Miracle-dz/UniFAR-FTUs huggingface dataset:
Definitions of the phenotypic manifestations of sickle cell disease

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD (∼100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype–phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed. Am. J. Hematol. 2010. © 2009 Wiley‐Liss, Inc.
Association of the muscle hypertrophy locus with carcass traits in beef cattle.

A locus near the centromere of bovine chromosome 2 is responsible for muscle hypertrophy (mh) in cattle. The objectives of this study were to refine the genomic region in which the locus resides and to assess the effects of a single copy of the mh allele on carcass and birth traits. Two half-sib families were developed using a Belgian Blue x MARC III (n = 246) or a Piedmontese x Angus (n = 209) sire. Traits analyzed were calving ease (CE), birth weight (BWT, kg), longissimus rib eye area (REA), retail product yield (RPYD), USDA yield grade (YG), marbling (MAR), fat thickness (FAT), estimated kidney, pelvic, and heart fat (KPH), and longissimus tenderness measured as Warner-Bratzler shear force at 3 (S3) and 14 (S14) d postmortem. Six microsatellites were used to determine the presence or absence of the mh allele and to confirm the location of the locus affecting the traits, which was assessed to be 4 cM from the beginning of the linkage group, with the 95% confidence interval between 2 and 6 cM. Cattle with an mh allele had increased (P < .01) REA, RPYD, and BWT and decreased MAR, YG, FAT, and KPH, compared with those without the allele. The effects of the mh allele (mh/+ vs +/+) were 1.35, 1.6, . 41, -1.01, -1.42, -. 84, and -. 86 residual standard deviations, respectively. There were no effects (P > .10) for CE, S3, and S14. Allelic differences due to the mh locus were similar for both sources (Belgian Blue or Piedmontese). Individuals inheriting a single mh allele had a leaner, more heavily muscled carcass compared with those inheriting the alternative allele. Thus, mating schemes that maximize production of mh/+ genotypes provide a viable approach for improving carcass composition.
Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas Note

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP‐13, MMP‐14 and TIMP‐2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP‐1, MMP‐7 and MMP‐9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP‐2, MMP‐14 and TIMP‐2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low‐grade malignant chondrosarcoma and a benign growing enchondroma.
Interpreting Anti-HLA Antibody Testing Data: A Practical Guide for Physicians

Abstract The development of sensitive methods for alloantibody detection has been a significant advance in clinical transplantation. However, the complexity of the data from solid phase and crossmatch assays has led to potential confusion about how to use the results for clinical decision making. The goal of this review is to provide a practical guide for transplant physicians for the interpretation of antibody data to supplement consultation with local tissue typing experts. Sources of variability in both the solid phase and crossmatch assay are discussed as are recent data regarding C1q binding antibodies and IgG subclass testing. Although definitive approaches to alloantibody testing are not possible with our current knowledge, we outline a pragmatic approach that we hope will enhance clinical management in this area.
Photoperiod‐Dependent and ‐Independent Regulation of Melatonin Receptors in the Forebrain of Songbirds

Melatonin was recently identified as playing a role in fine‐tuning the effects of gonadal steroids in the regulation of seasonal neuroplasticity within the telencephalic song control system of European starlings. The present study investigated possible seasonal regulation of melatonin receptors (MelR) within the starling song control system, in the presence or absence of gonadal steroids. Brains were sampled from photosensitive starlings exposed to short days, photostimulated starlings exposed to long days and photorefractory starlings also exposed to long days. Each condition contained a group of gonad‐intact birds and a group of castrated birds. Melatonin receptor distribution was assessed in vitro by 125–iodomelatonin (IMEL) receptor autoradiography. In general, MelR distribution was similar to that described in other songbird species. However, there was a striking downregulation of MelR in the song control nucleus Area X of intact and castrated photostimulated birds on long days compared to their photorefractory counterparts on the same long days and to the short‐day groups. Downregulation of MelR occurred independently of gonadal steroids. Nevertheless, superimposed on this general pattern of MelR downregulation during photostimulation, IMEL binding was observed in a medial subdivision of Area X when gonadal steroids were present. Downregulation of MelR in Area X during the short breeding season has implications for seasonal regulation of the song control system. Subsequent upregulation of MelR as birds become photorefractory, in the absence of any change in photoperiod, gonadal steroids or melatonin signal is the first description of photoperiod‐independent regulation of MelR in adults of any vertebrate class.
Outdoor use, tonic immobility, heterophil/lymphocyte ratio and feather condition in free-range laying hens of different genotype

1. Movement (frequency of changes) between inside and outside housing areas, time spent in each area, tonic immobility (TI) and differential blood cell counts were studied in relation to feather condition in laying hens of two genotypes, white (LSL) and brown (LT). 2. From 18 weeks of age, LSL and LT were kept in 4 groups of 50 birds in a poultry house with passages to a roofed scratching room and a grassland area with a stocking density of one bird/10 m2. 3. All birds had transponders to record the movements of each hen between inside and outside areas and the time spent in each area during 24 h. Feather scoring was carried out at 6 ages from 20 to 48 weeks. At 44 weeks of age, TI reactions of 40 hens (20 from each genotype) were quantified and blood smears from 20 hens (10 from each genotype) were analysed for differential leucocyte counts. 4. LSL hens moved more frequently to outdoor areas than LT hens (44.66 vs 28.78 least square/d). However, the proportion of time spent on grassland was greater in LT than in LSL hens, whereas time (%) spent by LT hens in the roofed scratching area was less than for LSl hens. 5. In LT hens TI was shorter while heterophil/lymphocyte ratio and basophilia were greater than in LSL hens. 6. Total body feather score was poorer in LSL than in LT hens. Incidence of footpad inflammation was higher in LSL than LT hens. 7. There was a positive association between TI and footpad inflammation. The percentage of time spent on grassland and feather damage were inversely correlated. 8. More movement between the areas, as in LSL hens, was positively associated with fearfulness, whereas long periods on grassland, as in LT hens, were associated with indicators of increased stress. The negative correlation between feather damage and time spent outside suggests that feather pecking risk decreases in birds attracted to grassland.
Ultrastructural organization of the noradrenergic innervation of the superficial gray layer of the hamster's superior colliculus

Immunocytochemistry with an antibody‐directed tyrosine hydroxylase (TH) was combined with electron microscopy and serial‐section analysis to examine the synaptic organization of the catecholaminergic projection to the stratum griseum superfciale (SGS) of the hamster's superior colliculus (SC). A total of 250 TH‐immunoreactive profiles within SGS were examined. Of these, 114 (45.6%) made synaptic contacts; 81 (71.1%) were axodendritic, and the remainder (33, 28.9%) were axo‐axonic. Serial‐section analysis was employed to evaluate the presence or absence of synaptic contacts for 26 profiles. Overall, 19 (73.1%) of the profiles followed through serial sections exhibited synaptic contacts. Double staining of single sections with antibodies directed against TH and dopamine‐ß‐hydroxylase (DßH) and examination in the light microscope indicated that virtually all TH‐positive fibers also contained DßH. This indicated that the fibers examined at the electron microscopic level were noradrenergic rather than dopaminergic. These results suggest that norepinephrine may have both pre‐ and postsynaptic actions in the hamster's SC and that at least some of these effects are mediated by conventional synapses.
Efficacy of Electroconvulsive Therapy Combined with Antipsychotic Medication in Treatment-Resistant Schizophrenia: A Prospective, Open Trial

This study examined the short-term efficacy of electroconvulsive therapy (ECT) combined with antipsychotic medication in treatment-resistant schizophrenia (TRS). Fifteen patients with TRS from an in-patient psychiatric rehabilitation unit participated. Patients completed a course of ECT consisting of 8 to 20 sessions, while their antipsychotic medications were continued throughout the study. Patients were assessed at baseline, 1 week, 1 month, and 2 months after their last ECT session. Assessment instruments included the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale, Scale for the Assessment of Negative Symptoms (SANS), Global Assessment Scale (GAS), Clinical Global Impression (CGI), Nurses' Observation Scale for In-Patient Evaluation, and occupational therapists' rating of the patients' functioning with respect to work, social, and leisure activities. Compared with the baseline assessment, at each posttreatment evaluation, patients showed statistically significant improvement in the GAS and CGI. In addition, they were significantly better in terms of BPRS and SANS scores, as well as work performance and social functioning at the 2-month post-ECT evaluation.
Long-term experience with 6-mercaptopurine in the treatment of Crohn's disease.

We report our observations after 20 yr of clinical experience with 6-mercaptopurine (6-MP) in 148 patients with Crohn's disease who had not satisfactorily responded to steroids and other drugs. Specific therapeutic goals were established for each patient, and the NFIC (now CCFA)-IOIBD index of Crohn's disease activity was calculated pre- and post-therapy. Defined therapeutic goals were achieved in 68%. Major successes include 1) elimination of steroids (66% p < 0.001); 2) healing of internal fistulas and abscesses or improvement by elimination of discharge and tenderness (64% p < 0.05); and 3) healing or improvement by elimination of pain, tenderness and discharge of perirectal fistulas and abscesses (87%, p < 0.05). Other therapeutic goals which achieved 100% success were 1) healing or marked improvement of Crohn's disease of the stomach and duodenum; 2) permitting surgery to be performed electively after 6-MP allowed margins for surgical resection to be delineated. 6-MP was less effective in achieving the therapeutic goals of preventing recurrent small bowel obstruction (43%) and elimination of abdominal masses (55%). Seventy-eight percent of patients showed a reduction in the activity index with a mean of 43% (95% C.I. 36-51%). 6-MP was once again demonstrated to be effective in achieving major therapeutic goals in two of three patients with severe Crohn's disease. Accordingly, the need for surgical resection and subsequent extension of the disease is often postponed or eliminated.
Canada’s Trade Policy Options under Donald Trump: NAFTA’s rules of origin, Canada U.S. security perimeter, and Canada’s geographical trade diversification opportunities

This paper analyses the trade policy options of Canada under Trump and reviews some arguments that have been made by economists and others in the current debate surrounding U.S. return to protectionism and mercantilism. For Canada, both imports and exports are vital, and trade with the U.S. and with the rest of the world is of key importance. The new mercantilist position of the U.S. administration under Trump requires Canada to reflect on how to communicate the Canada-U.S. trade relation in terms of win-win strategies. A good starting point for this exercise, however, is to emphasize that NAFTA, as a trade preferential arrangement, is not as valuable as it used to be in the 1990s because NAFTA margins of preferences are no more sufficiently attractive to offset the cost of complying with NAFTA Rules of Origins requirements. Second, Canada-U.S. border security measures introduced after the terrorist attacks of 2001 have also offset NAFTA’s tariff preferences. Finally, the paper discusses the benefits of diversifying Canada’s trade geographically in a world where North America has become a smaller share of the global pie.
Effect of the improved sweet potato varieties on household food security: empirical evidence from Kenya

This study evaluates the effect of improved sweet potato varieties on household food security. Data was collected from cross sectional survey of 164 sweet potato farmers in Kenya. Food security was measured using the Household Dietary diversity Score (HDDS) and endogenous switching probit model used to assess the effect of improved sweet potato varieties on household food security. Off-farm income, output of sweet potato, farm size, land tenure and government extension were the main drivers of food security. Findings were that adopters of improved varieties were likely to be food secure compared to their counterfactual case of not adopting the improved varieties. Additionally, non adopters would do no better or worse than a random individual if they adopt the improved sweet potato varieties. Policies that increase improved sweet potato variety productivity and ease farmers’ adoption constraints can ensure that farmers diversify farm income to enhance the food security of households
Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer.

AIM To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with Oligofectamine(TM) to knock down the MIF expression, with the NC group and mock group (Oligofectamine(TM) alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific siRNA compared with the control siRNA and mock groups (P < 0.001 for all). CONCLUSION MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.
A comparison of existing global DNA methylation assays to low-coverage whole-genome bisulfite sequencing for epidemiological studies

ABSTRACT DNA methylation is an epigenetic mark at the interface of genetic and environmental factors relevant to human disease. Quantitative assessments of global DNA methylation levels have therefore become important tools in epidemiology research, particularly for understanding effects of environmental exposures in complex diseases. Among the available methods of quantitative DNA methylation measurements, bisulfite sequencing is considered the gold standard, but whole-genome bisulfite sequencing (WGBS) has previously been considered too costly for epidemiology studies with high sample numbers. Pyrosequencing of repetitive sequences within bisulfite-treated DNA has been routinely used as a surrogate for global DNA methylation, but a comparison of pyrosequencing to WGBS for accuracy and reproducibility of methylation levels has not been performed. This study compared the global methylation levels measured from uniquely mappable (non-repetitive) WGBS sequences to pyrosequencing assays of several repeat sequences and repeat assay-matched WGBS data and determined uniquely mappable WGBS data to be the most reproducible and accurate measurement of global DNA methylation levels. We determined sources of variation in repetitive pyrosequencing assays to be PCR amplification bias, PCR primer selection bias in methylation levels of targeted sequences, and inherent variability in methylation levels of repeat sequences. Low-coverage, uniquely mappable WGBS showed the strongest correlation between replicates of all assays. By using multiplexing by indexed bar codes, the cost of WGBS can be lowered significantly to improve the accuracy of global DNA methylation assessments for human studies.
Delayed block LMS algorithm and concurrent architecture for high-speed implementation of adaptive FIR filters

In this paper, we propose a block least mean square algorithm with delayed weight adaptation for hardware implementation of finite impulse response (FIR) adaptive filters. We have referred to the proposed algorithm as delayed block least mean square (DBLMS) algorithm. Unlike the delayed least mean square (DLMS) algorithm, the DBLMS algorithm takes a block of L input samples and yields a block of L output in every training cycle. The simulation result shows that the DBLMS algorithm has convergence performance equivalent to that of the DLMS algorithm. We have exploited the parallelism inherent in the DBLMS algorithm to derive a highly concurrent systolic architecture for FIR adaptive filters. The proposed architecture can support L time higher sampling rate compared with the best of the existing pipelined designs and, therefore, it would involve less samples of adaptation delays and would provide a more efficient implementation of LMS-based adaptive filters.
Microbial Factors Associated with Postoperative Crohn’s Disease Recurrence

Background and Aims: The intestinal microbiota is a key antigenic driver in Crohn’s disease [CD]. We aimed to identify changes in the gut microbiome associated with, and predictive of, disease recurrence and remission. Methods: A total of 141 mucosal biopsy samples from 34 CD patients were obtained at surgical resection and at colonoscopy 6 and/or 18 months postoperatively; 28 control samples were obtained: 12 from healthy patients [healthy controls] and 16 from hemicolectomy patients [surgical controls]. Bacterial 16S ribosomal profiling was performed using the Illumina MiSeq platform. Results: CD was associated with reduced alpha diversity when compared with healthy controls but not surgical controls [p < 0.001 and p = 0.666, respectively]. Beta diversity [composition] differed significantly between CD and both healthy [p < 0.001] and surgical [p = 0.022] controls, but did not differ significantly between those with and without endoscopic recurrence. There were significant taxonomic differences between recurrence and remission. Patients experiencing recurrence demonstrated elevated Proteus genera [p = 0.008] and reduced Faecalibacterium [p< 0.001]. Active smoking was associated with elevated levels of Proteus [p = 0.013] postoperatively. Low abundance of Faecalibacterium [< 0.1%] and detectable Proteus in the postoperative ileal mucosa was associated with a higher risk of recurrence (odds ratio [OR] 14 [1.7–110], p = 0.013 and 13 [1.1–150], p = 0.039, respectively) when corrected for smoking. A model of recurrence comprising the presence of Proteus, abundance of Faecalibacterium, and smoking status showed moderate accuracy (area under the curve [AUC] 0.740, 95% confidence interval [CI] [0.69–0.79]). Conclusions: CD is associated with a microbial signature distinct from health. Microbial factors and smoking independently influence postoperative CD recurrence. The genus Proteus may play a role in the development of CD.