Advancements in Serum Biomarkers for Early Diagnosis and Prognostic Assessment of Aortic Dissection.

Aortic dissection (AD) is a potentially fatal cardiovascular issue that needs to be diagnosed and treated very away. While early detection is essential for bettering patient outcomes, there are substantial obstacles with the diagnostic techniques used today. Promising pathways for improving AD prognosis evaluation and early detection are presented by recent developments in serum biomarkers. The most recent research on serum biomarkers for AD is reviewed here, with an emphasis on the prognostic and diagnostic utility of these indicators. A number of biomarkers, including as matrix metalloproteinases, soluble elastin fragments, smooth muscle myosin heavy chain, and D-dimer, have been identified as putative markers of AD. These indicators are indicative of multiple pathophysiological mechanisms associated with AD, including inflammation, extracellular matrix remodeling, and vascular damage. Research has indicated that they are useful in differentiating AD from other acute cardiovascular diseases, facilitating prompt diagnosis and risk assessment.

Artificial intelligence in gastrointestinal endoscopy: a comprehensive review.

Integrating artificial intelligence (AI) into gastrointestinal (GI) endoscopy heralds a significant leap forward in managing GI disorders. AI-enabled applications, such as computer-aided detection and computer-aided diagnosis, have significantly advanced GI endoscopy, improving early detection, diagnosis and personalized treatment planning. AI algorithms have shown promise in the analysis of endoscopic data, critical in conditions with traditionally low diagnostic sensitivity, such as indeterminate biliary strictures and pancreatic cancer. Convolutional neural networks can markedly improve the diagnostic process when integrated with cholangioscopy or endoscopic ultrasound, especially in the detection of malignant biliary strictures and cholangiocarcinoma. AI's capacity to analyze complex image data and offer real-time feedback can streamline endoscopic procedures, reduce the need for invasive biopsies, and decrease associated adverse events. However, the clinical implementation of AI faces challenges, including data quality issues and the risk of overfitting, underscoring the need for further research and validation. As the technology matures, AI is poised to become an indispensable tool in the gastroenterologist's arsenal, necessitating the integration of robust, validated AI applications into routine clinical practice. Despite remarkable advances, challenges such as operator-dependent accuracy and the need for intricate examinations persist. This review delves into the transformative role of AI in enhancing endoscopic diagnostic accuracy, particularly highlighting its utility in the early detection and personalized treatment of GI diseases.

Artificial intelligence-enhanced electrocardiography for accurate diagnosis and management of cardiovascular diseases.

Electrocardiography (ECG), improved by artificial intelligence (AI), has become a potential technique for the precise diagnosis and treatment of cardiovascular disorders. The conventional ECG is a frequently used, inexpensive, and easily accessible test that offers important information about the physiological and anatomical state of the heart. However, the ECG can be interpreted differently by humans depending on the interpreter's level of training and experience, which could make diagnosis more difficult. Using AI, especially deep learning convolutional neural networks (CNNs), to look at single, continuous, and intermittent ECG leads that has led to fully automated AI models that can interpret the ECG like a human, possibly more accurately and consistently. These AI algorithms are effective non-invasive biomarkers for cardiovascular illnesses because they can identify subtle patterns and signals in the ECG that may not be readily apparent to human interpreters. The use of AI in ECG analysis has several benefits, including the quick and precise detection of problems like arrhythmias, silent cardiac illnesses, and left ventricular failure. It has the potential to help doctors with interpretation, diagnosis, risk assessment, and illness management. Aside from that, AI-enhanced ECGs have been demonstrated to boost the identification of heart failure and other cardiovascular disorders, particularly in emergency department settings, allowing for quicker and more precise treatment options. The use of AI in cardiology, however, has several limitations and obstacles, despite its potential. The effective implementation of AI-powered ECG analysis is limited by issues such as systematic bias. Biases based on age, gender, and race result from unbalanced datasets. A model's performance is impacted when diverse demographics are inadequately represented. Potentially disregarded age-related ECG variations may result from skewed age data in training sets. ECG patterns are affected by physiological differences between the sexes; a dataset that is inclined toward one sex may compromise the accuracy of the others. Genetic variations influence ECG readings, so racial diversity in datasets is significant. Furthermore, issues such as inadequate generalization, regulatory barriers, and interpretability concerns contribute to deployment difficulties. The lack of robustness in models when applied to disparate populations frequently hinders their practical applicability. The exhaustive validation required by regulatory requirements causes a delay in deployment. Difficult models that are not interpretable erode the confidence of clinicians. Diverse dataset curation, bias mitigation strategies, continuous validation across populations, and collaborative efforts for regulatory approval are essential for the successful deployment of AI ECG in clinical settings and must be undertaken to address these issues. To guarantee a safe and successful deployment in clinical practice, the use of AI in cardiology must be done with a thorough understanding of the algorithms and their limits. In summary, AI-enhanced electrocardiography has enormous potential to improve the management of cardiovascular illness by delivering precise and timely diagnostic insights, aiding clinicians, and enhancing patient outcomes. Further study and development are required to fully realize AI's promise for improving cardiology practices and patient care as technology continues to advance.

Dual-chamber versus single chamber pacemakers, a systemic review and meta-analysis on sick sinus syndrome and atrioventricular block patients.

Aims: The atrioventricular block (AVB) is a conduction system problem that results from the impairment in the transmission of an impulse from the atria to the ventricle, the disease has many etiologies. This article aimed to evaluate the efficacy and safety of dual and single-chamber pacemakers in patients with SSS and AVB. Methods: An electronic search of PubMed (Medline), EMBASE, and Google Scholar was performed from 2000 till August 15th, 2022. Retrieved articles were exported to Endnote Reference Library Software, where duplicate studies were removed from the list, and only articles meeting the eligibility criteria of this study were selected. RevMan 5.4 and STATA 16 software were used for the analysis. The modified Cochrane Collaboration's risk of bias and New-castle Ottawa scale were used for quality assessment of RCTs and observational studies respectively. Results: This study is composed of 8953 patients with sick-sinus syndrome and atrioventricular block. A total of thirteen outcomes are included in this meta-analysis, out of which atrial fibrillation significantly favored dual chamber [OR = 1.29; 95 % CI = 1.05-1.59; P = 0.01 I2 = 29 %] and overall complications [OR = 0.48; 95 % CI = 0.29-0.77; p = 0.03 I2 = 0 %] and pneumothorax [OR = 0.31; 95 % CI = 0.10-0.93; p = 0.04, I2 = 0 %] were satisfied by single-chamber pacing. Conclusion: This study concluded that neither single-chamber nor dual-chamber pacemakers are superior to each other, but they are unique in their own ways as the results of this study manifest remarkable reduction in atrial fibrillation rates and pneumothorax using dual-chamber and single-chamber pacemakers respectively.

Impacts of the advancement in artificial intelligence on laboratory medicine in low- and middle-income countries: Challenges and recommendations-A literature review.

Background and Aims: Artificial intelligence (AI) has emerged as a transformative force in laboratory medicine, promising significant advancements in healthcare delivery. This study explores the potential impact of AI on diagnostics and patient management within the context of laboratory medicine, with a particular focus on low- and middle-income countries (LMICs). Methods: In writing this article, we conducted a thorough search of databases such as PubMed, ResearchGate, Web of Science, Scopus, and Google Scholar within 20 years. The study examines AI's capabilities, including learning, reasoning, and decision-making, mirroring human cognitive processes. It highlights AI's adeptness at processing vast data sets, identifying patterns, and expediting the extraction of actionable insights, particularly in medical imaging interpretation and laboratory test data analysis. The research emphasizes the potential benefits of AI in early disease detection, therapeutic interventions, and personalized treatment strategies. Results: In the realm of laboratory medicine, AI demonstrates remarkable precision in interpreting medical images such as radiography, computed tomography, and magnetic resonance imaging. Its predictive analytical capabilities extend to forecasting patient trajectories and informing personalized treatment strategies using comprehensive data sets comprising clinical outcomes, patient records, and laboratory results. The study underscores the significance of AI in addressing healthcare challenges, especially in resource-constrained LMICs. Conclusion: While acknowledging the profound impact of AI on laboratory medicine in LMICs, the study recognizes challenges such as inadequate data availability, digital infrastructure deficiencies, and ethical considerations. Successful implementation necessitates substantial investments in digital infrastructure, the establishment of data-sharing networks, and the formulation of regulatory frameworks. The study concludes that collaborative efforts among stakeholders, including international organizations, governments, and nongovernmental entities, are crucial for overcoming obstacles and responsibly integrating AI into laboratory medicine in LMICs. A comprehensive, coordinated approach is essential for realizing AI's transformative potential and advancing health care in LMICs.

Meningitis in Niger Republic amidst COVID-19: current issues and novel recommendations.

Amidst coronavirus disease 2019 (COVID-19), there has been a misplaced priority on meningitis in the Niger Republic, thus refocusing resources and attention away from the continuing meningitis campaign in the Niger Republic. The over-strained state of public health resources and staff has also led to decreased surveillance, postponed diagnoses, and constrained immunization efforts in Niger Republic. This review aims to bridge the gaps regarding meningitis amid COVID-19 in Niger Republic and offer recommendations to government to mitigate meningitis in the country, with the hope of finding a permanent solution to this debilitating disease. The authors reviewed 45 past and present pieces of literature on meningitis and COVID-19 from 2013 to 2023 in well-renowned scientific databases such as PubMed, ResearchGate, Google Scholar, African Journals Online, Medline, and Embase. Since 2015, Niger Republic has experienced multiple meningitis epidemics that have resulted in 20, 789 cases and 1, 369 deaths [a case fatality rate (CFR) of 6.6%]. A total of 231 cases of meningitis were reported from 1 November 2021 to 31 January 2022. And recently, 559 cases of meningitis (of which 111 are laboratory confirmed), including 18 deaths (overall CFR 3.2%), occurred in the Zinder region, southeast of Niger Republic, from 1 November 2022 to 27 January 2023. Meningitis remains a public health concern in the world, especially in Niger Republic, which could lead to serious long-term complications. Therefore, adequate and novel measures and therapeutic actions should be implemented by the Niger Government to lessen the burden of the disease in the country.

Antihypertensive Effects of Sacubitril/Valsartan Versus Olmesartan: An Updated Systemic Review and Meta-Analysis of Randomized Controlled Trials.

Sacubitril/valsartan is a drug commonly prescribed for the management of hypertension. However, the complete understanding of its efficacy and safety as an antihypertensive agent remains a subject of ongoing investigation. To address this gap, a meta-analysis was conducted to assess and compare the efficacy and safety of sacubitril/valsartan in relation to olmesartan, an angiotensin receptor blocker (ARB). A thorough search of PubMed, Google Scholar, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) and observational studies that could contribute to this meta-analysis. The selected studies were evaluated for their efficacy and safety parameters, including mean sitting and ambulatory blood pressure measurements, common side effects, adverse events, and drug discontinuation rates. A total of eight studies, involving 4488 hypertensive patients, were included in this analysis. Among the participants, 63.5% were administered sacubitril/valsartan, while 36.5% received olmesartan. The analysis revealed significant changes in mean sitting systolic blood pressure (MsSBP), mean sitting diastolic blood pressure (MsDBP), and mean sitting pulse pressure (MsPP) favoring sacubitril/valsartan, with p-values <0.00001, 0.07, and <0.00001, respectively. Additionally, sacubitril/valsartan demonstrated a significant reduction in mean ambulatory systolic blood pressure (MaSBP), mean ambulatory diastolic blood pressure (MaDBP), and mean ambulatory pulse pressure (MaPP) with p-values of 0.001, 0.001, and 0.02, respectively. However, it is important to note that safety outcomes indicated that sacubitril/valsartan was associated with slightly less favorable results compared to olmesartan. This meta-analysis highlights that sacubitril/valsartan exhibits superior efficacy in reducing blood pressure parameters compared to olmesartan in hypertensive patients. Nevertheless, its safety profile appears to be slightly less favorable. To reinforce these findings and provide more robust evidence, further studies with larger sample sizes should be conducted in the future. This comprehensive review serves as a valuable resource for healthcare professionals and researchers seeking to make informed decisions regarding antihypertensive treatment options.

Efficacy of tumour-treating fields therapy in recurrent glioblastoma: A narrative review of current evidence.

Recurrent Glioblastoma presents a formidable challenge in oncology due to its aggressive nature and limited treatment options. Tumour-Treating Fields (TTFields) Therapy, a novel therapeutic modality, has emerged as a promising approach to address this clinical conundrum. This review synthesizes the current evidence surrounding the efficacy of TTFields Therapy in the context of recurrent Glioblastoma. Diverse academic databases were explored to identify relevant studies published within the last decade. Strategic keyword selection facilitated the inclusion of studies focusing on TTFields Therapy's efficacy, treatment outcomes, and patient-specific factors. The review reveals a growing body of evidence suggesting the potential clinical benefits of TTFields Therapy for patients with recurrent Glioblastoma. Studies consistently demonstrate its positive impact on overall survival (OS) and progression-free survival (PFS). The therapy's safety profile remains favorable, with mild to moderate skin reactions being the most commonly reported adverse events. Our analysis highlights the importance of patient selection criteria, with emerging biomarkers such as PTEN mutation status influencing therapy response. Additionally, investigations into combining TTFields Therapy with other treatments, including surgical interventions and novel approaches, offer promising avenues for enhancing therapeutic outcomes. The synthesis of diverse studies underscores the potential of TTFields Therapy as a valuable addition to the armamentarium against recurrent Glioblastoma. The narrative review comprehensively explains the therapy's mechanisms, clinical benefits, adverse events, and future directions. The insights gathered herein serve as a foundation for clinicians and researchers striving to optimize treatment strategies for patients facing the challenging landscape of recurrent Glioblastoma.

Cannulation Strategies in Type A Aortic Dissection: Overlooked Details and Novel Approaches.

Aortic dissection type A is a life-threatening condition that frequently necessitates surgical intervention. This review focuses on central aortic cannulation, arch branch vessel (ABV) cannulation, and proximal arch cannulation as key techniques during aortic surgery. It discusses innovative solutions for addressing these challenges. The review synthesizes findings from recent studies and emphasizes the significance of meticulous planning and execution of cannulation in aortic dissection repair. This review aims to contribute to the advancement of surgical practices and the enhancement of patient outcomes in the management of type A aortic dissection (AAD) by addressing these frequently overlooked details.

Precision Medicine Approaches to Diabetic Kidney Disease: Personalized Interventions on the Horizon.

Diabetic kidney disease (DKD) is a significant complication of diabetes that requires innovative interventions to address its increasing impact. Precision medicine is a rapidly emerging paradigm that shows excellent promise in tailoring therapeutic strategies to the unique profiles of individual patients. This abstract examines the potential of precision medicine in managing DKD. It explores the genetic and molecular foundations, identifies biomarkers for risk assessment, provides insights into pharmacogenomics, and discusses targeted therapies. Integrating omics data and data analytics provides a comprehensive landscape for making informed decisions. The abstract highlights the difficulties encountered during the clinical implementation process, the ethical factors to be considered, and the importance of involving patients. In addition, it showcases case studies that demonstrate the effectiveness of precision-based interventions. As the field progresses, the abstract anticipates a future characterized by the integration of artificial intelligence in diagnostics and treatment. It highlights the significant impact that precision medicine can have in revolutionizing the provision of care for DKD.

Individualizing Medicinal Therapy Post Heart Stent Implantation: Tailoring for Patient Factors.

The field of cardiovascular medicine is undergoing a transformative shift towards personalized medicinal therapy, particularly in the context of post stent implantation. This narrative review explores the significance, challenges, and future directions of individualized treatment strategies for patients with coronary stents. The review highlights the pivotal role of personalized approaches in optimizing treatment efficacy and minimizing adverse events. Real-world clinical studies and trials underscore the importance of tailoring antiplatelet therapy based on platelet function testing, genetic testing, and risk scoring. These studies reveal that personalized medicinal treatment improves clinical outcomes by balancing preventing thrombotic events and mitigating bleeding risks. Challenges, including cost, test availability, patient adherence, and ethical considerations, are discussed in depth, shedding light on the complexities of implementing personalized approaches. Technological advancements, including omics data integration, artificial intelligence, and big data analytics, shape the future of personalized medicinal therapy. These tools enable precise pharmacogenomic selection of medications and the development of integrated risk-scoring systems. Patient engagement and education are also central, with empowered patients and remote monitoring contributing to collaborative decision-making. In conclusion, the narrative review underscores that personalized medicinal therapy post stent implantation holds immense promise for revolutionizing cardiovascular care. By embracing a comprehensive approach that considers genetics, clinical factors, and patient preferences, healthcare providers can optimize treatment outcomes and improve patient quality of life. The evolving landscape of personalized medicine offers a glimpse into a future where tailored treatment strategies become the cornerstone of precision cardiovascular care.

Frequency and Factors of Sleep Paralysis Among Medical Students of Karachi.

INTRODUCTION: Sleep paralysis is a prevalent phenomenon characterized by suffocation, immobility, and hallucinations. Its causes remain unknown, although the neurotransmitter imbalance is suggested as a potential factor. This condition is closely associated with hallucinations and a sense of intrusion, often observed in patients with narcolepsy, hypertension, and seizures. METHODS: A cross-sectional study was conducted in various medical colleges in Karachi, involving 297 participants aged 18 to 30 years. The participants were divided into groups based on gender and year of study. They were surveyed about the frequency of sleep paralysis episodes, their beliefs about the phenomenon, sleep routines, and academic impacts. RESULTS: Among the respondents, a significant number of females (n=209, 70.3%) reported experiencing sleep paralysis. The overall mean age was 20±2.0 years. Correlation analysis revealed an insignificant relationship between depression and mental anxiety (p=0.147). Similarly, no significant association was found when comparing the occurrence of sleep paralysis (p=0.16). However, a notable finding was the significant link between sleep paralysis and its impact on academics (p=0.043). CONCLUSION: This study highlighted the frequency of sleep paralysis among medical students, particularly among females. Furthermore, it emphasizes the diverse beliefs held by individuals regarding these frightening episodes. To address this neglected issue, it is essential to conduct awareness sessions aimed at understanding and alleviating sleep paralysis in individuals' lives.

Advancements in Inflammatory Bowel Disease: A Narrative Review of Diagnostics, Management, Epidemiology, Prevalence, Patient Outcomes, Quality of Life, and Clinical Presentation.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, immune-mediated disorder that impacts the gastrointestinal tract. Significant advancements in the diagnosis and treatment of IBD have been made during the past few decades, improving patient outcomes. This narrative review aims to provide an overview of recent developments in the diagnosis and treatment of IBD. Both from an evaluative and therapeutic standpoint, the management of IBD has undergone significant change. The standard of treatment for treating UC and CD patients has changed due to several medical developments. These developments include amino-salicylates, immunosuppressants, biological agents, and new therapeutics. The review also addresses the difficulties in applying these developments in clinical practice. Globally, the prevalence of IBD is rising, with Asia among the regions with the highest rates. These environments provide particular difficulties, such as poor disease knowledge, a lack of diagnostic services, and infectious IBD mimics. These issues must be resolved to diagnose and manage IBD in these populations accurately. New imaging modalities and other improvements in diagnostic methods have increased the precision and early identification of IBD. To reduce problems and improve patient outcomes, healthcare professionals treating patients with IBD must work effectively as a team. An extensive summary of current developments in the diagnosis and treatment of IBD is given in this narrative review. It draws attention to the therapeutic possibilities, difficulties, and uncertainties of integrating these developments into clinical practice. By keeping up with these changes, healthcare practitioners can better care for patients with IBD and improve their quality of life.

Does thiamine supplementation affect heart failure? A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Heart failure is a pathophysiological condition where decreased cardiac output is observed subsequent to any structural deformity or cessation of normal function. Thiamine deficiency is one of the risk factors responsible for causing HF; other risk factors include hypertension, smoking, and obesity. OBJECTIVE: We conducted a systemic review and meta-analysis of RCTs to scrutinize whether the heart failure patients would benefit from thiamine supplementation or not when compared to placebo. METHODS: We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with symptomatic heart failure. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data. RESULTS: The 6 RCTs selected for the statistical analysis consisted of 298 participants (158 in the intervention group, 140 in the placebo group). The outcomes resulted to be non-significant with LVEF p-value= 0.08, NT-pro BNP p-value= 0.94, LVEDV p-value= 0.53, 6MWT p-value=0.59, mortality p-value= 0.61, hospitalization p-value= 0.53 and dyspnea p-value= 0.77. Heart rate is the only significant outcome with a p-value=0.04. CONCLUSION: To conclude, except for heart rate, thiamine supplementation had no effect on the outcomes of heart failure patients.

Diagnosis and Treatment of Liver Disease: Current Trends and Future Directions.

This narrative review delves into the intricate landscape of liver diseases, providing a comprehensive background of the diverse conditions that afflict this vital organ. Liver diseases, ranging from viral hepatitis and non-alcoholic fatty liver disease (NAFLD) to cirrhosis and hepatocellular carcinoma (HCC), pose significant global health challenges. Understanding these diseases' multifaceted origins and progression is pivotal for developing effective diagnostic and therapeutic strategies. The epidemiology and etiology of liver diseases emphasize the global impact of viral hepatitis, with hepatitis B and C as significant contributors. Concurrently, the rising prevalence of NAFLD, linked to lifestyle factors and metabolic syndrome, underscores the intricate relationship between modern living and liver health. Chronic liver diseases often evolve insidiously, progressing from inflammation to fibrosis and, ultimately, to cirrhosis - a stage characterized by irreversible scarring and compromised function. The heightened risk of HCC in advanced liver disease stages further underscores the urgency of effective diagnostic and therapeutic interventions. The evolving landscape of non-invasive diagnostic tools is explored for their role in enabling early detection and accurate staging of liver diseases. In the realm of treatment, there is a continuous transition toward personalized medicine, customized to suit the unique profiles of individual patients. This shift encompasses a broad spectrum, ranging from personalized pharmacological interventions to lifestyle modifications and surgical options. Delving into innovative therapies, such as gene editing and immunomodulation, offers a glimpse into the promising future directions that have the potential to redefine the landscape of liver disease diagnosis and treatment.

Neurological Manifestations of Infectious Diseases: Insights From Recent Cases.

This narrative review examines the complex connection between infectious diseases and their neurological effects. It provides a detailed analysis of recent instances and insights derived from various pathogens. As we explore the realm of infectious agents, including viruses, bacteria, parasites, and fungi, a thorough and diverse analysis reveals the intricacies of neurological problems. The review begins by examining viral infections, specifically focusing on how viruses invade the neurological system and its subsequent effects. Significant instances from recent widespread disease outbreaks function as instructive benchmarks, highlighting the progressing comprehension of these ever-changing interconnections. The article examines the complex pathophysiology of neurological problems caused by bacterial infections. It presents current cases that illustrate the various ways these complications might manifest and the difficulties faced in their therapeutic management. Parasitic and fungal infections, which are typically overlooked, are being carefully examined to emphasize their distinct role in causing neurological complications. The mentioned cases highlight the importance of being thoroughly aware of these less-explored areas ranging from protozoan parasites to opportunistic fungal infections. In addition to the immediate effects caused by infectious agents, the review investigates autoimmune responses activated by infections. It provides a detailed examination of specific instances that shed light on the complex relationship between viral triggers and future neurological problems. This text elaborates on the intricacy of autoimmune-related neurological issues, highlighting the necessity for a comprehensive approach to diagnosing and treating them. The narrative next redirects its attention to the diagnostic difficulties that arise when interpreting the neurological symptoms of viral disorders. This article provides a thorough examination of existing diagnostic tools, along with an investigation into new technologies that have the potential to improve our capacity to identify and comprehend complex presentations. This debate connects to the following examination of treatment methods, where current cases that showcase successful interventions are carefully examined to extract valuable insights into good clinical management. The discussion focuses on the public health implications of preventive efforts against infectious infections, including their neurological consequences. The story emphasizes the link between infectious diseases and overall societal health, advocating for a proactive strategy to reduce the impact of neurological complications. The abstract concludes by providing a prospective viewpoint, highlighting areas of research that still need to be addressed, and suggesting potential future avenues. This narrative review seeks to provide a comprehensive resource for physicians, researchers, and public health professionals dealing with the complex field of neurological manifestations in infectious diseases. It combines recent examples, synthesizes current information, and offers a holistic perspective.