by Western blotting. Ex vivo culture of the inferior turbinate tissue was performed to confirm the effects of ASD. Results ASD upregulated ROS levels, and this in turn promoted IL-6 and IL-8 expression through the MAPK (JNK and ERK) and CREB signaling pathways in nasal fibroblasts. However, ASD did not induce phosphorylation of p38. Specific inhibitors of each pathway (ROS, JNK, ERK, and CREB inhibitors) suppressed ASD-induced IL-6 and IL-8 upregulation. Conclusions ASD induces pro-inflammatory mediators, and the increased levels of IL-6 and IL-8 might be associated with the pathogenesis of chronic rhinosinusitis.
Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma

Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that when used as adjuvants induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigens. However, traditional entrapped archaeosome formulations have only low entrapment efficiency, therefore we have developed a novel admixed formulation which offers many advantages, including reduced loss of antigen, consistency of batch-to-batch production as well as providing the option to formulate the vaccine immediately before use, which is beneficial for next generation cancer therapy platforms that include patient specific neo-antigens or for use with antigens that are less stable. Herein, we demonstrate that, when used in combination with anti-CTLA-4 and anti-PD-1 checkpoint therapy, this novel admixed archaeosome formulation, comprised of preformed sulfated lactosyl archaeol (SLA) archaeosomes admixed with OVA antigen (SLA–OVA (adm)), was as effective at inducing strong CD8+ T cell responses and protection from a B16-OVA melanoma tumor challenge as the traditionally formulated archaeosomes with encapsulated OVA protein. Furthermore, archaeosome vaccine formulations combined with anti-CTLA-4 and anti-PD-1 therapy, induced OVA-CD8+ T cells within the tumor and immunohistochemical analysis revealed the presence of CD8+ T cells associated with dying or dead tumor cells as well as within or around tumor blood vessels. Overall, archaeosomes constitute an attractive option for use with combinatorial checkpoint inhibitor cancer therapy platforms.
Regulation of auxin transcriptional responses

The plant hormone auxin acts as a signaling molecule to regulate a vast number of developmental responses throughout all stages of plant growth. Tight control and coordination of auxin signaling is required for the generation of specific auxin‐response outputs. The nuclear auxin signaling pathway controls auxin‐responsive gene transcription through the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F‐BOX pathway. Recent work has uncovered important details into how regulation of auxin signaling components can generate unique and specific responses to determine auxin outputs. In this review, we discuss what is known about the core auxin signaling components and explore mechanisms important for regulating auxin response specificity.
MicroRNA Extracellular Vesicle Stowaways in Cell-Cell Communication and Organ Crosstalk.

Extracellular vesicles (EVs) function as mediators of cell-cell communication1 and organ crosstalk,2 but a complete understanding of the mechanistic roles this critical communication process plays in cardiovascular and associated diseases is lacking. In normal conditions, EV crosstalk is important for proper cell and organ function, but in diseased conditions EV cargos can be altered in a way that promotes disease pathology. Multiple cargos have been observed in EVs, including RNAs, such as microRNA, DNA, proteins, and lipids, which can be encased within EVs or associated with EV membranes. Given this critical function, identifying the communication roles of EVs in normal physiology and diseasedriving mechanisms holds great therapeutic promise. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Chang et al3 propose EV transport as a major pathway in which miR-92a is transported from endothelial cells to macrophages that, in turn, contributes to the development of atherosclerosis. This study identifies a key mechanism of how miR-92a cell-cell communication occurs in atherosclerotic vasculature and raises the potential of EV-associated miR-92a as a disease biomarker and therapeutic target.
Current challenges in biotherapeutic particles manufacturing

ABSTRACT Introduction: The development of novel complex biotherapeutics led to new challenges in biopharmaceutical industry. The potential of these particles has been demonstrated by the approval of several products, in the different fields of gene therapy, oncolytic therapy, and tumor vaccines. However, their manufacturing still presents challenges related to the high dosages and purity required. Areas covered: The main challenges that biopharmaceutical industry faces today and the most recent developments in the manufacturing of different biotherapeutic particles are reported here. Several unit operations and downstream trains to purify virus, virus-like particles and extracellular vesicles are described. Innovations on the different purification steps are also highlighted with an eye on the implementation of continuous and integrated processes. Expert opinion: Manufacturing platforms that consist of a low number of unit operations, with higher-yielding processes and reduced costs will be highly appreciated by the industry. The pipeline of complex therapeutic particles is expanding and there is a clear need for advanced tools and manufacturing capacity. The use of single-use technologies, as well as continuous integrated operations, are gaining ground in the biopharmaceutical industry and should be supported by more accurate and faster analytical methods.
A high rate of recurrent tuberculosis in western Kenya independent of human immunodeficiency virus infection.

SUMMARY Background: Previous studies have shown that recurrent TB develops in about 2-5% of the patients after curative treatment with short-course anti-TB chemotherapy. With the advent of HIV/AIDS, the rate TB recurrence is anticipated to rise. Objectives: To determine whether HIV infection and TB recurrence are associated with anti-TB drug resistance and the rates of ZN microscopy and culture positivity among the recurrent TB cases in western Kenya. Design and methods: A cross-sectional study was carried out between 2007 and 2009. Sputa from 872 tuberculosis suspects underwent mycobacteriologic evaluation using Ziehl Neelsen smear microscopy, LowensteinJensen and BACTEC MGIT 960 culturing, and Hain’s GenoType ® Mycobacterium CM and GenoType ® Mycobacterium AS molecular identification tests. Consenting participants were screened for HIV infection using Uni-Gold TM test and positives were confirmed with the enzyme linked immunosorbent assay. Results: In total, 361/872 (41%) of the suspects mycobacterial disease (346 TB, 4.2% non-tuberculous mycobacterial disease). HIV testing was accepted by 695 (79.7%) and 39.1% of these (272/695) were found positive. Recurrence of TB constituted 44.8% (155/346) of the TB cases, with 41.9% (65/155) of them co-infected with HIV. There was no significant difference in TB recurrence rates with HIV status [OR = 0.57; 95% CI: 0.29-1.13; P = 0.10]. Conclusions and recommendations: This study reports a much higher (44.8%) rate of recurrent TB, compared to that of National TB control Programme of 5% in 2008 and a combined retreatment rate of 14% in 2009. The HIV co-infection and TB recurrence were not associated with anti-TB drug resistance. The majority of TB recurrent cases were ZN smear negative (67.7%) and culture negative (80%). The high TB recurrence observed in this study calls for studies to determine the proportions of the disease attributable to endogenous re-activation (relapse) and exogenous re-infection.
Increased Cell Detachment Ratio of Mesenchymal-Type Lung Cancer Cells on pH-Responsive Chitosan through the β3 Integrin

Chitosan is sensitive to environmental pH values due to its electric property. This study investigates whether the pH-responsive chitosan assay can provide a simple method to evaluate the aggressive behavior of cancer cells with cell detachment ratio. The epithelial–mesenchymal transition (EMT) is induced with transforming growth factor-β1 (TGF-β1) in the human non-small cell lung cancer cell line (A549). EMT-induced cells and untreated cells are cultured on chitosan substrates at pH 6.99 for 24 h, followed by pH 7.65 for 1 h. The cell detachment ratio (CDR) on pH-responsive chitosan rises with an increasing of the TGF-β1 concentration. The protein array reveals that the expression levels of the α2, α3, α5, β2, and β3 integrins are higher in EMT-induced A549 cells than in untreated cells. A further inhibition assay shows that adding β3 integrin blocking antibodies significantly decreases the CDR of EMT-induced cells from 32.7 ± 5.7% to 17.8 ± 2.1%. The CDR of mesenchymal-type lung cancer cells increases on pH-responsive chitosan through the β3 integrin. Notably, the CDR can be theoretically predicted according to the individual CDR on the pH-responsive chitosan surface, irrespective of heterogeneous cell mixture. The pH-responsive chitosan assay serves as a simple in vitro model to investigate the aggressive behavior of lung cancer including the heterogeneous cell population.