From Theory to Practice: Implementing Next-Generation Sequencing and Public Health Genomics in Healthcare Systems.

If Europe's health systems make a conscious decision to increase their utilization of technology and techniques that can enhance prevention and expedite early-stage diagnosis, they can effectively address the growing challenges of disease. By embracing these advancements, these health systems can significantly improve their response to emerging health issues.However, at present the effective integration and exploitation of these opportunities remains hesitant and suboptimal, and health and health services underperform accordingly, with patients suffering from the continuing variations in diagnosis and access to innovation. This paper presents a comprehensive study that examines the current state of various influential disciplines and factors in European countries. It specifically focuses on the adoption of Next Generation Screening technologies and the development stage of Public Health Genomics. The assessment of these areas is presented in the context of a rapidly changing policy environment, which provides an opportunity for a fundamental reconsideration of how and where new tools can be integrated into healthcare systems and routine practices. Top of Form.

Demographic Analysis of Cancer Research Priorities and Treatment Correlations.

Understanding the diversity in cancer research priorities and the correlations among different treatment modalities is essential to address the evolving landscape of oncology. This study, conducted in collaboration with the European Cancer Patient Coalition (ECPC) and Childhood Cancer International-Europe (CCI-E) as part of the "UNCAN.eu" initiative, analyzed data from a comprehensive survey to explore the complex interplay of demographics, time since cancer diagnosis, and types of treatments received. Demographic analysis revealed intriguing trends, highlighting the importance of tailoring cancer research efforts to specific age groups and genders. Individuals aged 45-69 exhibited highly aligned research priorities, emphasizing the need to address the unique concerns of middle-aged and older populations. In contrast, patients over 70 years demonstrated a divergence in research priorities, underscoring the importance of recognising the distinct needs of older individuals in cancer research. The analysis of correlations among different types of cancer treatments underscored the multidisciplinary approach to cancer care, with surgery, radiotherapy, chemotherapy, precision therapy, and biological therapies playing integral roles. These findings support the need for personalized and combined treatment strategies to achieve optimal outcomes. In conclusion, this study provides valuable insights into the complexity of cancer research priorities and treatment correlations in a European context. It emphasizes the importance of a multifaceted, patient-centred approach to cancer research and treatment, highlighting the need for ongoing support, adaptation, and collaboration to address the ever-changing landscape of oncology.

Correction: Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications.

[This corrects the article DOI: 10.1039/D3RA01364B.].

Tackling the implementation gap for the uptake of NGS and advanced molecular diagnostics into healthcare systems.

Next-generation sequencing (NGS) and liquid biopsy (LB) showed positive results in the fight against different cancer types. This paper aims to assess the uptake of advanced molecular diagnostics/NGS for quick and efficient genetic profiles of tumour cells. For that purpose, the European Alliance for Personalised Medicine conducted a series of expert interviews to ascertain the current status across member states. One stakeholder meeting was additionally conducted to prioritize relevant factors by stakeholders. Seven common pillars were identified, and twenty-five measures were defined based on these pillars. Results showed that a multi-faceted approach is necessary for successful NGS implementation and that regional differences may be influenced by healthcare policies, resources, and infrastructure. It is important to consider different correlations when interpreting the results and to use them as a starting point for further discussion.

Aligning Cancer Research Priorities in Europe with Recommendations for Conquering Cancer: A Comprehensive Analysis.

Improvements in cancer care require a new degree of collaboration beyond the purely medical sphere, extending deeply into the world of other stakeholders-preeminently patients but also the other stakeholders in the hardware and software of care. Cancer remains a global health challenge, necessitating collaborative efforts to understand, prevent, and treat this complex disease. To achieve this goal, a comprehensive analysis was conducted, aligning the prioritization of cancer research measures in 13 European countries with 13 key recommendations for conquering cancer in the region. The study utilized a survey involving both patients and citizens, alongside data from IQVIA, a global healthcare data provider, to assess the availability and access to single-biomarker tests in multiple European countries. The results revealed a focused approach toward understanding, preventing, and treating cancer, with each country emphasizing specific research measures tailored to its strengths and healthcare objectives. This analysis highlights the intricate relationship between research priorities, access to biomarker tests, and financial support. Timely access to tests and increased availability positively influence research areas such as cancer prevention, early detection, ageing, and data utilization. The alignment of these country-specific measures with 13 recommendations for conquering cancer in Europe underscores the importance of tailored strategies for understanding, preventing, and treating cancer.

Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications.

The field of photoredox catalysis has been transformed by the use of organic photocatalysts, which give access to re-activities that were previously only possible with transition-metal photocatalysts. Recent advancements in the use of an acridinium photocatalyst in organic synthesis are covered in this review. Both the late-stage functionalization of biorelevant molecules and the activation of inert chemical bonds are explored, with an emphasis on their mechanistic features.

Oncocytoma of the parotid gland: A rare benign tumour.

Oncocytomas are one of the infrequent neoplasms seen in the oral cavity accounting for less than 2% of all neoplasms in the oral cavity with less than 1% chance of malignant transformation. They affect the major salivary glands and have a female predilection. The cognisance of the unique clinical and histopathological features is very important to conclude a confirmatory diagnosis. This paper reviews a case of oncocytoma presented in our department and also elucidates the diagnostic criteria for the same.

Trios Lidisi Veneer, Transforming Smiles Using an Intraoral Scanner - A Case Report.

INTRODUCTION: The need to perform restorations with a natural appearance is one of the most challenging aspects of dentistry, and reproducing the colour of natural teeth in restorations is a clinical challenge due to the complex optical characteristics of dentition. Various procedures have been advocated in the literature to correct dental anomalies, particularly in the aesthetic region, such as tooth discoloration due to fluorosis or dentition spacing due to changes in tooth shape, such as peg laterals. CLINICAL APPLICATIONS: Veneer are one of the most commonly used treatment modalities in such cases. As the use of ceramics necessitates the use of more opaque restorative materials or different thickness, obtaining adequate results in terms of the final colour of the restoration becomes increasingly difficult. The purpose of this study is to present a clinical case of smile rehabilitation in the anterior region with facets made of lithium disilicate, with the goal of achieving colour uniformity and demonstrating the benefits and achieving smile aesthetics. TAKEAWAY LESSONS: Technological advancement such as intraoral scanner for impression making have significant improved the success of prosthesis. This case report presents conservative and aesthetic procedure in the management of closing the space in maxillary anterior region using lithium disilicate laminate veneers with trios software.

Evaluation of salivary oxidative stress in oral lichen planus using malonaldehyde.

Background: Oral lichen planus is a chronic, mucocutaneous, inflammatory disease, with an unknown etiology. Reactive oxygen species and oxidative damage to the tissues might be the cause. Malonaldehyde (MDA), a low molecular weight end product of lipid peroxidation reaction is a suitable biomarker of endogenous DNA damage. monitoring the oxidant-antioxidant status of saliva may serve as an efficient marker of disease development in oral lichen planus patients. Aim and Objectives: To evaluate salivary oxidative stress in oral lichen planus subject using MDA and compare it with control subjects. Furthermore, to compare MDA levels in erosive and hypertrophic lichen planus. Materials and Methods: The current study is case-control study. Unstimulated salivary samples in the morning hours were taken from oral lichen planus subjects (n = 25) and controls subjects without any oral disease (n = 25). The saliva was centrifuged at 900 g for 10 min at a temperature of 4°C. Then, the entire filtrate was transferred to Eppendorf test tubes and frozen at-80°C until analysis. Salivary MDA was done through thiobarbituric acid reactive substance assay as per the protocol laid down by the manufacturer (Sigma Aldrich Lipid Peroxidation Assay Kit). Results: The data were expressed as the mean ± standard deviation and the statistical analysis was done using Student's t-test using SPSS version 21 IBM software. The salivary level of MDA was significantly higher than that of controls (P < 0.05). Conclusion: The higher level of MDA in patients with oral lichen planus suggests that free radicals and the resulting oxidative damage may be important in the pathogenesis of oral lichen planus lesions.

Mitofusin-2 Negatively Regulates Melanogenesis by Modulating Mitochondrial ROS Generation.

Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion-fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-silenced cells leads to the complete rescue of the phenotype at the cellular and molecular levels. Mechanistically, MFN2-silencing elevates mitochondrial reactive-oxygen-species (ROS) levels which in turn increases melanogenesis. ROS quenching with the antioxidant N-acetyl cysteine (NAC) reverses the MFN2-knockdown-mediated increase in melanogenesis. Moreover, MFN2 expression is significantly lower in the darkly pigmented primary human melanocytes in comparison to lightly pigmented melanocytes, highlighting a potential contribution of lower MFN2 levels to higher physiological pigmentation. Taken together, our work establishes MFN2 as a novel negative regulator of melanogenesis.

Expression of ß-catenin in oral leukoplakia and oral submucous fibrosis: An immunohistochemical study.

BACKGROUND: Oral potentially malignant disorders have increased propensity to turn malignant than its apparently normal counterparts. Histopathological examination, although gold standard, needs adjunct technique to give accurate diagnosis. Immunohistochemistry has proved to be a promising adjunct to aid in the diagnosis so far. The quest for a definitive marker is still on. Beta-catenin (ß-catenin), a structural protein has been evaluated to identify its likely role in malignant transformation of potentially malignant lesions and possibly designate it as one of the identifiable signature molecules in the transformation. AIM AND OBJECTIVE: To evaluate and estimate the expression of ß-catenin in different grades of dysplasia, oral submucous fibrosis (OSMF) and normal mucosa and compare the same. METHODOLOGY: A total number of 40 cases including different grades of dysplasia, OSMF and normal mucosa were immunohistochemically stained, location and intensity of its expression were evaluated for ß-catenin. The results were statistically analyzed using the one-way analysis of variance and Chi-square test. RESULTS: The expression of ß-Catenin in the cytoplasm as well as in the nucleus increased from mild-to-moderate dysplasia to OSMF and to severe epithelial dysplasia in an increasing order. The expression is seen to translocate from membranous to cytoplasm to nucleus indicating a proliferative potential in these group of lesions. CONCLUSION: ß-catenin is a promising marker which indicates the malignant transformation potential in the higher grades of dysplasia and OSMF.

Diagnostic efficacy of neutrophil to lymphocyte ratio (NLR) in oral potentially malignant disorders and oral cancer.

BACKGROUND AND AIMS: Inflammation is considered to be the seventh hallmark of cancer and plays a pivotal role in all stages of tumor development. Systemic inflammatory responses in particular neutrophil to lymphocyte ratio (NLR) have garnered immense attention of current researchers and its role is well proven in various solid malignancies. Its prognostic role in oral cancer have been extensively studied. However, its diagnostic role is yet to be explored. The current study aims to investigate diagnostic utility of NLR in oral potentially malignant disorders and oral cancer, when compared to normal subjects. METHODS: A total of 150 subjects were involved in the study, a total of 2.5 ml of blood was drawn from the median cubital vein of the patient in an EDTA vial and hematological parameters were assessed using Erba-Transasia B7256 Autoanalyzer and reassessed manually by two experts. STATISTICAL ANALYSIS: The NLR values were recorded and tabulated as Mean ± S.D. and comparisons were analyzed using Kruskal Wallis and Mann Whitney post hoc U test. ROC curve analysis was performed to estimate cut-off values. RESULTS: The NLR values when compared between the 3 groups were statistically significant (P < 0.001). The cut off value between disease and normal subject was 2.33, while the cut-off value between potentially malignant and malignant condition is 3.20. CONCLUSION: NLR can be a valuable diagnostic adjunct in oral cancer and potentially malignant disorders of oral cavity.

Molecular machinery regulating mitochondrial calcium levels: The nuts and bolts of mitochondrial calcium dynamics.

Mitochondria play vital role in regulating the cellular energetics and metabolism. Further, it is a signaling hub for cell survival and apoptotic pathways. One of the key determinants that calibrate both cellular energetics and survival functions is mitochondrial calcium (Ca2+) dynamics. Mitochondrial Ca2+ regulates three Ca2+-sensitive dehydrogenase enzymes involved in tricarboxylic acid cycle (TCA) cycle thereby directly controlling ATP synthesis. On the other hand, excessive Ca2+ concentration within the mitochondrial matrix elevates mitochondrial reactive oxygen species (mROS) levels and causes mitochondrial membrane depolarization. This leads to opening of the mitochondrial permeability transition pore (mPTP) and release of cytochrome c into cytosol eventually triggering apoptosis. Therefore, it is critical for cell to maintain mitochondrial Ca2+ concentration. Since cells can neither synthesize nor metabolize Ca2+, it is the dynamic interplay of Ca2+ handling proteins involved in mitochondrial Ca2+ influx and efflux that take the center stage. In this review we would discuss the key molecular machinery regulating mitochondrial Ca2+ concentration. We would focus on the channel complex involved in bringing Ca2+ into mitochondrial matrix i.e. Mitochondrial Ca2+ Uniporter (MCU) and its key regulators Mitochondrial Ca2+ Uptake proteins (MICU1, 2 and 3), MCU regulatory subunit b (MCUb), Essential MCU Regulator (EMRE) and Mitochondrial Ca2+ Uniporter Regulator 1 (MCUR1). Further, we would deliberate on major mitochondrial Ca2+ efflux proteins i.e. Mitochondrial Na+/Ca2+/Li+ exchanger (NCLX) and Leucine zipper EF hand-containing transmembrane1 (Letm1). Moreover, we would highlight the physiological functions of these proteins and discuss their relevance in human pathophysiology. Finally, we would highlight key outstanding questions in the field.

Tongue and its ties: Posterior tongue width in gender estimation - A forensic gratuity.

BACKGROUND AND OBJECTIVES: Human identification is one of the challenging areas that man has been confronted with. The forensic odontologist deals with human identification based on unique features of the oral cavity. The human tongue is sheathed within the oral cavity, where it lies protected against the external atmosphere, just as the palatine folds. It is can be easily showed for inspection but at the same time be protected from the external environment. AIM AND OBJECTIVE: The objective of this study is to examine the uniqueness of tongue morphology and find out parameters to estimate gender of an individual using the same. METHODOLOGY: A total of 30 subjects (15 girls and 15 boys) were taken for this study whose tongue were examined, photographed and alginate impression were taken to create a database of tongue morphology. RESULT: The mean posterior width of the tongue was higher among the males in both cast as well as photographs.

Burden of scrub typhus among patients with acute febrile illness attending tertiary care hospital in Chitwan, Nepal.

OBJECTIVES: Scrub typhus is an emerging neglected tropical disease, reported from many parts of Asia including Nepal. This study aims to determine the seroepidemiology of scrub typhus among febrile patients attending Chitwan Medical College Teaching Hospital (CMC-TH), Bharatpur, Nepal. STUDY DESIGN AND SETTING: This was a hospital laboratory-based prospective study conducted in CMC-TH (a 750-bed hospital) located in Bharatpur, Chitwan district of Nepal. PARTICIPANTS: A total of 1797 patients visiting CMC-TH with acute febrile illness (temperature more than 38°C) were enrolled in this study. METHODS: A total of 1797 blood samples were collected from patients presenting with acute febrile illness. The samples were processed for detection of antibody for scrub typhus by ELISA for specific IgM antibody and Weil-Felix test. RESULTS: Out of 1797 serum sample of febrile patients, 524 (29.2%) were scrub typhus positive. Maximum seropositive cases were from Chitwan district, 271 (51.7%) with predominance among women, 314 (35.9%). Scrub typhus was common among age group 51-60 years (37.2%) and farmers, 182 (37.8%). Highest seropositivity was found in July, 60 (57.7%). Fever was common clinical symptom. Thrombocytopenia was seen in 386 (73.7%) and raised transaminase aspartate aminotransferase, 399 (76.1%) among seropositive cases. Weil-Felix test positive were 397 (22.1%) and IgM ELISA positive were 524 (29.2%). The correlation between IgM ELISA and Weil-Felix test showed statistically significant association (r=0.319, p<0.001). CONCLUSION: High prevalence of scrub typhus implies that patients with acute febrile illness should be investigated for scrub typhus with high priority. There is utmost need of reliable diagnostic facilities at all levels of healthcare system in Nepal. Infection with scrub typhus was found high and this calls for an urgent need to introduce vaccine against scrub typhus. More sustain and vigorous awareness programmes need to be promoted for early diagnosis, treatment and control.

Prevalence of oral cancer and oral epithelial dysplasia among North Indian population: A retrospective institutional study.

BACKGROUND: Despite our sincere and serious efforts, oral cancer (particularly oral squamous cell carcinoma [OSCC]) is the major cause of morbidity and mortality in the Indian population. Oral precancerous lesions show quite high malignant transformation rate. Epidemiological data of oral epithelial dysplasia (OED) and OSCC could help in early diagnosis and thus may improve the prognosis. The current study aims to retrospectively analyze the epidemiological profile of patients with different grades of OED and OSCCs. MATERIALS AND METHODS: The current study is a retrospective analysis of OED and OSCC reported in 5 years in our institution from 2014 to 2018. Data for the analysis were attained from the case sheets from the patients diagnosed with OED and OSCC. RESULTS: The mean prevalence of OED and OSCC was 5.71% and 9.85%, respectively. Among the dysplastic lesions, severe dysplasia was more common, while well-differentiated squamous cell carcinoma was more common among the carcinomatous lesions. The peak age prevalence of both the lesions was third to fifth decade. Males were more frequently affected than females, with buccal mucosa being the most common site. CONCLUSION: The data attained from this study highlight the need for community-based screening and awareness programs for general population and thus obtain a healthier society.

Nucleophilic Acylation with Aromatic Aldehydes to 2 Bromoacetonitrile: An Umpolung Strategy for the Synthesis of Active Methylene Compounds.

BACKGROUND: A novel one-pot N-heterocyclic carbene (NHC)-catalysed acylation of 2- bromoacetonitrile with aromatic aldehydes is reported. The protocol involves carbonyl umpolung reactivity of aldehydes in which the carbonyl carbon attacks nucleophilically (as d1 nucleophile) on the electrophilic terminal of 2-bromoacetonitrile to afford 3-aryl-3-oxopropanenitrile. The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. MATERIALS AND METHODS: A flame-dried round bottom flask was charged with Imidazolium salts (3a) (0.20 mmol). Aldehyde 1a (1.0 mmol), 2-bromoacetonitrile 2 (1.0 mmol), and THF / t-BuOH 5 mL; 10:1) were added at positive nitrogen pressure followed by the addition of DBU (0.15 mmol) through stirring. The resulting yellow- orange solution was stirred at room temperature for 5-6 h. After completion of the reaction (TLC monitored), the reaction mixture was concentrated under reduced pressure. The product was purified using hexane / EtOAc (10:1) as an eluent to provide analytically pure compound 4a. Physical data of representative compounds and the NMR spectroscopic data are in agreement with the literature value. RESULTS AND DISCUSSION: The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. CONCLUSION: To sum up, we have developed a convenient, efficient and one-pot route for 3-oxo-3- phenylpropanenitrile synthesis from NHC promoted direct nucleophilic acylation of aromatic aldehydes using 2- bromoacetonitrile. This method provided a wide range of products and good yields. To best of our knowledge, this is the new report for the synthesis of 3-oxo-3-phenylpropanenitrile through NHC promoted nucleophilic acylation of aromatic aldehyde.

How addicted are newly admitted undergraduate medical students to smartphones?: a cross-sectional study from Chitwan medical college, Nepal.

BACKGROUND: Increasing smartphone use among adolescents in todays' world has made this handy device an indispensable electronic tool, however, it comes at a price of problematic overuse or addiction. We aim to investigate the prevalence of smartphone addiction among undergraduate medical students and explore its association with various demographic and personal factors. METHODS: A pool of 250 undergraduate students completed a survey composed of socio-demographics information, smartphone-use related variables and 10-point Smartphone Addiction Scale-Short Version in February 2019. RESULTS: Smartphone addiction among medical students was estimated at around 36.8% with higher percentage of male smartphone addicts. Phubbing was reported by 37.6% participants with more than 60% reporting overuse. Statistically significant association was observed between smartphone addiction and gender and overuse. Self-acknowledgement of addiction was found to be the biggest predictor of smartphone addiction. CONCLUSION: This study provides preliminary insights into smartphone use, smartphone addiction and various factors predicting smartphone addiction among early undergraduate medical students from Nepal, which should be extended in future studies. Education policymakers and educators need to develop some strategies encouraging student's smartphone utilization to enhance academic performance.

DBU Catalysis: An Efficient Synthetic Strategy for 5,7-disubstituted-1,2,4- triazolo[1,5-a]pyrimidines.

AIMS AND OBJECTIVES: An efficient and facile DBU catalysed synthesis of highly significant motif 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines under solvent-free condition has been reported. MATERIALS AND METHODS: To a round bottom flask, 1.0 mmol of chalcone (1), 1.5 mmol of 3-amino-1,2,4- triazole (2) and 30 mol% of DBU were added at 70 °C and stirred in solvent-free condition. After the completion of the reaction (monitored by TLC), water (10 ml) was added. The aqueous layer was extracted with ethyl acetate (3 ×10 ml). The combined organic layers were dried over anhydrous Na2SO4. The combined organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate and hexane as eluent. RESULTS: Reaction using chalcone and 3-amino-1,2,4-triazole as model substrates were carried out under different reaction conditions and it was observed that 30 mol% of DBU under the solvent-free condition at 70 °C was the optimum temperature for the proposed synthesis. CONCLUSION: Use of DBU (an organocatalyst) as a base, operational simplicity, high yield of products and short reaction time are some of the significant advantages associated with the proposed strategy.

Metabolic, Hormonal, Immunologic, and Genetic Factors Associated With the Incidence of Thyroid Disorders in Polycystic Ovarian Syndrome Patients.

Many endocrinopathies have been increasingly affecting females of reproductive age. Polycystic ovary syndrome (PCOS) and hypothyroidism are some of the most common endocrinopathies seen in females. The aim of this study is to find a relationship between the incidence of thyroiditis in polycystic ovarian syndrome patients. Literature review search was conducted via a series of systematic searches using multiple databases which lead to cross-referencing of articles within assigned criteria. Our study resulted in a review of 42 articles pertaining to our study. In this literature review article, factors were identified associating PCOS with thyroiditis. A viable relationship was found between the incidence of PCOS and thyroiditis. The combination of factors seen in this study proposes that clinicians may need to focus on certain markers regarding the screening of the incidence of thyroiditis. We also recommend future cohort studies to be conducted to further confirm the associations identified in this article.