Miracle-dz/UniFAR-FTUs huggingface dataset:
Does current scientific and clinical evidence support the use of phosphodiesterase type 5 inhibitors for the treatment of premature ejaculation? a systematic review and meta-analysis.

INTRODUCTION Premature ejaculation (PE) is a highly prevalent and complex syndrome that remains poorly defined and inadequately characterized. Pharmacotherapy represents the current basis of lifelong PE treatment. AIM The goal of this study was to assess the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of patients with PE without associated erectile dysfunction (ED). MAIN OUTCOME MEASURE The posttreatment intravaginal ejaculatory latency time was used as the primary end point of efficacy. METHODS A systematic review of the literature was performed by electronically searching the MedLine database for peer-reviewed articles regarding the mechanism of action and the clinical trials of PDE5 in the management of PE. A meta-analysis of these clinical studies was performed to pool the efficacy. RESULTS Twenty-nine articles that examined the supposed mechanisms of action and 14 articles that reported data from clinical studies were reviewed. The PDE5 may exert their influence by increasing the levels of nitric oxide both centrally (reducing sympathetic drive) and peripherally (leading to smooth-muscle dilatation of the seminal tract). These drugs may also induce peripheral analgesia to prolong the duration of the erection, increase confidence, improve the perception of ejaculatory control and overall sexual satisfaction, and decrease the postorgasmic refractory time for achieving a second erection after ejaculation. Concerning the efficacy, the meta-analysis shows an overall positive effect for the use of PDE5 as monotherapy or as components of a combination regimen in the treatment of PE. The major limitations of the published literature included poor study design, the absence of solid methodology, which was characterized by the lack of a unique PE definition, and the lack of appropriate endpoints for outcome evaluation of a placebo control arm and of Institutional Review Board approval. CONCLUSION There is inadequate, partial basic, and clinical evidence to support the use of PDE5 for the treatment of PE.
Connective tissue growth factor expression in human intervertebral disc: implications for angiogenesis in intervertebral disc degeneration

Intervertebral disc (IVD) degeneration is strongly associated with chronic low back pain, one of the most common causes of morbidity in the West. While normal healthy IVD is avascular, angiogenesis is a constant feature of IVD degeneration and has been shown to be associated with in-growth of nerves. Connective tissue growth factor (CTGF) plays a pivotal role in angiogenesis. To investigate the expression of CTGF in both normal and degenerated IVD, 21 IVDs were obtained from patients at surgery or postmortem examination and grouped according to the severity of histological degeneration. The immunohistochemical expression of CTGF was correlated with the degree of degeneration. CD31 immunohistochemistry was used to correlate IVD degeneration with vasculature. Our results showed that CTGF is expressed in non-degenerated and degenerated human IVDs and increased expression of CTGF is associated with degenerated discs, particularly within areas of neovascularization. We suggest that CTGF may play a role in angiogenesis in the human degenerated IVD.
Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies

Variants identified in recent genome‐wide association studies based on the common‐disease common‐variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare‐variant analysis and refined this design framework for future large‐scale association studies on quantitative traits. We first proposed a power calculation approach for a likelihood‐based analysis method. We then used this approach to demonstrate the potential advantages of extreme phenotype sampling for rare variants. Next, we discussed how this design can influence future sequencing‐based association studies from a cost‐efficiency (with the phenotyping cost included) perspective. Moreover, we discussed the potential of a two‐stage design with the extreme sample as the first stage and the remaining nonextreme subjects as the second stage. We demonstrated that this two‐stage design is a cost‐efficient alternative to the one‐stage cross‐sectional design or traditional two‐stage design. We then discussed the analysis strategies for this extreme two‐stage design and proposed a corresponding design optimization procedure. To address many practical concerns, for example measurement error or phenotypic heterogeneity at the very extremes, we examined an approach in which individuals with very extreme phenotypes are discarded. We demonstrated that even with a substantial proportion of these extreme individuals discarded, an extreme‐based sampling can still be more efficient. Finally, we expanded the current analysis and design framework to accommodate the CMC approach where multiple rare‐variants in the same gene region are analyzed jointly. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc. 35:790‐799, 2011
Multispectral images segmentation using new fuzzy cluster centroid modified

The presence of outliers, noise, corrupt pieces of data and great quantity of samples in a multispectral image, makes the segmentation analysis work tedious. The fuzzy clustering approach, specially, is susceptible to inhomogeneity of characteristics. Furthermore, many algorithms such us FCM, PFCM, FCC, FWCM and modification aim to solve these problems by integrating spacial information. This process is carried through the analysis of the sample's neighborhood. This paper proposes the integration of the sample presence probability into a ”term” like form inside the existent model NFCC. This algorithm presents the basic steps for fuzzy clustering. With a middle variant that integrates the measure between each sample to all the centroids, this replaces the existent term by a new term. This new term integrates the spatial relationship between each sample of the multispectral image into a fitting term. The method is applied to multispectral images. Overall accuracy indicates that the term integrated to NFCC model decrease the overall cluster overlapping.
Contribution of Na+,HCO3−‐cotransport to cellular pH control in human breast cancer: A role for the breast cancer susceptibility locus NBCn1 (SLC4A7)

Genome‐wide association studies recently linked the locus for Na+,HCO3−‐cotransporter NBCn1 (SLC4A7) to breast cancer susceptibility, yet functional insights have been lacking. To determine whether NBCn1, by transporting HCO3− into cells, may dispose of acid produced during high metabolic activity, we studied the expression of NBCn1 and the functional impact of Na+,HCO3−‐cotransport in human breast cancer. We found that the plasmalemmal density of NBCn1 was 20–30% higher in primary breast carcinomas and metastases compared to matched normal breast tissue. The increase in NBCn1 density was similar in magnitude to that observed for Na+/H+‐exchanger NHE1 (SLC9A1), a transporter previously implicated in cell migration, proliferation and malignancy. In primary breast carcinomas, the apparent molecular weight for NBCn1 was increased compared to normal tissue. Using pH‐sensitive fluorophores, we showed that Na+,HCO3−‐cotransport is the predominant mechanism of acid extrusion and is inhibited 34 ± 9% by 200 μM 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid in human primary breast carcinomas. At intracellular pH (pHi) levels >6.6, CO2/HCO3−‐dependent mechanisms accounted for >90% of total net acid extrusion. Na+/H+‐exchange activity was prominent only at lower pHi‐values. Furthermore, steady‐state pHi was 0.35 ± 0.06 units lower in the absence than in the presence of CO2/HCO3−. In conclusion, expression of NBCn1 is upregulated in human primary breast carcinomas and metastases compared to normal breast tissue. Na+,HCO3−‐cotransport is a major determinant of pHi in breast cancer and the modest DIDS‐sensitivity is consistent with NBCn1 being predominantly responsible. Hence, our results suggest a major pathophysiological role for NBCn1 that may be clinically relevant.
Anomalous transport effects on switching currents of graphene-based Josephson junctions

We explore the effect of noise on the ballistic graphene-based small Josephson junctions in the framework of the resistively and capacitively shunted model. We use the non-sinusoidal current–phase relation specific for graphene layers partially covered by superconducting electrodes. The noise induced escapes from the metastable states, when the external bias current is ramped, given the switching current distribution, i.e. the probability distribution of the passages to finite voltage from the superconducting state as a function of the bias current, that is the information more promptly available in the experiments. We consider a noise source that is a mixture of two different types of processes: a Gaussian contribution to simulate an uncorrelated ordinary thermal bath, and non-Gaussian, α-stable (or Lévy) term, generally associated to non-equilibrium transport phenomena. We find that the analysis of the switching current distribution makes it possible to efficiently detect a non-Gaussian noise component in a Gaussian background.
Epigenetic correlates of neonatal contact in humans

Abstract Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.
Co-chemotactic effect of Gc-globulin (vitamin D binding protein) for C5a. Transient conversion into an active co-chemotaxin by neutrophils.

Gc-globulin (vitamin D binding protein) has been shown to augment significantly the leukocyte chemotactic activity of the activated C peptides C5a and C5adesArg (i.e., the co-chemotactic effect). However, the mechanism of chemotaxis enhancement is not known. To investigate the role that the neutrophil plays in this process, cells were co-incubated with Gc-globulin for up to 45 min and washed, and their subsequent chemotactic response to a suboptimal concentration of C5a alone was measured during a 30-min assay. The generation of co-chemotactic activity during the preincubation period was time dependent, showed minimal activity for the first 10 min and a steep rise from 10 to 20 min, and was maximal and stable at 30 min. The binding of radiolabeled Gc-globulin by neutrophils at 37 degrees C mirrored this time-dependent generation of C5a co-chemotactic activity, with stable cellular levels achieved between 30 and 45 min at 36 +/- 4 fmol (2 +/- 0.1 ng)/10(6) cells. The binding of radiolabeled Gc-globulin and the generation of co-chemotactic activity were dependent upon physiologic temperatures (37 degrees C) and levels of Ca2+ (1.3 mM) and Mg2+ (0.8 mM), and were inhibited by an Ab to Gc-globulin. Finally, the C5a co-chemotactic activity of Gc-globulin would decay rapidly if neutrophils were washed and then incubated a second time at 37 degrees C before chemotaxis to C5a. These results demonstrate that neutrophils bind exogenous Gc-globulin and generate C5a co-chemotactic activity in a time-, temperature-, and divalent cation-dependent manner. Moreover, this activity is transient if neutrophils lack a continuous supply of Gc-globulin.
Increased Urinary Angiotensinogen Is Precedent to Increased Urinary Albumin in Patients With Type 1 Diabetes

Background:We previously reported that kidney and urinary angiotensinogen levels were significantly increased before the development of diabetic nephropathy in diabetic rats. To address this system in humans, we have developed an enzyme-linked immunosorbent assay for human angiotensinogen and reported that urinary excretion of angiotensinogen levels is enhanced in patients with chronic kidney disease, including patients with type 2 diabetes. On the basis of these findings, this study was performed to demonstrate that urinary angiotensinogen levels increased before the onset of microalbuminuria and that urinary angiotensinogen can be an early biomarker of intrarenal renin-angiotensin system status in normoalbuminuric patients with type 1 diabetes compared with age- and sex-matched control subjects. Methods:The study included 28 patients with type 1 diabetes and 21 control subjects. No subject received renin-angiotensin system blockades. Random spot urine samples as well as blood samples were obtained and analyzed. Results:Urinary albumin:creatinine ratio or urinary protein:creatinine ratio did not increase in patients compared with control subjects, suggesting that these patients were in their premicroalbuminuric phase of diabetic nephropathy. However, the urinary angiotensinogen:creatinine ratio was significantly higher in patients than in control subjects (12.1 ± 3.2 &mgr;g/g versus 4.2 ± 0.7 &mgr;g/g). Importantly, an increase in plasma angiotensinogen levels was not observed (26.3 ± 1.3 &mgr;g/mL versus 29.5 ± 3.3 &mgr;g/mL). Conclusions:Thus, in patients, an increase in urinary angiotensinogen levels is observed, and this increase is precedent to an increase in urinary albumin levels, suggesting that urinary angiotensinogen may function as an early marker of diabetic nephropathy.
Indexing multimedia databases

The tutorial surveys state-of-the-art methods for storing and retrieving multimedia data from large databases. Records (= documents) may consist of formatted fields, text, images, voice, animation etc. . 4 sample query that we would like to support is ‘in a collection of 2-d color images, find images that are similar to a sunset photograph’. Indexing for images and other media is a new, active area of research; the tutorial will present recent approaches and prototype systems, for 2-d and 3-d medical image databases, 2-d color image databases, and l-d time series databases.
Impact Analysis of Front End Practices in Innovative New Product Development in Japanese Manufacturing Companies

Recently, increased attention has been paid to the front end of New Product Development (NPD). In this paper, we report on the key factors for success with regard to the front end activities of NPD in 513 Japanese companies. We develop and test a causal model of relationships among key variables relating to front end factors and success. The causal model is tested with AMOS using information from 513 completed NPD projects from Japanese manufacturing firms. The results of this study are summarised as follows: First, the more both market uncertainty and technical uncertainties are reduced during the front end, the higher is the effectiveness of NPD projects. Second, the more intensively new projects are planned prior to the start of development, the more both market and technical uncertainties are reduced. Finally, in industry goods firms, it is easy for managers to develop Initial Planning, which has a greater impact on Reduction of Market Uncertainty compared to consumer goods firms. In contrast, as it is very difficult for managers in consumer goods firms to develop an initial plan, managers involve several function members within their project team, and often bring in external resources to reduce market uncertainty
The Psychological Self as Actor, Agent, and Author

The psychological self may be construed as a reflexive arrangement of the subjective “I” and the constructed “Me,” evolving and expanding over the human life course. The psychological self begins life as a social actor, construed in terms of performance traits and social roles. By the end of childhood, the self has become a motivated agent, too, as personal goals, motives, values, and envisioned projects for the future become central features of how the I conceives of the Me. A third layer of selfhood begins to form in the adolescent and emerging adulthood years, when the self as autobiographical author aims to construct a story of the Me, to provide adult life with broad purpose and a dynamic sense of temporal continuity. An integrative theory that envisions the psychological self as a developing I–Me configuration of actor, agent, and author helps to synthesize a wide range of conceptions and findings on the self from social, personality, cognitive, cultural, and developmental psychology and from sociology and other social sciences. The actor–agent–author framework also sheds new light on studies of self-regulation, self-esteem, self-continuity, and the relationship between self and culture.
Assessing physical performance in free-living older adults with a wearable computer

This study investigates the use of a chest-worn wearable computer, the eButton, to assess physical performance of older adults. The Short Physical Performance Battery (SPPB), a standard clinical test, is first conducted on older human subjects. Then, a triaxial accelerometer and a triaxial gyroscope within the eButton are utilized to record acceleration and angular velocity of body motion on the same subjects for one week. The sensor data corresponding to walking episodes are segmented and features in the time and frequency domains are extracted. Comparison between these features and the total SPPB scores shows that the sensor data acquired in free-living conditions can be used as indicators of the subjects physical performance.
Knee range of motion during the first two years after use of posterior cruciate-stabilizing or posterior cruciate-retaining total knee prostheses. A randomized clinical trial.

BACKGROUND The impact of posterior cruciate ligament-substituting and posterior cruciate ligament-retaining devices on the range of motion of the knee following primary total knee arthroplasty is unclear. The primary objective of our study was to compare the range of motion of the knee over the first two postoperative years between subjects who had received the ligament-substituting design and those who had received the ligament-retaining design. Secondarily, pain, function, and health-related quality of life were compared between the two groups. METHODS We undertook a prospective randomized study of 100 patients with noninflammatory osteoarthritis who were undergoing primary total knee arthroplasty. Patients were randomized at the time of surgery to receive one of the two study prosthesis designs. They were evaluated preoperatively, at the time of hospital discharge, at three months postoperatively, and at up to two years postoperatively by a physical therapist who was blinded to the group allocation. Active knee flexion and extension, measured with a goniometer, were the primary outcome measures. Self-reported pain, function, and health-related quality of life were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the RAND 36-Item Health Survey (RAND-36). Complications and revision rates were determined through hospital record review and at each patient evaluation. RESULTS Eighty percent (seventy-eight) of the ninety-eight available patients returned for the final assessment. At two years postoperatively, the mean difference between the groups with regard to knee flexion was 0.03 degrees (95% confidence interval, -5.9 degrees to 6.0 degrees ) and the mean difference in knee extension was 1.0 degrees (95% confidence interval, -0.36 degrees to 2.4 degrees ). Ninety-one (93%) of the ninety-eight available patients completed questionnaires at the time of the final assessment. The two treatment groups had similar pain, function, and quality-of-life scores and complication rates. One subject in the cruciate-retaining group required revision, secondary to a deep joint infection, and one subject in the cruciate-substituting group required manipulation to address poor knee flexion. CONCLUSIONS Overall, the two treatment groups had a similar range of motion of the knee over the initial two-year postoperative time period. A satisfactory range of motion was achieved by three months postoperatively and was maintained at the final assessment.
A Qualitative and Quantitative Interaction Technique for Freehand 3D Ultrasound Imaging

Conventional freehand 3D ultrasound imaging techniques separate the scanning and reconstruction steps from the visualization step. Several approaches that enable real-time volume reconstruction and visualization during acquisition have been described in the literature in recent years. However, these approaches are not fully interactive, since they do not provide sufficient feedbacks on volume reconstruction. In this paper, we present a qualitative and quantitative interaction technique (QAQIT) which can provide accurate feedbacks on volume reconstruction in real time during acquisition. Two threads are designed for data acquisition: one is to acquire B-scan images from the ultrasound scanner sequentially, and the other is to obtain positions and orientations from the position sensor continuously. A matching thread matches the latest acquired image with its relative position and orientation (PAO), and then reconstructs the image into a predefined volume. After the 3D reconstruction of each image, we calculate the reconstructed ratio (RR) and increased ratio (IR) of the reconstruction volume (RV), then update the display of the RR, and drive the volume rendering of the RV according to the IR. A freehand system based on the QAQIT has been developed on a personal computer (PC). We demonstrate our system on an embryo phantom
Rapid HIV Antibody Testing in the New York State Anonymous HIV Counseling and Testing Program: Experience From the Field

Objectives:To assess rapid and conventional HIV test use, client satisfaction, and counselors' comfort. Methods:At 61 HIV test sites in New York State, we compared HIV test use during the first 6 months of rapid testing in 2003 with the same time period in 2002. We administered surveys to clients at each site during the first 30 days of rapid testing and to counselors before and after training and after 12 weeks of using rapid tests in the field. Results:Almost all (1249 [96.5%] of 1294) clients surveyed selected rapid over conventional HIV testing. During the evaluation period, 6187 HIV tests were reported, 1667 (36.9%) more than during the same period in 2002. All 5771 (100%) of 5771 clients received their rapid HIV test results compared with 333 (85.8%) of 388 clients (P < 0.0001) who had elected conventional testing. After performing rapid testing for 12 weeks, 32 (80%) of 40 trained counselors reported feeling “very comfortable” delivering reactive rapid test results compared with 14 (35%) of 40 trained counselors (P < 0.001) before training. Conclusions:Rapid testing presents a key opportunity to increase the number of people undergoing HIV testing and the proportion receiving their test results.