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BACKGROUND: The iron intake requirement distribution for premenopausal females is not symmetric, which invalidates the EAR cut-point approach for assessing the prevalence of iron inadequacy. Therefore, Beaton's Full Probability Approach (PA) must be used. Although the PA requires information on the entire iron intake requirement distribution, the European Food Safety Authority (EFSA) only provided the EAR (50th percentile), 90th, 95th (population reference intake), and 97.5th percentiles. OBJECTIVES: This study aimed to reliably estimate the prevalence of iron inadequacy in premenopausal females using the PA, based on the intake requirements established by EFSA, and compare the results with those obtained from the EAR cut-point method. METHODS: Habitual iron intakes were calculated using the statistical program to assess dietary exposure with data from 484 females (20-45 y) from the Dutch National Food Consumption Survey 2012-2016. Iron requirements of EFSA (including additionally obtained information) were applied. Results from the PA were compared to results obtained with the EAR cut-point method. Sensitivity analyses examined the impact of lower iron intake distributions on differences in estimated inadequate intakes between PA and EAR cut-point methods. RESULTS: A 2-fold higher prevalence of iron inadequacy among Dutch premenopausal females was observed when employing the PA compared to the EAR cut-point method, using EFSA's reference values. Sensitivity analysis showed that the EAR cut-point method could also result in large overestimations for populations with lower intake distributions. CONCLUSIONS: This study provided an example of using the PA method by using additionally derived information on the full requirement distribution underlying EFSA's reference values. Results showed once more the unsuitability of the EAR cut-point method to calculate the prevalence of iron inadequacy in premenopausal females. Hence, we recommend that institutions deriving dietary reference values provide all the information needed to use the correct method to determine inadequate intakes in the population.

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OBJECTIVES: Diagnostic errors are the leading cause of preventable harm in clinical practice. Implementable tools to quantify and target this problem are needed. To address this gap, we aimed to generalize the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) framework by developing its computable phenotype and then demonstrated how that schema could be applied in multiple clinical contexts. METHODS: We created an information model for the SPADE processes, then mapped data fields from electronic health records (EHR) and claims data in use to that model to create the SPADE information model (intention) and the SPADE computable phenotype (extension). Later we validated the computable phenotype and tested it in four case studies in three different health systems to demonstrate its utility. RESULTS: We mapped and tested the SPADE computable phenotype in three different sites using four different case studies. We showed that data fields to compute an SPADE base measure are fully available in the EHR Data Warehouse for extraction and can operationalize the SPADE framework from provider and/or insurer perspective, and they could be implemented on numerous health systems for future work in monitor misdiagnosis-related harms. CONCLUSIONS: Data for the SPADE base measure is readily available in EHR and administrative claims. The method of data extraction is potentially universally applicable, and the data extracted is conveniently available within a network system. Further study is needed to validate the computable phenotype across different settings with different data infrastructures.

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Apical hypertrophic cardiomyopathy, also called Yamaguchi syndrome, is a rare variant of hypertrophic cardiomyopathy. Yamaguchi syndrome is characterized by hypertrophy almost confined to the apical region of the left ventricle rather than the left ventricular septum. A case of 65-year-old Saudi man presented to the ER with angina, and the ECG, echocardiogram, and nuclear study confirmed the diagnosis with Yamaguchi. Reporting this case serves to help physicians broaden their vision in approaching patients with symptoms mimicking acute coronary syndrome.

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Silicon photonics is an emerging platform for acoustic sensing, offering exceptional miniaturization and sensitivity. While efforts have focused on silicon-based resonators, silicon nitride resonators can potentially achieve higher Q-factors, further enhancing sensitivity. In this work, a 30 µm silicon nitride microring resonator was fabricated and coated with an elastomer to optimize acoustic sensitivity and signal fidelity. The resonator was characterized acoustically, and its capability for optoacoustic tomography was demonstrated. An acoustic bandwidth of 120 MHz and a noise-equivalent pressure of ∼ 7 mPa/Hz1/2 were demonstrated. The spatially dependent impulse response agreed with theoretical predictions, and spurious acoustic signals, such as reverberations and surface acoustic waves, had a marginal impact. High image fidelity optoacoustic tomography of a 20 µm knot was achieved, confirming the detector's imaging capabilities. The results show that silicon nitride offers low signal distortion and high-resolution optoacoustic imaging, proving its versatility for acoustic imaging applications.

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BACKGROUND: In recent years, low-dose computed tomography (LDCT) has played an important role in the diagnosis CT to reduce the potential adverse effects of X-ray radiation on patients, while maintaining the same diagnostic image quality. PURPOSE: Deep learning (DL)-based methods have played an increasingly important role in the field of LDCT imaging. However, its performance is highly dependent on the consistency of feature distributions between training data and test data. Due to patient's breathing movements during data acquisition, the paired LDCT and normal dose CT images are difficult to obtain from realistic imaging scenarios. Moreover, LDCT images from simulation or clinical CT examination often have different feature distributions due to the pollution by different amounts and types of image noises. If a network model trained with a simulated dataset is used to directly test clinical patients' LDCT data, its denoising performance may be degraded. Based on this, we propose a novel domain-adaptive denoising network (DADN) via noise estimation and transfer learning to resolve the out-of-distribution problem in LDCT imaging. METHODS: To overcome the previous adaptation issue, a novel network model consisting of a reconstruction network and a noise estimation network was designed. The noise estimation network based on a double branch structure is used for image noise extraction and adaptation. Meanwhile, the U-Net-based reconstruction network uses several spatially adaptive normalization modules to fuse multi-scale noise input. Moreover, to facilitate the adaptation of the proposed DADN network to new imaging scenarios, we set a two-stage network training plan. In the first stage, the public simulated dataset is used for training. In the second transfer training stage, we will continue to fine-tune the network model with a torso phantom dataset, while some parameters are frozen. The main reason using the two-stage training scheme is based on the fact that the feature distribution of image content from the public dataset is complex and diverse, whereas the feature distribution of noise pattern from the torso phantom dataset is closer to realistic imaging scenarios. RESULTS: In an evaluation study, the trained DADN model is applied to both the public and clinical patient LDCT datasets. Through the comparison of visual inspection and quantitative results, it is shown that the proposed DADN network model can perform well in terms of noise and artifact suppression, while effectively preserving image contrast and details. CONCLUSIONS: In this paper, we have proposed a new DL network to overcome the domain adaptation problem in LDCT image denoising. Moreover, the results demonstrate the feasibility and effectiveness of the application of our proposed DADN network model as a new DL-based LDCT image denoising method.

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PURPOSE: Few studies have examined experiences of stigma and factors associated with symptoms among cervical cancer survivors from diverse racial and ethnic backgrounds. We investigated survivorship experiences and patient-reported outcomes in the SPADE symptom cluster (sleep disturbance, pain interference, anxiety, depression, and energy/fatigue) among Black, Latina, and Chinese American women diagnosed with cervical cancer. METHODS: In two phases of research with cervical cancer survivors, we collected qualitative data through individual interviews (N=12; recruited through community referrals) and quantitative data from an observational cohort study (N=91; recruited through 4 national cancer registries). We coded interview transcripts to describe the survivors' experiences. We then evaluated associations between social support, spirituality, and SPADE symptom cluster domains using linear regression models. RESULTS: Qualitative analysis yielded four themes: perceptions of stigma, empowerment, physical and psychological effects, and social support. These concepts revolved around internal and external stigmas, emotional responses, strengthened faith, and different social support types. Quantitative analyses indicated that greater spirituality was associated with lower symptom burden on all five SPADE domains (p<0.01). We observed nuanced associations between specific types of social support and SPADE domains. CONCLUSIONS: The survivorship experiences of Black, Latina, and Chinese American women with cervical cancer are negatively influenced by perceptions of stigma. Higher scores on spirituality and varied types of social support were significantly associated with fewer symptoms in the SPADE symptom cluster. IMPLICATIONS FOR CANCER SURVIVORS: Results suggest targets for future interventions to reduce symptom burden among women diagnosed with cervical cancer by leveraging spirituality and social support.

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As one of the law resources of Muslim society, hadith is very important to learn. Unlike most hadith-related research, which studies more about content, we examine the relationship pattern between hadith narrators. In the study of hadith science, a series of hadith narrators who narrate a hadith is referred to as a sanad. This hadith sanad must be connected to the Prophet as the primary source of a hadith. Therefore, research related to the relationship between narrators is fundamental because it affects the quality and validity of a hadith. This paper analyzes the pattern of hadith narrators using Sequential Pattern Discovery using Equivalence Classes (SPADE). We separate the data of the narrators from the content, whereas, in the hadith books we use, the two are still mixed. This study, therefore, provides detailed information on the steps in the analysis of the patterns of hadith narrators. Some of the highlights of this paper are:•Algorithm 1 provides the detailed steps in data preprocessing to obtain the "clean data" needed in analyzing the pattern of narrator relationships.•Algorithm 2 provides a detailed description of analyzing the pattern between hadith narrators using SPADE.

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BACKGROUND: Depression is one of the most common perinatal mental health problems that affect pregnant women. Antenatal depression can adversely affect the well-being of the pregnant woman and her foetus. Depression is rarely detected by midwives due to the unavailability of relevant screening instruments in Malawi. A Screening Protocol for Antenatal Depression (SPADe) was developed and recommended for possible use to screen for depression in antenatal clinics in the country. The acceptability and feasibility of using the SPADe protocol to screen for depression has not been established. The aim of this study was to assess the acceptability and feasibility of screening for depression by midwives using SPADe in antenatal clinics in Blantyre district. METHODS: This study used a quantitative survey design to collect data among 60 midwives in three antenatal clinics in primary care settings. All inclusive sampling of all 60 midwives were used. The Structured Assessment of FEasibility and Ottawa Acceptability of Decision Rules Instruments were used to collect the data. Descriptive statistics and Chi square tests were used to analyse the data. RESULTS: This study found that it was feasible to implement SPADe and the following enablers for screening depression had the highest ratings: the SPADe is applicable to pregnant women (M = 3.9, sd = 0.4); the intended goal of the SPADe matches the prioritised goals of Malawi Ministry of Health (M = 3.9, sd = 0.5); and the SPADe is likely to be effective (M = 3.8, sd = 0.6). On the other hand, barriers for implementing the SPADe were: the need for specific training to deliver the SPADe (M = 3.7, sd = 0.7); ongoing support and supervision (M = 3.5, sd = 0.8); and additional resources (M = 3.0, sd = 0.9). This study also found that the implementation of the SPADe was acceptable to respondents. The overall mean score for respondents on acceptability of screening antenatal depression using SPADe was found to be high (M = 4.6, sd = 0.6). However the differences in the respondents' mean scores on acceptability of screening for depression in antenatal clinics using SPADe in relation to their demographic characteristics were not significant (p > .05). CONCLUSION: This study suggests that midwives feel that it is feasible and acceptable for them to implement the SPADe in antenatal clinics with ongoing training, support and clinical supervision.

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Fidelity monitoring is the degree to which a clinical trial intervention is implemented as intended by a research protocol. Consistent implementation of research protocols supported with extant fidelity monitoring plans contribute rigor and validity of study results. Fidelity monitoring plans should be comprehensive yet practical to accommodate the realities of conducting research, particularly a pragmatic clinical trial, in dynamic settings with heterogeneous patient populations. The purposes of this paper are to describe the (1) iterative development and implementation of protocols for intervention fidelity monitoring, (2) pilot testing of the fidelity monitoring plan, (3) the identification of interventionist training deficiencies, and (4) opportunities to enhance protocol rigor for a cancer symptom management intervention delivered through the electronic health record patient portal and telephone as part of a complex, multi-component pragmatic clinical trial to uncover training deficits and bolster protocol integrity. The intervention focuses on prominent symptoms reported among medical oncology patients including sleep disturbance, pain, anxiety, depression, low energy (fatigue) and physical function. In this pragmatic trial, the role of interventionist is a registered nurse symptom care manager (RN SCM). A three-part fidelity monitoring plan with checklists audit: Part-1 RN SCM role training activities in research components, clinical training components, and protocol simulation training; Part-2 RN SCM adherence to the intervention core components delivered over the telephone; and Part-3 maintenance of adherence to core intervention components. The goal is ≥ 80% adherence to components of each of the three checklists. An initial pilot test of the fidelity monitoring plan was conducted to evaluate the checklists and the RN SCM adherence to core protocol components. RN SCM skills and training deficits were identified during the pilot phase, as were opportunities to improve protocol integrity. Overall, approximately 50% of the audited RN SCM telephone calls had ≥80% fidelity to the core components. There remains on-going need for RN SCM training and skill building in action planning. The content presented in this paper is intended to begin to fill the gap of fidelity monitoring plans for complex interventions tested in pragmatic clinical trials and delivered remotely in an effort to strengthen protocol integrity.

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The spatial-temporal assessment of vector diseases is imperative to design effective action plans and establish preventive strategies. Therefore, such assessments have potential public health planning-related implications. In this context, we here propose an integrated spatial disease evaluation (I-SpaDE) framework. The I-SpaDE integrates various techniques such as the Kernel Density Estimation, the Optimized Hot Spot Analysis, space-time assessment and prediction, and the Geographically Weighted Regression (GWR). It makes it possible to systematically assess the disease concentrations, patterns/trends, clustering, prediction dynamics, and spatially varying relationships between disease and different associated factors. To demonstrate the applicability and effectiveness of the I-SpaDE, we apply it in the second largest city of Pakistan, namely Lahore, using Dengue Fever (DF) during 2007-2016 as an example vector disease. The most significant clustering is evident during the years 2007-2008, 2010-2011, 2013, and 2016. Mostly, the clusters are found within the city's central functional area. The prediction analysis shows an inclination of DF distribution from less to more urbanized areas. The results from the GWR show that among various socio-ecological factors, the temperature is the most significantly associated with the DF followed by vegetation and built-up area. While the results are important to understand the DF situation in the study area and have useful implications for public health planning, the proposed framework is flexible, replicable, and robust to be utilized in other similar regions, particularly in developing countries in the tropics and sub-tropics.

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Acute myeloid leukemias (AMLs) are a group of hematologic malignancies that are heterogeneous in their molecular and immunophenotypic profiles. Identification of the immunophenotypic differences between AML blasts and normal myeloid hematopoietic precursors (myHPCs) is a prerequisite to achieving better performance in AML measurable residual disease follow-ups. In the present study, we applied high-dimensional analysis algorithms provided by the Infinicyt 2.0 and Cytobank software to evaluate the efficacy of antibody combinations of the EuroFlow AML/myelodysplastic syndrome panel to distinguish AML blasts with recurrent genetic abnormalities (n = 39 AML samples) from normal CD45low CD117+ myHPCs (n = 23 normal bone marrow samples). Two types of scores were established to evaluate the abilities of the various methods to identify the most useful parameters/markers for distinguishing between AML blasts and normal myHPCs, as well as to distinguish between different AML groups. The Infinicyt Compass database-guided analysis was found to be a more user-friendly tool than other analysis methods implemented in the Cytobank software. According to the developed scoring systems, the principal component analysis based algorithms resulted in better discrimination between AML blasts and myHPCs, as well as between blasts from different AML groups. The most informative markers for the discrimination between myHPCs and AML blasts were CD34, CD36, human leukocyte antigen-DR (HLA-DR), CD13, CD105, CD71, and SSC, which were highly rated by all evaluated analysis algorithms. The HLA-DR, CD34, CD13, CD64, CD33, CD117, CD71, CD36, CD11b, SSC, and FSC were found to be useful for the distinction between blasts from different AML groups associated with recurrent genetic abnormalities. This study identified both benefits and the drawbacks of integrating multiple high-dimensional algorithms to gain complementary insights into the flow-cytometry data.

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Diabetic neuropathic pain is a common and devastating complication of type 1 diabetes, but the mechanism by which it develops and persists is yet to be fully elucidated. This study utilised high-dimensional suspension mass cytometry in a pilot cohort to investigate differences in peripheral blood immunophenotypes between type 1 diabetes patients with (n â€‹= â€‹9) and without (n â€‹= â€‹9) peripheral neuropathic pain. The abundance and activation of several leukocyte subsets were investigated with unsupervised clustering approaches FlowSOM and SPADE, as well as by manual gating. Major findings included a proportional increase in CD4+ central memory T cells and an absolute increase in classical monocytes, non-classical monocytes, and mature natural killer cells in type 1 diabetes patients with pain compared to those without pain. The expression of CD27, CD127, and CD39 was upregulated on select T cell populations, and the phosphorylated form of pro-inflammatory transcription factor MK2 was upregulated across most populations. These results provide evidence that distinct immunological signatures are associated with painful neuropathy in type 1 diabetes patients. Further research may link these changes to mechanisms by which pain in type 1 diabetes is initiated and maintained, paving the way for much needed targeted treatments.

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BACKGROUND: Individuals who are 'moderately' or 'severely' dependent consume alcohol at levels that are likely to have a severe impact on their own health and mortality, the health and behaviours of others (family members) and to have economic and social implications. Treatment guidelines suggest that treatment needs to be planned with medically assisted withdrawal (also referred to as detoxification), and aftercare support but outcomes are poor with low proportions engaging in after care and high relapse rates. An approach of structured preparation before alcohol detoxification (SPADe) puts an emphasis on introducing lifestyle changes, development of coping strategies for cravings, stress and emotions as well as introducing changes to the immediate family and social environment in advance of alcohol cessation. Such a pre-habilitation paradigm compliments the established treatment approach. The key research question was: can we design a large scale, randomised controlled trial (RCT) that will answer whether such an approach is more effective than usual care in helping individuals to maintain longer periods of alcohol abstinence? METHODS: This is a pragmatic, parallel, two-arm, feasibility RCT comparing SPADe and usual care against usual care only in maintaining alcohol abstinence in adults with alcohol dependence receiving care in two community addiction services in London. Feasibility outcomes, exploration of primary and secondary clinical outcomes and health economic outcomes are analysed. The trial follows the guidelines of phase 2 of the Medical Research Council (MRC) for complex interventions. RESULTS: We were able to recruit 48/50 participants during a period of 9 months. Retention in the trial for the whole period of the 12 months was 75%. Treatment compliance was overall 44%. Data completion for the primary outcome was 65%, 50% and 63% at 3, 6 and 12 months, respectively. The intervention group had more days abstinent in the previous 90 days at the 12 months (n = 54.5) versus control (n = 41.5). CONCLUSIONS: The results of this feasibility trial indicate that with the appropriate modifications, a full multicentred trial would be possible to test the effectiveness and cost-effectiveness of a pre-habilitation approach such as the SPADe group intervention in addition to usual care against usual care only. TRIAL REGISTRATION: Name of registry: ISRCTN; Trial Registration Number: 14621127 ; Date of Registration: 22/02/2017.

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Myeloid derived suppressor cells (MDSCs) can be subset into monocytic (M-), granulocytic (G-) or polymorphonuclear (PMN-), and immature (i-) or early MDSCs and have a role in many disease states. In cancer patients, the frequencies of MDSCs can positively correlate with stage, grade, and survival. Most clinical studies into MDSCs have been undertaken with peripheral blood (PB); however, in the present studies, we uniquely examined MDSCs in the spleens and PB from patients with gastrointestinal cancers. In our studies, MDSCs were rigorously subset using the following markers: Lineage (LIN) (CD3, CD19 and CD56), human leukocyte antigen (HLA)-DR, CD11b, CD14, CD15, CD33, CD34, CD45, and CD16. We observed a significantly higher frequency of PMN- and M-MDSCs in the PB of cancer patients as compared to their spleens. Expression of the T-cell suppressive enzymes arginase (ARG1) and inducible nitric oxide synthase (i-NOS) were higher on all MDSC subsets for both cancer patients PB and spleen cells as compared to MDSCs from the PB of normal donors. Similar findings for the activation markers lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), program death ligand 1 (PD-L1) and program cell death protein 1 (PD-1) were observed. Interestingly, the total MDSC cell number exported to clustering analyses was similar between all sample types; however, clustering analyses of these MDSCs, using these markers, uniquely documented novel subsets of PMN-, M- and i-MDSCs. In summary, we report a comparison of splenic MDSC frequency, subtypes, and functionality in cancer patients to their PB by clustering and cytometric analyses.

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OBJECTIVE: The suicides of Kate Spade and Anthony Bourdain, two major American icons, in a span of days in June 2018 represent a unique and tragic natural experiment to characterize associations with actual suicides in the aftermath of celebrity suicides. The aim of this study was to identify changes in suicide counts after their deaths. METHODS: Suicide data were obtained from the United States' Centers for Disease Control and Prevention's public-use mortality file. A time-series analysis was performed, examining monthly suicide data by age group (⩽19, 20-44, 45-64 and ⩾65 years), for both men and women, for all suicide methods and for hanging versus non-hanging methods, from January 1999 to December 2018. Seasonal autoregressive integrated moving-average models were fitted to the pre-June 2018 period, estimating suicides in subsequent months and identifying deviations from expected values. The volume of Twitter posts about Kate Spade and Anthony Bourdain was used as a proxy of societal attention. RESULTS: Tweets about the celebrities were mainly concentrated in June 2018 and faded quickly in July. Total suicides exceeded the 95% confidence interval for June and approximated the upper limit of the 95% confidence interval in July. Over this 2-month span, there were 418 (95% confidence interval = [184, 652]) more suicides than expected, including 275 (95% confidence interval = [79, 471]) excess suicides in men and 182 (95% confidence interval = [93, 271]) in women. These equate to 4.8%, 4.1% and 9.1% increases above expected counts. There were 392 (95% confidence interval = [271, 514]) excess suicides by hanging, a 14.5% increase, with no significant increase in all other methods combined. CONCLUSION AND RELEVANCE: These findings demonstrate that mortality following celebrity suicides can occur at a similar magnitude to that observed for other public health emergencies. They underscore the urgency for interventions to mitigate imitation effects after celebrity suicide reporting.

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Soil trace evidence can be useful in criminal investigations. A homicide which had occurred in South Brazil been concluded through the courts with a guilty conviction. A spade with soil traces adhering to it was seized from the confessed killer's house, it having been established that it had been used to bury parts of the victim's body. In the context of this confession, it provided an opportunity to test a protocol of analysis and verify the potential of discriminate soil sample analysis in such case works. This allowed us to test the practice of sequential analysis which had been developed for forensic case works in Brazil, with three sequential extractions: (i) 0.2 mol/L pH 3.0 ammonium oxalate; (ii) dithionite-citrate-bicarbonate; and (iii) 0.5 mol/L NaOH. It was possible to predict the sequence of events related to the homicide by using the sequential extraction technique and to conclude that: (i) the A horizon soil from the burial location of the torso was found to be very similar to the soil samples which had been recovered from the spade, which was able to be established despite there only being a small amount of soil adhering to the spade; (ii) the location where the legs were buried contributed a low amount of soil adhering to the spade. Therefore, it is suggested that, where possible, sequential extractions should be prioritized from a questioned sample to best provide information about the likely sequence of contact places and this test likely scenarios and criminal events.

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Acne keloidalis (AK) is one of the primary cicatricial alopecias and predominantly affects men of African descent. Reports in Asians are scant. This study aimed to retrospectively review the clinical and histopathological features of AK patients in southern Taiwan and identify the pathognomonic features of AK. There were 15 patients with histopathologically confirmed AK in National Cheng Kung University Hospital between 1988 and 2018. The median onset age was 24 years (range, 14-71). The male : female ratio was 14:1. In the acute stage of AK, the lymphocytic and neutrophilic peri-infundibular inflammatory infiltrates with microabscess formation and edema corresponded to the clinical finding of isolated papules or pustules. Subsequently, the inflammatory infiltrates involved the mid-dermis and the isthmus of hair follicles. The "spade sign", a thin and dilated space resembling the shape of a balloon or spade symbol of playing cards at the level of lower isthmus, was identified in eight biopsies from five patients and may be a pathognomonic sign in the subacute stage of AK. At the chronic stage, the segments of hair shafts remained in the upper to mid-dermis and induced chronic inflammation and extensive fibrosis, resulting in the clinical keloid-like appearance. The restriction of inflammation and fibrosis in the upper to mid-dermis was another unique and pathognomonic feature of AK.

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Recently, presence of mineral oil in numerous foods has been detected. The analysis of mineral oil in food is convoluted since it comprises MOSH (saturated hydrocarbons) and variable amounts of mainly alkylated MOAH (aromatic hydrocarbons). Both fractions have a different toxicological profile and therefore they need to be assessed separately. For Belgium, occurrence data are available comprising concentrations of 217 food samples. These data were used, in combination with the 2014/15 Belgian Food Consumption Survey data, in a lower bound scenario to evaluate the dietary exposure of the Belgian population. Exposure to mineral oil was much lower compared to the results previously reported by EFSA and RIVM. The main contributors in Belgium were similar to previous studies (i.e. cereal products and oils), but an important additional contribution of non-alcoholic drinks was identified due to the presence of mineral oil in coffee. However, the concentration of mineral oil was determined from the dry product by applying a dilution factor with transfer rate of 100%, and not in the prepared coffee.This study gives an account of the dietary exposure of the Belgian population to mineral oil for the first time and reports the associated uncertainties.

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Human induced pluripotent stem cells (hiPSCs) are reprogrammed from somatic cells and are regarded as promising sources for regenerative medicine and disease research. Recently, techniques for analyses of individual cells, such as single-cell RNA-Seq and mass cytometry, have been used to understand the stem cell reprogramming process in the mouse. However, the reprogramming process in hiPSCs remains poorly understood. Here we used mass cytometry to analyze the expression of pluripotency and cell cycle markers in the reprogramming of human stem cells. We confirmed that, during reprogramming, the main cell population was shifted to an intermediate population consisting of neither fibroblasts nor hiPSCs. Detailed population analyses using computational approaches, including dimensional reduction by spanning-tree progression analysis of density-normalized events, PhenoGraph, and diffusion mapping, revealed several distinct cell clusters representing the cells along the reprogramming route. Interestingly, correlation analysis of various markers in hiPSCs revealed that the pluripotency marker TRA-1-60 behaves in a pattern that is different from other pluripotency markers. Furthermore, we found that the expression pattern of another pluripotency marker, octamer-binding protein 4 (OCT4), was distinctive in the pHistone-H3high population (M phase) of the cell cycle. To the best of our knowledge, this is the first mass cytometry-based investigation of human reprogramming and pluripotency. Our analysis elucidates several aspects of hiPSC reprogramming, including several intermediate cell clusters active during the process of reprogramming and distinctive marker expression patterns in hiPSCs.

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Apical hypertrophic cardiomyopathy is a variant of hypertrophic cardiomyopathy characterized by apical hypertrophy, deep T-wave inversions in precordial electrocardiogram (EKG) leads, and a ventriculogram shaped like the "Ace of Spades." Patients are often asymptomatic but sometimes present with atypical chest pain, angina, or atrial fibrillation. The deep T-wave inversions on EKG often mimic acute coronary syndrome. Coronary angiogram in these patients is unrevealing, but the characteristic left ventriculogram establishes this diagnosis. The deep T-wave inversions can appear suddenly or deepen over years, making the diagnosis difficult to establish early in the disease. Transthoracic echocardiogram may miss the hypertrophied apex, but echo contrast imaging or cardiac magnetic resonance imaging can reliably confirm the diagnosis and detect apical aneurysms. We present a case of apical hypertrophic cardiomyopathy which was not evident despite many admissions, EKGs, cardiac catheterizations and echocardiograms until the diagnosis was confirmed with left ventriculogram and cardiac magnetic resonance imaging 20 years after initial presentation.

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