Conclusions: The 10 major research hot spots could provide some h

Conclusions: The 10 major research hot spots could provide some hints for researchers when launching new projects. The output of research on Internet health information seeking behavior is gradually increasing. Compared to the United States, the relatively small number of publications indexed by PubMed from other developed and developing countries indicates to some extent that the field might be still underdeveloped

in many countries. More studies on Internet health information Erismodegib seeking behavior could give some references for health information providers.”
“Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens

present in the saliva from the biting midges, Culicoides ssp, and BGJ398 chemical structure occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly

polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p(raw)=2.34×10(-5)), with the same allele (COR112:274) https://www.selleckchem.com/products/DAPT-GSI-IX.html associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p=0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.

In this review, we describe recent advances in our understanding

In this review, we describe recent advances in our understanding of microRNA function GW4869 price at synapses, the specialized

structures required for communication between neurons and their targets. We also propose how these advances might inform the molecular model of memory. [BMB reports 2009; 42(3): 131-135]“
“Introduction: This study describes the results of the Belgian ‘MabThera In Rheumatoid Arthritis (MIRA)’ registry: effectiveness, safety and evaluation of the current retreatment practice on the background of the Belgian reimbursement criteria for rituximab.\n\nMethods: All Belgian rheumatologists had the possibility to participate in the study. Patients entered the registry in November 2006 and the entry is still open.\n\nResults: By mid-September 2009, 401 patients had entered the registry with a mean follow-up time of 70 weeks. Overall, DAS28-ESR decreased from 6.0 at baseline to 4.2 at week 16. Further decrease of disease activity was observed at the end of year 1 and year 2 with mean DAS28-ESR of 4.0 and 3.7 at these respective time points. More than 80% of patients showed a EULAR response at week 16. Patients could be retreated if they had DAS scores of > 3.2 at least 6 months https://www.selleckchem.com/products/bromosporine.html after the previous course. Second and third courses were given in 224 and 104 patients, respectively. At month 6 after the second course, significantly lower DAS28-ESR

values were observed compared to the first course. This was especially the case for patients who were retreated before they showed an obvious flare (DAS increase > 1.2).\n\nConclusions: This study describes the follow-up of a daily clinical practice cohort of 401 RA patients with long-standing refractory disease treated with rituximab. Relatively high DAS28 values at the start of each retreatment, compared to values 6 months after each treatment course, were noted. Moreover, further decrease of DAS28 scores after the second course was significantly Rabusertib cost more pronounced in those patients who

didn’t show an obvious flare. These two elements suggest that treatment of RA patients with rituximab could be optimized by earlier retreatment.”
“Ubidecarenone (coenzyme Q10) has been widely used as a complementary therapy in heart failure and as a dietary supplement for over two decades. Ubidecarenone is manufactured by organic synthesis, yeast (non-Saccharomyces cerevisiae) fermentation, or bacteria fermentation. There are many reports on the safety of ubidecarenone. However, genotoxicity of ubidecarenone manufactured by bacteria fermentation has not been reported. We carried out genotoxicity evaluation of ubidecarenone manufactured by bacteria fermentation through the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the Japanese guidelines oil genotoxicity testing of pharmaceuticals and the Organization for Economic Co-operation and Development (OECD) guidelines for testing chemicals.


“Streptococcus agalactiae, or group B Streptococcus (GBS),


“Streptococcus agalactiae, or group B Streptococcus (GBS), is an important opportunistic pathogen that causes pneumonia, sepsis, and meningitis in neonates and severe diseases in immunocompromised adults. We have performed

comparative genomics of prevalent GBS serotypes of Indian origin (i.e. Ia, III, V, and VII). Pilus-proteins were commonly found up-regulated, and their expression was studied by using antiserum for GBS80 (backbone protein of pilus island-I), GBS67 (ancillary protein of PI-2a), and SAN1518 (backbone protein of PI-2b) by whole cell and Western blot analysis. To check the role of pilus proteins in adherence and invasion, an inhibition assay was performed. Comparative immunoblotting experiments revealed that expression of pili proteins does not differ in geographically different 3-MA concentration selected serotypes, Ia and V, of India and the United States. In the case of A549 cells, we found that GBS VII invasion and adherence was inhibited by pilus protein-specific antiserum SAN1518 significantly (p < 0.001) by 88.5 and 91%, respectively. We found that mutant strains, deficient in the pilus proteins (Delta gbs80 and Delta san1518) exhibit a significant decrease in adherence in the case of type Ia, III, and VII. In the

case of type VII, we have found a 95% reduction in invasion when Delta san1518 was used with A549 cells. Because the pilus proteins were identified previously as vaccine candidates against GBS serotypes of developed CAL101 countries, we also found their role in the attachment and invasion VX-680 of GBS of Indian origin. Thus, the present work supports the idea of making a more effective pilus protein-based vaccine that can be used universally.”
“A three-marker C-A-T dysbindin haplotype identified by Williams et al (PMID: 15066891) is associated with increased risk for schizophrenia, decreased

mRNA expression, poorer cognitive performance, and early sensory processing deficits. We investigated whether this same dysbindin risk haplotype was also associated with structural variation in the gray matter volume (GMV). Using voxel-based morphometry, whole-volume analysis revealed significantly reduced GMVs in both the right dorsolateral prefrontal and left occipital cortex, corresponding to the behavioral findings of impaired spatial working memory and EEG findings of impaired visual processing already reported. These data provide important evidence of the influence of dysbindin risk variants on brain structure, and suggest a possible mechanism by which disease risk is being increased. Neuropsychopharmacology (2010) 35, 368-373; doi: 10.1038/npp.2009.140; published online 30 September 2009″
“Human leukocyte antigen (HLA) phenotype DQ2 is considered the most important genetic marker for un-responsiveness to hepatitis B vaccine.

Six other calves were histologic and immunohistochemical controls

Six other calves were histologic and immunohistochemical controls. In the LVAD group, the pulsatility index was significantly lower (0.28 +/- 0.07 LVAD vs 0.56 +/- 0.08 RVAD, vs 0.53 +/- 0.10 TAH; P < 0.01), and we observed severe periarteritis in all cases in the LVAD group. The number of angiotensin II type 1 receptor-positive cells and angiotensin converting enzyme-positive cells in periarterial areas was significantly higher in the LVAD group ( angiotensin II type 1 receptor: 350 +/- 139 LVAD vs 8 +/- 6 RVAD, vs 3 +/- 2 TAH, vs 3

+/- 2 control; P < .001; angiotensin-converting enzyme: 325 +/- 59 LVAD vs 6 +/- 4 RVAD, vs 6 +/- 5 TAH, vs 3 +/- 1 control; P <.001).\n\nConclusions: The reduced pulsatility produced by a continuous Selleck C59 wnt flow LVAD implantation induced severe periarteritis in the kidneys. The local renin-angiotensin system

was up-regulated in the inflammatory cells only in the continuous flow LVAD group.”
“Background: Information on the occurrence of zinc finger protein motifs in genomes is crucial to the developing field of molecular genome engineering. The knowledge of their target DNA-binding sequences is vital to develop chimeric proteins for targeted genome engineering and site-specific gene correction. There is A-1155463 price a need to develop a computational resource of zinc finger proteins (ZFP) to identify drug discovery the potential binding sites and its location, which reduce the time of in vivo task, and overcome the difficulties in selecting the specific type of zinc finger protein and the target site in the DNA sequence.\n\nDescription:

ZifBASE provides an extensive collection of various natural and engineered ZFP. It uses standard names and a genetic and structural classification scheme to present data retrieved from UniProtKB, GenBank, Protein Data Bank, ModBase, Protein Model Portal and the literature. It also incorporates specialized features of ZFP including finger sequences and positions, number of fingers, physiochemical properties, classes, framework, PubMed citations with links to experimental structures (PDB, if available) and modeled structures of natural zinc finger proteins. ZifBASE provides information on zinc finger proteins (both natural and engineered ones), the number of finger units in each of the zinc finger proteins (with multiple fingers), the synergy between the adjacent fingers and their positions. Additionally, it gives the individual finger sequence and their target DNA site to which it binds for better and clear understanding on the interactions of adjacent fingers. The current version of ZifBASE contains 139 entries of which 89 are engineered ZFPs, containing 3-7F totaling to 296 fingers. There are 50 natural zinc finger protein entries ranging from 2-13F, totaling to 307 fingers.

05), and depression (P <0 001) and in particular, in women wit

05), and depression (P <0.001) and in particular, in women with coexistence anxiety and depression (P <0.001) compared with unaffected participants.

Compared with the non-depressed PCOS patients, the depressed women had significantly higher menstrual irregularities (P = 0.008). Moreover, we found significant difference in FAI level between the depressed and non depressed (p = 0.05), the anxious and non anxious patients (p < 0.001) compare to non affected PCOS check details women.\n\nConclusions: The high prevalence of depression and anxiety in this population suggests that initial evaluation of all women with PCOS should also include assessment of mental health disorders. The clinician should further pay attention to background of their patients especially in view of the factors influencing psychological well-being.”
“During the process of degenerative aging of the intervertebral disc (IVD), the extracellular matrix (ECM) environment changes, with osmolarity and oxygen (O(2)) concentration important components

of such changes. The IVD cells respond to maintain the homeostasis and function of the IVD by several mechanisms. Aquaporin-1 (AQP-1) is a transmembrane channel protein that is permeable to water and O(2), which prevents rapid volume deformation under osmotic stress and facilitates O(2) diffusion across the plasma membrane. One hypothesis is that AQP-1 has potential roles in aging degeneration of IVDs.\n\nIn this study, AQP-1 expression levels were investigated in aging rabbit nucleus KU-57788 concentration pulposus (NP) LDK378 cells using immunohistochemistry and Western blotting in vivo, and different osmolarities and O(2) concentrations

in vitro by quantitative real-time PCR.\n\nThe results showed that AQP-1 was expressed at different levels in aging rabbit’s NPs and AQP-1 was regulated by the NP cells in different ECM environmental conditions. AQP-1 was downregulated under hypo-osmotic stress to prevent rapid swelling deformation and was upregulated under hypoxic stress to facilitate O(2) utilization.\n\nIt is suggested that AQP-1 may reflect the status of aged IVDs and have a potential role in reflecting the adaptability of NP cells under different adverse ECM environments in aging degenerated IVDs.”
“Cells regulate gene expression at multiple levels leading to a balance between robustness and complexity within their proteome. One core molecular step contributing to this important balance during metazoan gene expression is RNA editing, such as the co-transcriptional recoding of RNA transcripts catalyzed by the adenosine deaminse acting on RNA (ADAR) family of enzymes. Understanding of the adenosine-to-inosine RNA editing process has been broadened considerably by the next generation sequencing (NGS) technology, which allows for in-depth demarcation of an RNA editome at nucleotide resolution.

Both larger size and a non-burrowing habit independently increase

Both larger size and a non-burrowing habit independently increased susceptibility to colonization. In 2005, over 50% of the final instars of the sprawlers Didymops transversa and Hagenius brevistylus were colonized, as well as younger instars. Rarely colonized were Progomphus obscurus and Dromogomphus

spinosus, whose larvae burrow under sand, and the sprawler Epitheca princeps, whose final instars were lightly covered with sand. Hagenius larvae that had been preyed upon carried more mussels than those dying of other causes. More generally, mussel attachment decreased the probability that sprawlers left the water to emerge, the distance that some species traveled before emerging, and the ability of an overturned sprawler to right itself. On average, final instars of Didymops and Hagenius remaining in the water carried three times as many mussels as individuals known to emerge. Compared see more to uncolonized individuals, Epitheca and Progomphus with mussels emerged closer to the water line. Among colonized Didymops, the distance traveled on land before emerging decreased with increasing mussel load. Of the colonized Didymops that could right themselves, righting time increased with mussel load. Because the two BI-D1870 molecular weight common species of sprawlers were disproportionately colonized,

and mussel attachment decreased their chances of emerging, our results suggest that D. polymorpha has the potential to affect the community structure of this guild of aquatic and terrestrial predators.”
“Despite recent advances in treatment modalities, the survival rate of patients with lung cancer has not significantly improved. Therefore, new avenues are being explored in the era of evolving FRAX597 in vivo personalized patient management by early detection. Cytology is now the, mainstay to address the diagnostic needs of pulmonary malignancies. Cytology specimens deliver diagnostic results equivalent to tissue biopsies. Fine-needle aspirations are equally useful to perform diagnostic, predictive, and prognostic immunohistochemical markers and molecular analysis: This article reviews the main new technologies that produced this

revolution. The new role of the cytopathologist in this time of interdisciplinary care is also discussed.”
“Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were “anti-inflammatory agents,” ” Clusiaceae,” and “animals, laboratory.” Results.

01) or 60-386 ng/L (p = 0 03) We conclude that elevated levels o

01) or 60-386 ng/L (p = 0.03). We conclude that elevated levels of neurofilament light in cerebrospinal fluid collected at diagnostic lumbar puncture were associated with unfavourable prognosis. These data suggest that the neurofilament light level could be used as a prognostic marker in early relapsing-remitting

multiple sclerosis.”
“A highly transparent and physically robust step-Al-doped MoO3 layer was successfully utilized as the interconnection layer (ICL) to fabricate high-efficiency inverted tandem polymer solar cells (PSCs). The inverted tandem cell constructed by the same PCDTBT:PC70BM active layer showed a power conversion efficiency (PCE) of 6.88% with equivalent www.selleckchem.com/products/nu7026.html external quantum efficiency of nearly 80%, implying a high charge-collection efficiency in tandem structure. Incorporation of two sub-cells with complementary absorption spectra leads to further increase of PCE over 7.31%, which is the best results

for tandem PSCs with PEDOT:PSS-free interconnection layer. (C) 2013 Elsevier B.V. All rights reserved.”
“Background: Whether older adults with sarcopenia who underperform controls on tests of physical performance and cognition also have a higher likelihood of combined cognitive-physical impairment is not clear. We assessed the impact of sarcopenia on impairment in both aspects of functionality Compound C solubility dmso and the relative contribution of its components, muscle mass and strength. Methods: Two hundred and twenty-three community-dwelling adults aged 40 years and older (mean age = 68.1 +/- 10.6 years; 65% female) were recruited and underwent physical functionality, anthropometry,

and cognitive testing. Participants with low muscle mass were categorized as pre-sarcopenic; those with low muscle mass and muscle strength as sarcopenic; those with higher muscle mass and low muscle strength only were categorized as non-sarcopenic and were compared on risk of cognitive impairment (Montreal Cognitive Assessment. 26; Ascertaining Dementia 8. 2), physical impairment (Mini Physical Performance Test. 12), both, or neither by ordinal logistic regression. Results: Compared to controls, those with sarcopenia were six times more likely AZD5363 datasheet to have combined cognitive impairment/physical impairment with a fully adjusted model showing a three-fold increased odds ratio. The results were consistent across different measures of global cognition (odds ratio = 3.46, 95% confidence interval = 1.07-11.45 for the Montreal Cognitive Assessment; odds ratio = 3.61, 95% confidence interval = 1.11-11.72 for Ascertaining Dementia 8). Pre-sarcopenic participants were not different from controls. The effect of sarcopenia on cognition is related to low muscle strength rather than low muscle mass.

C-films offered different filmogenic properties, proving to be pr

C-films offered different filmogenic properties, proving to be promising biodegradable packaging materials. (C) 2013 Elsevier Ltd. All rights reserved.”
“Lead-free piezoelectric (K,Na)(Nb,Ta)O-3 thin films were prepared by chemical solution deposition. Perovskite single-phase (K-0.5-Na-0.5)(Nb0.8Ta0.2)O-3 and Mn-doped (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films were successfully

fabricated at 600 degrees C on Pt/TiOx/SiO2/Si substrates by controlling the excess amounts of K and Na, and Mn by doping. The (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films showed poor ferroelectric polarizations due to the insufficient insulating resistance at room temperature. The leakage current density of the (K0.5Na0.5)(Nb0.8Ta0.2)O-3 films, especially in the high-applied-field region, was markedly reduced by doping with a small amount of Mn. Also, the ferroelectric properties of the (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films were markedly improved by Mn doping. 0.5 and 1.0 mol% Mn-doped Ulixertinib nmr (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films exhibited well-shaped ferroelectric polarization-electric field (P-E) hysteresis loops at room temperature. The remanent polarization (P-r) and coercive field (E-c) values of the 0.5

and 1.0 mol% Mn-doped (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films at 1 kHz were approximately 14 and 21 mu C/cm(2), and 111 and 86 kV/cm, respectively. Furthermore, these films showed a typical field-induced butterfly loop, and the estimated effective d(33) values were 58 pm/V for the 0.5 mol% Mn-doped (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films www.selleckchem.com/products/ly333531.html and 41 pm/V for the 1.0 mol% Mn-doped (K0.5Na0.5)(Nb0.8Ta0.2)O-3 thin films. (C) 2010 The Japan Society of Applied Physics”
“A recent find of an articulated skeleton of Silesaurus opolensis at its early Late Triassic type locality Krasiejow (Poland), with skull, neck, pectoral girdle, and thorax, supplemented by additional preparation of previously collected articulated specimens, enables complete restoration of the vertebral column and associated skeletal parts. Cervical ribs of Silesaurus, well preserved in their original disposition, NSC23766 in vitro are parallel to the neck and extend backward for a few vertebral lengths. There is a sudden change in their morphology

behind the seventh vertebra, although otherwise the transition from the cervical to the dorsal vertebrae is very gradual. Parapophyses slowly migrate upward along the anterior margin of the centrum and leave the centrum at the sixth or seventh dorsal vertebra. Narrowing of the dorsal extremities of the neural spines of the fourth and neighboring vertebrae suggests the ability of this region of the vertebral column to bent upward. There is thus a disparity between the structural and functional neck-thorax transition. The presence of three sacrals firmly connected by their ribs with the ilia and the long tail of Silesaurus, providing a counterbalance to the weight of the body in front of the pelvis, suggests the ability for fast bipedal running.

4% of the tumors by pyrosequencing (PS) and MSP methods, respecti

4% of the tumors by pyrosequencing (PS) and MSP methods, respectively. RASSF1A methylation evaluated by the two methods

Napabucasin mouse was more frequent in ever-smokers and tumors with TP53 mutation than in never-smokers and tumors without TP53 mutation, respectively. Univariate and multivariate analyses revealed that strong methylation was an unfavorable prognostic factor with stage I (adjusted HR, 2.25; 95% CI 1.03-4.90; P=0.003) and squamous cell carcinoma patients (adjusted HR=2.2:5, 95% CI 1.03-4.90, P=0.042). Taken together, these results suggested that quantitative PS could gain wider applications in clinical samples as a promising method for early detection screening and prognosis compared with MSP.”
“Necrotizing fasciitis is a life-threatening soft-tissue infection of bacterial origin, which involves mainly the deep fascia. Early recognition of this condition may be hampered by the uncommon nature of the disease and non-specificity of initial clinical signs and symptoms in less fulminant cases, making the role of imaging important. MRI is the most useful imaging modality in the diagnosis of necrotizing fasciitis. The presence of thick (>3 mm) hyperintense signal in the deep fascia (particularly intermuscular fascia) on fat-suppressed T-2 weighted or short tau inversion-recovery Metabolism inhibitor images is an important marker for necrotizing fasciitis. Contrast enhancement of the thickened necrotic fascia can be variable, with a mixed-pattern of

enhancement being more commonly encountered. Involvement SN-38 concentration of multiple musculofascial compartments increases the likelihood of necrotizing fasciitis. It is important to remember that T-2-hyperintense signal in the deep fascia is not specific to necrotizing fasciitis

and can also be seen in cases such as non-infective inflammatory fasciitis or muscle tear. In this pictorial essay, we aim to review the MRI findings in necrotizing fasciitis, discuss its limitations and pitfalls and identify differentiating features from non-necrotizing soft-tissue infections, such as cellulitis and infective myositis/pyomyositis, conditions which may clinically mimic necrotizing fasciitis.”
“Osteoclasts acidify bone resorption lacunae through proton translocation by plasma membrane V-ATPase (vacuolar-type ATPase) which has an alpha 3 isoform, one of the four isoforms of the trans-membrane a subunit (Toyomura et al., J. Biol. Chem., 278,22023-22030,2003). d2, a kidney- and epididymis-specific isoform of the d subunit, was also induced in osteoclast-like cells derived from the RAW264.7 line, and formed V-ATPase with a3. The amount of d2 in osteoclasts was 4-fold higher than that of d1, a ubiquitous isoform. These results indicate that V-ATPase with d2/alpha 3 is a major osteoclast proton pump. Essentially the same results were obtained with osteodasts derived from mouse spleen macrophages. Macrophages from alpha 3-knock-out mice could differentiate into multi-nuclear cells with osteoclast-specific enzymes.

392) The aneurysm dome size showed a negative linear

392).\n\nThe aneurysm dome size showed a negative linear

correlation with intra-aneurysmal flow velocity and WSS. CAL-101 Wide-necked aneurysm geometry was associated with faster intra-aneurysmal flow velocity.”
“Penile precancerous and invasive lesions exhibit a variegated morphology. Although the diagnosis and classification of penile tumors is straightforward in most cases, a few entities are problematic, especially to pathologists from countries in which penile cancer is rarely encountered. The differential diagnosis of squamous hyperplasias from differentiated penile intraepithelial neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic and verrucous carcinomas) may be particularly https://www.selleckchem.com/products/VX-680(MK-0457).html difficult. Similarly, given the morphologic features shared by all verruciform tumors (ie, verrucous, warty, papillary, and cuniculatum carcinomas, along with giant condylomas), it is challenging at times to distinguish one from another. At the other end of the spectrum, because of their lack of differentiation, it is sometimes difficult to classify high-grade carcinomas, such as basaloid and sarcomatoid,

which may have etiologic/prognostic implications. Penile mixed tumors, harboring more than 1 histologic subtype and grade, constitute a frequent finding in routine pathology. The recognition of distinctive morphologic patterns and histologic grades in these tumors is important because these features could be related to etiologic factors, such as human papillomavirus infection, or they could influence outcome. Penile tumors with glandular features (eg,

adenosquamous and mucoepidermoid carcinomas), although rare, may be confused with ARN-509 solubility dmso the more common pseudoglandular (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker. In this review we provide clues that may help in the differential diagnosis of these lesions. (C) 2012 Elsevier Inc. All rights reserved.”
“Diagnostic accuracy can be improved considerably by combining multiple biomarkers. Although the likelihood ratio provides optimal solution to combination of biomarkers, the method is sensitive to distributional assumptions which are often difficult to justify. Alternatively simple linear combinations can be considered whose empirical solution may encounter intensive computation when the number of biomarkers is relatively large. Moreover, the optimal linear combinations derived under multivariate normality may suffer substantial loss of efficiency if the distributions are apart from normality. In this paper, we propose a new approach that linearly combines the minimum and maximum values of the biomarkers. Such combination only involves searching for a single combination coefficient that maximizes the area under the receiver operating characteristic (ROC) curves and is thus computation-effective.