Histology-based classifier to distinguish early mycosis fungoides from atopic dermatitis.

BACKGROUND: Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters. OBJECTIVE: To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD). METHODS: In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis-free prediction model was developed and validated on an independent patient's cohort. RESULTS: A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter-individual investigator differences. LIMITATIONS: The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria. CONCLUSION: Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.

Coronary Artery Disease as a Relevant Risk Factor in Screening of Abdominal Aortic Ectasia and Aneurysm.

BACKGROUND: The aim of this study was to investigate the prevalence of abdominal aortic aneurysm (AAA) and abdominal aortic ectasia (AAE) in coronary artery disease (CAD) patients in a multicenter setting to obtain significant data to establish an AAA screening program in our departments. METHODS: Between January and September 2016, 500 patients with suspected or diagnosed CAD planned for coronary angiography or coronary artery bypass graft (CABG) underwent a sonographic examination of the infrarenal abdominal aorta to diagnose AAA or AAE. We calculated the prevalence of AAA and AAE in patients diagnosed of CAD and investigated factors potentially associated with the occurrence of AAA. RESULTS: The overall prevalence in all grades of CAD for AAE was 35.1% and for AAA 5.4%. In patients with three-vessel CAD, the prevalence of AAE was 34% and of AAA 6.8%. Significant correlation was found between the three-vessel CAD and AAA (p = 0.039). The logistic regression analysis showed significant correlation between AAA and age > 65 years (p = 0.05). The multivariate analysis of risk factors and CAD revealed significant correlations between one-vessel CAD and arterial hypertension (AH) (p = 0.004) and age > 65 years (p = 0.001) as well as between three-vessel CAD and AH (p = 0.01), peripheral artery disease (p = 0.01), and age > 65 years (p = 0.03). CONCLUSION: Our results confirm, that in comparison to other data, the prevalence of AAA in patients with CAD is high. Thus, it is recommended to include patients with CAD, especially elderly patients with three-vessel CAD, in future AAA screening programs.

Bottom-Up Design of Composite Supraparticles for Powder-Based Additive Manufacturing.

Additive manufacturing promises high flexibility and customized product design. Powder bed fusion processes use a laser to melt a polymer powder at predefined locations and iterate the scheme to build 3D objects. The design of flowable powders is a critical parameter for a successful fabrication process that currently limits the choice of available materials. Here, a bottom-up process is introduced to fabricate tailored polymer- and composite supraparticles for powder-based additive manufacturing processes by controlled aggregation of colloidal primary particles. These supraparticles exhibit a near-spherical shape and tailored composition, morphology, and surface roughness. These parameters can be precisely controlled by the mixing and size ratio of the primary particles. Polystyrene/silica composite particles are chosen as a model system to establish structure-property relations connecting shape, morphology, and surface roughness to the adhesion within the powder, which is accessed by tensile strength measurements. The adhesive properties are then connected to powder flowability and it is shown that the resulting powders allow the formation of dense powder films with uniform coverage. Finally, successful powder bed fusion is demonstrated by producing macroscopic single layer specimens with uniform distribution of nanoscale silica additives.

Thiophene-linked tetramethylbodipy-labeled nucleotide for viscosity-sensitive oligonucleotide probes of hybridization and protein-DNA interactions.

Cytosine 2'-deoxyribonucleoside dCTBdp and its triphosphate (dCTBdpTP) bearing tetramethylated thiophene-bodipy fluorophore attached at position 5 were designed and synthesized. The green fluorescent nucleoside dCTBdp showed a perfect dependence of fluorescence lifetime on the viscosity. The modified triphosphate dCTBdpTP was substrate to several DNA polymerases and was used for in vitro enzymatic synthesis of labeled oligonucleotides (ONs) or DNA by primer extension. The labeled single-stranded ONs showed a significant decrease in mean fluorescence lifetime when hybridized to the complementary strand of DNA or RNA and were also sensitive to mismatches. The labeled dsDNA sensed protein binding (p53), which resulted in the increase of its fluorescence lifetime. The triphosphate dCTBdpTP was transported to live cells where its interactions could be detected by FLIM but it did not show incorporation to genomic DNA in cellulo.

A novel reporter construct for screening small molecule inhibitors that specifically target self-renewing cancer cells.

Cancer stem cells (CSCs) are a subset of cancer cells, which possess self-renewal ability, and lead to tumor progression, metastasis, and resistance to therapy. Live detection and isolation of CSCs are important to understand the biology of CSCs as well as to screen drugs that target them. Even though CSCs are detected using surface markers, there is a lot of inconsistencies for that in a given cancer type. At the same time, self-renewal markers like ALDH1A1, OCT4A and SOX2, which are intracellular molecules, are reliable markers for CSCs in different cancers. In the present study, we generated a reporter construct for self-renewing CSCs, based on ALDH1A1 expression. Oral cancer cells harboring ALDH1A1-DsRed2 were used to screen inhibitors that target CSCs. Our results showed that Comb1, a cocktail of inhibitors for EGF and TGF-ß pathways and their intermediates, effectively reduced the DsRed2 population to 34%. Our immunohistochemical analysis on primary oral cancer corroborated the importance of EGF and TGF-ß pathways in sustaining CSCs. Since these two pathways are also critical for the self-renewal and differentiation of normal stem cells, Comb1 might abolish them as well. On analysis of the effect of Comb1 on normal murine bone marrow cells, there was no significant change in the stem cell self-renewal and differentiation potential in the treated group compared to untreated cells. To conclude, we claim that ALDH1A1-DsRed2 is a useful tool to detect CSCs, and Comb1 is effective in targeting CSCs without affecting normal stem cells.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Fine motor skills and mental imagery: Is it all in the mind?

Previous work has indicated that children's fine motor skills (FMS) contribute to cognitive performance in a number of domains. A philosophically and scientifically central aspect of cognitive skill is the ability to mentally simulate external events; however, very little research has examined whether FMS relate to mental imagery. Children aged 35-129 months (N = 294) were administered measures of FMS and mental imagery. Control variables included working memory, vocabulary, visual closure, chronological age, and a vast array of stimulus lexical features. Multilevel linear models indicated that FMS uniquely predicted mental imagery abilities, as did visual closure, chronological age, and various lexical features, whereas working memory and vocabulary did not. Findings are taken to support the idea that both mental imagery and FMS share, in part, similar functional systems.

Radiation dose due to radon and thoron progeny inhalation in high-level natural radiation areas of Kerala, India.

In order to evaluate internal exposure to radon and thoron, concentrations for radon, thoron, and thoron progeny were measured for 259 dwellings located in high background radiation areas (HBRAs, outdoor external dose: 3-5 mGy y-1) and low background radiation areas (control areas, outdoor external dose: 1 mGy y-1) in Karunagappally Taluk, Kerala, India. The measurements were conducted using passive-type radon-thoron detectors and thoron progeny detectors over two six-month measurement periods from June 2010 to June 2011. The results showed no major differences in radon and thoron progeny concentrations between the HBRAs and the control areas. The geometric mean of the annual effective dose due to radon and thoron was calculated as 0.10 and 0.44 mSv, respectively. The doses were small, but not negligible compared with the external dose in the two areas.

Detection of cervical lesions by multivariate analysis of diffuse reflectance spectra: a clinical study.

Diffuse reflectance (DR) spectroscopy is a non-invasive, real-time, and cost-effective tool for early detection of malignant changes in squamous epithelial tissues. The present study aims to evaluate the diagnostic power of diffuse reflectance spectroscopy for non-invasive discrimination of cervical lesions in vivo. A clinical trial was carried out on 48 sites in 34 patients by recording DR spectra using a point-monitoring device with white light illumination. The acquired data were analyzed and classified using multivariate statistical analysis based on principal component analysis (PCA) and linear discriminant analysis (LDA). Diagnostic accuracies were validated using random number generators. The receiver operating characteristic (ROC) curves were plotted for evaluating the discriminating power of the proposed statistical technique. An algorithm was developed and used to classify non-diseased (normal) from diseased sites (abnormal) with a sensitivity of 72 % and specificity of 87 %. While low-grade squamous intraepithelial lesion (LSIL) could be discriminated from normal with a sensitivity of 56 % and specificity of 80 %, and high-grade squamous intraepithelial lesion (HSIL) from normal with a sensitivity of 89 % and specificity of 97 %, LSIL could be discriminated from HSIL with 100 % sensitivity and specificity. The areas under the ROC curves were 0.993 (95 % confidence interval (CI) 0.0 to 1) and 1 (95 % CI 1) for the discrimination of HSIL from normal and HSIL from LSIL, respectively. The results of the study show that DR spectroscopy could be used along with multivariate analytical techniques as a non-invasive technique to monitor cervical disease status in real time.

Delivery of affordable and equitable cancer care in India.

The delivery of affordable and equitable cancer care is one of India's greatest public health challenges. Public expenditure on cancer in India remains below US$10 per person (compared with more than US$100 per person in high-income countries), and overall public expenditure on health care is still only slightly above 1% of gross domestic product. Out-of-pocket payments, which account for more than three-quarters of cancer expenditures in India, are one of the greatest threats to patients and families, and a cancer diagnosis is increasingly responsible for catastrophic expenditures that negatively affect not only the patient but also the welfare and education of several generations of their family. We explore the complex nature of cancer care systems across India, from state to government levels, and address the crucial issues of infrastructure, manpower shortages, and the pressing need to develop cross-state solutions to prevention and early detection of cancer, in addition to governance of the largely unregulated private sector and the cost of new technologies and drugs. We discuss the role of public insurance schemes, the need to develop new political mandates and authority to set priorities, the necessity to greatly improve the quality of care, and the drive to understand and deliver cost-effective cancer care programmes.

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

Anterior tongue cancer with no history of tobacco and alcohol use may be a distinct molecular and clinical entity.

BACKGROUND: A small, albeit significant, number of head and neck squamous cell carcinoma (HNSCC) patients has no history of tobacco and alcohol use. Such non-habits associated HNSCCs may represent a distinct clinical entity and exhibit increased aggressiveness. The objective of the study was to understand differences in molecular etiology of habits, and non-habits associated tongue carcinomas. MATERIALS AND METHODS: High-throughput gene expression profiling of 22 tumor samples was carried out. This was followed by quantitative real-time PCR validation of four of the identified differentially expressed genes. RESULTS AND CONCLUSION: Eighteen genes were identified that correlate strongly with the habits- and non-habits distinction. Among the genes significantly overexpressed in the non-habits group are CCND1, a key cell-cycle regulator, DACT3, a modulator of the Wnt/beta-catenin pathway, and three genes associated with the Notch signaling pathway. CCND1 and DACT3 overexpression in non-habits associated tongue carcinomas were subsequently validated by quantitative real-time PCR in an independent cohort (n = 18) of patient samples. Gene expression data were integrated with publicly available protein interaction data to build a small protein interaction network containing five of 18 differentially expressed genes. This suggested that a functional 'network module' can be implicated in the subgroup distinction. All the tumors analyzed here were human papillomavirus (HPV) negative samples. An association between CCND1 overexpression in oral tumors and poor prognosis has previously been reported. Thus, CCND1 overexpression in non-habits associated anterior tongue carcinomas may contribute to their increased clinical aggressiveness.

Fine motor skills and finger gnosia contribute to preschool children's numerical competencies.

Facets of fine motor skills (FMS) and finger gnosia have been reported to predict young children's numerical competencies, possibly by affecting early finger counting experiences. Furthermore, neuronal connections between areas involved in finger motor movement, finger gnosia, and numerical processing have been posited. In this study, FMS and finger gnosia were investigated as predictors for preschool children's performance in numerical tasks. Preschool children (N = 153) completed FMS tasks measuring finger agility and finger dexterity as well as a non-motor finger gnosia task. Furthermore, children completed numerical tasks that involved finger use (i.e., finger counting and finger montring), and tasks that did not (i.e., picture-aided calculation and number line estimation). To control for possible confounding influences of domain general skills, we included measures of reasoning and spatial working memory. We found associations between FMS and both finger counting and calculation, but not finger montring. In contrast, finger gnosia was only associated with finger montring, but not finger counting and calculation. Surprisingly, there were no associations between FMS or finger gnosia with number line estimation. Findings highlight that the relationship between finger gnosia, FMS, and numerical skills is specific to task requirements. Possible implications are discussed.

Enhancing Photoelectric Powder Deposition of Polymers by Charge Control Substances.

Charge control substances (CCS) as additives for polymer powders are investigated to make polymer powders suitable for the electrophotographic powder deposition in powder-based additive manufacturing. The use of CCS unifies the occurring charge of a powder, which is crucial for this novel deposition method. Therefore, commercially available polymer powder is functionalized via dry coating in a shaker mixer with two different CCS and analyzed afterwards. The flowability and the degree of coverage of additives on the surface are used to evaluate the coating process. The thermal properties are analyzed by use of differential scanning calorimetry. Most important, the influence of the CCS on the powder charge is shown by measurements of the electrostatic surface potential at first and the powder deposition itself is performed and analyzed with selected formulations afterwards to show the potential of this method. Finally, tensile strength specimens are produced with the conventional deposition method in order to show the usability of the CCS for current machines.

Program organization rather than choice of test determines success of cervical cancer screening: Case studies from Bangladesh and India.

The call for elimination of cervical cancer as a public health problem by the World Health Organization has led to intense focus on the burden of disease, available resources, and the possibility of introducing efficient systems for screening and treatment that allow effective cancer control in limited-resource settings. Presently, the focus is on the introduction of rapid, technologically less-demanding, affordable HPV testing. However, until such tests become widely available, the momentum that has been gained using visual inspection with acetic acid (VIA) should not be lost. Countries with limited resources and a heavy burden of cervical cancer, such as Bangladesh and India, introduced and scaled up VIA-based programs with varying degrees of programmatic organization and performance. Despite its limitations, VIA's simplicity and affordability has allowed these countries to build infrastructure, increase numbers of trained healthcare personnel, and develop a system of multilevel coordination within the health system. Such efforts will have long-term advantages provided that countries have access to an appropriate HPV test and build on their efforts to improve program organization through a strengthened health system, translating lessons learned in program implementation, logistics, and compliance with the new paradigm.

ß-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells.

Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.

Validation of an Intelligibility Assessment Tool in an Indian Language for Perceptual Speech Analysis in Oral Cancer Patients.

This study aimed to develop a speech intelligibility tool in Malayalam, an Indian language, based on the perceptual analysis. The tool had components of vowel, consonant, word, passage, and overall intelligibility. After face and content validation, a sample of 30 consecutive oral cancer patients underwent preliminary testing for internal consistency, inter- and intra-rater reliability, concurrent, and known-group validity. Subsequent validation was done in 80 T1-T4 patients from two centers. The scale had a high level of internal consistency; the Cronbach's alpha was 0.847 and good intra-rater and inter-rater agreement amongst all raters. There was a strong correlation between the Malayalam and the English passage. Pearson correlation coefficient of 0.646 proved concurrent validity. On known-group and subsequent validation, the tool showed expected differences between the treatment groups. The speech tool proved to be reliable and valid for perceptual evaluation of speech intelligibility in oral cancer patients.

Neurovascular Complications After Neck Dissection: a Prospective Analysis at a Tertiary Care Centre in South India.

Owing to high incidence of oral cancers in India, neck dissection is the most commonly performed procedure in any head and neck oncology setup. This surgery is particularly prone to various neurovascular complications due to intricate anatomy of neck, but the exact incidence has been studied less especially in Indian subcontinent. A prospective observational study was done on 105 patients of oral cancer who underwent neck dissection at Regional Cancer Centre, Trivandrum, and various short-term and long-term neurovascular complications were recorded. There was high temporary praxia of marginal mandibular and greater auricular nerve of 32.5% and 36.1%, respectively, immediate post-operative period which reduced significantly during 6 months. Eight patients had long-term shoulder abduction difficulty. There were isolated cases of IJV thrombosis and phrenic nerve paralysis. Despite our best intentions, complications arise due to complex anatomy of the neck, but if surgeon remains cognisant of the potential complications, their impact on patients' health, pocket and hospital resources can be minimized.

Cigarettes and Other Tobacco Products Act (COTPA) implementation in education institutions in India: A crosssectional study.

INTRODUCTION: Tobacco use is a major risk factor for cancer and other non-communicable diseases and is the single largest cause of preventable deaths worldwide causing premature death. There are various laws and legislations for tobacco control in India. The Cigarettes and Other Tobacco Products Act (COTPA) 2003 was enacted in 2004 but is not enforced rigorously. The aim of this study was to determine any violation of COTPA Section 4 (prohibition of smoking in public places) around educational institutions and Section 6b (prohibition of sale of tobacco products near educational institutions). METHODS: A cross-sectional, observational study was conducted in 307 schools and colleges selected across 12 districts in 5 states in India. Data were collected by the tobacco control coordinators. From the centre of the city, the coordinators travelled in four different directions to a maximum distance of 10 km radius. Along the path, any educational institutions that were encountered were surveyed for violation of COTPA Sections 4 and 6b. RESULTS: Out of 307 schools surveyed across the five states, an average of 85% of the schools violated Section 4 and an average of 69% violated Section 6b. CONCLUSIONS: A coordinated effort by all stakeholders, especially by the police, educational institutions, and the community, is required. Adherence to the guidelines on Tobacco-Free Educational Institutions can improve the implementation of COTPA in and around educational institutions.