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Fulltext Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment

Kumar S, Karuppanan K, Subramaniam G

J Med Virol, 2022 Oct;94(10):4780-4791.
PMID: 35680610 DOI: 10.1002/jmv.27927

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.
Fulltext Unravelling the connection between COVID-19 and Alzheimer's disease: a comprehensive review

Shajahan SR, Kumar S, Ramli MDC

Front Aging Neurosci, 2023;15:1274452.
PMID: 38259635 DOI: 10.3389/fnagi.2023.1274452

Currently, there exists a limited comprehension regarding the correlation between COVID-19 and Alzheimer's disease (AD). To elucidate the interrelationship and its impact on outcomes, a comprehensive investigation was carried out utilising time-unrestricted searches of reputable databases such as Scopus, PubMed, Web of Science, and Google Scholar. Our objective was to evaluate the impact of various medical conditions on severe COVID-19-related events. We focused on identifying and analysing articles that discussed the clinical characteristics of COVID-19 patients, particularly those pertaining to severe events such as ICU admission, mechanical ventilation, pneumonia, mortality and acute respiratory distress syndrome (ARDS) a serious lung condition that causes low blood oxygen. Through careful data analysis and information gathering, we tried to figure out how likely it was that people with conditions, like AD, would have serious events. Our research investigated potential mechanisms that link AD and COVID-19. The ability of the virus to directly invade the central nervous system and the role of ACE-2 receptors were investigated. Furthermore, the OAS1 gene served as the genetic link between AD and COVID-19. In the context of COVID-19, our findings suggest that individuals with AD may be more susceptible to experiencing severe outcomes. Consequently, it is crucial to provide personalised care and management for this demographic. Further investigation is required to attain a comprehensive comprehension of the intricate correlation between Alzheimer's disease and COVID-19, as well as its ramifications for patient outcomes.
Fulltext Bibliometric Insights Into the Evolving Landscape of Antibiotic Resistance Research: Trends, Collaborations, and Key Foci (1965-2023)

Dagli N, Haque M, Kumar S

Cureus, 2024 Feb;16(2):e53508.
PMID: 38314393 DOI: 10.7759/cureus.53508

Conducted on randomized clinical trials (RCTs) addressing antibiotic resistance in the PubMed database, this bibliometric analysis explores relevant sources, keyword co-occurrence, institutional co-authorship, global collaboration patterns, and evolving research trends. Utilizing an electronic search on January 13, 2024, employing the term "antibiotic resistance," 252,657 results were retrieved, of which 2,962 RCTs were analyzed. The dissemination of RCTs exhibited a variable distribution from 1965 to 2023, with a peak in 2014, noteworthy peaks in 1993-1994 and 2002-2003, contrasting declines in 1990-1991 and 2007-2008, and a consistent decrease post 2018. The University of California emerged as a predominant institution, and the journal "Antimicrobial Agents and Chemotherapy" substantially contributed. The annual growth rate stood at 1.2%, with 97 single-authored documents, an average of 8.76 co-authors per document, and 8.89% international co-authorships. Co-occurrence analysis highlighted prevalent themes, including double-blind clinical trials and significant keywords like human immunodeficiency virus (HIV) infections, Helicobacter infections, metronidazole, and amoxicillin. Trend analysis revealed a chronological shift from penicillin to HIV and Helicobacter drug therapies, culminating in combination antibacterial therapy for multiple bacterial strains. The prevailing trend in antibiotic resistance publications involved single-country endeavors, with the United States leading in collaboration frequency. The findings indicate a need to foster international collaboration, promote interdisciplinary research, support emerging trends, encourage open-access publication, and address declines in research activity, particularly RCTs.
Rapid metastasis of breast cancer cells from primary tumour to liver

Kumar SS, Radhakrishnan AK, Cheong SK

Pak J Biol Sci, 2010 Apr 01;13(7):303-15.
PMID: 20836285

The aim of this study was to establish an animal model of mammary carcinoma metastasis to discern the in vivo effects of growth and spread of breast cancer. Six-week-old female BALB/c mice were inoculated with 4T1 murine breast cancer cells. Mice weight and primary tumour mass volume were regularly recorded to study the physical effects of a vigorously growing and spreading of cancer cell line. Gross and histological studies were carried out to determine the approximate day of metastatic onset. Production of IFN-gamma was assessed by ELISA to understand its role in tumour growth and metastasis. Lymphocyte markers such as CD8+, CD25 and CD49b were analysed to elucidate its role in tumour growth and progression. Present study showed that the metastatic onset occurs approximately 11 days after the mice were inoculated with the 4T1 murine breast cancer cells. Gross studies showed hepatosplenomegaly. The breast cancer cells from primary tumour were found to spread rapidly to the liver on day 11. IFN-gamma production was higher in inoculated mice serum compared to control mice serum. Higher numbers of CD8+, CD25 and CD49b cells were observed in the peripheral blood of inoculated mice, compared to control mice. In conclusion, the 4T1 murine breast cancer cells can migrate and metastasise rapidly to the liver, eliciting various immune responses.
Mediation analysis quantifying the magnitude of stillbirth risk attributable to small for gestational age infants

Crawford K, Hong J, Kumar S

Am J Obstet Gynecol MFM, 2023 Dec;5(12):101187.
PMID: 37832646 DOI: 10.1016/j.ajogmf.2023.101187

BACKGROUND: Many risk factors for stillbirth are linked to placental dysfunction, which leads to suboptimal intrauterine growth and small for gestational age infants. Such infants also have an increased risk for stillbirth.
OBJECTIVE: This study aimed to investigate the effect of known causal risk factors for stillbirth, and to identify those that have a large proportion of their risk mediated through small for gestational age birth.
STUDY DESIGN: This retrospective cohort study used data from all births in the state of Queensland, Australia between 2000 and 2018. The total effects of exposures on the odds of stillbirth were determined using multivariable, clustered logistic regression models. Mediation analysis was performed using a counterfactual approach to determine the indirect effect and percentage of effect mediated through small for gestational age. For risk factors significantly mediated through small for gestational age, the relative risks of stillbirth were compared between small for gestational age and appropriate for gestational age infants. We also investigated the proportion of risk mediated via small for gestational age for late stillbirths (≥28 weeks).
RESULTS: The initial data set consisted of 1,105,612 births. After exclusions, the final study cohort constituted 925,053 births. Small for gestational age births occurred in 9.9% (91,859/925,053) of the study cohort. Stillbirths occurred in 0.5% of all births (4234/925,053) and 1.5% of small for gestational age births (1414/91,859). Births at ≥28 weeks occurred in 99.4% (919,650/925,053) of the study cohort and in 98.9% (90,804/91,859) of all small for gestational age births. Of the ≥28-week births, stillbirths occurred in 0.2% (2156/919,650) of all births and 0.8% (677/90,804) of the small for gestational age births. Overall, increased odds of stillbirth were significantly mediated through small for gestational age for age <20 years, low socioeconomic status, Indigenous ethnicity, birth in sub-Saharan and North Africa or the Middle East, smoking, nulliparity, multiple pregnancy, assisted conception, previous stillbirth, preeclampsia, and renal disease. Preeclampsia had the largest proportion mediated through small for gestational age (66.7%), followed by nulliparity (61.6%), smoking (29.4%), North-African or Middle Eastern ethnicity (27.6%), multiple pregnancy (26.3%), low socioeconomic status (25.8%), and Indigenous status (18.7%). Sensitivity analysis showed that for late stillbirths, the portions mediated through small for gestational age remained very similar for many of the risk factors.
CONCLUSION: Although small for gestational age is an important mediator between many pregnancy risk factors and stillbirth, mitigating the risk of small for gestational age is likely to be of value only when it is a major contributor in the pathway to fetal demise.
Fulltext Mapping the Evolution of Clinical Trials on Drug-Resistant Tuberculosis: A Bibliometric Overview (1965-2023)

Dagli N, Haque M, Kumar S

Cureus, 2024 Feb;16(2):e55190.
PMID: 38425326 DOI: 10.7759/cureus.55190

This study provides a comprehensive overview of the current landscape in drug-resistant tuberculosis research. An extensive electronic search was conducted on PubMed and Scopus databases to identify clinical trials related to drug-resistant tuberculosis. Network analysis and visualization were performed on the data using the Biblioshiny App and VOSviewer software. This bibliometric study focuses on revealing publication trends, leading contributors, key institutions, thematic focuses, and citation patterns. The analysis of research paper publications reveals a consistent upward trajectory over the years, characterized by periodic declines and subsequent surges. Noteworthy peaks in 2013 and 2010 are observed in Scopus and PubMed, respectively, followed by marked declines, particularly notable between 2021 and 2023. PubMed and Scopus data indicate that the United States and South Africa are the leading contributors. According to the PubMed and Scopus databases, the University of Cape Town and Stellenbosch University are the institutions that contribute the most. Keyword and thematic analyses underscore the primary research focuses on drug-resistant tuberculosis (DR-TB), including drug combination therapy, microbiological analysis of sputum, therapeutic uses of antitubercular agents, drug resistance (DR), multidrug resistance (MDR), and Mycobacterium tuberculosis. The trend-topic analysis reveals dynamic shifts in research focus over time, transitioning from single-drug therapy to addressing drug resistance and highlighting the emerging need for effective drug therapy in cases of multidrug-resistant tuberculosis. Notably, most research papers on drug-resistant tuberculosis are single-country publications. Citation analysis in the Scopus database indicates that the average citation per year and mean total citation per year peaked during 2005-2006. This suggests a period of heightened impact and recognition within the research community during that timeframe. The study's findings may inform strategic planning for combating drug-resistant tuberculosis, ultimately contributing to future enhanced prevention, diagnosis, and treatment strategies.
Exploring the Perspective of Oral Microbiome Studies in PubMed Database: A Bibliometric Appraisal

Dagli N, Sinha S, Haque M, Kumar S

Cureus, 2024 Feb;16(2):e53824.
PMID: 38332998 DOI: 10.7759/cureus.53824

This research aims to postulate an exhaustive sketch of the current research background on the oral microbiome to emphasize prevailing research trends. On November 25, 2023, a digital exploration was conducted on the PubMed platform. The search strategy employed was- '(Microbiome, Microbiota, Microorganisms, Bacteria, Virus, Fungi) AND (Oral, Dental, Saliva, Plaque, Gingival Crevicular Fluid)'. Inclusive criteria comprised review articles, clinical trials, and meta-analyses. The Biblioshiny app and VOSviewer software were used to create and visualize bibliometric maps for network, thematic, and factorial analyses. The PubMed database search unveiled 215,068 published research studies on the oral microbiome, indicating a fluctuating publication pattern with an all-embracing mounting trajectory. Notably, there was a substantial increase in publications in 2020 and 2021, succeeded by a marked decline in 2022 and 2023. Sichuan University and the International Journal of Molecular Sciences emerged as the most prolific contributors among organizations and relevant sources. Keyword analysis revealed a research emphasis on the COVID-19 pandemic and the SARS-CoV-2 virus since 2019. Thematic mapping categorized key terms into motor, primary, niche, and emerging themes. The emerging terms identified are viral immunogenicity, antibodies, and vaccines, which support the revelation that COVID-19 and related terms will be the most pertinent subjects in oral microbiome studies in the future. Factorial analysis delineated the relationships between topics and subtopics in this domain.
Fulltext Mechanisms of Antibiotic Resistance and Developments in Therapeutic Strategies to Combat Klebsiella pneumoniae Infection

Li Y, Kumar S, Zhang L

Infect Drug Resist, 2024;17:1107-1119.
PMID: 38525477 DOI: 10.2147/IDR.S453025

Infections with drug-resistant bacteria have become one of the greatest public health challenges, and K. pneumoniae is among the top six drug-resistant bacteria. K. pneumoniae often causes nosocomial infections, leading to illnesses such as pneumonia, liver abscesses, soft tissue infections, urinary tract infections, bacteremia, and in some cases death. As the pathogen continues to evolve and its multidrug resistance increases, K. pneumoniae poses a direct threat to humans. Drug resistance in K. pneumoniae may occur due to the formation of biofilms, efflux pumps, and the production of β-lactamases. In many cases, resistance is further enhanced by enzymatic modification and loss of porins. Drug resistance to K. pneumoniae has led to a decline in the effectiveness of conventional therapies against this pathogen. Therefore, there is an urgent need to accelerate the development of new antibiotics and explore new therapeutic approaches such as antimicrobial peptides, phages, traditional Chinese medicine, immunotherapy, Antimicrobial nanoparticle technology, antisense oligonucleotides and gene editing technologies. In this review, we discuss the mechanisms of drug resistance in K. pneumoniae and compare several new potential therapeutic strategies to overcome drug resistance in the treatment of K. pneumoniae infections.
Bibliometric Analysis of Research Papers on Academic Stress (1989-2023)

Dagli N, Ahmad R, Haque M, Kumar S

Cureus, 2024 Mar;16(3):e55536.
PMID: 38449911 DOI: 10.7759/cureus.55536

This extensive study provides a comprehensive overview of the contemporary research landscape about academic stress, emphasizing on identifying the most relevant contributors and understanding prevalent trends. The analysis included 5,375 results from the PubMed database and revealed a consistent upward trajectory with fluctuations in research paper publications over the years. Network analysis and visualization were performed using the Biblioshiny app and VOSviewer software. The analysis identified that the University of Oslo has published the highest number of research papers related to academic stress. In contrast, the Netherlands, the USA, and Australia demonstrated the highest frequency of collaboration. Analysis of keywords and their co-occurrence provides an overview of the research focus and the areas associated with psychological stress due to academics. Thematic evaluation and topic trend analysis provided insights into the evolving nature of research in academic stress. The thematic map depicts two categories of themes - motor themes, including psychological stress, its epidemiology, the influence of the COVID-19 pandemic, and the mental health of university students, particularly those in medical programs; and emerging themes, including oxidative stress and risk factors, indicated evolving areas of interest. A notable observation was the scarcity of research on primary school students, signaling a gap in the existing academic stress literature. Citation analysis identified the most cited authors, countries, universities, and sources. This multifaceted examination provides a nuanced understanding of academic stress research's current state and dynamics, offering valuable insights into trends, collaborations, and thematic shifts that will guide future research in this critical field.
Fulltext Exploring the Bacteriophage Frontier: A Bibliometric Analysis of Clinical Trials Between 1965 and 2024

Dagli N, Haque M, Kumar S

Cureus, 2024 Mar;16(3):e56266.
PMID: 38495963 DOI: 10.7759/cureus.56266

In recent years, the rise of antibiotic-resistant bacteria has posed a severe threat to global public health, necessitating innovative and alternative approaches to combat this escalating crisis. Bacteriophages, viruses that infect and replicate within bacteria, have emerged as promising candidates for therapeutic intervention against antibiotic-resistant pathogens. This study delves into the intricate landscape of bacteriophage research, unraveling the trends and impact of research in the field. The analysis considers the chronological evolution of research, identifying key contributors, collaborative networks, and thematic trends that have shaped the trajectory of this rapidly growing field. Out of 101717 search results in the PubMed database, 163 clinical trials were identified, revealing a dynamic landscape of research activity between 1965 and 2024. The annual scientific publication analysis unveiled fluctuations in the number of publications, indicating an overall increasing trend. Notably, 2011 emerged as a peak year, signifying heightened activity in bacteriophage research. Employing Lotka's law, the authors' productivity analysis illustrated an inherent imbalance in author contributions, with a majority contributing to a single clinical trial. Co-authorship analysis highlighted leading collaborators. Co-occurrence analysis of keywords unveiled thematic clusters, providing insights into the diverse aspects of bacteriophage research. A word cloud emphasized significant terms, while a thematic map categorized themes into various developmental stages. Antimicrobial Agents, Chemotherapy, and Poultry Science were the most relevant journals based on the number of publications. The analysis of countries' contributions revealed the United States as a leading contributor, with Switzerland and China following suit. Collaboration patterns suggested predominantly independent research, with potential for increased international partnerships in certain regions. Additionally, temporal analysis of authors, institutions, sources, and countries revealed productivity patterns, historical context, and research shifts. By scrutinizing a vast array of scientific literature, this investigation aims to provide a panoramic view of how the scientific community has explored the potential of bacteriophages in the context of antibiotic resistance.
Fulltext Complete chloroplast genome sequence of MD-2 pineapple and its comparative analysis among nine other plants from the subclass Commelinidae

Redwan RM, Saidin A, Kumar SV

BMC Plant Biol, 2015;15:196.
PMID: 26264372 DOI: 10.1186/s12870-015-0587-1

Pineapple (Ananas comosus var. comosus) is known as the king of fruits for its crown and is the third most important tropical fruit after banana and citrus. The plant, which is indigenous to South America, is the most important species in the Bromeliaceae family and is largely traded for fresh fruit consumption. Here, we report the complete chloroplast sequence of the MD-2 pineapple that was sequenced using the PacBio sequencing technology.
Bibliometric Analysis and Visualization of Clinical Trials on the Therapeutic Potential of Essential Oils (1967-2024)

Dagli N, Haque M, Kumar S

Cureus, 2024 Apr;16(4):e57430.
PMID: 38572180 DOI: 10.7759/cureus.57430

Essential oils, aromatic compounds extracted from various parts of plants, have garnered significant attention in recent years due to their diverse therapeutic properties and potential applications in healthcare. This analysis delves into the publication trends, productivity patterns, most relevant contributors, coauthorship networks, most frequently used keywords, and their co-occurrence, topic trends, thematic evolution, and collaboration between various countries in clinical trials exploring the therapeutic potential of essential oils. Six hundred sixty-one clinical trials were selected from the PubMed database for analysis, authored by 2959 authors, and published across 359 sources. The analysis identified Horrobin DF as the most contributing author based on the number of published clinical trials, followed by Kasper S, McGuire JA, and Schlafke S. Lotka's law underscores the distribution of authors' productivity, revealing a small number of highly productive authors. Coauthorship analysis identifies significant collaborations among authors and institutions, with prominent contributors like Siegfried Kasper and institutions like Shiraz University of Medical Sciences. Furthermore, the analysis highlights leading journals like Complementary Therapies in Clinical Practice and the Journal of Alternative and Complementary Medicine. Using keyword clustering, connections between various subjects and their chronological presence are uncovered, offering insights into the changing research landscape. The thematic examination exposes changes in research emphasis over time, progressing from fundamental studies on essential oil components to broader utilization and focused inquiries into oils and therapeutic domains. Analysis of the countries of corresponding authors revealed that Iran has the highest number of multiple-country publications. Moreover, international collaboration trends have been unveiled. Together, these analyses furnish holistic understandings of keyword relationships, thematic shifts, and global partnerships in essential oil research, presenting valuable perspectives on trends and focal points within this domain.
Fulltext Bibliometric Analysis and Visualization of Clinical Trials on Psychological Stress and Oral Health (1967-2024)

Dagli N, Haque M, Kumar S

Cureus, 2024 Apr;16(4):e57865.
PMID: 38596209 DOI: 10.7759/cureus.57865

Stress is ubiquitous in modern life, influencing various facets of human health and well-being. While the impact of stress on mental and physical health is well-documented, its effects on oral health have garnered increasing attention in recent years. This bibliometric analysis explores the literature on the impact of stress on oral health. The study utilizes data from the PubMed database, focusing on publication trends, influential contributors and the temporal analysis of their publications, coauthorship analysis of authors and institutions, key thematic clusters, thematic evolution, and collaboration between various countries. Examining clinical trials investigating the impact of stress on oral health unveils significant trends and insights. Over time, there has been a steady rise in publication frequency, although with occasional fluctuations, indicating an increasing interest in the subject. The University of California has been identified as a leading institution, while Psychoneuroendocrinology emerges as a pivotal journal for disseminating research findings in the field. Keyword analysis reveals diverse thematic clusters, reflecting the multifaceted nature of the impact of stress on oral health. The analysis of topic trends showcases significant shifts over different periods, from basic correlations between mental health conditions and physiological indicators to a broader exploration of psychological interventions and social contexts in recent years. Thematic evolution analysis further elucidates this progression, categorizing themes into motor, basic, niche, and emerging or declining categories. Additionally, the analysis of corresponding authors' countries uncovers patterns of collaborative efforts, with the United States leading in collaboration levels. In summary, these analyses collectively highlight an evolving comprehension of the impact of stress on oral health, providing valuable insights for clinical practice and guiding future research endeavors.
Fulltext The Interplay Between Diabetes and Oral Health: A Comprehensive Bibliometric Analysis of Clinical Trials (1967-2024)

Dagli N, Haque M, Kumar S

Cureus, 2024 Apr;16(4):e58667.
PMID: 38644951 DOI: 10.7759/cureus.58667

Recognizing the complex interaction between diabetes and oral health is crucial, considering the increasing worldwide prevalence of these conditions. This bibliometric analysis delves into the extensive body of literature concerning the impact of diabetes on oral health, utilizing data retrieved from PubMed. The publishing trends indicate a growing research interest in the field over time, with notable peaks and declines. Coauthorship analyses of authors and institutions illuminated collaborative networks within the research community. Two departments at Ahvaz Jundishapur University of Medical Sciences in Iran, namely the Department of Periodontology within the School of Dentistry and the Diabetes Research Center within the Health Research Institute, demonstrated the highest total link strength. The co-occurrence analysis of keywords also unveiled thematic clusters, reflecting research focus areas and evolving trends. The analysis of topic trends highlighted persistent research interests in topics, such as type 2 diabetes mellitus, glycated hemoglobin, periodontitis, and therapy for chronic periodontitis, with shifts in therapeutic modalities investigated. The thematic map suggests that dental implants and tumor necrosis factor-alpha are emerging terms in the field that have gained more traction recently. Furthermore, the analysis of scientific production by country indicated varied contributions, with Brazil leading in publication output. Analysis of collaboration among corresponding authors' countries identified Italy exhibiting substantial international collaboration, while most of the countries primarily produced single-country publications. This comprehensive analysis provides insights into the multifaceted landscape of research on diabetes and oral health, emphasizing ongoing efforts to understand and address the complex interplay between these conditions.
A Bibliometric Analysis of Literature on the Impact of Rheumatoid Arthritis on Oral Health (1987-2024)

Dagli N, Haque M, Kumar S

Cureus, 2024 Apr;16(4):e58891.
PMID: 38659710 DOI: 10.7759/cureus.58891

This bibliometric analysis investigates the research landscape concerning the impact of rheumatoid arthritis (RA) on oral health through a comprehensive literature review. The study includes all English-language articles retrieved from the PubMed database, focusing on the relationship between RA and various aspects of oral health without any filter. The analysis of 261 publications revealed fluctuations in publication patterns from 1987 to 2024, with notable surges and declines in research activity. Collaborative networks among authors and institutions were identified, highlighting key contributors and prolific institutions such as Karolinska Institutet. The themes prevalent in the research included demographics, oral microbiota, biomarkers, treatment outcomes, and molecular mechanisms. Trend topic and thematic evolution analyses elucidated shifts in research focus from traditional concerns to emerging areas such as oral microbiology and immunological mechanisms. Key findings underscored the need for more clinical trials to comprehend the impact of RA on oral health, enhanced interdisciplinary collaboration, exploration of emerging areas, and longitudinal studies. This analysis provides valuable insights into the evolving research landscape, informing future investigations and interventions to improve oral health outcomes in individuals with RA.
A Bibliometric Analysis of Literature on the Impact of Diet on Oral Health

Dagli N, Haque M, Kumar S

Cureus, 2024 Apr;16(4):e59418.
PMID: 38694642 DOI: 10.7759/cureus.59418

The complex connection between oral health and dietary habits is fundamental to holistic well-being. Oral health is closely linked to dietary choices, both as a reflection and a factor in overall health. This bibliometric analysis investigates clinical trials published in the PubMed database spanning six decades to understand the landscape of research on the impact of diet on oral health. The analysis reveals a fluctuating yet generally increasing trend over the decades, with significant growth periods interspersed with occasional declines, culminating in a recent slight decrease in research output. With strong collaborative networks, Devizio and Proskin emerge as primary contributors. The University of Sydney has published the maximum number of clinical trials. Thematic clusters highlight diverse research facets, including physiological measurements, socio-economic influences, and biochemical aspects. The evolution in research priorities from experimental studies to longitudinal evaluations underscores the interdisciplinary nature of the field. The analysis of country-wise research output revealed that the United States, Germany, and Australia lead in scientific research output, with notable contributions to the global landscape. While larger countries like China and India are represented, their frequencies are relatively lower, suggesting potential areas for further exploration. Collaboration patterns vary between countries, influencing the global impact of their scientific output. Despite the limitations inherent in database selection, this study integrates bibliometric and thematic analyses to offer comprehensive insights into research trends and priorities.
Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction

Hong J, Crawford K, Cavanagh E, da Silva Costa F, Kumar S

Ultrasound Obstet Gynecol, 2024 May;63(5):635-643.
PMID: 37820083 DOI: 10.1002/uog.27513

OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR).
METHODS: This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB ( 95th centile or UtA-PI > 95th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF 95th centile and UtA-PI > 95th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32).
CONCLUSIONS: Low maternal serum PlGF level ( 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
A Bibliometric Analysis of Clinical Trials on Salivary Biomarkers for Mental Health (2003-2024)

Dagli N, Haque M, Kumar S

Cureus, 2024 Jul;16(7):e64635.
PMID: 39021745 DOI: 10.7759/cureus.64635

Mental health conditions, such as depression, anxiety, and stress-related disorders, are often difficult to diagnose and monitor using traditional methods. Salivary biomarkers offer a promising alternative due to their non-invasive nature, ease of collection, and the potential to reflect real-time physiological changes associated with mental health. This bibliometric analysis examines 95 clinical trials on stress biomarkers for mental health, published between 2003 and 2024. The field is characterized by extensive collaboration and global participation, involving 593 authors and publications across 73 journals. Despite a consistent annual publication rate, notable increases in 2011, 2014, and 2018 indicate growing research interest. The United States leads in research output, followed by Australia, Germany, and Japan, with Psychoneuroendocrinology being the most prominent journal. Co-occurrence analysis identified nine research clusters, suggesting diverse directions such as the impact of stress-related hormones, circadian rhythms, mindfulness, various therapies, aging, psychological adaptation mechanisms, exercise therapy, anxiety disorders, and the autonomic nervous system on salivary biomarkers. Key terms such as "biomarkers/metabolism," AND "hydrocortisone/metabolism," AND "saliva/metabolism" were central, with significant activity from 2012 to 2018. This analysis highlights a growing focus on the metabolic processes and therapeutic applications of salivary biomarkers in mental health. This bibliometric analysis calls attention to the promising potential of salivary biomarkers to revolutionize mental health diagnostics and treatment through non-invasive methods, fostering interdisciplinary research, technological advancements, and global health improvements.
Select critically ill patients at risk of augmented renal clearance: experience in a Malaysian intensive care unit

Adnan S, Ratnam S, Kumar S, Paterson D, Lipman J, Roberts J, et al.

Anaesth Intensive Care, 2014 Nov;42(6):715-22.
PMID: 25342403

Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of <24 hours plus an admission serum creatinine concentration <120 µmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency (P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl (P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with 'normal' serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.
Blastocystis sp. subtype 3 triggers higher proliferation of human colorectal cancer cells, HCT116

Kumarasamy V, Kuppusamy UR, Samudi C, Kumar S

Parasitol Res, 2013 Oct;112(10):3551-5.
PMID: 23933809 DOI: 10.1007/s00436-013-3538-5

Blastocystis sp. is a commonly found intestinal microorganism and was reported to cause many nonspecific gastrointestinal symptoms. Various subtypes have been previously reported, and the pathogenicity of different subtypes of Blastocystis is unclear and remains as a controversial issue. A recent study has shown that the Blastocystis antigen isolated from an unknown subtype could facilitate the proliferation of colon cancer cells. Current study was conducted to compare the effect of solubilized antigen isolated from five different subtypes of Blastocystis on colon cancer cells, HCT116. A statistically significant proliferation of these cells was observed when exposed to 1.0 μg/ml solubilized antigen isolated from subtype 3 Blastocystis (37.22%, p < 0.05). Real-time polymerase chain reaction demonstrated the upregulation of Th2 cytokines especially transforming growth factor beta in subtype 3-treated cancer cells (p < 0.01, 3.71-fold difference). Of interest, subtype 3 Blastocystis antigen also caused a significantly higher upregulation of cathepsin B (subtypes 1 and 2, p < 0.01; subtypes 4 and 5, p < 0.001; 6.71-fold difference) which lead to the postulation that it may enhance the exacerbation of existing colon cancer cells by weakening the cellular immune response. The dysregulation of IFN-γ and p53 expression also suggest Blastocystis as a proponent of carcinogenesis. Therefore, it is very likely for subtype 3 Blastocystis to have higher pathogenic potential as it caused an increased propagation of cancer cells and substantial amount of inflammatory reaction compared to other subtypes.

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