A comprehensive review of dengue with a focus on emerging solutions for precision and timely detection.

Dengue is a global health problem, caused by the dengue virus (DENV), which belongs to the Flaviviridae family of viruses. The transmission of DENV occurs through vectors, Ae. aegypti and Ae. Albopictus mosquitoes, to the human host, classifying it as a vector-borne disease. The disease incidence is increasing at an alarming rate and needs to be tackled to reduce the morbidity and mortality caused by the disease. Environmental and clinical surveillance, detection of the virus, and diagnostics are critical tools to address this issue. In this comprehensive review, we explore various diagnostic techniques and the associated challenges within the context of dengue. While we briefly touch upon dengue's epidemiology, serotypes, and pathogenesis, our primary emphasis remains on diagnostics. We delve into the intricacies of these diagnostic methods, considering both the challenges they entail and the potential they hold in terms of accuracy and accessibility. It's important to note that the review does not extensively cover clinical aspects or regional variations of the disease.

Nucleic Acid Based Testing (NABing): A Game Changer Technology for Public Health.

Timely and accurate detection of the causal agent of a disease is crucial to restrict suffering and save lives. Mere symptoms are often not enough to detect the root cause of the disease. Better diagnostics applied for screening at a population level and sensitive detection assays remain the crucial component of disease surveillance which may include clinical, plant, and environmental samples, including wastewater. The recent advances in genome sequencing, nucleic acid amplification, and detection methods have revolutionized nucleic acid-based testing (NABing) and screening assays. A typical NABing assay consists of three modules: isolation of the nucleic acid from the collected sample, identification of the target sequence, and final reading the target with the help of a signal, which may be in the form of color, fluorescence, etc. Here, we review current NABing assays covering the different aspects of all three modules. We also describe the frequently used target amplification or signal amplification procedures along with the variety of applications of this fast-evolving technology and challenges in implementation of NABing in the context of disease management especially in low-resource settings.

Building cross-border collaborations to increase diversity and accelerate rare disease drug development - meeting report from the inaugural IndoUSrare Annual Conference 2021.

The inaugural IndoUSrare Annual Conference was held virtually from 29 November to 2 December 2021 and was organized by the Indo US Organization for Rare Diseases (IndoUSrare). The event saw participation from over 250 stakeholders of rare diseases who joined in virtually by audio/video on the Zoom platform from around the world, with a majority of attendees concentrated in the Indian subcontinent and the United States. The conference was held over 4 days from 10:00 a.m. to 12:30 p.m. Eastern Time on each day, which accommodated participation by speakers and attendees from both the eastern and western hemispheres. The agenda over 4 days holistically covered broad topics of interest to different stakeholder groups such as representatives from organizations working toward policy frameworks for rare diseases or orphan drugs (Days 1, 4), biomedical research institutions (Day 2), patient advocacy organizations (Day 3), and patient advocacy and engagement offices within Industry (Day 4). In this meeting report, we summarize the key highlights from each day of this conference, with a perspective on future directions encouraging cross-border multistakeholder collaborations to maximize diversity, equity, and inclusion (DEI) in rare disease diagnosis, research, clinical trials, and treatment access. Each day included a keynote lecture on the theme of the day followed by a series of individual speaker presentations and/or a panel discussion. The goal was to understand current barriers and bottlenecks in the rare disease ecosystem. The discussions also helped highlight gaps and identify potential solutions that can be achieved through building multistakeholder collaborations across international borders, which we believe IndoUSrare is uniquely positioned to do with organizational programs such as rare patient foundation alliance, technology-enabled patient concierge, research corps, and corporate alliance program. The inaugural conference of the then 2+-year-old IndoUSrare organization laid the foundation for ongoing engagement of stakeholders between the two countries - the United States and India. The long-term goal is to scale the conference more broadly and serve as a model for other low- and middle-income countries (LMICs). Plain language summary: IndoUSrare held its inaugural Annual Conference from 29 November to 2 December 2021. It was focused on the theme of cross-border collaborations for rare disease drug development, with each day dedicated to a specific patient-focused discussion topic, ranging from patient-led advocacy (Advocacy Day), research (Research Day), rare disease community support and engagement (Patients Alliance Day), to industry collaborations (Industry Day). The 4-day conference was held in virtual mode and attracted over 250 attendees from across the globe. This meeting report provides the key highlights of the event and summarizes learnings and future directions encouraging cross-border collaborations to increase diversity, equity, and inclusion (DEI) in rare disease research and clinical trials.

Insights into interplay of immunopathophysiological events and molecular mechanistic cascades in psoriasis and its associated comorbidities.

Psoriasis is an inflammatory skin disease with complex pathogenesis and multiple etiological factors. Besides the essential role of autoreactive T cells and constellation of cytokines, the discovery of IL-23/Th17 axis as a central signaling pathway has unraveled the mechanism of accelerated inflammation in psoriasis. This has provided insights into psoriasis pathogenesis and revolutionized the development of effective biological therapies. Moreover, genome-wide association studies have identified several candidate genes and susceptibility loci associated with this disease. Although involvement of cellular innate and adaptive immune responses and dysregulation of immune cells have been implicated in psoriasis initiation and maintenance, there is still a lack of unifying mechanism for understanding the pathogenesis of this disease. Emerging evidence suggests that psoriasis is a high-mortality disease with additional burden of comorbidities, which adversely affects the treatment response and overall quality of life of patients. Furthermore, changing trends of psoriasis-associated comorbidities and shared patterns of genetic susceptibility, risk factors and pathophysiological mechanisms manifest psoriasis as a multifactorial systemic disease. This review highlights the recent progress in understanding the crucial role of different immune cells, proinflammatory cytokines and microRNAs in psoriasis pathogenesis. In addition, we comprehensively discuss the involvement of various complex signaling pathways and their interplay with immune cell markers to comprehend the underlying pathophysiological mechanism, which may lead to exploration of new therapeutic targets and development of novel treatment strategies to reduce the disastrous nature of psoriasis and associated comorbidities.

Chorismate synthase from malaria parasites is bifunctional enzyme.

Chorismate synthase (Cs) is the last enzyme of the main trunk of shikimate pathway and catalyzes formation of chorismate, a major aromatic metabolite precursor. We have previously reported that Cs is highly conserved across different Plasmodium sp. Here we report that Cs from malaria parasites are bifunctional enzymes through expression and functional studies of two recombinant proteins rPfCs (Cs from P. falciparum) and rPvCs (Cs from P. vivax). We confirm bifunctional activity of both rPfCs and rPvCs based on their ability to catalyze formation of chorismate under aerobic conditions as well as their ability to catalyze generation of reduced flavin mononucleotide (FMN) as assessed through diaphorase assay.

Therapeutic Potential, Challenges and Future Perspective of Cancer Stem Cells in Translational Oncology: A Critical Review.

Stem cell research is a rapidly developing field that offers effective treatment for a variety of malignant and non-malignant diseases. Stem cell is a regenerative medicine associated with the replacement, repair, and restoration of injured tissue. Stem cell research is a promising field having maximum therapeutic potential. Cancer stem cells (CSCs) are the cells within the tumor that posses capacity of selfrenewal and have a root cause for the failure of traditional therapies leading to re-occurrence of cancer. CSCs have been identified in blood, breast, brain, and colon cancer. Traditional therapies target only fast growing tumor mass, but not slow-dividing cancer stem cells. It has been shown that embryonic pathways such as Wnt, Hedgehog and Notch, control self-renewal capacity and involved in cancer stem cell maintenance. Targeting of these pathways may be effective in eradicating cancer stem cells and preventing chemotherapy and radiotherapy resistance. Targeting CSCs has become one of the most effective approaches to improve the cancer survival by eradicating the main root cause of cancer. The present review will address, in brief, the importance of cancer stem cells in targeting cancer as better and effective treatment along with a concluding outlook on the scope and challenges in the implication of cancer stem cells in translational oncology.