Takshan/R1 huggingface dataset:
A new correction method serving to eliminate the parabola effect of flatbed scanners used in radiochromic film dosimetry.

PURPOSE: The purpose of this study is the correction of the lateral scanner artifact, i.e., the effect that, on a large homogeneously exposed EBT3 film, a flatbed scanner measures different optical densities at different positions along the x axis, the axis parallel to the elongated light source. At constant dose, the measured optical density profiles along this axis have a parabolic shape with significant dose dependent curvature. Therefore, the effect is shortly called the parabola effect. The objective of the algorithm developed in this study is to correct for the parabola effect. Any optical density measured at given position x is transformed into the equivalent optical density c at the apex of the parabola and then converted into the corresponding dose via the calibration of c versus dose. METHODS: For the present study EBT3 films and an Epson 10000XL scanner including transparency unit were used for the analysis of the parabola effect. The films were irradiated with 6 MV photons from an Elekta Synergy accelerator in a RW3 slab phantom. In order to quantify the effect, ten film pieces with doses graded from 0 to 20.9 Gy were sequentially scanned at eight positions along the x axis and at six positions along the z axis (the movement direction of the light source) both for the portrait and landscape film orientations. In order to test the effectiveness of the new correction algorithm, the dose profiles of an open square field and an IMRT plan were measured by EBT3 films and compared with ionization chamber and ionization chamber array measurement. RESULTS: The parabola effect has been numerically studied over the whole measuring field of the Epson 10000XL scanner for doses up to 20.9 Gy and for both film orientations. The presented algorithm transforms any optical density at position x into the equivalent optical density that would be measured at the same dose at the apex of the parabola. This correction method has been validated up to doses of 5.2 Gy all over the scanner bed with 2D dose distributions of an open square photon field and an IMRT distribution. CONCLUSIONS: The algorithm presented in this study quantifies and corrects the parabola effect of EBT3 films scanned in commonly used commercial flatbed scanners at doses up to 5.2 Gy. It is easy to implement, and no additional work steps are necessary in daily routine film dosimetry.
IL-8 -251T/A and IL-12B 1188A/C polymorphisms are associated with gout in a Chinese male population.

OBJECTIVES: Gout is caused by monosodium urate (MSU) crystal-induced inflammation of the joints and periarticular tissues. MSU crystals activate NALP3 and mediate interleukin (IL)-1β generation from its inactive pro-form, resulting in cellular activation and an IL-8-mediated neutrophil influx into the joint. IL-8 and IL-12 are important chemokines related to the initiation and amplification of acute and chronic inflammatory processes. In this study, we investigated whether the IL-8 -251T/A and IL-12 1188A/C polymorphisms are associated with susceptibility to gout in a Chinese Han male population. METHODS: Overall, 387 patients with gout and 576 controls were included in this study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). An association analysis was carried out using the χ2 test. A genotype-phenotype analysis was also conducted. RESULTS: The T allele of IL-8 -251 was associated with risk of gout [p = 0.031 (odds ratio (OR) 1.229, 95% confidence interval (CI) 1.019-1.483]. There was a clear link between the IL-12 1188 AA and AC genotypic and A allelic frequencies between gout cases and controls (p < 0.001, df = 2 by genotype; p < 0.001, OR 1.404, 95% CI 1.165-1.691 by allele). CONCLUSIONS: Our results suggest that the IL-8 -251T/A and IL-12B 1188A/C polymorphisms may be relevant host susceptibility factors for the development of gout.
Polymorphisms -1082 G/A and -819 C/T in the interleukin-10 gene are not associated with gout susceptibility in the Chinese Han male population.

BACKGROUND: Gout is caused by monosodium urate crystal-induced inflammation of the joints and periarticular tissues. Interleukin 10 (IL-10) is an important immunoregulatory cytokine, levels of which can be influenced by functional single-nucleotide polymorphisms in the promoter. OBJECTIVE: To investigate the association of -1082 G/A and -819 C/T polymorphisms in the IL-10 promoter with gout susceptibility in the Chinese Han male population. METHODS: A case-control study was performed in 302 patients and 284 controls. Genotyping of IL-10 -1082 G/A and -819 C/T polymorphisms was performed by DNA sequencing techniques. An association analysis was analyzed by the χ(2) test. RESULTS: No significant differences were found in -819T/C and -1082 A/G genotypic and allelic frequencies between gout cases and controls (for -819T/C, χ(2)=0.212, df=1, p=0.645 by genotype; χ(2)=0.079, df=1, p=0.779 by allele; for -1082 A/G, χ(2)=2.116, df=1, p=0.146 by genotype; χ(2)=1.854, df=1, p=0.173 by allele). CONCLUSIONS: IL-10 -1082 G/A and -819 C/T polymorphisms may not be associated with susceptibility to gout and thus do not play a major role in the development of gout in the Chinese Han male population.
Cat, dog and house dust mite allergen levels on children's soft toys.

OBJECTIVE: Children's soft toys are known to harbour house dust mite (HDM) allergens, but little is known whether they harbour cat or dog allergens. The objective of the study was to measure cat (Fel d 1), dog (Can f 1) and HDM allergens on children's soft toys. METHODS: Dust was collected from 40 children's soft toys and their mattresses. Data were collected on pet ownership. Dust samples were analysed for Fel d 1, Can f 1, Der p 1 and Der f 1 by enzyme-linked immunosorbent assay (ELISA) and results are expressed as median levels with inter-quartile ranges. RESULTS: Thirty-five (87.5%) soft toys had detectable Fel d 1 levels (median: 0.73 µg/g; inter-quartile range: 0.26-2.56 µg/g) while 34 (85%) had detectable Can f 1 levels (1.20 µg/g; 0.53-2.68). Correspondingly, 32 (80%) mattresses had detectable Fel d 1 levels (0.18 µg/g, 0.07-1.01) while 34 (85%) had detectable Can f 1 levels (0.50 µg/g; 0.33-1.06). All mattresses and soft toys had detectable HDM allergen (Der p 1 + Der f 1) levels with soft toys containing about three times higher levels than mattresses. In homes with cats (n = 10) Fel d 1 levels were higher on soft toys than homes without cats (2.49 versus 0.48 µg/g; p = 0.0009). In homes with dogs (n = 25) Can f 1 levels were generally higher on soft toys (1.38 versus 0.63 µg/g; p = 0.10). CONCLUSIONS: This study has shown that soft toys can harbour cat and dog allergen as well as HDM allergens, some with very high levels. Cat and dog ownership resulted in higher Fel d 1 and Can f 1 levels on soft toys and mattresses. The levels of Fel d 1, Can f 1 and HDM allergens on soft toys could be of importance to sensitized asthmatic children.
Daily vacuuming of mattresses significantly reduces house dust mite allergens, bacterial endotoxin, and fungal β-glucan.

BACKGROUND AND AIMS: Atopic patients are advised to cover their mattresses with occlusive coverings; however, these are not cheap. We investigated whether daily vacuum cleaning of mattresses significantly reduces content of house dust mite allergens, bacterial endotoxin, and fungal β-glucan. METHODS: Twenty volunteers vacuumed their mattress daily for 8 weeks. Dust samples collected at two weekly intervals were analyzed for house dust mite allergens (Der p 1 and Der f 1) by double monoclonal antibody ELISA and for endotoxin and β-glucan by the Limulus amoebocyte lysate kinetic assay. Results are presented as geometric means with 95% confidence interval (CI). RESULTS: Total house dust mite allergens (Der p 1 + Der f 1) significantly reduced from a geometric mean (95% CI) of 4.07 μg (2.44-6.79) at the start to 0.42 μg (0.21-0.81) at week 8. Total endotoxin and β-glucan were also significantly reduced from 13.6 EU (8.6-21.4) to 3.4 EU (2.3-5.0) and from 94.4 μg (57.1-156.2) to 19.7 μg (10.2-37.9), respectively (p for trend >.0001). Percentage reductions in total house dust mite allergens, endotoxin, and β-glucan after 8 weeks of daily vacuum cleaning were 85.1% (80.1-90.1), 71.0% (70.4-81.0), and 75.7% (70.4-81.0), respectively. This was mainly due to a 77.7% (70.8-84.7) reduction in total dust. CONCLUSION: Daily vacuum cleaning of mattresses over time significantly reduces house dust mite allergens, endotoxin, and β-glucan. This gives atopic patients a practical and cheaper alternative to reduce their exposure to indoor house dust mite allergens and microbial bio-contaminants.
The effect of 1g of acetaminophen twice daily for 12 weeks on alanine transaminase levels--A randomized placebo-controlled trial.

OBJECTIVE: Acetaminophen is often used on a regular, daily basis for the treatment of chronic pain; however, the safety of regular acetaminophen is still debated. This study determined whether 12 weeks of treatment with acetaminophen at half the maximum recommended daily dose causes an increase in alanine transaminase (ALT) in healthy adults participating in a clinical trial of the effect of acetaminophen on asthma control and severity. DESIGN AND METHODS: 94 healthy adults aged 18-65 years with mild to moderate asthma and with no history of previous liver dysfunction and an ALT within 1.5 times the upper limit of normal at baseline participated in a randomized, double-blind, placebo-controlled, parallel-group, clinical trial of 1g of acetaminophen twice daily or placebo twice daily for 12 weeks. Liver function monitoring was undertaken at baseline, weeks 2, 4, 6 and 12. The primary outcome variable was mean ALT levels at week 12 compared to baseline in the acetaminophen group versus placebo group. RESULTS: 94 participants were randomized and commenced study treatment. One participant in each treatment group was withdrawn due to an increase in ALT to greater than three times the upper limit of normal. Mean ALT at week 12 was 25.4I U/L (SD 9.7) in the acetaminophen group (N=31) and 19.0 IU/L (SD 6.0) in the placebo group (N=54). After controlling for baseline this represented a statistically significant difference of 3.6 IU/L (95% CI 1.3 to 6.0, P=0.003). There was no progressive increase in ALT demonstrated throughout the trial. CONCLUSIONS: Regular, daily use of acetaminophen at half the maximum recommended daily dose for 12 weeks in a healthy adult population is associated with a small elevation in mean ALT of no probable clinical significance. Further assessment of the effects on liver function of the maximum recommended dose of acetaminophen is required.
Hunger influenced life expectancy in war-torn Sub-Saharan African countries.

BACKGROUND: Malnutrition is a global public health problem especially in developing countries experiencing war/conflicts. War might be one of the socio-political factors influencing malnutrition in Sub-Saharan African (SSA) countries. This study aims at determining the influence of war on corruption, population (POP), number of population malnourished (NPU), food security and life expectancy (LE) in war-torn SSA countries (WTSSA) by comparing their malnutrition indicators. METHODS: Fourteen countries in WTSSA were stratified into zones according to war incidences. Countries' secondary data on population (POP), NPU, Food Security Index (FSI), corruption perceptions index (CPI), Global Hunger Index (GHI) and LE were obtained from global published data. T test, multivariate and Pearson correlation analyses were performed to determine the relationship between CPI, POP, GHI, FSI, NPU, male LE (MLE) and female LE (FLE) in WTSSA at p < .05. Data were presented in tables, means, standard deviation and percentages. RESULTS: Mean NPU, CPI, GHI, POP, FSI, MLE and FLE in WTSSA were 5.0 million, 28.3%, 18.2%, 33.8 million, 30.8%, 54.7 years and 57.1 years, respectively. GHI significantly influenced LE in both male and female POP in WTSSA. NPU, CPI, FSI, GHI and FLE were not significantly different according to zones except in MLE. CONCLUSIONS: Malnutrition indicators were similarly affected in WTSSA. Hunger influenced life expectancy. Policies promoting good governance, equity, peaceful co-existence, respect for human right and adequate food supply will aid malnutrition eradication and prevent war occurrences in Sub-Saharan African countries.
Maser: one-stop platform for NGS big data from analysis to visualization.

Database URL: http://cell-innovation.nig.ac.jp/maser/.
(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. RESULTS: The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. CONCLUSION: These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.
Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis.

BACKGROUND: There is a pressing need in rheumatoid arthritis (RA) to identify patients who will not respond to first-line disease-modifying anti-rheumatic drugs (DMARD). We explored whether differences in genomic architecture represented by a chromosome conformation signature (CCS) in blood taken from early RA patients before methotrexate (MTX) treatment could assist in identifying non-response to DMARD and, whether there is an association between such a signature and RA specific expression quantitative trait loci (eQTL). METHODS: We looked for the presence of a CCS in blood from early RA patients commencing MTX using chromosome conformation capture by EpiSwitch™. Using blood samples from MTX responders, non-responders and healthy controls, a custom designed biomarker discovery array was refined to a 5-marker CCS that could discriminate between responders and non-responders to MTX. We cross-validated the predictive power of the CCS by generating 150 randomized groups of 59 early RA patients (30 responders and 29 non-responders) before MTX treatment. The CCS was validated using a blinded, independent cohort of 19 early RA patients (9 responders and 10 non-responders). Last, the loci of the CCS markers were mapped to RA-specific eQTL. RESULTS: We identified a 5-marker CCS that could identify, at baseline, responders and non-responders to MTX. The CCS consisted of binary chromosome conformations in the genomic regions of IFNAR1, IL-21R, IL-23, CXCL13 and IL-17A. When tested on a cohort of 59 RA patients, the CCS provided a negative predictive value of 90.0% for MTX response. When tested on a blinded independent validation cohort of 19 early RA patients, the signature demonstrated a true negative response rate of 86 and a 90% sensitivity for detection of non-responders to MTX. Only conformations in responders mapped to RA-specific eQTL. CONCLUSIONS: Here we demonstrate that detection of a CCS in blood in early RA is able to predict inadequate response to MTX with a high degree of accuracy. Our results provide a proof of principle that a priori stratification of response to MTX is possible, offering a mechanism to provide alternative treatments for non-responders to MTX earlier in the course of the disease.
Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patients With Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD) via mechanisms that have not yet been defined. Inflammatory pathways, in particular within the vascular adventitia, are implicated in the pathogenesis of primary CVD but could be amplified in RA at the local tissue level. The aim of this study was to examine the aortic adventitia of coronary artery disease (CAD) patients with or without RA to determine the cytokine profile contained therein. METHODS: Aortic adventitia and internal thoracic artery biopsy specimens obtained from 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery were examined by immunohistochemistry. RESULTS: Interleukin-18 (IL-18), IL-33, and tumor necrosis factor (TNF) were expressed in aortic adventitia biopsy specimens from both groups, and expression of these cytokines was significantly higher in RA patients. In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion. CONCLUSION: The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization. In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.
Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology.

OBJECTIVE: Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. METHODS: OA was induced in wild-type (WT) and PAR2-deficient (PAR2(-/-)) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2(-/-) mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. RESULTS: Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2(-/-) mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2(-/-) mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2(-/-) mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. CONCLUSIONS: This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.
Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases.

Introduction: Rituximab (RTX) is a monoclonal antibody targeting CD20, a transmembrane protein expressed on B cells, causing B cell depletion. RTX has shown great efficacy in studies of pemphigus vulgaris, but data of pemphigoid diseases are limited. Objective: To assess the effectiveness and safety of RTX in pemphigoid diseases. Methods: The medical records of 28 patients with pemphigoid diseases that were treated with RTX were reviewed retrospectively. Early and late endpoints, defined according to international consensus, were disease control (DC), partial remission (PR), complete remission (CR), and relapses. Safety was measured by reported adverse events. Results: Patients with bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 14), epidermolysis bullosa acquisita (n = 5), and linear IgA disease (n = 1) were included. Treatment with 500 mg RTX (n = 6) or 1,000 mg RTX (n = 22) was administered on days 1 and 15. Eight patients received additional 500 mg RTX at months 6 and 12. Overall, DC was achieved in 67.9%, PR in 57.1%, and CR in 21.4% of the cases. During follow-up, 66.7% patients relapsed. Repeated treatment with RTX led to remission (PR or CR) in 85.7% of the retreated cases. No significant difference in response between pemphigoid subtypes was found. IgA-dominant cases (n = 5) achieved less DC (20 vs. 81.3%; p = 0.007), less PR (20 vs. 62.5%; p = 0.149), and less CR (0 vs. 18.8%; p = 0.549) compared to IgG-dominant cases (n = 16). Five severe adverse events and three deaths were reported. One death was possibly related to RTX and one death was disease related. Conclusion: RTX can be effective in recalcitrant IgG-dominant pemphigoid diseases, however not in those where IgA is dominant.
Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies.

OBJECTIVE: Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis. METHODS: Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14(+) monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted. RESULTS: EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14(+) cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect. CONCLUSIONS: Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.