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An introduction to the journal is presented in which the author discusses various topics within the issue including the sociology of diagnosis, digital addiction, and neuro-reductionism in the diagnosis of diseases.

Although decades of research have shown the importance of neurobiological factors in the development of mental health problems in children and adolescents, the translation of this knowledge to use in clinical practice has proven difficult. One of the pitfalls is the false assumption that biological factors are so fundamental that they overrule all other factors and can be used as stand‐alone biomarkers or tests for diagnostic purposes and treatment decisions. This assumption is false because all neurodevelopmental disorders result from complex interactions between biology and environment. Therefore, neurobiological assessments should never be used as a shortcut for diagnostic assessments that include the environment, including family, peers, and society at large. Instead, they should be integrated in the diagnostic process. This calls for empirically supported guidance on how to weigh information from neurobiological and psychosocial assessments in the diagnostic and treatment decision process. [ABSTRACT FROM AUTHOR]

The author discusses the article "Genome-wide Investigation of Persistence of Treatment With Methotrexate in Early Rheumatoid Arthritis" by Öberg Sysoeve and colleagues, published in the issue. She talks about the use of methotrexate (MTX), the clinical practice issues that can influence tolerance and effectiveness of MTX, and studies from the U.S. about the underutilization and underdosing of MTX.

The authors discuss key design issues from studies evaluating the benefit afforded from vitamin D supplementation using as examples the Vitamin D and Omega-3 Trial (VITAL) study and the Nonlinear Mendelian Randomization Study. Topics include key concepts in clinical study design related to studies evaluating the benefit afforded from vitamin D supplementation and reason that evaluating the functional form of the risk factor-outcome link is a hallmark of etiological research.

An editorial is presented on Acute Disease Quality Initiative (ADQI) has a more than two-decade legacy. Topics include relates to the current state of practice of diagnosis and management of acute kidney injury and other conditions in critical care nephrology; and have a focus on AKI education in resource-plentiful and resource-challenged areas.

The article offers information on the diagnosis and management of urinary tract infection (UTI) in young children, emphasizing the challenges and importance of accurate diagnosis due to the associated morbidity. Topics include the difficulty of obtaining clean urine samples from infants, leading to the adoption of rapid screening methods such as urinalysis with a dipstick.

The author reflects on the effectiveness of renal angina index alone and in combination with biomarkers in the diagnosis of acute kidney injury (AKI) in children. Also cited are the etiologies of AKI in neonates like sepsis, hypernatremic dehydration, and posterior urethral valves, as well as the Risk, Injury, Failure, Loss and End Stage (RIFLE) and Acute Kidney Injury Network (AKIN) criteria in classifying AKI.

The article focuses on recent advancements in salivary research, highlighting the use of artificial intelligence (AI) for biomarker discovery, cell-based therapies for salivary dysfunctions, and the role of tight junctions in salivary gland secretion. Topics discussed include AI techniques in salivary biomarker discovery, cell therapies for salivary gland dysfunction, and the regulation of salivary secretion by tight junctions.

Background: Osteonecrosis of the femoral head (ONFH) is a common disabling disease with considerable social and economic impacts. Although extensive studies related to ONFH have been conducted in recent years, a specific bibliometric analysis on this topic has not yet been performed. Our study attempted to summarize the comprehensive knowledge map, development landscape, and future directions of ONFH research with the bibliometric approach. Methods: All publications concerning ONFH published from 2001 to 2020 were identified from Web of Science Core Collection. Key bibliometric indicators were calculated and evaluated using CiteSpace, VOSviewer, and the online bibliometric analysis platform. Results: A total of 2594 publications were included. Our analysis revealed a significant exponential growth trend in the annual number of publications over the past 20 years (R2 = 0.9663). China, the USA, and Japan were the major contributors both from the quality and quantity points of view. Correlation analysis indicated that there was a high positive correlation between the number of publications and gross domestic product (r = 0.774), and a moderate positive correlation between publications and demographic factor (r = 0.673). All keywords were categorized into four clusters including Cluster 1 (etiology and risk factors study); Cluster 2 (basic research and stem cell therapy); cluster 3 (hip-preserving study); and Cluster 4 (hip replacement study). Stem cell therapy-related research has been recognized as an important research hotspot in this field. Several topics including exosomes, autophagy, biomarkers, osteogenic differentiation, microRNAs, steroid-induced osteonecrosis, mesenchymal stem cells, double-blind, early-stage osteonecrosis, and asymptomatic osteonecrosis were considered as research focuses in the near future. Conclusion: Over the past two decades, increasing attention has been paid to global ONFH-related research. Our bibliometric findings provide valuable information for researchers to understand the basic knowledge structure, identify the current research hotspots, potential collaborators, and future research frontiers in this field. [ABSTRACT FROM AUTHOR]

The author discusses a study by K. A. Marill and colleagues in the issue which showed that some of the electrocardiographic (ECG) parameters accepted as high-risk markers for imminent torsade-de-pointes, are not as reliable as expected. Patients and controls in the study were matched for age, gender, and heart rate. Also cited are the influence of gender on risk, lessons to be learned from the study, and difficulties in predicting torsade-de-pointes in patients with QT prolongation.

This editorial comments on the article by Maurer et al. in this issue. [ABSTRACT FROM AUTHOR]

An editorial is presented on Gestational diabetes mellitus (GDM) known to be associated with adverse pregnancy outcomes. Topics include appropriate management of the women during pregnancy followed by suitable lifestyle interventions in the mother in the postpartum period; and biomarkers for prediction of GDM showing infammatory markers and adipocytokines.

An introduction is presented in which the author discusses articles within the special section of the journal on topics including challenges and the potential use of artificial intelligence (AI) in diagnosing and grading breast carcinomas, advances in understanding the pathogenesis and novel diagnostic tools of salivary-gland like carcinomas of the breast, and applications of immunohistochemical stains for diagnosing breast lesions.

The article presents the discussion on progress on migraine research and chronic pain research. Topics include biomarker having sufficient sensitivity and specificity not only allowing the diagnosis of disease; and relating to the lack of presentation to general practitioners and lack of referral to tertiary neurological care.

An introduction is presented in which the editor discusses various topics within the issue like dietary assessment tools, nutritional epidemiology, and the Australian Guide to Healthy Eating (AGHE).

The article discusses the possible prediction of right atrial flutter via constant pacing on collision of the two wavefronts on the lateral wall of the right atrium. Topics covered include the use of right atrial collision time (RACT) as a marker for development of typical atrial flutter (AFL), and the non-association of larger right/left atrial volumes on AFL development. Also noted is the association of comorbidities like systemic hypertension with AFL patients.

The article focuses on the application of artificial intelligence (AI) and machine learning in transfusion medicine. It highlights the use of AI to improve the safety and efficacy of blood transfusions; the role of omics and big data coupled with machine learning algorithms in analyzing complex biological datasets for the development of new biomarkers; and the application of these technologies in veterinary transfusion medicine to enhance animal health and welfare.

The article presents the provide reflection and discussion as to why women do not appear to differ by sexual orientation when assessing allostatic load (AL). Topics include the AL refers to the multisystemic ‘‘wear and tear'' of chronic stress in synergy with unhealthy behaviors that can be indexed, and the literature has emerged that applies the AL model to assess sexual diversity and to indirectly assess whether stigma can impact AL and health trajectories.

The author reflects on the challenges and issues in the treatment of systemic juvenile idiopathic arthritis (SJIA) and macrophage activation syndrome (MAS). SJIA is a distinct subtype of childhood arthritis, while MAS is a prototypical cytokine storm syndrome. Also cited is the study which examined the association of interleukin-18 (IL-18)/IFNγ axis in SJIA with MAS and treatment responses.

An introduction is presented in which the editor discusses articles in the issue on topics including investigated the association of urinary matrix metalloproteinase 7, and urinary epidermal growth factor (EGF) level and progression of chronic kidney disease in several cohorts of patients.

The article offers perspectives on pericoronary adipose tissue (PCAT) in atherosclerosis. It provides an overview of two research studies on the expression of mircoRNAs within PCAT close to coronary atherosclerotic lesions and plaque-free segments and the expression of microRNAs in PCAT of coronary artery disease (CAD) patients undergoing coronary artery bypass surgery (CABG). It suggests the potential use of PCAT attenuation to reclassify cardiovascular risk and diagnose atherosclerosis.

Kinase activating missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenically linked to neurodegenerative Parkinson's disease (PD). Over the past decade, substantial effort has been devoted to the development of potent and selective small molecule inhibitors of LRRK2, as well as their preclinical testing across different Parkinson's disease models. This review outlines the genetic and biochemical evidence that pathogenic missense mutations increase LRRK2 kinase activity, which in turn provides the rationale for the development of small molecule inhibitors as potential PD therapeutics. An overview of progress in the development of LRRK2 inhibitors is provided, which in particular indicates that highly selective and potent compounds capable of clinical utility have been developed. We outline evidence from rodent- and human-induced pluripotent stem cell models that support a pathogenic role for LRRK2 kinase activity, and review the substantial experiments aimed at evaluating the safety of LRRK2 inhibitors. We address challenges still to overcome in the translational therapeutic pipeline, including biomarker development and clinical trial strategies, and finally outline the potential utility of LRRK2 inhibitors for other genetic forms of PD and ultimately sporadic PD. Collective evidence supports the ongoing clinical translation of LRRK2 inhibitors as a therapeutic intervention for PD is greatly needed. [ABSTRACT FROM AUTHOR]

The article focuses on the Juvenile idiopathic arthritis (JIA) and the Gut Microbiome. Topics include JIA's missing heritability problem in various corners of scientific inquiry, including epigenetics, and epidemiology; mentions data on the gut microbiome in children with JIA have emerged over recent years from case–control studies across 3 continents; and also mentions all publications on JIA and the gut microbiome have described differences in bacterial composition between cases and controls.

Over the last 40 years, researchers have made considerable progress identifying the ways in which attachment security shapes individuals' social and emotional functioning. In recent years, new investigations have shed light on connections between attachment and physiological systems in the body. The goal of this special issue is to focus attention on how attachment may be related to biological markers that relate to physical health, including inflammation, cortisol, and cardiometabolic risk. The papers in this special issue, highlighted in this introduction, demonstrate that these links may exist across the lifespan. We conclude with several examples of extensions of this work might emerge in the years to come. [ABSTRACT FROM AUTHOR]

The authors reflect on the study by M. Peer and colleagues on adiponectin and aldosterone as independent predictors of left ventricular hypertrophy (LVF). Topics they discussed include the interplay between aldosterone and adiponectin in LVH pathogenesis, the feasibility of aldosterone inhibition and adiponectin increase to benefit LVH patients, and the use of atorvastatin and amlodipine to reverse LVH in hypertension patients.

The article discusses high-profile journals such as Science and Nature have published and endorsed several guidelines and checklists to promote transparency and reproducibility. Topics include the lack of transparent, adequate reporting of analytical method validation has undermine credibility and reduce the relevance of a clinical study; and values for a given patient sample has vary significantly between assays from different manufacturers.

The author reflects on the accomplishments in efforts to treat autoimmune disorders like systemic lupus erythematosus (SLE) and lupus nephritis (LN) as of December 2020. Topics include the neuropsychiatric (NP) and renal manifestations of SLE and LN, the importance of biomarkers in diagnosis, and the key role played by B cell activating factor (BAFF) in SLE and LN.

Adrenomedullin (ADM) is a 52 amino acid containing free circulating vasoactive peptide hormone found to be active in various pathophysiological states including sepsis. High ADM levels at admission have been correlated with vasopressor requirements, organ dysfunction, and mortality in sepsis patients. ADM stimulation results in vasodilation and loss of vascular resistance in humans resulting in hypotension with the potential for negative impact in septic shock. However, in vitro human and animal experiments have shown that ADM decreases hyperpermeability and capillary leak, thus having an endothelial barrier stabilizing effect during septic shock. Adrenomedullin thus appears to be a double-edged weapon. This editorial critically reviews the article by Daga et al. who evaluated serum ADM as a prognostic marker to review the gender-related difference in mortality pattern, and also the correlation of ADM level to APACHE II and SOFA scores. The role of adrenomedullin in sepsis and the potential developments in the future have been discussed concisely. [ABSTRACT FROM AUTHOR]

The authors discuss a study published in the issue which analysed the prevalence and clinicopathological associations of autoantibodies in a large cohort of inflammatory myopathy patients from Australia and a comparator group of patients with systemic sclerosis (SSc). Topics include the role of the autoantibody as a diagnostic marker of myositis subtype, boundaries between myositis and dystrophies, and antibody that could be the missing link between inflammation and muscle tissue degeneration.

The article offers information on Paradigm Shift in the Triage of Sick Febrile Patients. It mentions that accessing to the health system is much more limited, diagnostic tools remain scarce, and management decisions by definition more subjective which may have much more profound implications; and presence of concomitant conditions, the geographical distribution and circulation of different pathogens.

The author discusses a study on the mechanisms that lead to local antibody production by CD4+ T cells in systemic lupus erythematosus (SLE). Highlights include the reason why T cells infiltrate the peripheral tissue in SLE, a subset of circulating peripheral helper T cells that show similarities to follicular helper T cells, and serological changes that occur in patients following B-cell depletion therapy.

An introduction to the journal is presented that focuses on issues related to cognitive aging neuroscience, with topics covered such as the impact of age on the neural signatures of familiarity, recollection, and post-retrieval processes for neutral and emotional information, and a study that focused on biomarkers for pathological aging, and the use of transcranial direct current stimulation to alter brain activity.

The author discusses a range of biomarkers that have been studied to determine whether there is potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis (axSpA). Highlights include HLA-B27 as the only biomarker with clinical utility for diagnostic purposes, an incomplete list of biomarkers that have been studied in axSpA, and the link between inflammation and bone formation in axSpA.