Miracle-dz/UniFAR-FTUs huggingface dataset:
Exclusion of the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1‐linked families

Several linkage studies provided evidence for the presence of the hereditary prostate cancer locus, HPCX1, at Xq27‐q28. The strongest linkage peak of prostate cancer overlies a variable region of ∼750 kb at Xq27 enriched by segmental duplications (SDs), suggesting that the predisposition to prostate cancer may be a genomic disorder caused by recombinational interaction between SDs. The large size of SDs and their sequence similarity make it difficult to examine this region for possible rearrangements using standard methods. To overcome this problem, direct isolation of a set of genomic segments by in vivo recombination in yeast (a TAR cloning technique) was used to perform a mutational analysis of the 750 kb region in X‐linked families. We did not detect disease‐specific rearrangements within this region. In addition, transcriptome and computational analyses were performed to search for nonannotated genes within the Xq27 region, which may be associated with genetic predisposition to prostate cancer. Two candidate genes were identified, one of which is a novel gene termed SPANXL that represents a highly diverged member of the SPANX gene family, and the previously described CDR1 gene that is expressed at a high level in both normal and malignant prostate cells, and mapped 210 kb of upstream the SPANX gene cluster. No disease‐specific alterations were identified in these genes. Our results exclude the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy. Adjacent regions appear to be the most likely candidates to identify the elusive HPCX1 locus. © 2012 Wiley Periodicals, Inc.
microRNAs in acute myeloid leukemia: Expression patterns, correlations with genetic and clinical parameters, and prognostic significance

Acute myeloid leukemia (AML) is a malignant disease of hematopoietic cells whose emergence, course, and prognosis is affected by specific recurrent genetic alterations like chromosome aberrations and point mutations, as well as by changes in the expression of certain genes. In the past 2 years, microRNAs (miRNAs)—a novel class of small RNA molecules involved in posttranscriptional gene regulation—have also been shown to be aberrantly expressed in AML. Furthermore, specific miRNA expression patterns were found to be associated with certain genetic and cytogenetic alterations in this disease, and two studies identified miRNAs whose expression levels were predictive of survival. Interestingly, the results of these analyses showed only very limited congruence. This review summarizes published reports on the expression patterns of miRNAs in AML, and discusses possible reasons for the differences in their results. © 2009 Wiley‐Liss, Inc.
Diffusion-Tensor Imaging at 3 T: Detection of White Matter Alterations in Neurological Patients on the Basis of Normal Values

Objective:Fractional anisotropy (FA) is a powerful measure to study the integrity of the cerebral white matter in vivo. However, because clinical FA assessments are frequently based on single slice evaluations, intra- and interindividual comparisons are highly dependent on image alignment. We attempted to develop an observer-independent, fully automated technique for quantitative FA assessment. Materials and Methods:We employed whole brain diffusion tensor imaging at 3 T with an echo planar imaging sequence (isotropic spatial resolution 1.8 mm) on 4 patients (2× Alzheimer disease, 1× microangiopathy, 1× paraneoplastic disease) and 2 normal control groups (group “young,” age 19–32 years; group “old,” age 59–69 years). The images were spatially normalized to the standard brain template of the Montreal Neurologic Institute. We introduced a fractional anisotropy index (FAI) as a single measure for the mean tissue anisotropy in certain brain regions of interest. The regions of interest were defined by masks in relation to the Montreal Neurologic Institute coordinate space. We varied the spatial extent of the masks. Confidence intervals of the FAIs for both control groups were calculated. Results:We found the resulting FAIs to be highly robust against considerable mask variations (product-moment correlation: r > 0.97). The FAIs of the 4 patients presented with neurologic conditions associated with white matter alterations significantly fell outside the confidence intervals for normal FA. Conclusion:FAIs based on mean fractional anisotropy values obtained from isotropic whole-head high-field diffusion tensor imaging by fully automated algorithms represent a robust and observer-independent measure for the comparative assessment of white matter integrity, ideally suited for further statistical treatments.
Performance investigation of opportunistic routing using log-normal and IEEE 802.15.6 CM 3A path loss models in WBANs

Wireless Body Area Network (WBAN) is a modern technology having a wide range of possible applications. The development scope of WBANs can diverse from hardware and applications design to network performance optimization. Reliability is a vital performance factor in WBANs. Body shadowing, environmental interference and inefficient routing can make a WBAN unreliable, which may severely affect the patient under observation. However, an opportunistic routing technique can improve the reliability via multihops by using opportunistic relays. We investigate the performance of opportunistic routing with two different path loss models for wearable WBANs, i.e., Log-normal path loss model and IEEE 802.15. 6 Channel Model (CM) 3A. The performance metrics for the analysis include network lifetime, Packet Loss Probability (PLP), end-to-end (ETE) delay, and energy used per data packet. By using opportunistic routing with IEEE 802.15. 6 CM 3A in comparison to Log-normal path loss model, reliability and energy efficiency are improved up to 16% and 25% respectively.
Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer.

STUDY OBJECTIVE To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder. DESIGN Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years. SETTING A general university teaching hospital serving both primary and referral patient populations. MEASUREMENTS AND MAIN RESULTS Sera collected prospectively from 1978 to 1980 from 261 patients undergoing imaging studies of the pancreas (ultrasound, computed tomography, endoscopic retrograde cholangiopancreatography) for a variety of symptoms were assayed for CA19-9 levels, and the results were compared with earlier determinations of other potential markers for pancreatic cancer. In 54 patients ultimately shown to have pancreatic cancer, the CA19-9 assay showed a sensitivity of 70% with a median value of 349 u/mL (normal less than 70 u/mL) and range, 7.3 to 2,859,964 u/mL, whereas specificity of the marker in this population was 87%. The positive predictive value was 59%, and the negative predictive value was 92%. Results of CA19-9 testing in the small group of patients with definitive staging information showed no difference in sensitivity between patients with local/regional disease (n = 6) and those with distant metastases (n = 14), 50% compared with 71% (P = 0.613). CONCLUSION CA19-9 was found to be a more sensitive and specific marker of pancreatic cancer than other serologic markers and should be a useful test in the patient with suspected pancreatic disease.
The Kinesthetic and Visual Imagery Questionnaire (KVIQ) for Assessing Motor Imagery in Persons with Physical Disabilities: A Reliability and Construct Validity Study

Purpose: To benefit from mental practice training after stroke, one must be able to engage in motor imagery, and thus reliable motor imagery assessment tools tailored to persons with sensorimotor impairments are needed. The aims of this study were to (1) examine the test-retest reliability of the Kinesthetic and Visual Imagery Questionnaire (KVIQ-20) and its short version (the KVIQ-10) in healthy subjects and subjects with stroke, (2) investigate the internal consistency of both KVIQ versions, and (3) explore the factorial structure of the two KVIQ versions. Methods: The KVIQ assesses on a five-point ordinal scale the clarity of the image (visual: V subscale) and the intensity of the sensations (kinesthetic: K subscale) that the subjects are able to imagine from the first-person perspective. Nineteen persons who had sustained a stroke (CVA group) and 46 healthy persons (CTL group) including an age-matched (aCTL: n = 19) control group were assessed twice by the same examiner 10 to 14 days apart. The test-retest reliability was assessed using intraclass correlation coefficients (ICCs). The internal consistency (Cronbach &agr;) and the factorial structure of both KVIQ versions were studied in a sample of 131 subjects. Results: In the CVA group, the ICCs ranged from 0.81 to 0.90, from 0.73 to 0.86 in the aCTL group, and from 0.72 to 0.81 in the CTL group. When imagining movements of the affected and unaffected limbs (upper and lower limbs combined) ICCs in the CVA group ranged, respectively, from 0.71 to.87 and from 0.86 to 0.94. Likewise, when imagining movement of the dominant and nondominant limbs, ICCs in the aCTL group ranged, respectively, from 0.75 to 0.89 and from 0.81 to.92. Cronbach &agr; values were, respectively, 0.94 (V) and 0.92 (K) for the KVIQ-20 and 0.89 (V) and 0.87(K) for the KVIQ-10. The factorial analyses indicated that two factors explained 63.4% and 67.7% of total variance, respectively. Conclusion: Both versions of the KVIQ present similar psychometric properties that support their use in healthy individuals and in persons post-stroke. Because the KVIQ-10 can be administered in half the time, however, it is a good choice when assessing persons with physical disabilities.
Hypertrophic obstructive cardiomyopathy: the Mayo Clinic experience.

BACKGROUND Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by left ventricular hypertrophy in the absence of other etiologies. Clinical presentation may vary from asymptomatic to sudden cardiac death. Medical treatment is the first-line therapy for symptomatic patients. Extended left ventricular septal myectomy is the procedure of choice if medical treatment is unsuccessful or intolerable. MAYO CLINIC EXPERIENCE More than 3,000 patients have had septal myectomy for HCM at the Mayo Clinic (MN, USA) from 1993 to 2016. Risk of hospital death after isolated septal myectomy for obstructive HCM is <1% and is similar to the risk of operation for elective mitral valve repair. Complications, such as complete heart block requiring permanent pacemaker, are uncommon (2%), although partial or complete left bundle branch block is a frequent finding on the postoperative ECG. Relief of left ventricular outflow tract (LVOT) obstruction with septal myectomy dramatically improves symptoms and exercise capacity in symptomatic patients with obstructive HCM. More than 90% of severely symptomatic patients have improvement by at least two functional classes, and reduction of outflow gradients by myectomy decreases or eliminates symptoms of dyspnea, angina and/or syncope. Basal obstruction with systolic anterior motion (SAM) is treated by transaortic myectomy. The transapical approach was applied in 115 patients with obstructive midventricular and apical variants of HCM between 1993 and 2012. All patients with midventricular obstruction had gradient relief and none developed an apical aneurysm or ventricular septal defect. Recurrent obstruction after satisfactory myectomy was rare. CONCLUSIONS Septal myectomy effectively and definitively relieves LVOT obstruction and cardiac symptoms in patients with obstructive HCM. In experienced centers, early mortality for isolated septal myectomy is less than 1%, and overall results are excellent and continue to improve in the current era.
Locomotor effects of a low-frequency fire alarm on C57BL/6 male mice: a preliminary study

Maintaining appropriate acoustic conditions for animal welfare and data collection are crucial in biomedical research facilities. Negative impacts of disruptive sound are known and can include auditory damage, immune function changes, and behavioral alterations. One type of disruptive sound occurring in research facilities is that of fire alarms. To ameliorate this problem, many facilities have incorporated the use of low-frequency fire alarms that emit tones outside the rodent audible range. The impact of these devices has been assumed to be negligible. However, this has yet to be evaluated with controlled behavioral experiments. Thus, our objective was to investigate the impact of low-frequency fire alarm exposure on locomotor behavior in the open field, a test sensitive to acoustic stimuli disruption. Male mice were randomized to three alarm exposure groups (No-Alarm; Alarm-During; and Alarm-After) and placed in individual photobeam-activated locomotor chambers. The Alarm-During group displayed significantly reduced horizontal locomotion, with a trend towards reduced vertical locomotion. These data suggest that a low-frequency brief alarm tone can temporarily disrupt movement, a valuable insight should an alarm be deployed. Further, findings support close collaboration between researchers and institutional facility staff to ensure appropriate acoustic conditions are maintained, whenever possible, for research animals.
A Positive Association between Leptin and Blood Pressure of Normal Range in Japanese Men

The results of previous studies on the relationship between leptin and blood pressure are discordant. We investigated to what extent the serum leptin level was related to blood pressure independent of the degree of insulin resistance. The subjects were 1,916 men aged 34–69 years whose mean body mass index (BMI) was 23.0 kg/m2. Blood pressure was regressed by leptin concentrations with adjustments for age, BMI, insulin resistance, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, physical activity, drinking habits and smoking status. Leptin was associated with diastolic blood pressure (DBP) (standardized β: 0.092, p=0.003), but not with systolic blood pressure (SBP) (standardized β: 0.035, p=0.25), although insulin resistance was positively associated with both SBP and DBP (standardized β: 0.175 for SBP, p<0.001 and 0.114 for DBP, p<0.001) among all subjects. After subjects were divided into those with normal blood pressure (SBP<130 mmHg and DBP<85 mmHg) and those with higher blood pressure, leptin was positively and significantly associated with DBP (standardized β: 0.106, p=0.012) independent of the degree of insulin resistance, but not with SBP (standardized β: 0.064, p=0.13) among subjects in the normal blood pressure range. Among the subjects with higher blood pressure, however, neither the association of leptin with SBP nor that of leptin with DBP was statistically significant. These findings suggest that leptin may maintain and increase arterial tone, resulting in the elevation of DBP only within normal blood pressure range. It is also likely that leptin is a physiological mediator—or at least a marker—of some degree of DBP elevation in obesity.
The in vitro study of Her-2 targeted gold nanoshell liquid fluorocarbon poly lactic-co-glycolic acid ultrasound microcapsule for ultrasound imaging and breast tumor photothermal therapy

Abstract Antibody-mediated targeting therapy has been successful in treating patients with breast cancer by improving the specificity and clinical efficacy. In this study, we constructed the human epidermal growth factor receptor-2 (Her2) antibody-conjugated ultrasound contrast agent with lactic-co-glycolic acid (PLGA) as film forming and perfluorocty bromide (PFOB) as internal material, which was coated by gold nanoshell (Her2-PFOB@PLGA@Au), to realize the integration of diagnosis and treatment. The contrast agent was spherical, with the diameter was 256.8 ± 53.4 nm, and had a good dispersion; Ultrasound imaging experiments in vitro showed that the gold nanoshell polylactic acid microcapsule was suitable for ultrasound contrast imaging with the exquisite and uniform dot intensive high echo. The agent had a great photothermal effect under the near-infrared (NIR) with no obvious biological toxicity for both Her2-positive and negative tumor cells; Moreover, both the results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) demonstrated the great specificity of Her2-PFOB@PLGA@Au conjugating with Her2 positive breast cancer cells (SKBR3). In conclusion, the successful synthesis of the Her2-PFOB@PLGA@Au microcapsule, offered a new therapeutic strategy of combining diagnosis with therapy for fighting against the breast cancer.
Quantitative Analyses of Force-Induced Amyloid Formation in Candida albicans Als5p: Activation by Standard Laboratory Procedures

Candida albicans adhesins have amyloid-forming sequences. In Als5p, these amyloid sequences cluster cell surface adhesins to create high avidity surface adhesion nanodomains. Such nanodomains form after force is applied to the cell surface by atomic force microscopy or laminar flow. Here we report centrifuging and resuspending S. cerevisiae cells expressing Als5p led to 1.7-fold increase in initial rate of adhesion to ligand coated beads. Furthermore, mechanical stress from vortex-mixing of Als5p cells or C. albicans cells also induced additional formation of amyloid nanodomains and consequent activation of adhesion. Vortex-mixing for 60 seconds increased the initial rate of adhesion 1.6-fold. The effects of vortex-mixing were replicated in heat-killed cells as well. Activation was accompanied by increases in thioflavin T cell surface fluorescence measured by flow cytometry or by confocal microscopy. There was no adhesion activation in cells expressing amyloid-impaired Als5pV326N or in cells incubated with inhibitory concentrations of anti-amyloid dyes. Together these results demonstrated the activation of cell surface amyloid nanodomains in yeast expressing Als adhesins, and further delineate the forces that can activate adhesion in vivo. Consequently there is quantitative support for the hypothesis that amyloid forming adhesins act as both force sensors and effectors.
Cathepsin D versus Other Prognostic Factors in Breast Cancer. Results and Controversies of a Multicenter Study on 2575 Cases

The aim of this study was the survey of cathepsin D determination in a large group of patients enrolled at several centers, under the coordination of the Italian Committee for Quality Control in the Oncological Laboratory. Cathepsin D was measured with the same method-ology, under control of an intra and interlaboratory quality control program, in order to verify the comparability of cathepsin D results from different institutions and to analyze the frequency of cathepsin D positive cases in subgroups of patients stratified according to other prognostic parameters. This retrospective study included 2575 patients with primary breast cancer evaluat-ed in 10 institutions. Cytosol from tumor tissue was the substrate for biochemical cathepsin D, estrogen receptor and progesterone receptor determination, with an interlaboratory quality control survey provided by the E.O. R.T. C. Receptor Group and the Italian Committee for Quality Control in the Oncological Laboratory. The results of the present study can be summarized as follows: 1) Cathepsin D is independent of menopausal status; 2) In spite of standardization of tissue handling and assay methods, different results may be obtained by different institutions. It is therefore essential that each laboratory calculates its own positive/negative cutoff values prior to any routine clinical use of the parameter. This should be a serious consideration when a multicenter study is planned.
Grade 2 Chondrosarcoma: Stage I or Stage II Tumor?

We analyzed chondrosarcomas of bone to assess whether Grade 2 tumors are more appropriately grouped with Grade 1 chondrosarcomas or Grade 3 and dedifferentiated chondrosarcomas (Musculoskeletal Tumor Society Stage I or Stage II). A retrospective chart review identified 109 patients who presented with nonmetastatic chondrosarcoma. Data were gathered on each tumor’s histologic grade, extent (intracompartmental versus extracompartmental), resection margin status, and site (axial versus appendicular). The cohort included 60 males and 49 females with a mean age of 50 years. Forty tumors were located in the axial skeleton and the remainder were distributed throughout the appendicular skeleton. Fifty-three tumors were Grade 1, 40 tumors were Grade 2, eight tumors were Grade 3, and eight tumors were dedifferentiated. Statistical analysis established grade as the only significant variable for this group of patients; extracompartmental tumor spread also correlated with outcome, but not independent of the grade. Margin status and site were not statistically significant with respect to outcome. Chi-square analysis also established that Grade 2 tumors are grouped more appropriately with the Grade 1 chondrosarcomas as Musculoskeletal Tumor Society Stage I neoplasms. These data should be considered when developing the surgical plan, particularly for patients with Grade 2 appendicular chondrosarcomas.
Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies

The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO2 max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD −0.52, 95% CI −0.89 to −0.16; p<0.01) and fasting glucose (SMD −0.35, 95% CI −0.62 to −0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD −0.20, 95% CI −0.38 to −0.01; p<0.05), % body fat (SMD −0.40, 95% CI −0.74 to −0.06; p<0.05), VO2 max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD −0.33, 95% CI −0.56 to −0.09; p<0.01), systolic blood pressure (SMD −0.35, 95% CI −0.60 to −0.09; p<0.01) and DBP (SMD −0.38, 95% CI −0.65 to −0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO2 max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO2 max and improve some cardiometabolic risk factors in overweight/obese populations.