Optimized cell type signatures revealed from single-cell data by combining principal feature analysis, mutual information, and machine learning.

Machine learning techniques are excellent to analyze expression data from single cells. These techniques impact all fields ranging from cell annotation and clustering to signature identification. The presented framework evaluates gene selection sets how far they optimally separate defined phenotypes or cell groups. This innovation overcomes the present limitation to objectively and correctly identify a small gene set of high information content regarding separating phenotypes for which corresponding code scripts are provided. The small but meaningful subset of the original genes (or feature space) facilitates human interpretability of the differences of the phenotypes including those found by machine learning results and may even turn correlations between genes and phenotypes into a causal explanation. For the feature selection task, the principal feature analysis is utilized which reduces redundant information while selecting genes that carry the information for separating the phenotypes. In this context, the presented framework shows explainability of unsupervised learning as it reveals cell-type specific signatures. Apart from a Seurat preprocessing tool and the PFA script, the pipeline uses mutual information to balance accuracy and size of the gene set if desired. A validation part to evaluate the gene selection for their information content regarding the separation of the phenotypes is provided as well, binary and multiclass classification of 3 or 4 groups are studied. Results from different single-cell data are presented. In each, only about ten out of more than 30000 genes are identified as carrying the relevant information. The code is provided in a GitHub repository at https://github.com/AC-PHD/Seurat_PFA_pipeline.

How health literacy associates with healthcare utilization and health promotion behaviours in Turkey?: Contributions to discussions concerning the Anderson model and ecological models.

BACKGROUND: This study examined how health literacy (HL) levels are associated with health care utilization (HCU) and health promotion behaviours (HPB) in Turkey. METHODS: We conducted face-to-face interviews and utilised the Turkish HL Scale-32 (n = 6228). RESULTS: HL score was inversely related to the number of outpatient admissions (OAs) (ß = -0.001) and emergency department admissions (EAs) (ß = -0.006) in the Poisson regression model. Sex, age, perceived health, income group, and education level were other variables related to the number of OAs and EAs. Health literacy levels were related to physical activity (PA) (for excellent HL, OR: 3.93 (95% CI: 2.54-6.08)) and acquiring healthy eating habits (HEHs) (for excellent HL, OR: 3.56 (95% CI: 2.40-5.29) in the logistic regression model. Education levels are related to PA, HEHs, and smoking cessation or reduction. Income groups, except those with very sufficient income, are related to PA and HEHs. CONCLUSION: Improving HL can help reduce health admissions. The relationship of HCU with gender, age, education, perceived health, and income group supports the Anderson model. Limited HL groups should be prioritised as risk groups in health promotion programs. The association of HL and socio-economic variables with HPB supports the ecological model.

Comparison of phenotypic features in patients with single vs multiple primary cutaneous melanomas: a prospective single-center study.

BACKGROUND: There is sparse data regarding total body nevus count (TBNC), nevus count in specific locations, phenotypic factors, anthropometric indices, sunburn, and the relation to multiple primary cutaneous melanomas (MPCM) development. We aim to compare these variables in a cohort of patients diagnosed with single primary melanoma (SPM) and MPCM with histologic diagnoses of melanoma in situ, superficial spreading, and nodular melanoma in our clinic. METHODS: Prospective observational studies for the evaluation of nevus counts in biopsy-proven melanoma patients from 2017 to 2020 at Ankara University were conducted. Age, gender, family history of melanoma, increased sun exposure, nonmelanoma skin cancers (NMSC), height, sunburn history, TBNC, and nevi count in specific anatomical locations were evaluated by multivariate logistic regression analysis. RESULTS: A total number of 156 patients consisting of 22 MPCM and 134 SPM were included. Mean TBNC for SPM vs MPCM patients were 96.87 (SD ± 124.71) vs 247.00 (SD ± 261.58), respectively (P < 0.0001). TBNC was correlated to the left arm, trunk, lower extremity, and head and neck nevus counts but not with the right arm nevus count. Multiple regression analysis showed that having more than 10 nevi on the head and neck area is associated with MPCM (OR, 3.882 [95% CI, 1.084-13.899]). TBNC and nevus count in specific locations were found to be significantly higher in MPCM. CONCLUSION: The risk of MPCM was associated with having ≥10 nevi on the head and neck.

AHD2FHIR: A Tool for Mapping of Natural Language Annotations to Fast Healthcare Interoperability Resources - A Technical Case Report.

A significant portion of data in Electronic Health Records is only available as unstructured text, such as surgical or finding reports, clinical notes and discharge summaries. To use this data for secondary purposes, natural language processing (NLP) tools are required to extract structured information. Furthermore, for interoperable use, harmonization of the data is necessary. HL7 Fast Healthcare Interoperability Resources (FHIR), an emerging standard for exchanging healthcare data, defines such a structured format. For German-language medical NLP, the tool Averbis Health Discovery (AHD) represents a comprehensive solution. AHD offers a proprietary REST interface for text analysis pipelines. To build a bridge between FHIR and this interface, we created a service that translates the communication around AHD from and to FHIR. The application is available under an open source license.

The Relationship Between Health Literacy Level and Media Used as a Source of Health-Related Information.

BACKGROUND: Previous studies have not shown the level of health literacy or associated factors on a national level in Turkey using a scale that has been adapted to the country and its culture. OBJECTIVE: This study aimed to determine health literacy levels in Turkey and to investigate the association of health literacy with socioeconomic factors as well as with the instruments used as sources of health-related information. METHODS: This cross-sectional, nationally representative study was conducted using a computer-assisted personal interview approach and included 6,228 households (response rate, 70.9%). The Turkey Health Literacy Scale was used to measure health literacy. Sources of health-related information, such as newspapers, television, internet, and smartphones, were included in the regression model for health literacy. KEY RESULTS: The proportion of participants with inadequate and problematic health literacy was 30.9% and 38%, respectively, showing that approximately 7 of 10 participants had limited health literacy. The frequencies of inadequate and problematic health literacy were higher in the disease prevention and promotion domains (37.4% and 34.2%, respectively) compared with those in the health care domain (27.1% and 31.3%, respectively). The most frequently used medium as a source of health-related information was the internet (48.6%), followed by television (33%). In controlled models, higher health literacy scores were associated with higher education and income levels. The effects of television (ß = 1,917), internet (ß = 2,803), newspapers (ß = 1,489), and smartphones (ß = 1,974) as sources of health-related information were statistically significant in the general health literacy index model. CONCLUSIONS: Health literacy in Turkey reflects social inequalities. The model accounting for socioeconomic variables demonstrated the relevance of sources of health information to level of health literacy. These findings emphasize the importance of improving sources of health information to improve health literacy. [HLRP: Health Literacy Research and Practice. 2021;5(2):e109-e117.] Plain Language Summary: This is a cross-sectional study that is representative of the population of Turkey. We reported that health literacy scores were higher for people in higher levels of socioeconomic status. We showed that using the television, internet, newspapers, and smartphones as a source of health-related information is associated with health literacy even when accounting for socioeconomic variables.

First Steps to Evaluate an NLP Tool's Medication Extraction Accuracy from Discharge Letters.

INTRODUCTION: The aim of this study is to evaluate the use of a natural language processing (NLP) software to extract medication statements from unstructured medical discharge letters. METHODS: Ten randomly selected discharge letters were extracted from the data warehouse of the University Hospital Erlangen (UHE) and manually annotated to create a gold standard. The AHD NLP tool, provided by MIRACUM's industry partner was used to annotate these discharge letters. Annotations by the NLP tool where then compared to the gold standard on two levels: phrase precision (whether or not the whole medication statement has been identified correctly) and token precision (whether or not the medication name has been identified correctly within correctly discovered medication phrases). RESULTS: The NLP tool detected medication related phrases with an overall F-measure of 0.852. The medication name has been identified correctly with an overall F-measure of 0.936. DISCUSSION: This proof-of-concept study is a first step towards an automated scalable evaluation system for MIRACUM's industry partner's NLP tool by using a gold standard. Medication phrases and names have been correctly identified in most cases by the NLP system. Future effort needs to be put into extending and validating the gold standard.

Evaluation of Different Learning Algorithms of Neural Networks for Drug Dosing Recommendations in Pediatrics.

Publicly accessible databases with evidence-based information on drug dosages for children and adolescents are not available in Germany. In previous work a prototypical web-based online platform for pediatric dosing recommendation has been developed. Quality assured maintenance of such a database is a time consuming effort. Recent work has shown that it is possible to use routinely documented data for machine learning approaches in order to create models for future decision support tools. This work describes the development of a prototype for pediatric dosing recommendations on the basis of routine drug prescriptions. Since they are structured for daily clinical use, not for machine learning, they include a substantial proportion of narrative text that requires preprocessing with consideration of medical and pharmaceutical knowledge. Three different learning algorithms have been applied and compared. The genetic algorithm with backpropagation has achieved the highest accuracy in the predictions. Our study constitutes a first step towards pediatric dosing recommendations, but there are multiple additional steps to be taken before a routine use might be considered, such as an evaluation by experienced physicians.

Risk Factors and Frequency of Ingrown Nails in Adult Diabetic Patients.

The present study evaluated the properties of nails, frequency of ingrown nails in patients with type 2 diabetes mellitus (DM), risk factors for developing ingrown nails, and effect of diabetic polyneuropathy and vasculopathy on the development and outcome of ingrown nails. Our 6-month epidemiologic prospective study included 300 patients with type 2 DM attending a DM outpatient clinic for routine examinations. The general characteristics and foot changes of the study population were investigated. Diabetic polyneuropathy and vasculopathy were evaluated using a biothesiometer, monofilament tests, and arterial Doppler ultrasonography. The frequency of ingrown nails was 13.6%. Multivariate analysis with logistic regression showed that body mass index (odds ratio [OR] 1.077, 95% confidence interval [CI] 1.007 to 1.15; p = .03), previous trauma (OR 2.828, 95% CI 1.017 to 7,867, p = .042), a weak dorsalis pedis pulse (OR 2.72, 95% CI 1.17 to 6.30, p = .02), trimming type (OR 2.3, 95 CI 1.06 to 4.98), p = .35), onychogryphosis (OR 9.036, 95% CI 2.34 to 34.87, p = .001), and subungual hyperkeratosis (OR 4.3, 95% CI 1.99 to 9.3, p = .001) were predictive variables for ingrown nails in our population. The incidence of onychomycosis was significantly greater in patients with ingrown nails (p = .032) than in patients without ingrown nails. The nail curvature ratio was greater in the patients with ingrown nails than in the group with normal nails. Arterial Doppler ultrasound examinations showed peripheral arterial disease in 19 patients (46.9%) with ingrown nails. The prevalence of ingrown nails was greater in the patients with DM than in the healthy population. Our results indicate that nail type, nail morphology, and diabetic vasculopathy affect the formation and evolution of ingrown nails.

Clinical Characteristics and Low Vision Rehabilitation Methods for Partially Sighted School-Age Children.

OBJECTIVES: To determine the clinical features and the distribution of diagnosis in partially sighted school-age children, to report the chosen low vision rehabilitation methods and to emphasize the importance of low vision rehabilitation. MATERIALS AND METHODS: The study included 150 partially sighted children between the ages of 6 and 18 years. The distribution of diagnosis, accompanying ocular findings, visual acuity of the children both for near and distance with and without low vision devices, and the methods of low vision rehabilitation (for distance and for near) were determined. The demographic characteristics of the children and the parental consanguinity were recorded. RESULTS: The mean age of children was 10.6 years and the median age was 10 years; 88 (58.7%) of them were male and 62 (41.3%) of them were female. According to distribution of diagnoses among the children, the most frequent diagnosis was hereditary fundus dystrophies (36%) followed by cortical visual impairment (18%). The most frequently used rehabilitation methods were: telescopic lenses (91.3%) for distance vision; magnifiers (38.7%) and telemicroscopic systems (26.0%) for near vision. A significant improvement in visual acuity both for distance and near vision were determined with low vision aids. CONCLUSION: A significant improvement in visual acuity can be achieved both for distance and near vision with low vision rehabilitation in partially sighted school-age children. It is important for ophthalmologists and pediatricians to guide parents and children to low vision rehabilitation.

Planar Indium Tin Oxide Heater for Improved Thermal Distribution for Metal Oxide Micromachined Gas Sensors.

Metal oxide gas sensors with integrated micro-hotplate structures are widely used in the industry and they are still being investigated and developed. Metal oxide gas sensors have the advantage of being sensitive to a wide range of organic and inorganic volatile compounds, although they lack selectivity. To introduce selectivity, the operating temperature of a single sensor is swept, and the measurements are fed to a discriminating algorithm. The efficiency of those data processing methods strongly depends on temperature uniformity across the active area of the sensor. To achieve this, hot plate structures with complex resistor geometries have been designed and additional heat-spreading structures have been introduced. In this work we designed and fabricated a metal oxide gas sensor integrated with a simple square planar indium tin oxide (ITO) heating element, by using conventional micromachining and thin-film deposition techniques. Power consumption-dependent surface temperature measurements were performed. A 420 °C working temperature was achieved at 120 mW power consumption. Temperature distribution uniformity was measured and a 17 °C difference between the hottest and the coldest points of the sensor at an operating temperature of 290 °C was achieved. Transient heat-up and cool-down cycle durations are measured as 40 ms and 20 ms, respectively.

Location and Visualization of Working p-n and/or n-p Junctions by XPS.

X-ray photoelectron spectroscopy (XPS) is used to follow some of the electrical properties of a segmented silicon photodetector, fabricated in a p-n-p configuration, during operation under various biasing configurations. Mapping of the binding energy position of Si2p reveals the shift in the position of the junctions with respect to the polarity of the DC bias applied. Use of squared and triangular shaped wave excitations, while recording XPS data, allows tapping different electrical properties of the device under normal operational conditions, as well as after exposing parts of it to harsh physical and chemical treatments. Unique and chemically specific electrical information can be gained with this noninvasive approach which can be useful especially for localized device characterization and failure analyses.

An analysis of the incidence of measles in Turkey since 1960.

BACKGROUND/AIM: The aims of this study were to evaluate measles incidence and the effect of elimination strategy interventions on the disease from 1960 to 2014 in Turkey. The administration of measles vaccine started in the rural regions in 1970; it was carried out as a campaign along with the National Vaccine Campaign in 1985, and it has been employed as combined measles, mumps, and rubella under the scope of the Measles Elimination Program (MEP) since 2006 in Turkey. While a dramatic decrease in the reporting of measles was observed between 2000 and 2010, the number of the cases has increased since 2011. MATERIALS AND METHODS: The time series of measles incidence was evaluated for possible structural changes with regression models using dummy variables, autocorrelated with error terms. RESULTS: The incidence of measles showed a statistically significant decline between 1985 and 1988 (P = 0.0072) and between 2005 and 2011 (P < 0.0001). However, a statistically significant increase in incidence was noted after 2013 (P = 0.0008). CONCLUSION: Over the last 54 years, the pattern of measles cases demonstrated a significant decline in incidence. However, the increase in incidence in 2013 should be carefully analyzed and interpreted in terms of the MEP.

Validation and reliability of the Cardiff Visual Ability Questionnaire for Children using Rasch analysis in a Turkish population.

AIM: To develop a Turkish version of the 25-item Cardiff Visual Ability Questionnaire for Children (CVAQC) and to evaluate the validity and reliability of the questionnaire. METHODS: The study involved two main phases. The first phase involved a cross-cultural adaptation of the CVAQC from English into Turkish. The second phase involved the completion of the Turkish version of the CVAQC by 150 partially sighted children (6-18 years old) and validity and reliability checks. Extent and construct validity were investigated using Rasch analysis and reliability by internal consistency and person separation index (PSI). RESULTS: An adequate conceptual equivalence was achieved following the linguistic adaptation process. The dataset for validation comprised 150 participants, 88 (58.7%) of whom were male. Evidence of disordered thresholds was found for one item (item 17). This item was recorded by collapsing two categories and ordered thresholds were evident. All items of the CVAQC were found to fit the Rasch model (χ² (df)=59.90 (2), p=0.159). The internal construct validity was good (mean item fit (SD) -0.054 (1.132), person fit (SD) -0.629 (2.079)) indicating a single underlying construct. The reliability was good with Cronbach's α of 0.91 and PSI of 0.94. Differential item functioning (DIF) was tested for age, sex, diagnosis, degree of visual impairment, and comorbidity. Evidence of DIF was found on age for one item (item 10, reading the board at school). CONCLUSIONS: The Turkish version of the CVAQC is a valid, reliable, and unidimensional questionnaire for partially sighted children aged 6-18 years. TRIAL REGISTRATION NUMBER: Ankara University Ethics Committees registry number 06-177-12.

Chemical Visualization of a GaN p-n junction by XPS.

We report on an operando XPS investigation of a GaN diode, by recording the Ga2p3/2 peak position under both forward and reverse bias. Areal maps of the peak positions under reverse bias are completely decoupled with respect to doped regions and allow a novel chemical visualization of the p-n junction in a 2-D fashion. Other electrical properties of the device, such as leakage current, resistivity of the domains are also tapped via recording line-scan spectra. Application of a triangular voltage excitation enables probing photoresponse of the device.

Spectral response modification of TiO2 MSM photodetector with an LSPR filter.

We fabricated UVB filtered TiO2 MSM photodetectors by the localized surface plasmon resonance effect. A plasmonic filter structure was designed using FDTD simulations. Final filter structure was fabricated with Al nano-cylinders with a 70 nm radius 180 nm period on 360 nm SiO2film. The spectral response of the TiO2 MSM photodetector was modified and the UVB response was reduced by approx. 60% with an LSPR structure, resulting in a peak responsivity shift of more than 40 nm. To our knowledge, this is the first published result for the spectral response modification of TiO2 photodetectors with LSPR technique.

Fighting against cigarette smoking among medical students: a success story.

A survey in the year 2007 among medical students of Ankara University Medical School to assess the smoking rates showed that 25.1 % of them were smoking. Moreover, the smoking rate was 35 % at sixth grade students and 60 % of the smokers specified that they started smoking at medical school. This report provides a successful approach to decrease smoking among medical students by measures against starting smoking. An "Antismoking Group" composed of voluntary academic staff, nurses, students, psychologists, and a social worker of the medical school was established to engage in lowering the smoking rate and eliminating it eventually among our students. Several methods including regular monthly meetings, annual "Smoking or Health" symposiums, and lectures to first, second, and third grade students to increase their awareness related to harms of smoking and their role in the fight against smoking were carried out. Our surveys in the years 2009 (641 students) and 2012 (975 students) showed that total smoking rates dropped to 15.0 and 11.0 %, respectively (p < 0.0002). Moreover, the smoking rate for the sixth grade students dropped from 35.0 % in 2007 to 21.8 and 8.8 % in the years 2009 and 2012, respectively (p < 0.0002). In 2012, the smoking rates of first year and sixth year students were 7.8 and 9.0 %, respectively. These close rates of smoking at the first and last years of medical school training and the significant drop in smoking rates in 5 years confirm that our group pursued a realistic and successful strategy against smoking.

Comparison of the levels of knowledge and approaches in relation with child abuse and neglect in residents of pediatrics, pediatricians and practitioners working in the province of Ankara.

AIM: In this study, it was aimed to evaluate the levels of knowledge and approaches related with child abuse and neglect in pediatricians and practitioners who have a significant role in recognition and prevention of child abuse and neglect. MATERIAL AND METHODS: Two hundred residents of pediatrics and 100 pediatricians working in university and education and research hospitals in the center of Ankara province and 250 practicioners working in primary health care centers were included in the study. A scale composed of five parts including history, physical examination, radiology, risk groups and symptoms was prepared to determine the level of knowledge of physician related with child abuse and neglect. The correct answers given to the questions included in the scale were added and knowledge scores for the subscales and the total score were calculated. Approval was obtained from Ankara University, Medical Faculty Ethics Committee for the study. The data were evaluated using Mann-Whitney U and Kruskal Wallis test. RESULTS: A total of 550 physicians (339 female and 221 male) were included in the study. The mean total knowledge score related with child abuse and neglect was found to be 12.4±4.5 in residents of pediatrics, 13.7±2.8 in pediatricians and 13.6±2.8 in practitioners. The level of knowledge was found to be significantly higher in women, married physicians, physicians who received education before and after graduation, physician who confronted with cases of abuse or suspicious abuse and made a legal notice. CONCLUSION: In the light of these findings, child abuse and neglect should be included in education programs before and after graduation for physicians who have a key role in the subject of child abuse and neglect.

Rapid and Sensitive Colorimetric ELISA using Silver Nanoparticles, Microwaves and Split Ring Resonator Structures.

We report a new approach to colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) that reduces the total assay time to < 2 min and the lower-detection-limit by 100-fold based on absorbance readout. The new approach combines the use of silver nanoparticles, microwaves and split ring resonators (SRR). The SRR structure is comprised of a square frame of copper thin film (30 µm thick, 1 mm wide, overall length of ~9.4 mm on each side) with a single split on one side, which was deposited onto a circuit board (2×2 cm(2)). A single micro-cuvette (10 µl volume capacity) was placed in the split of the SRR structures. Theoretical simulations predict that electric fields are focused in and above the micro-cuvette without the accumulation of electrical charge that breaks down the copper film. Subsequently, the walls and the bottom of the micro-cuvette were coated with silver nanoparticles using a modified Tollen's reaction scheme. The silver nanoparticles served as a mediator for the creation of thermal gradient between the bioassay medium and the silver surface, where the bioassay is constructed. Upon exposure to low power microwave heating, the bioassay medium in the micro-cuvette was rapidly and uniformly heated by the focused electric fields. In addition, the creation of thermal gradient resulted in the rapid assembly of the proteins on the surface of silver nanoparticles without denaturing the proteins. The proof-of-principle of the new approach to ELISA was demonstrated for the detection of a model protein (biotinylated-bovine serum albumin, b-BSA). In this regard, the detection of b-BSA with bulk concentrations (1 µM to 1 pM) was carried out on commercially available 96-well high throughput screening (HTS) plates and silver nanoparticle-deposited SRR structures at room temperature and with microwave heating, respectively. While the room temperature bioassay (without microwave heating) took 70 min to complete, the identical bioassay took < 2 min to complete using the SRR structures (with microwave heating). A lower detection limit of 0.01 nM for b-BSA (100-fold lower than room temperature ELISA) was observed using the SRR structures.

Ultrafast and sensitive bioassay using split ring resonator structures and microwave heating.

In this paper, we have reported that split ring resonators (SRRs) structures can be used for bioassay applications in order to further improve the assay time and sensitivity. The proof-of-principle demonstration of the ultrafast bioassays was accomplished by using a model biotin-avidin bioassay. While the identical room temperature bioassay (without microwave heating) took 70 min to complete, the identical bioassay took less than 2 min to complete by using SRR structures (with microwave heating). A lower detection limit of 0.01 nM for biotinylated-bovine serum albumin (100-fold lower than the room temperature bioassay) was observed by using SRR structures.