Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced Expression of CXCR4 on Circulating CD34+ Cells Is Associated with Hematopoietic Progenitor Cells (HPC) Mobilization in Patients with Myelofibrosis with Myeloid Metaplasia (MMM).

Abstract Spontaneous mobilization of HPC is a key feature of MMM. We investigated the CXCR4/SDF-1 (stromal derived factor-1) axis in 52 consecutive MMM patients. The percentage of circulating CD34+ cells co-expressing CXCR4 at the cytofluorimetric analysis was significantly lower (P=0.02) in MMM patients (median, 37%, range, 0 to 92%) than in the normal controls (n=12; median, 75%; range, 39 to 91%). CXCR4 mean fluorescence intensity was also highly significantly lower in MMM patients (median 0.73; range, 0.06 to 7.05) than in normal controls (median, 1.84; range, 0.41 to 6.69; P=0.004). By analyzing the association between CXCR4 expression and the mobilization of progenitor cells, an inverse correlation was found between CXCR4 expression and the number of circulating CD45+/CD34+ HPC (R=−0.40; P=0.005). By restricting the relation analysis of CXCR4 expression and clinical features to those patients who were not receiving cytoreductive treatment (n=41), there was no correlation between CXCR4 expression and patients' sex, hemoglobin concentration, WBC, prefibrotic stage. By contrast, CXCR4 expression was inversely correlated with clinical characteristics that portrayed an advanced disease, such as older age (R=−0.31; P=0.026), longer disease duration (R=−0.37; P=0.008), larger splenomegaly (r=−0.33; P=0.015) and lower platelet count (r=0.42; P=0.007). The levels of CXCR4 mRNA, measured in peripheral blood CD34+ cells of patients with MMM were lower as compared with those of cells purified from normal peripheral blood (ΔCT by real time RT-PCR using GAPDH as housekeeping reference gene: 5.33 ± 0.49 vs. 1.53 ± 0.79, mean ± SD; P=0.003). SDF-1 plasma levels were significantly increased in patients with MMM but no correlation was documented with CXCR4 expression. We conclude that reduced expression of CXCR4 on CD34+ cells is a mechanism for the constitutive mobilization of HPC in MMM.
On-the-Job Pain and Injury as Related to Adaptive Ergonomic Equipment in the Sonographer’s Workplace and Area

The proportion of sonographers who scan in pain is increasing, in spite of recommendations and guidelines for proper body mechanics and for the use of ergonomic equipment in the workplace. No study has examined in detail the type of equipment that is available to sonographers in the workplace and whether sonographers who have access to ergonomic equipment are scanning in pain. This study evaluated the proportions of sonographers who had access to various types of ergonomic equipment and compared the results with the prevalence of scanning-related pain. Most sonographers had access to ergonomic features manufactured into ultrasound machines but had less access to equipment provided by employers, such as scanning chairs and cable braces. Sonographers who had access to machines that had swiveling keyboards reported less pain and injury than those who did not.
Comparative phylogeographic inference with genome‐wide data from aggregated population pairs

Comparing divergences across multiple sister population pairs has been a focus in phylogeography since its inception. Initial approaches used organelle genetic data and involved qualitative comparisons of phylogenetic patterns to evaluate hypotheses of shared and variable evolutionary responses. This endeavor has progressed with coalescent model‐based statistical techniques and advances in next‐generation sequencing, yet there remains a need for methods that can exploit aggregated genomic‐scale data within a unified analytical framework. To this end, we introduce the aggregate joint site frequency spectrum (ajSFS) by validating its use within a hierarchical Bayesian framework through several in silico experiments. Subsequently, we applied our method against two published restriction site–associated DNA marker datasets consisting of eight local replicates of a lamprey species pair and six co‐distributed passerine taxon pairs, respectively, with the aim of inferring variability in co‐divergence and co‐migration histories. We found that the lamprey population pairs exhibited temporal synchrony in both co‐divergence and collective secondary contact times, yet an idiosyncratic pattern in secondary migration intensities. In contrast, the bird population pairs displayed thoroughly asynchronous co‐divergence histories. Our results demonstrate that the ajSFS can be exploited for complex and flexible co‐demographic inference, opening up new possibilities for comparative phylogeography and population genomic studies.
Consolidation with Radioimmunotherapy May Prolong Survival in First Remission of Mantle Cell Lymphoma Patients Uneligible for Stem Cell Transplantation, An Analysis of the International RIT-Network.

Abstract 3746 Poster Board III-682 Background Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of Non Hodgkin Lymphoma (NHL) with a relatively poor prognosis (5-year survival Methods and Patients In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age – 63 (range 31-78); males – 70.4%, stage III/IV – 92%. RIT (i.e. application of ibritumomab tiuxetan) was a part of the first line therapy in 48 pts. (43%). Further 38 pts. (33%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 33 pts. (24%) after completing 3-8 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response; the rest of the patients received ibritumomab tiuxetan because of relapse/refractory disease. At the moment follow up data are available for 74 MCL patients. Results After RIT the patients achieved high response rate: CR 60.8%, PR 25.7%, and SD 2.7%. Only 10.8% of the patients progressed. For survival analysis many data had to be censored since the documentation had not been completed yet. The projected 3-year overall survival (OAS, fig.1 – image 001.gif) after radioimmunotherapy was 72% for pts. subjected to RIT consolidation versus 29% for those treated in relapse/refractory disease (p=0.03). RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 45, 40 and 38 days respectively. Conclusion Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may prolong survival of patients who achieved clinical response after chemotherapy. Therefore, this consolidation approach should be considered as a treatment strategy for those, who are not eligible for ASCT. RIT also has a potential role as a palliation therapy in relapsing/resistant cases. Disclosures: Off Label Use: Ibritumomab Tiuxetan (Zevalin) for MCL.
A Genome‐wide Association Study of Circulating Levels of Atorvastatin and Its Major Metabolites

Atorvastatin (ATV) is frequently prescribed and generally well tolerated, but can lead to myotoxicity, especially at higher doses. A genome‐wide association study of circulating levels of ATV, 2‐hydroxy (2‐OH) ATV, ATV lactone (ATV L), and 2‐OH ATV L was performed in 590 patients who had been hospitalized with a non‐ST elevation acute coronary syndrome 1 month earlier and were on high‐dose ATV (80 mg or 40 mg daily). The UGT1A locus (lead single nucleotide polymorphism, rs887829) was strongly associated with both increased 2‐OH ATV/ATV (P = 7.25 × 10−16) and 2‐OH ATV L/ATV L (P = 3.95 × 10−15) metabolic ratios. Moreover, rs45446698, which tags CYP3A7*1C, was nominally associated with increased 2‐OH ATV/ATV (P = 6.18 × 10−7), and SLCO1B1 rs4149056 with increased ATV (P = 2.21 × 10−6) and 2‐OH ATV (P = 1.09 × 10−6) levels. In a subset of these patients whose levels of ATV and metabolites had also been measured at 12 months after hospitalization (n = 149), all of these associations remained, except for 2‐OH ATV and rs4149056 (P = 0.057). Clinically, rs4149056 was associated with increased muscular symptoms (odds ratio (OR) 3.97; 95% confidence interval (CI) 1.29–12.27; P = 0.016) and ATV intolerance (OR 1.55; 95% CI 1.09–2.19; P = 0.014) in patients (n = 870) primarily discharged on high‐dose ATV. In summary, both novel and recognized genetic associations have been identified with circulating levels of ATV and its major metabolites. Further study is warranted to determine the clinical utility of genotyping rs4149056 in patients on high‐dose ATV.
Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress‐induced depression‐like behavior

According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of “lily disease”, the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High‐performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme‐linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ‐aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural‐immunity. GABAergic and glutamatergic synapses as well as brain‐derived neurotrophic factor (BDNF)/TrkB‐dependent phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin‐1 (mTOR1), might be the main signaling pathways underlying the multi‐target therapeutic effects of LBRD against depression.
QUANTIFICATION OF VERTEBRAL TRABECULAR BONE STRAIN VIA FEATURE-BASED IMAGE REGISTRATION

Strain is a robust indicator of bone failure initiation. Previous work has demonstrated the measurement of vertebral trabecular bone strain by Digital Volume Correlation (DVC) of µCT scan in both a loaded and an unloaded configuration. This project aims to improve previous strain measurement methods relying on image registration, improving resolution to resolve trabecula level strain and to improve accuracy by applying feature based registration algorithms to µCT images of vertebral trabecular bone to quantify strain. It is hypothesised that extracting reliable corresponding feature points from loaded and unloaded µCT scans can be used to produce higher resolution strain fields compared to DVC techniques. The feature based strain calculation algorithm has two steps: 1) a displacement field is calculated by finding corresponding feature points identified in both the loaded and unloaded µCT scans 2) strain fields are calculated from the displacement fields. Two methods of feature point extraction, Scale Invariant Feature Transform (SIFT) and Skeletonisation, were applied to unloaded (fixed) and loaded (moving) µCT images of a rat tail vertebra. Spatially non-uniform displacement fields were generated by automatically matching corresponding feature points in the unloaded and loaded scans. The Thin Plate Spline method and a Moving Least Squares Meshless Method were both tested for calculating strain from the displacement fields. Verification of the algorithms was performed by testing against known artificial strain/displacement fields. A uniform and a linearly varying 2% compressive strain field were applied separately to an unloaded 2D sagittal µCT slice to simulate the moving image. SIFT was unable to reliably match identified feature points leading to large errors in displacement. Skeletonisation generated a more accurate and precise displacement field. TPS was not tolerant to small displacement field errors, which resulted in inaccurate strain fields. The Meshless Methods proved much more resilient to displacement field errors. The combination of Skeletonisation with the Meshless Method resulted in best performance with an accuracy of −405µstrain and a detection limit of 1210µstrain at a strain resolution of 221. 5µm. The DVC algorithm verified using the same validation test yielded a similar detection limit (1190µstrain), but with a lower accuracy for the same test (2370µstrain) for a lower resolution strain field (770µm) (Hardisty, 2009). The Skeletonisation algorithm combined with the Meshless Method calculated strain at a higher resolution, but with a similar detection limit, to that of traditional DVC methods. Future improvements to this method include the implementation of subpixel feature point identification and adapting this method of strain measurement into a 3D domain. Ultimately, a hybrid DVC/feature registration algorithm may further improve the ability to measure trabecular bone strain using µCT based image registration.
Enhanced Sulfate Production by Nitrate Photolysis in the Presence of Halide Ions in Atmospheric Particles.

Heterogeneous oxidation of SO2 is an effective production pathway of sulfate in the atmosphere. We recently reported a novel pathway for the heterogeneous oxidation of SO2 by in-particle oxidants (OH, NO2 and NO2-/HNO2) produced from particulate nitrate photolysis (Environ. Sci. Technol. 2019, 53, 8757-8766). Particulate nitrate is often found to coexist with chloride and other halide ions, especially in aged sea-salt aerosols and combustion aerosols. Reactive uptake experiments of SO2 with UV-irradiated nitrate particles showed that sulfate production rates were enhanced by a factor of 1.4, 1.3, and 2.0 in the presence of Cl-, Br-, and I-, respectively, compared to those in the absence of halide ions. The larger sulfate production was attributed to enhanced nitrate photolysis promoted by the increased incomplete solvation of nitrate at the air-particle interface due to the presence of surface-active halide ions. Modeling results based on the experimental data show that the nitrate photolysis rate constants increase by a factor of 2.0, 1.7, and 3.7 in the presence of Cl-, Br-, and I-, respectively. A linear relation was found between the nitrate photolysis rate constant, jNO3-, and the initial molar ratio of Cl- to NO3-, [Cl-]0/[NO3-]0, as jNO3-=9.7×10-5[Cl-]0/[NO3-]0 + 1.9×10-5 at [Cl-]0/[NO3-]0 below 0.2. The present study demonstrates that the presence of halide ions enhances sulfate production produced during particulate nitrate photolysis and provides insights into the enhanced formation of in-particle oxidants that may increase atmospheric oxidative capacity.
Comorbidity Clusters and Healthcare Use in Individuals With COPD

BACKGROUND: Individuals who share the same comorbidity profile are usually similar with regard to their disease severity, use of health care, and clinical outcomes. The identification of comorbidity clusters therefore bears prognostic information. The objective of this study was to identify and characterize comorbidity clusters in individuals with COPD in Denmark. METHODS: Data from the Danish national registers were used. The study population included all individuals ≥16 y old who lived in the Danish Capital Region on January 1, 2012, and were diagnosed with COPD (N = 70,274). Comorbid chronic conditions were identified using diagnostic algorithms. A 2-step cluster analysis was performed. RESULTS: 81% of subjects with COPD had chronic comorbidities; the most common was hypertension (47.6%), and the least common was anxiety (0.1%). Three comorbidity clusters were identified. Cluster 1 contained 16% of the studied individuals with COPD, with all having heart disease in addition to the remaining comorbidities. Cluster 2 contained 30% of the studied individuals with COPD, of whom approximately 1 in 3 suffered from allergies, while the rest had no comorbidities. Cluster 3 contained 54% of the studied individuals with COPD, where all comorbidities but heart disease were represented. Cluster 1 contained the highest proportion of individuals over the age of 65 y, as well as the individuals with the lowest education. After adjusting for sociodemographic characteristics, individuals in Cluster 1 had the highest rates of hospitalizations and bed days. CONCLUSIONS: The presence of heart disease in individuals with COPD is a strong prognostic factor for socioeconomic and health vulnerability.
Development of photo‐amino acid derivative reactivity assay: a novel in chemico alternative method for predicting photoallergy

Photoallergy test of cosmetics and several types of pharmaceutical substances is often necessary for obtaining approval from authorities. However, there are no official test guidelines for photoallergy evaluation. Therefore, we tried to establish a photoallergy test by utilizing an in chemico alternative sensitization method, amino acid derivative reactivity assay (ADRA). To determine the criteria for judging the photoallergy potential, photo‐ADRA with or without photoirradiation was performed using 60 photoallergenic chemicals, and cysteine and lysine derivatives were detected using high‐performance liquid chromatography either by absorbance or fluorescence measurement. The accuracy of prediction was 81.4% (48 of 59) and 80.0% (48 of 60) using the absorbance and fluorescence methods, respectively. However, as chemicals can breakdown into multiple chemicals during photoirradiation, the absorbance method often cannot perform accurate detection due to co‐elution, whereas the fluorescence method can do this due to lack of co‐elution. Moreover, all eight chemicals that were found to be negative or false‐positive for photoirritation in the 3T3 neutral red uptake phototoxicity test were confirmed as positive for photoallergy using this method. Furthermore, we prepared three types of pseudo‐mixtures where we added one photoallergen along with five nonphotoallergens and performed the photo‐ADRA by the ultraviolet and fluorescence methods. The result of the fluorescence method was almost the same as that obtained with the use of a single photoallergen and hence the outcome was not affected by the mixture. Thus, this study not only showed a method of evaluating the photoallergy potential of a single chemical but also a mixture, making it useful as an in chemico photoallergy alternative test.
Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups

Abstract Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18–75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism–tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype–hypertension association was confined to adults aged ≤50 years.
Results of a Prospective Randomised Open Label Phase III Study Comparing Rituximab Plus Mitoxantrone, Chlorambucile, Prednisolone Chemotherapy (R-MCP) Versus MCP Alone in Untreated Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) and Mantle-Cell-Lymphoma (MCL).

Rituximab proved to be effective in relapsed and refractory indolent NHL as a single agent and generated impressive results in phase II studies in combination with chemotherapy. In a prospective randomized trial we compared the efficacy and toxicity of rituximab (375 mg/m² d 1) plus MCP-chemotherapy ( mitoxantrone 8 mg/m² d 3 + 4, chlorambucile 3 x 3 mg/m² d 3 – 7, prednisolone 25 mg/m² d 3 – 7 ) given every 28 days for a total of 8 cycles versus MCP (d 1 – 5) x 8 cycles alone in advanced indolent NHL and MCL. Efficacy endpoints included overall and complete response rates, event free survival, progression free survival, overall survival and toxicity. For response assessment classical definitions have been used. Between 10/98 and 09/03 we randomized 358 patients (pts) with advanced stage follicular lymphoma (FL) (grade 1 + 2), lymphoplasmacytic lymphoma and MCL to either R-MCP or MCP. The study arms are well balanced for all demographic factors. 201/358 pts (56%) had FL. Both regimens were well tolerated with a low incidence of serious adverse events. The overall response rate (RR) and the complete response rate (CR) for all pts was 85,5% and 42% in the R-MCP arm versus 65,5% and 20% in the MCP arm (p