Vertical heterostructure of graphite-MoS2 for gas sensing.

2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): a good practice guide, pictorial review, and new perspectives.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but emerging T-cell non-Hodgkin lymphoma. It has two distinct subtypes, "effusion-only" or "mass-forming" disease, arising around implants in patients with in situ or previous history of textured-surface breast implants. The clinical, histopathological and imaging features are unique and nuanced as compared to primary breast malignancy and other lymphoma categories. Prompt recognition and diagnosis triggers referral to appropriate BIA-ALCL centres and initiation of treatment, with potential for excellent prognosis. Definitive management of both subtypes involves implant and capsule removal; systemic therapy is reserved for mass-forming disease and advanced-stage disease. There have been recent crucial advances in the diagnostic pathway, with publication of national and international guidelines: from the UK Medicines Healthcare products Regulatory Agency (MHRA) Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group (PRASEAG), and the United States National Comprehensive Cancer Network (NCCN). This review provides a practical guide to the clinical work-up of BIA-ALCL, enabling optimisation of the diagnostic imaging pathway, with representative cases.

Chronic lymphocytic leukaemia and Richter's transformation: multimodal review and new imaging paradigms.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults. It is a malignancy of CD5 B-cells characterised by small, mature-appearing lymphocytes accumulating in the blood, bone marrow, and lymphoid tissues. Richer transformation (RT) is an important adverse complication. Detection of RT is critical to allow initiation of appropriate therapy. CLL staging and response evaluation is complicated and nuanced. From our extensive tertiary centre experience of several hundred CLL cases over the last decade, we detail key computed tomography (CT) and positron-emission tomography (PET) imaging features of the natural history of CLL. The authors present an original imaging-based patient-management paradigm for the investigation of potential RT, which will inform global practice. Potential applications of whole-body diffusion weighted imaging, novel PET radiotracers, minimal residual disease, and ct-DNA are addressed.

Current and future best practice in imaging, staging, and response assessment for Non-Hodgkin's lymphomas: the Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) paradigm shift.

Non-Hodgkin's lymphoma (NHL) encompasses over 40 different haematological malignancies, including low and high-grade neoplasms, such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) respectively. A key clinical issue in the context of NHL is delayed and inaccurate diagnosis, which contributes adversely to patient morbidity and mortality. This article will address relevant imaging aspects, with particular reference to advancements in NHL imaging, including computed tomography (CT), integrated positron-emission tomography (PET)-CT, and magnetic resonance imaging (MRI). We provide multiparametric (anato-functional) imaging display items, including histological correlation. We will also introduce our original concept of "Specialist Integrated Haematological Malignancy Imaging Reporting" (SIHMIR), a paradigm shift in lymphoma radiology.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Risk factors, comorbiditiEs and Atherogenic dysLipidaemia in Indian YOUNG patients with dyslipidaemia attending hospital/clinic: REAL YOUNG (dyslipidaemia) study.

OBJECTIVE: To evaluate the pattern of dyslipidaemia, risk factors, and comorbidities in young Indian adults with dyslipidaemia. METHODS: A retrospective, multi-centric real-world study included individuals with dyslipidaemia, aged 18 - 45 years, attending to 623 hospitals/clinics across India. Data were collected retrospectively from medical records to note demographics, risk factors (smoking, alcohol consumption, sedentary lifestyle, family history of dyslipidaemia, diabetes mellitus, and hypertension), and clinical details (height, weight, waist circumference, body mass index (BMI), blood pressure, blood sugar, glycated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL-C), and high-density lipoprotein (HDL-C)).A descriptive analysis and comparative analysis (Mann-Whitney U test and Chi-square test) were done. RESULTS: Of the total 8135 patients, the majority were men (65.0%). Overall, 87.1% of population had one or multiple comorbidities which included the presence of dyslipidaemia alone (12.9%), dyslipidaemia with diabetes and hypertension (39.1%), dyslipidaemia with diabetes (33.6%), and dyslipidaemia with hypertension (14.4%). Sedentary lifestyle was prevalent observation in >50% of the population. Youngest age (18 - 25) group had higher prevalence of hypertriglyceridemia (63.2%), high LDL-C levels (56.8%), and low HDL-C levels (64.6%), while patients from the age group >25 to ≤35 years had the highest incidence of hypercholesterolemia (66.6%). Atherogenic dyslipidaemia was observed in 41.9%, 25.5%, and 23.2% of patients from age groups of ≥18 to ≤25, >25 to ≤35, and >35 to ≤45 years, respectively. Patients with HbA1c ≥6.5% had significantly higher levels of TG, TC, LDL-C, and lower HDL-C compared to those with HbA1c <6.5%. CONCLUSION: Hypertriglyceridemia, high LDL-C, low HDL-C, and atherogenic dyslipidaemia were prevalent in the young Indian cohort and sedentary lifestyle, and HbA1c ≥ 6.5% were the predominant risk factors of dyslipidaemia.

Premature coronary artery disease in India: coronary artery disease in the young (CADY) registry.

BACKGROUND: Coronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD). METHODS: We recruited 997 young patients (men <55, women <65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported. RESULTS: Mean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had "possible familial hypercholesterolemia". Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p<0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%. CONCLUSIONS: Conventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.

Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells.

The mechanisms by which some melanoma cells adapt to Serine/threonine-protein kinase B-Raf (BRAF) inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF mutant and PTEN null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5ß1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of FN expression could be overcome through combined treatment with a BRAF and PI3K inhibitor.

Predicting DNA mutations during cancer evolution.

Bio-systems are inherently complex information processing systems. Their physiological complexities limit the formulation and testing of a hypothesis for their behaviour. Our goal here was to test a computational framework utilising published data from a longitudinal study of patients with acute myeloid leukaemia (AML), whose DNA from both normal and malignant tissues were subjected to NGS analysis at various points in time. By processing the sequencing data before relapse time, we tested our framework by predicting the regions of the genome to be mutated at relapse time and, later, by comparing our results with the actual regions that showed mutations (discovered by genome sequencing at relapse time). After a detailed statistical analysis, the resulting correlation coefficient (degree of matching of proposed framework with real data) is 0.9816 ± 0.009 at 95% confidence interval. This high performance from our proposed framework opens new research opportunities for bioinformatics researchers and clinical doctors.

Driver Missense Mutation Identification Using Feature Selection and Model Fusion.

Driver mutations propel oncogenesis and occur much less frequently than passenger mutations. The need for automatic and accurate identification of driver mutations has increased dramatically with the exponential growth of mutation data. Current computational solutions to identify driver mutations rely on sequence homology. Here we construct a machine learning-based framework that does not rely on sequence homology or domain knowledge to predict driver missense mutations. A windowing approach to represent the local environment of the sequence around the mutation point as a mutation sample is applied, followed by extraction of three sequence-level features from each sample. After selecting the most significant features, the support vector machine and multimodal fusion strategies are employed to give final predictions. The proposed framework achieves relatively high performance and outperforms current state-of-the-art algorithms. The ease of deploying the proposed framework and the relatively accurate performance make this solution applicable to large-scale mutation data analyses.

Prevalence, treatments and outcomes of coronary artery disease in Indians: A systematic review.

AIM: To conduct a systematic review on the prevalence, risk factors, treatments and outcomes of Coronary Artery Disease (CAD) in Indians. METHODS AND RESULTS: We conducted a systematic review of studies in Indians with CAD from Jan 1969 to Oct 2012. Initial search yielded 3885 studies and after review 288 observational studies were included. The prevalence of CAD in urban areas was 2.5%-12.6% and in rural areas, 1.4%-4.6%. The prevalence of risk factors was: smoking (8.9-40.5%), hypertension (13.1-36.9%) and diabetes mellitus (0.2-24.0%). The median time to reach hospital after an MI was 360 min. In hospital rates of drug use were: antiplatelets 68%-97.9%, beta blockers 47.3%-65.8% and ACEIs 27.8-56.8%. CONCLUSIONS: In this first systematic review of CAD in India, prevalence of risk factors is high, treatments delayed and use of evidence based treatments variable.

Gnathic osteosarcoma: a retrospective analysis over a 20 year period.

BACKGROUND: Osteosarcomas are very rare malignant mesenchymal neoplasms affecting jaw bones. Only few studies are reported about this lesion in this particular region. OBJECTIVE: We wanted to assess the demography and tumor behaviour and histopathological pattern, retrospectively in the available cases. METHODS: A retrospective analysis of hospital records for 20 years was carried out. Clinical features, radiographic findings, histopathological details and treatment aspect of each of the lesions was considered. RESULTS: Findings of this study revealed only 13 cases of gnathic osteosarcomas, usually occurring in middle age, with equal sex predilection and predominantly seen in maxilla. Histopathologically, most of them belonged to osteogenic variant. CONCLUSION: Only few cases of gnathic osteosarcomas are reported in this region mainly in the young males. Interestingly many of them has history of dental extraction before the onset of disease.

Design of an expert system for mitigating trace element toxicity in cancer risk management.

Cancer risk management involves obliterating excess concentration of cancer causing trace elements by the natural immune system and hence intake of nutritious diet is of paramount importance. Human diet should consist of essential macronutrients that have to be consumed in large quantities and trace elements are to be consumed in very little amount. As some of these trace elements are causative factors for various types of cancer and build up at the expense of macronutrients, cancer risk management of these trace elements should be based on their initial concentration in the blood of each individual and not on their tolerable upper intake level. We propose an information theory based Expert System (ES) for estimating the lowest limit of toxicity association between the trace elements and the macronutrients. Such an estimate would enable the physician to prescribe required medication containing the macronutrients to annul the toxicity of cancer risk trace elements. The lowest limit of toxicity association is achieved by minimizing the correlated information of the concentration correlation matrix using the concept of Mutual Information (MI) and an algorithm based on a Technique of Determinant Inequalities (TDI) developed by the authors. The novelty of our ES is that it provides the lowest limit of toxicity profile for all trace elements in the blood not restricted to a group of compounds having similar structure. We demonstrate the superiority our algorithm over Principal Component Analysis in mitigating trace element toxicity in blood samples.

Computed tomography to diagnose coronary artery disease: a reduction in radiation dose increases applicability.

AIM: To assess the effects of dose-saving algorithms on the radiation dose in an established computed tomography coronary angiography (CTCA) clinical service. MATERIALS AND METHODS: A 3 year retrospective analysis of all patients attending for a clinically indicated CTCA was performed. The effective dose was calculated using a cardiac-specific conversion factor [0.028 mSv(mGy·cm)(-1)]. Patients were stratified by the advent of new scanning technology and dose-saving protocols. RESULTS: Between September 2007 and August 2010, 1736 examinations were performed. In the first 6 months, 150 examinations were performed with a mean effective dose of 29.6 mSv (99% CI 26.6-33 mSv). In March 2008 prospective electrocardiogram (ECG) gating was installed; reducing the effective dose to 13.6 mSv (99% CI 12.5-14.9 mSv). In March 2009, the scanner parameters were set to a minimal exposure time and 100 kV in patients with a body mass index (BMI) of <30. This reduced the mean dose to 7.4 mSv (99% CI 6.8-8 mSv). For the final six months the mean radiation dose for a cardiac scan was 5.9 mSv (99% CI 5.4-6.5 mSv) this figure incorporates all examinations performed irrespective of the protocol used. CONCLUSION: With the implementation of evidence-based protocols, the effective dose from cardiac CT has significantly reduced. As CTCA services develop dose-saving algorithms should be adopted to keep the radiation dose as low as reasonably practical.

Wavelet analysis in current cancer genome research: a survey.

With the rapid development of next generation sequencing technology, the amount of biological sequence data of the cancer genome increases exponentially, which calls for efficient and effective algorithms that may identify patterns hidden underneath the raw data that may distinguish cancer Achilles' heels. From a signal processing point of view, biological units of information, including DNA and protein sequences, have been viewed as one-dimensional signals. Therefore, researchers have been applying signal processing techniques to mine the potentially significant patterns within these sequences. More specifically, in recent years, wavelet transforms have become an important mathematical analysis tool, with a wide and ever increasing range of applications. The versatility of wavelet analytic techniques has forged new interdisciplinary bounds by offering common solutions to apparently diverse problems and providing a new unifying perspective on problems of cancer genome research. In this paper, we provide a survey of how wavelet analysis has been applied to cancer bioinformatics questions. Specifically, we discuss several approaches of representing the biological sequence data numerically and methods of using wavelet analysis on the numerical sequences.

Prevalence, risk factors and awareness of hypertension in India: a systematic review.

Indians have high rates of cardiovascular disease. Hypertension (HTN) is an important modifiable risk factor. There are no comprehensive reviews or a nationally representative study of the burden, treatments and outcomes of HTN in India. A systematic review was conducted to study the trends in prevalence, risk factors and awareness of HTN in India. We searched MEDLINE from January 1969 to July 2011 using prespecified medical subject heading (MeSH) terms. Of 3372 studies, 206 were included for data extraction and 174 were observational studies. Prevalence was reported in 48 studies with sample size varying from 206 to 167 331. A significant positive trend (P<0.0001) was observed over time in prevalence of HTN by region and gender. Awareness and control of HTN (11 studies) ranged from 20 to 54% and 7.5 to 25%, respectively. Increasing age, body mass index, smoking, diabetes and extra salt intake were common risk factors. In conclusion, from this systematic review, we record an increasing trend in prevalence of HTN in India by region and gender. The awareness of HTN in India is low with suboptimal control rates. There are few long-term studies to assess outcomes. Good quality long-term studies will help to understand HTN better and implement effective prevention and management programs.