ES2524669T3 - Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos - Google Patents
Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos Download PDFInfo
- Publication number
- ES2524669T3 ES2524669T3 ES08850110.1T ES08850110T ES2524669T3 ES 2524669 T3 ES2524669 T3 ES 2524669T3 ES 08850110 T ES08850110 T ES 08850110T ES 2524669 T3 ES2524669 T3 ES 2524669T3
- Authority
- ES
- Spain
- Prior art keywords
- pro
- hepcidin
- septicemia
- sepsis
- subject
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010040047 Sepsis Diseases 0.000 title abstract description 20
- 238000000034 method Methods 0.000 title abstract description 3
- 208000013223 septicemia Diseases 0.000 title description 14
- 239000000090 biomarker Substances 0.000 title description 2
- 238000003745 diagnosis Methods 0.000 title 1
- 238000004393 prognosis Methods 0.000 title 1
- 102000018511 hepcidin Human genes 0.000 abstract description 8
- 108060003558 hepcidin Proteins 0.000 abstract description 8
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- 102100036284 Hepcidin Human genes 0.000 abstract 3
- 101001021253 Homo sapiens Hepcidin Proteins 0.000 abstract 3
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 abstract 2
- XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 abstract 1
- 229940066919 hepcidin Drugs 0.000 abstract 1
- 238000003066 decision tree Methods 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 102100031051 Cysteine and glycine-rich protein 1 Human genes 0.000 description 1
- 241000288113 Gallirallus australis Species 0.000 description 1
- 101001082142 Homo sapiens Pentraxin-related protein PTX3 Proteins 0.000 description 1
- 102100036836 Natriuretic peptides B Human genes 0.000 description 1
- 101710187802 Natriuretic peptides B Proteins 0.000 description 1
- BFHAYPLBUQVNNJ-UHFFFAOYSA-N Pectenotoxin 3 Natural products OC1C(C)CCOC1(O)C1OC2C=CC(C)=CC(C)CC(C)(O3)CCC3C(O3)(O4)CCC3(C=O)CC4C(O3)C(=O)CC3(C)C(O)C(O3)CCC3(O3)CCCC3C(C)C(=O)OC2C1 BFHAYPLBUQVNNJ-UHFFFAOYSA-N 0.000 description 1
- 102100027351 Pentraxin-related protein PTX3 Human genes 0.000 description 1
- 108091006374 cAMP receptor proteins Proteins 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
- C07K17/02—Peptides being immobilised on, or in, an organic carrier
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/26—Infectious diseases, e.g. generalised sepsis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Un procedimiento para el diagnóstico de septicemia en un sujeto o de distinción entre una afección de septicemia y SRIS en un sujeto que comprende: (a) medir el nivel de pro-hepcidina (pro-HEPC) en una muestra de sangre tomada de dicho sujeto; y (b) comparar dicho nivel de pro-5 hepcidina (pro-HEPC) con un nivel de referencia de pro-hepcidina (pro-HEPC) obtenido de un paciente que tiene septicemia, SIRS o de un sujeto sano, por medio de lo que un incremento de la cantidad de pro-hepcidina en la muestra a un nivel más alto que el intervalo de un valor normal de pro-hepcidina es indicativo de septicemia, o por medio de lo que una cantidad comparable de pro-hepcidina en dicha muestra al intervalo de los valores de pro-hepcidina en sujetos con septicemia es indicativo de septicemia.
Description
E08850110
24-11-2014
- Tabla 3: Conjunto de datos de las medidas de ELISA (conc. en ng/ml)
- Marcador
- PCT CRP sTNFR2 PTX-3 M-CSF Pro-HEPC pro-BNP
- Paciente
- Clase X4 X2 X5 X3 X1
- HGE67
- SEPTICEMIA 128,5 369 12,25 54,015 5,91 52,62 9,84
- UGE22
- SEPTICEMIA 226,1 224 9,59 72,085 2,727 138,19 18,21
- HGE74
- SEPTICEMIA 5,2 335 6,82 17,937 2,022 73,9 3,86
- UGE41
- SEPTICEMIA 4,5 347 7,89 15,945 3,62 105,78 5,71
- UGE10
- SEPTICEMIA 27,37 197 11,1 26,519 1,17 133,27 21,46
- UGE14
- SEPTICEMIA 51,00 297 9,96 53,807 5,69 155,26 9,13
- UGE50
- SEPTICEMIA 23,43 288 15,74 40,763 * 62,32 0,00
- HGE73
- SEPTICEMIA 46,70 225 4,3 16,94 1,19 82,69 4,68
- UGE45
- SEPTICEMIA 9,33 247 5,22 49,435 1,11 114,36 4,71
- HGE63
- SEPTICEMIA 46,76 257 12,66 68,764 * 153,57 0,00
- HGE81
- SEPTICEMIA 11,73 373 6,24 108,419 2,07 52,01 8,79
- UGE12
- SRIS 2,46 174 2,54 7,012 0,91 114,81 2,71
- UGE17
- SRIS 1,41 177 1,72 6,837 * 173,35 0,00
- UGE20
- SRIS 9,62 280 2,16 3,007 0,644 220,93 1,78
- UGE32
- SRIS 24,86 286 5,34 17,158 0,844 149,96 2,47
- UGE40
- SRIS 1,10 155 9,44 13,575 2,006 85,1 5,42
- UGE42
- SRIS 1,39 328 3,44 7,476 0,621 186,43 4,20
- UGE46
- SRIS 2,99 412 6,15 12,197 3,91 203,89 2,93
- UGE53
- SRIS 7,30 108 2,83 5,366 0,64 182,65 4,84
- UGE60
- SRIS 0,21 208 2,63 6,953 1,35 95,13 2,07
- * Los datos de MCF ausentes se incluyen por media de columna.
Los presentes inventores predijeron la capacidad de los diferentes biomarcadores, tanto solos como en combinación, para diferenciar entre muestras de sangre obtenidas de pacientes que tienen SRIS o septicemia. Los resultados se facilitan en las Figuras 6-12. Las representaciones muestran medidas de ELISA para PCT, CRP, pro-hepcidina, M-CSF,
5 proBNP, TNRF2 y PTX3 (en ese orden). Los rectángulos representan septicemia, los triángulos representan SRIS. La línea negra muestra el umbral óptimo calculado a partir de todos los pacientes usando entropía.
Para predecir la potencia diferenciadora de los marcadores, los presentes inventores usaron un clasificador lineal simple inducido a partir de los datos usando solo una proteína. Los árboles de decisión representan un enfoque supervisado a la clasificación. Un árbol de decisión es una estructura simple en la que nodos no terminales representan pruebas en uno o 10 más atributos y nodos terminales reflejan resultados de decisión. J.R. Quinlan ha popularizado el enfoque de árboles de decisión con esta investigación que abarca más de 15 años. La implementación del dominio público más reciente del modelo de Quinlan es C4.5. El paquete de clasificador de Weka tiene su propia versión de C4.5 conocido como J48. El programa 1R es normal en la mayoría de los sentidos. Clasifica atributos según la tasa de errores (en el conjunto de entrenamiento), a diferencia de la medida basada en entropía usada en C4. Trata todos los atributos numéricamente
15 evaluados como continuos y usa un procedimiento directo para dividir el intervalo de valores en varios intervalos disjuntos. Manipula valores ausentes tratando “ausente” como un valor legítimo.
Como se ha explicado anteriormente, los presentes inventores pueden calcular el error de generalización de tal clasificador usando LOO:
20
Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07120929 | 2007-11-16 | ||
| EP07120929 | 2007-11-16 | ||
| PCT/EP2008/065364 WO2009062948A1 (en) | 2007-11-16 | 2008-11-12 | Biomarkers and methods for diagnosing, predicting and/or prognosing sepsis and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2524669T3 true ES2524669T3 (es) | 2014-12-10 |
Family
ID=40399211
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10166054.6T Active ES2486268T3 (es) | 2007-11-16 | 2008-11-12 | Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos |
| ES08850110.1T Active ES2524669T3 (es) | 2007-11-16 | 2008-11-12 | Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10166054.6T Active ES2486268T3 (es) | 2007-11-16 | 2008-11-12 | Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20100292131A1 (es) |
| EP (2) | EP2223119B1 (es) |
| ES (2) | ES2486268T3 (es) |
| WO (1) | WO2009062948A1 (es) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110053268A1 (en) * | 2006-10-17 | 2011-03-03 | Naohisa Tomosugi | Method for diagnosis of abnormal iron metabolism using active hepcidin as indicator |
| JPWO2008146903A1 (ja) * | 2007-05-31 | 2010-08-19 | 直久 友杉 | 活性型ヘプシジンを指標とした、急性虚血性疾患の診断方法 |
| EP3384939A1 (en) | 2011-03-11 | 2018-10-10 | Vib Vzw | Molecules and methods for inhibition and detection of proteins |
| EP2756118A4 (en) * | 2011-09-16 | 2015-09-16 | Cepheid | METHOD FOR DETECTING SEPSIS |
| GB201309358D0 (en) | 2013-05-24 | 2013-07-10 | King S College London | Aiding assessment of prognosis in inflammatory disease |
| WO2015007326A1 (en) | 2013-07-18 | 2015-01-22 | Institut D'investigació Biomèdica De Bellvitge (Idibell) | Agents comprising a terminal alpha-galactosyl moiety for use in prevention and/or treatment of inflammatory diseases |
| WO2016128383A1 (en) | 2015-02-10 | 2016-08-18 | B.R.A.H.M.S Gmbh | Free histone proteins as biomarkers |
| GB201605110D0 (en) * | 2016-03-24 | 2016-05-11 | Mologic Ltd | Detecting sepsis |
| GB201616557D0 (en) * | 2016-09-29 | 2016-11-16 | Secretary Of State For Health The | Assay for distinguishing between sepsis and systemic inflammatory response syndrome |
| JP7173495B2 (ja) * | 2016-11-04 | 2022-11-16 | セントロ デ インベスティガシオン ビオメディカ エン レッド | 敗血症又は敗血症性ショック（ｓｓ）患者に由来する血漿中の循環ヒストンｈ３及びｈ２ｂを検出する質量分析ベースの方法 |
| WO2018118691A1 (en) | 2016-12-19 | 2018-06-28 | Indiana University Research & Technology Corporation | Dna methylation in inflammatory disease |
| EP3631460B1 (en) | 2017-05-31 | 2023-11-15 | B.R.A.H.M.S GmbH | Mmp-8 as a marker for identifying infectious disease |
| EP3438668A1 (en) | 2017-08-04 | 2019-02-06 | B.R.A.H.M.S GmbH | Diagnosis and risk stratification of fungal infections |
| CN107688096A (zh) * | 2017-08-19 | 2018-02-13 | 杭州飞悦生物技术有限公司 | 检测降钙素原的酶联免疫试剂盒及制备方法及检测方法 |
| EP3971572A1 (en) | 2017-09-13 | 2022-03-23 | B.R.A.H.M.S GmbH | Proadrenomedullin as a marker for abnormal platelet levels |
| CN117705713B (zh) * | 2023-12-13 | 2024-06-11 | 上海长征医院 | 一种脓毒症检测系统 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6458539B1 (en) | 1993-09-17 | 2002-10-01 | Somalogic, Inc. | Photoselection of nucleic acid ligands |
| GB9617021D0 (en) * | 1996-08-13 | 1996-09-25 | Salpep Biotechnology Inc | Novel peptides for treatment of inflammation and shock |
| US6081612A (en) * | 1997-02-28 | 2000-06-27 | Electro Optical Sciences Inc. | Systems and methods for the multispectral imaging and characterization of skin tissue |
| US6329145B1 (en) | 1999-02-09 | 2001-12-11 | Gilead Science, Inc. | Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligand |
| US20040096917A1 (en) * | 2002-11-12 | 2004-05-20 | Becton, Dickinson And Company | Diagnosis of sepsis or SIRS using biomarker profiles |
| DE10349124A1 (de) * | 2003-10-22 | 2005-05-19 | Roche Diagnostics Gmbh | Differenzialdiagnostik mit Hepcidin |
| US20060195266A1 (en) * | 2005-02-25 | 2006-08-31 | Yeatman Timothy J | Methods for predicting cancer outcome and gene signatures for use therein |
| WO2007041623A2 (en) | 2005-10-03 | 2007-04-12 | Biosite Incorporated | Methods and compositions for diagnosis and/or prognosis in systemic inflammatory response syndromes |
| MX2009000685A (es) * | 2006-07-21 | 2009-01-30 | Amgen Inc | Metodo para detectar y/o cuantificar hepcidina en una muestra. |
| JP2011503012A (ja) * | 2007-11-06 | 2011-01-27 | オクラホマ・メディカル・リサーチ・ファウンデーション | 予後に関するバイオマーカーおよび治療の分子標的としての細胞外ヒストン |
-
2008
- 2008-11-12 US US12/742,647 patent/US20100292131A1/en not_active Abandoned
- 2008-11-12 EP EP08850110.1A patent/EP2223119B1/en not_active Not-in-force
- 2008-11-12 ES ES10166054.6T patent/ES2486268T3/es active Active
- 2008-11-12 WO PCT/EP2008/065364 patent/WO2009062948A1/en active Application Filing
- 2008-11-12 EP EP10166054.6A patent/EP2230519B1/en not_active Not-in-force
- 2008-11-12 ES ES08850110.1T patent/ES2524669T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20100292131A1 (en) | 2010-11-18 |
| EP2223119A1 (en) | 2010-09-01 |
| EP2230519A1 (en) | 2010-09-22 |
| EP2230519B1 (en) | 2014-05-14 |
| ES2486268T3 (es) | 2014-08-18 |
| EP2223119B1 (en) | 2014-09-10 |
| WO2009062948A1 (en) | 2009-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2524669T3 (es) | Biomarcadores y procedimientos de diagnóstico, predicción y/o pronóstico de septicemia y usos de los mismos | |
| Kelty et al. | Barrett's oesophagus: intestinal metaplasia is not essential for cancer risk | |
| Holakouie-Naieni et al. | Spatial modeling of cutaneous leishmaniasis in Iran from 1983 to 2013 | |
| von Ellenrieder et al. | Interaction with slow waves during sleep improves discrimination of physiologic and pathologic high‐frequency oscillations (80–500 Hz) | |
| Günay et al. | Can platelet indices predict obstruction level of pulmonary vascular bed in patients with acute pulmonary embolism? | |
| Cleland et al. | Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction | |
| D’Olivo et al. | Long-term records of coral calcification across the central Great Barrier Reef: assessing the impacts of river runoff and climate change | |
| Shinya et al. | Procalcitonin as a useful biomarker for determining the need to perform emergency biliary drainage in cases of acute cholangitis | |
| Attorre et al. | A methodological approach for assessing the effects of disturbance factors on the conservation status of Mediterranean coastal dune systems | |
| Mutuku et al. | Impact of drought on the spatial pattern of transmission of Schistosoma haematobium in coastal Kenya | |
| Akpinar et al. | Performance evaluation of MR-proadrenomedullin and other scoring systems in severe sepsis with pneumonia | |
| Düzlü et al. | Neutrophil-lymphocyte ratio findings and larynx carcinoma: a preliminary study in Turkey | |
| Brugts et al. | The predictive value of cardiac biomarkers in prognosis and risk stratification of patients with atrial fibrillation | |
| Lee et al. | Adenomas of cervical maldescended parathyroid glands: pearls and pitfalls | |
| Shah et al. | Influences of desmin and keratin 19 on passive biomechanical properties of mouse skeletal muscle | |
| Balashov et al. | Percent predicted value for the 6-minute walk test: using norm-referenced equations to characterize severity in persons with CHF | |
| Sanyal et al. | Direct cost for initial management of prostate cancer: a systematic review | |
| Japee et al. | Automated method for tracking individual red blood cells within capillaries to compute velocity and oxygen saturation | |
| Béduer et al. | Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling | |
| PT1608982E (pt) | Diagnóstico de autismo | |
| Gurleyik et al. | The Rare Coincidence: Nonrecurrent Laryngeal Nerve Pointed by a Zuckerkandl′ s Tubercle | |
| Reece-Smith et al. | A multi-centre analysis of the impact of updated risk stratification on follow-up of gastric gastro-intestinal stromal tumours in the post-imatinib era | |
| Feng et al. | Sudden cardiac death rates in an Australian population: a data linkage study | |
| Canu et al. | Risk factors of permanent hypoparathyroidism after total thyroidectomy. Retrospective analysis of 285 consecutive patients | |
| Chen et al. | Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy |