Relation Prediction over Biomedical Knowledge Bases for Drug Repositioning

Identifying new potential treatment options for medical conditions that cause human disease burden is a central task of biomedical research. Since all candidate drugs cannot be tested with animal and clinical trials, in vitro approaches are first attempted to identify promising candidates. Likewise, identifying other essential relations (e.g., causation, prevention) between biomedical entities is also critical to understand biomedical processes. Hence, it is crucial to develop automated relation prediction systems that can yield plausible biomedical relations to expedite the discovery process. In this dissertation, we demonstrate three approaches to predict treatment relations between biomedical entities for the drug repositioning task using existing biomedical knowledge bases. Our approaches can be broadly labeled as link prediction or knowledge base completion in computer science literature. Specifically, first we investigate the predictive power of graph paths connecting entities in the publicly available biomedical knowledge base, SemMedDB (the entities and relations constitute a large knowledge graph as a whole). To that end, we build logistic regression models utilizing semantic graph pattern features extracted from the SemMedDB to predict treatment and causative relations in Unified Medical Language System (UMLS) Metathesaurus. Second, we study matrix and tensor factorization algorithms for predicting drug repositioning pairs in repoDB, a general purpose gold standard database of approved and failed drug–disease indications. The idea here is to predict repoDB pairs by approximating the given input matrix/tensor structure where the value of a cell represents the existence of a relation coming from SemMedDB and UMLS knowledge bases. The essential goal is to predict the test pairs that have a blank cell in the input matrix/tensor based on the shared biomedical context among existing non-blank cells. Our final approach involves graph convolutional neural networks where entities and relation types are embedded in a vector space involving neighborhood information. Basically, we minimize an objective function to guide our model to concept/relation embeddings such that distance scores for positive relation pairs are lower than those for the negative ones. Overall, our results demonstrate that recent link prediction methods applied to automatically curated, and hence imprecise, knowledge bases can nevertheless result in high accuracy drug candidate prediction with appropriate configuration of both the methods and datasets used

Necrosis of the Ventral Penile Skin Flap: A Complication of Hypospadias Surgery in Children

Objectives. To review cases of hypospadias that were repaired with TIPU method and consequently resulted in the necrosis of ventral penile skin flaps. Methods. Eighty-three patients with hypospadias underwent TIPU procedure by two surgeons. Neourethra in all patients was covered with dartos flap prepared from the preputium or penile shaft. In cases where ventral skin could not be covered primarily, closure was ensured by using preputial Ombredanne or Byars’ flaps to repair ventral defects. Results. The median age of patients was 4 years. Twenty-five (30.12%) patients that underwent hypospadias repair had urethral opening at the coronal level, 33 (39.75%) at the distal penis, 10 (12.04%) at the midpenis, and 15 (18.07%) at the proximal penis. The ventral skin defect could not be primarily covered in 10 patients with penile shaft hypospadias. Consequently, Byars’ method was used in 8 of these patients to cover the defect and the Ombredanne method was used in the remaining 2. Ventral skin flap necrosis developed in 5 patients (4 Byars and 1 Ombredanne). It was medically treated in 4 patients. Urethral fistula developed in the other patient whose necrosis was deeper. The mean hospital stay was 7 days for patients without necrosis, and 14 for those with necrosis. Conclusion. We are of the opinion that dartos flaps used in the TIPU method in order to cover neourethra and decrease the incidence of fistula development lead to necrosis in the Ombredanne or Byars’ flaps by causing low blood supply to the preputium and thus extend hospital stay

Determinants of high sensitivity troponin T concentration in chronic stable patients with heart failure: Ischemic heart failure versus non-ischemic dilated cardiomyopathy

Background: Cardiac troponin T is a marker of myocardial injury, especially when measured by means of the high-sensitivity assay (hs-cTnT). The echocardiographic and clinical predictors of hs-cTnT may be different in ischemic heart failure (IHF) and non-ischemic dilated cardiomyopathy (DCM).Methods: Sixty consecutive patients (19 female, 41 male; mean age 56.3 ± 13.9 years) with stable congestive heart failure (33 patient with IHF and 27 patients with DCM), with New York Heart Association functional class I–II symptoms, and left ventricular ejection fraction < 40% were included.Results: In patients with IHF peak early mitral inflow velocity (E), E/peak early diastolic mitral annular tissue Doppler velocity (Em) lateral, peak systolic mitral annular tissue Doppler velocity (Sm) lateral and logBNP were univariate predictors of hs-cTnT above median. But only E/Em lateral was an independent predictor of hs-cTnT above median (p = 0.04, HR: 1.2,CI: 1–1.4). In patients with DCM; left atrial volume index, male sex, Sm lateral and global longitudinal strain (LV-GLS) were included in multivariate model and LV-GLS was detected to be an independent predictor for hs-cTnT above median (p < 0.05, HR: 0.7, CI: 0.4–1.0).Conclusions: While LV-GLS is an independent predictor of hs-cTnT concentrations in patients with DCM, E/Em lateral predicted hs-TnT concentrations in patients with IHF

ST yükselmeli miyokart enfarktüsü hastalarında çekilen pıhtının histopatolojik özelliklerinin uzun dönem sol ventrikül fonksiyonuyla ilişkisi

Objective: This study was an investigation of the severity ofinflammation (SOI) in aspirated material and thrombus age toexamine any association with pre-discharge and long-term leftventricular (LV) function after ST-elevation myocardial infarction (STEMI).Methods: The study group comprised 25 patients with STEMIfrom whom an occlusive thrombus was aspirated from the infarct-related artery with a 7-F catheter. The SOI in the aspirate was determined according to the mean leukocyte countin 5 high-power magnification fields and graded as mild in thepresence of ≤100 leukocytes per field or significant if therewere >100 leukocytes per field. The thrombi were categorizedas fresh or lytic/organized (L/O) using predefined criteria.Echocardiographic assessment was performed prior to discharge and at 1 year. Adverse left ventricular remodeling (LVR)was defined as a 20% increase in LV end-diastolic volume incomparison with baseline values.Results: LVR was observed in 8 patients. The mean leukocytecount of the aspirate (127.5±86.0 vs 227.2±120.7; p=0.026)and frequency of significant inflammation (35% vs 75%;p=0.046) were significantly higher in the group with LVR. Theserum high-sensitivity C-reactive protein (hsCRP) level wassignificantly correlated with the leukocyte count of the aspirate (r=0.532; p=0.006). An L/O thrombus was related to betterpre-discharge and long-term LV volumes and ejection fractionvalues compared with a fresh thrombus.Conclusion: A significant increase in the leukocyte count inthe aspirate and a fresh thrombus might predict long-term LVfunctional deterioration irrespective of the clinical and procedure-related characteristics. In addition, serum markers of inflammation, like hsCRP, might also reflect the intensity of thelocal inflammatory response at the site of occlusion.Amaç: Bu çalışmada, ST yükselmeli miyokart enfarktüsü(STYME) sonrası emme yöntemiyle alınan pıhtının yaşı veyangı düzeyinin (YD), taburculuk öncesi ve uzun dönem solventrikül (SV) fonksiyonlarıyla olası ilişkisi araştırıldı.Yöntemler: Çalışmaya enfarktüsle ilişkili arterden tıkayıcı pıhtının 7-F kateter yardımıyla alındığı 25 STYME hastası dahiledildi. Pıhtının YD, beş yüksek düzeyde büyütme alanındagörülen ortalama lökosit sayısına göre derecelendirildi: alanbaşına hafif ≤100 lökosit ve belirgin >100 lökosit. Ayrıca, örnek daha önceden tanımlanmış kriterlere göre taze veya litik/organize (L/O) olarak da sınıflandırıldı. Ekokardiyografik değerlendirme taburculuk öncesi ve birinci yılda yapıldı. Olumsuzsol ventrikül yeniden biçimlenmesi (SVYB), SV diyastol sonuhacminde başlangıç değerine göre %20 artış olması şeklindetanımlandı.Bulgular: SVYB sekiz hastada gözlendi. Alınan örneğin ortalama lökosit sayımı (127.5±86.0 ve 227.2±120.7; p=0.026) vebelirgin yangısı olan hastaların sıklığı (%35 ve %75; p=0.046)SVYB gözlenen grupta anlamlı olarak daha yüksekti. Serumyüksek duyarlıklı keratin C-reaktif protein (hsCRP) düzeyi, örneğin lökosit sayımıyla anlamlı biçimde orantılıydı (r=0.532,p=0.006). Örneğin L/O yapısı, taze pıhtı varlığına kıyasla dahaiyi taburculuk öncesi ve uzun dönem SV hacimleri ve ejeksiyonfraksiyonu değerleriyle ilişkiliydi.Sonuç: Örnekte artmış lökosit sayısı ve taze pıhtı varlığı, klinikve işlemle ilişkili özelliklerden bağımsız olarak SV fonksiyonlarında uzun dönemde bozulma ile ilişkili olabilir. Bunun yanında, hsCRP gibi serum yangı belirteçleri tıkanıklık bölgesindekiyangısal cevabın şiddetini yansıtabilir

Assessment of Foreign Body Aspiration Material Using A Virtual Bronchoscopy Model: Time-Density and Time-Volume Relationships

Background: During foreign body aspiration (FBA), identifying the type of object is frequently problematic. Objectives: This study assessed density changes over time in the most common organic, FBA materials using virtual bronchoscopy. We also examined volumetric changes in materials to determine the optimal removal time for each type of foreign body. Materials and Methods: Size-appropriate slots for each type of foreign body were created on a 2 x 30 x 30 cm sponge plate. Objects ( shelled and blanched peanuts, roasted chickpeas, hazelnuts, walnuts, almonds, pistachios, watermelon seeds, shelled and unshelled sunflower seeds, shelled and unshelled pumpkin seeds, chickpeas, beans, lemon seeds, and apple seeds) were placed into the slots, after which a second sponge, with identical dimensions, was placed over the top of the first sponge to achieve closure. A moist environment was maintained for 7 days at body temperature (37 degrees C). Multidetector computed tomography (MDCT) images of the sponges, volume and density measurements of objects performed each day were recorded. Intra-object differences in density and volume over time on MDCT were evaluated using time-density and time-volume curves, respectively. The SPSS for Windows software package (ver. 21.0; SPSS Inc., Chicago, IL, USA) was used to perform analyses. Pearson correlation analyses were used to determine differences in the volume and density of FBA materials across days. A time volumetric graph was also obtained. P < 0.05 was considered as significant. Results: Following aspiration, organic material volumes on day 7 were below baseline values, although objects exhibited a 30% average increase in volume during the first 4 days. The density values of objects increased between days 2 and 5, and decreased thereafter. Conclusions: Measuring daily changes in density allows for the identification of FBA materials. Our data indicate that object removal during days 1 - 3, and on day 7 should be easier compared to days 4 - 6

Continuous intrathecal baclofen delivery in severely disabling spasticity

Background/Aim. Spasticity is the consequence of several clinical conditions including cerebral palsy, brain injury, spinal cord injury, multiple sclerosis, aneurysm bleeding, and some other neurological disorders. The aim of this study was to determine the efficacy of intrathecal baclofen (ITB) treatment in medically intractable severely disabling spasticity and present the challenges encountered during pump implantation surgery on these patients. Methods. The patients who underwent intrathecal baclofen pump implantation surgery between the years 2012 and 2015 with minimum follow-up of six months were recruited from the clinic archives. Twenty two patients with severe spasticity who had Modified Asworth Spasticity Scale (MASS) score of 3 or 4 were enrolled in our series. Eight of twenty-two patients were at pediatric age and they all were non-ambulant before surgery. Results. All of the patients underwent programmable intrathecal baclofen pump implantation surgery. Catheters were placed via percutaneous technique into to the subarachnoid space in 18 patients while, we had to perform partial hemi-laminectomy in order to place the catheters in 4 patients. All the patients improved significantly and 5 began using upper extremities and 3 adults became ambulant following physical therapy. Mean of the MASS scores improved from 3.59 to 1.32 (p < 0.001). Conclusion. The ITB therapy obviously increased quality of life and functional outcome in patients with disabling spasticity. As a result, physical treatment was more useful for these patients. Although some spinal abnormalities due to spasticity may necessitate partial hemilaminectomy to implant the pump, patients with intractable spasticity should be given the chance of intrathecal baclofen treatment at the earliest period of their lifetime disability

Left atrial expansion index is an independent predictor of diastolic dysfunction in patients with preserved left ventricular systolic function: A three dimensional echocardiography study

WOS: 000342453600015PubMed ID: 24958524In the absence of mitral valve disease left atrial (LA) volume is a marker of diastolic dysfunction and its severity. This study investigated the relationship between left ventricular (LV) end diastolic pressure (LVEDP) and LA volumes and phasic atrial functions detected by real-time full volume three-dimensional echocardiography (RT3DE), in a patient population with preserved LV systolic function. Seventy-two (39 female and 33 male; mean age 56.1 +/- A 9.0 years) stable patients with normal LV ejection fraction (EF) undergoing cardiac catheterization were studied. All patients underwent comprehensive echocardiographic examination just before catheterization and LVEDP was obtained. In addition to conventional echocardiographic measurements and Doppler indices; by using RT3DE LA maximum, minimum and pre-a-wave volumes were measured; LA total, passive and active emptying volumes and fractions were calculated. LV systolic function was assessed by EF and global longitudinal strain by speckle tracking. RT3DE minimum LA volume index, RT3DE active LAEF and LA expansion index (EI) were statistically significant univariate predictors of LVEDP a parts per thousand yen 16 mmHg. When age and hypertension adjusted multivariate analysis was performed EI [beta = -1.741, p = 0.015; OR 0.175; 95 % CI (0.043-0.717)] was an independent predictor of elevated LVEDP. RT3DE evaluation of LA function during entire cardiac cycle has incremental value for the diagnosis of diastolic dysfunction in patients with preserved EF. We suggest that RT3DE evaluation of LA may find clinical application in this field

Left atrial expansion index is an independent predictor of diastolic dysfunction in patients with preserved left ventricular systolic function: A three dimensional echocardiography study

WOS: 000342453600015PubMed ID: 24958524In the absence of mitral valve disease left atrial (LA) volume is a marker of diastolic dysfunction and its severity. This study investigated the relationship between left ventricular (LV) end diastolic pressure (LVEDP) and LA volumes and phasic atrial functions detected by real-time full volume three-dimensional echocardiography (RT3DE), in a patient population with preserved LV systolic function. Seventy-two (39 female and 33 male; mean age 56.1 +/- A 9.0 years) stable patients with normal LV ejection fraction (EF) undergoing cardiac catheterization were studied. All patients underwent comprehensive echocardiographic examination just before catheterization and LVEDP was obtained. In addition to conventional echocardiographic measurements and Doppler indices; by using RT3DE LA maximum, minimum and pre-a-wave volumes were measured; LA total, passive and active emptying volumes and fractions were calculated. LV systolic function was assessed by EF and global longitudinal strain by speckle tracking. RT3DE minimum LA volume index, RT3DE active LAEF and LA expansion index (EI) were statistically significant univariate predictors of LVEDP a parts per thousand yen 16 mmHg. When age and hypertension adjusted multivariate analysis was performed EI [beta = -1.741, p = 0.015; OR 0.175; 95 % CI (0.043-0.717)] was an independent predictor of elevated LVEDP. RT3DE evaluation of LA function during entire cardiac cycle has incremental value for the diagnosis of diastolic dysfunction in patients with preserved EF. We suggest that RT3DE evaluation of LA may find clinical application in this field