Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency of breast cancer attributable to BRCA1 in a population-based series of American women.

CONTEXT Previous studies of BRCA1 mutation prevalence have been based on high-risk groups, yielding estimates that do not reflect the experience of the general population of US patients with breast cancer. OBJECTIVE To determine prevalence of known disease-related mutations and other variants in BRCA1 and how it differs by race, age at diagnosis, and family history status in a population-based sample of white and black patients with breast cancer unselected for family history. DESIGN Case-control study. SETTING A 24-county area of central and eastern North Carolina. PARTICIPANTS Cases were women aged 20 to 74 years diagnosed as having a first invasive breast cancer between May 1993 and June 1996. Controls were frequency matched to cases by 5-year age range and race. The first 211 cases and 188 controls regardless of race and the subsequent 99 cases and 108 controls of African American ancestry are included in this report. MAIN OUTCOME MEASURE Germline variants at any site in the coding sequence, splice junctions, 5' untranslated region, or 3' untranslated region of the BRCA1 gene were analyzed in cases, and selected variants were analyzed in controls. Screening was performed using multiplex single-strand conformation analysis, with all potential variants confirmed using genomic sequencing. RESULTS Three of 211 patients with breast cancer had disease-related variants at BRCA1, all of which were protein-truncating mutations. After adjustment for sampling probabilities, the proportion of patients with breast cancer with disease-related variants was 3.3% (95% confidence interval, 0%-7.2%) in white women and 0% in black women. Young age at diagnosis alone did not predict BRCA1 carrier status in this population. In white women, prevalence of inherited mutation was 23% for cases with family history of ovarian cancer, 13% for cases from families with at least 4 cases of breast cancer with or without ovarian cancer, and 33% for cases from families with both breast and ovarian cancer and at least 4 affected relatives. Because these results are based on few families at the highest levels of risk, confidence intervals around these estimates are wide. An additional 5 patients had rare missense mutations or a single amino acid deletion, the biological significance of which is unknown. In black women, a variant in the 3' untranslated region was statistically significantly more common in cases than in controls. CONCLUSIONS These data suggest that in the general US population, widespread screening of BRCA1 is not warranted. In contrast, BRCA1 mutations are sufficiently frequent in families with both breast and ovarian cancer, or at least 4 cases of breast cancer (at any age), that genotyping might be considered. The emerging picture of BRCA1 population genetics involves complex interactions of family history, age, and genetic ancestry, all of which should be taken into account when considering testing or interpreting results.
Identification of a New Glycerol-3-phosphate Acyltransferase Isoenzyme, mtGPAT2, in Mitochondria*

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial and rate-limiting step of glycerolipid synthesis. Two distinct GPAT isoenzymes had been identified in mammalian tissues, an N-ethylmaleimide (NEM)-sensitive isoform in the endoplasmic reticulum membrane (microsomal GPAT) and an NEM-resistant form in the outer mitochondrial membrane (mtGPAT). Although only mtGPAT has been cloned, the microsomal and mitochondrial GPAT isoforms can be distinguished, because they differ in acyl-CoA substrate preference, sensitivity to inhibition by dihydroxyacetone phosphate and polymixin B, temperature sensitivity, and ability to be activated by acetone. The preponderance of evidence supports a role for mtGPAT in synthesizing the precursors for triacylglycerol synthesis. In mtGPAT-/- mice, PCR genotyping and Northern analysis showed successful knockout of mtGPAT; however, we detected a novel NEM-sensitive GPAT activity in mitochondrial fractions and an anti-mtGPAT immunoreactive protein in liver mitochondria, but not in microsomes. Rigorous analysis using two-dimensional gel electrophoresis revealed that the anti-mtGPAT immunoreactive proteins in wild type and mtGPAT-/- liver mitochondria have different isoelectric points. These results suggested the presence of a second GPAT in liver mitochondria from mtGPAT-/- mice. Characterization of this GPAT activity in liver from mtGPAT null mice showed that, unlike the mtGPAT activity in wild type samples, activity in mtGPAT knockout mitochondria did not prefer palmitoyl-CoA, was sensitive to inactivation by NEM, was inhibited by dihydroxyacetone phosphate and polymixin B, was temperature-sensitive, and was not activated by acetone. We conclude that a novel GPAT (mtGPAT2) with antigenic epitopes similar to those of mtGPAT is detectable in mitochondria from the livers of mtGPAT-/- mice.
Reconstruction aspects of spiral scan magnetic resonance imaging

Reconstruction aspects of spiral-scan magnetic resonance imaging are investigated with polar and rectangular coordinates based reconstruction. Several reconstruction algorithms based on these coordinates are tested, and reconstructed image qualities are compared with a mathematically built phantom. An improved reconstruction algorithm with dc-offset correction in projection domain is proposed, which provides the best reconstructed image quality from simulation. Image artifact with existing algorithms is also completely removed with the proposed method.
Pharmacogenetic Angiogenesis Profiling for First-Line Chemotherapy in Patients With Advanced Gastric Cancer

We retrospectively investigated germline polymorphisms in angiogenesis pathway genes (14 SNPs) and their correlation to clinical outcome (progression free survival and overall survival) in 128 patients with unresectable-advanced gastric carcinoma (AGC) treated with first-line chemotherapy. Our analysis revealed that Endostatin +4349 G>A polymorphism exhibited a worse progression free survival (PFS) and overall survival (OS) compared with the GG genotype. Significant OS difference was also observed in the endothelial nitric oxide synthase (eNOS)-786 T>C polymorphism. Hence, common germline variants in Endostatin and eNOS genes have predictive significance for clinical outcome and survivality in AGC patients treated with first-line chemotherapy.
Turbulence measurements of dye concentration and effects of secondary flow on distribution in open channel flows

This paper presents simultaneous turbulence measurements of velocity and tracer concentration using a combination of laser Doppler anemometer (LDA) and laser induced fluorescence (LIF) in rectangular and compound channels. Secondary flow, Reynolds stresses, Reynolds fluxes, and dye concentration distributions were measured near the water surface in both channels. An investigation of the effect of secondary flow on passive contaminant diffusion processes was carried out with relatively weak secondary flow in the rectangular channel and relatively strong secondary flow in the compound channel. The results show that the secondary flow clearly influences the spreading of the tracer concentration and the location of concentration peak, being different from the injection location. The transport rate of solute due to the secondary flow is not significant in the rectangular channel case but significant in the compound channel case. The transverse eddy viscosity is demonstrated to be equal to the transverse eddy d.
Stiffness Perception During Active Ankle and Knee Movement

Objective: Recently, human joint impedance—the instantaneous mechanical response to a perturbation—has been quantified during gait, providing new insight beyond the traditional biomechanical descriptions of kinetics and kinematics. However, the role of joint impedance in neuromotor control and the development of exoskeletons and other wearable robotic systems remains unknown. One approach to studying the role of impedance in neuromotor control involves characterizing the human ability to discriminate changes in external impedance properties. Thus, the purpose of this work is to quantify the minimum detectable change in the stiffness component of impedance when interacting with an external mechanical impedance at the human ankle or knee. Methods: A dynamometer coupled to subjects’ right ankle or knee rendered the dynamics of a virtual rotational spring-mass-damper system. The minimum detectable change, or just noticeable difference, was determined via a weighted up–down staircase method in which subjects compared the stiffness values of two different controller configurations. Results: We found that subjects could reliably detect stiffness changes of at least 12% at the ankle and 13% at the knee. Conclusion: Stiffness errors or variations produced by an external mechanical device will be undetected if they remain below the 12–13% threshold. Significance: Our results provide novel insight into how the sensorimotor system senses joint impedance, information that may improve the design and control of impedance-based wearable robotic technologies.
A new ultrasound parameter for osteoporosis diagnosis: Clinical validation on normal- and under-weight women

Aim of this work was to evaluate the effectiveness of a recently introduced ultrasound (US) method for osteoporosis diagnosis, when extensively used in a clinical context to investigate adult women of variable age. A total of 384 female patients (46-65 years; body mass index <; 25 kg/m2) underwent a spinal dual X-ray absorptiometry (DXA) and an abdominal US scan of lumbar spine, acquiring both echographic images and unprocessed radiofrequency signals. US data were analyzed through a new fully automatic algorithm, which performed a series of spectral and statistical analyses to calculate the parameter called Osteoporosis Score (O.S.). Diagnostic effectiveness of O.S. was assessed through a direct comparison with DXA measurements (assumed as the gold standard reference), quantifying the agreement between the two methods through accuracy calculation, Cohen's kappa (k) and Pearson correlation coefficient (r). The overall accuracy of O.S. -based diagnoses resulted 84.6%, ranging from a minimum of 81.7% for the oldest patients (aged in 61-65 y) to a maximum of 87.2% for the youngest patients (aged in 46-50 y). Cohen's kappa showed an analogous trend, confirming a significant agreement between DXA and US-based diagnoses along the whole considered age interval (k=0.758, p<;0.0001). A good correlation was also found between O.S. -derived BMD values and corresponding DXA measurements (r=0.72, p<;0.001). These results demonstrated that US-measured O.S. is significantly correlated with spinal BMD in normal- and under-weight adult women belonging to a wide age interval. Therefore, the routine clinical application of this innovative approach to osteoporosis diagnosis can be envisioned.
Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study

Objectives To study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART). Methods The APROCO/COPILOTE cohort enrolled patients initiating a protease inhibitor-containing ART in 1997–1999. The association between occurrence of first non AIDS-defining severe events (NADE) and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4), CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4< 500/mm3, CD4 > 500/mm3 and CD4/CD8 ratio < 1, CD4 > 500/mm3 and CD4/CD8 ratio > 1). Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion. Results We included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2–11.4). Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2–0.5) at baseline and 0.6 (IQR: 0.4–0.9) after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%), cardiovascular events (14%) and cancers (10%). For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32–3.44). Conclusions CD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.
Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors.

PURPOSE OF INVESTIGATION To determine the expression of matrix metalloproteinase-9 (MMP-9) expression in malignant and borderline ovarian tumors and its correlation to prognosis. METHODS Forty-five patients with primary epithelial ovarian tumors were enrolled in this retrospective study from 1988 to 2002. Only malignant (n = 30) and borderline (n = 15) ovarian tumors constituted the study group. All cases were surgically staged according to FIGO criteria. Patient characteristics and clinico-pathological findings were obtained from hospital records. Paraffin-embedded tissue blocks were treated with MMP-9 immunohistochemical stain. The percentage of the total number of tumors staining positively was categorised and awarded a score of 0 to 4: < 5% as 0, < or = 6-25% as 1, 26-50% as 2, 51-75% as 3 and 76-100% as 4. The intensity of immunostaining was scored on a 3-point scale: 1, weak; 2, moderate and 3, intense. A weighed score for each tumor specimen was produced by multiplying the percentage score with the intensity score and was defined as the 'epithelial MMP-9 score'. Stromal staining was also assessed as weak, moderate and intense. Cases with final epithelial MMP-9 scores < or = 6 and > 6 were then recategorised into two groups, accordingly. Based on degree of stromal staining, cases were recategorised into two final groups as mildly stained and intense or moderately stained. Tumor stages were regrouped as early (Stage I-II) and late (Stage III-IV), respectively. RESULTS Mean ages of cases with malignant and borderline ovarian tumors were 57.2 +/- 3.1 and 49.7 +/- 2.1 years, respectively. Epithelial MMP-9 scores were higher in malignant tumors compared to borderline tumors (p = 0.014). However, with regard to stromal MMP-9 staining, no significant difference was observed among malignant and borderline tumors (p = 0.113). Among malignant ovarian tumors, epithelial MMP-9 scores did not differ between early versus late-staged and well versus poorly differentiated tumors. Median survival time of cases with epithelial MMP-9 scores < or = 6 and > 6 were 24 months and 32 months, respectively (log-rank: 0.93, p = 0.335). Cases with weak stromal MMP-9 staining had a longer median survival (48 months) compared to cases with moderate or intense stromal MMP-9 staining (24 months, log-rank: 4.46, p = 0.03). CONCLUSION Epithelial MMP-9 expression generally appears in the malignant form of ovarian tumors compared to borderline tumors. MMP-9 expression in the stroma but not in the epithelium contributes to poor survival in ovarian cancers.
Candida spp. bloodstream infection: influence of antifungal treatment on outcome.

OBJECTIVES To assess the influence of new antifungal treatments on candidaemia outcome. METHODS Candidaemia episodes prospectively collected through a blood culture surveillance programme in a single institution. The study was divided into two periods of time, 1994-2003 (A) and 2004-2008 (B), according to the introduction of echinocandin treatment. Non-conditional logistic regression methods with mortality as the dependent variable were used. RESULTS Four hundred and thirty-three (3%) candidaemias out of 15 628 bloodstream infection episodes were analysed. Candida albicans was the most frequent species (211; 49%). Mortality was noted in 132 cases (30%). A total of 262 and 171 candidaemias were reported in period A and B, respectively. There were 94 deaths in period A (36%) and 38 in period B (22%, P = 0.03). Treatment in period A was amphotericin B in 89 patients (41 dead, 46%) and fluconazole in 151 (41 dead, 27%, P = 0.003). In period B, 113 patients received a triazole (26 dead, 23%), 30 an echinocandin (3 dead, 10%, P = 0.08) and 9 (0 dead) were treated with combined therapy (echinocandin and triazole). Mortality was higher in period A (94 dead, 36%) than in period B (38 dead, 27%), P = 0.03. Independent risk factors associated with mortality in period B were: age, chronic renal failure, ultimately or rapidly fatal prognosis of underlying disease and shock. Echinocandin alone or in combination therapy was associated with better outcome (odds ratio = 0.22, 95% confidence interval = 0.06-0.81, P = 0.02). CONCLUSIONS In patients with candidaemia, echinocandin therapy results in a better outcome.
Rapid Identification of UCA1 as a Very Sensitive and Specific Unique Marker for Human Bladder Carcinoma

Purpose: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. Experimental Design: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. Results:UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. Conclusions: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.
Semantic Annotation of Mobile Data for Language Access

Mobile devices both host and collect significant amount of data that could be interesting to users. To make this data easily accessible, it has to be stored in semantic repositories using a well-defined ontology. Relationships between data from various sources should be explicit. Natural language interface to such data is an attractive option for information access. However, there are semantic gaps between the data repositories and the formal representation of meaning produced by language understanding systems. This paper describes a solution to the issues above. We have implemented a system that converts the mobile data into RDF format and annotates it with information necessary for efficient access via natural language. We have designed and implemented Natural Query system that automates the interface of natural language system and the semantic data repository. Language tags are used to map between the natural language meaning representation and the repository elements. Repository graph search is used to discover the knowledge about the repository structure.
Extinct spreading on the Cocos Ridge

Using recently acquired marine magnetic data and existing magnetic and bathymetric data sets together with ODP Leg 170 age determinations we present a revised plate tectonic model for the southern Cocos and northern Nazca plate area. According to this model the formation of the southern Cocos plate was governed by spreading at different ridge axes with alternations between spreading ridges producing a complex magnetic anomaly pattern. In the Cocos and Malpelo ridge area we have identified two precursors of the recently active Cocos–Nacza spreading system which were active from 22.8 to 14.7 Ma, with a change in spreading direction from NW–SE to ENE–WSW at 19.5 Ma. The oceanic crust of these abandoned spreading systems was subsequently thickened and overprinted by hotspot volcanism that formed the Cocos and Malpelo ridges. The centre of this hotspot volcanism is about 500 km away from, but most probably related to, the Galapagos hotspot.
Expression of Multiple Outer Membrane Protein Sequence Variants from a Single Genomic Locus of Anaplasma phagocytophilum

ABSTRACT Anaplasma phagocytophilum is the causative agent of an emerging tick-borne zoonosis in the United States and Europe. The organism causes a febrile illness accompanied by other nonspecific symptoms and can be fatal, especially if treatment is delayed. Persistence of A. phagocytophilum within mammalian reservoir hosts is important for ensuring continued disease transmission. In the related organism Anaplasma marginale, persistence is associated with antigenic variation of the immunoprotective outer membrane protein MSP2. Extensive diversity of MSP2 is achieved by combinatorial gene conversion of a genomic expression site by truncated pseudogenes. The major outer membrane protein of A. phagocytophilum, MSP2(P44), is homologous to MSP2 of A. marginale, has a similar organization of conserved and variable regions, and is also encoded by a multigene family containing some truncated gene copies. This suggests that the two organisms could use similar mechanisms to generate diversity in outer membrane proteins from their small genomes. We define here a genomic expression site for MSP2(P44) in A. phagocytophilum. As in A. marginale, the msp2(p44) gene in this expression site is polymorphic in all populations of organisms we have examined, whether organisms are obtained from in vitro culture in human HL-60 cells, from culture in the tick cell line ISE6, or from infected human blood. Changes in culture conditions were found to favor the growth and predominance of certain msp2(p44) variants. Insertions, deletions, and substitutions in the region of the genomic expression site encoding the central hypervariable region matched sequence polymorphisms in msp2(p44) mRNA. These data suggest that, similarly to A. marginale, A. phagocytophilum uses combinatorial mechanisms to generate a large array of outer membrane protein variants. Such gene polymorphism has profound implications for the design of vaccines, diagnostic tests, and therapy.