bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale Network Approaches to Decode the Complexity of Common Human Diseases
Authors: Wang Minghui , Liu Yiyuan , Schadt Eric , Zhang Bin 
Published: January 2025

Abstract
The study of common human diseases is embracing large-scale multi-omic data at both bulk and single-cell levels. The enormous amount of data provides an excellent opportunity to gain unprecedented insights into molecular mechanisms of diseases, but it also poses a great challenge in distinguishing signals from noises and causality from correlations at a system level. This chapter introduces a multiscale network analysis framework to integrate multiple modals of large-scale biological data in diseases into multiple complementary, actionable molecular network models that enable not only a holistic understanding of dysregulated pathways but also the identification of key molecular drivers of diseases. This chapter illustrates the procedure of the multiscale network analysis of bulk and single-cell functional genomics data in a disease. It further outlines challenges and future directions in network biology and systems biology in general to dissect multi-omic data in diseases toward precision medicine.
Neuromodulation and Psychiatric Disorders
Authors: Smith Andrew H. , Figee Martijn , Mayberg Helen S. 
Published: January 2025

Abstract
A remarkable recent development in psychiatric neuromodulation is convergence of circuit-level findings from multiple independent lines of inquiry. For common and often treatment-refractory illnesses such as major depressive disorder and obsessive–compulsive disorder, causal brain networks have been identified by investigators utilizing a variety of target sites (cortical vs. subcortical), device types (noninvasive vs. invasive), and trial designs (randomization at outset vs. at discontinuation). This chapter highlights how emerging evidence from across these diverse neuromodulation paradigms has revealed the structural and functional pathways mediating successful treatment of each disorder. It also shows how recent work has borne out the fundamental insight that particular subnetworks can be relevant to particular symptom domains irrespective of traditional diagnostic categories. In keeping with the unique way in which neuromodulation integrates neuroscience and clinical practice, this chapter is grounded in discussions of the most robustly validated and widely adopted neuromodulatory therapies.
Diagnosis and Epidemiology of Psychotic Disorders
Authors: Walsh-Messinger Julie , Nikou Ariella Farzan , Malaspina Dolores 
Published: January 2025

Abstract
This chapter discusses current and historic approaches to describe the phenomenology of schizophrenia-related and bipolar psychosis for classifications into diagnostic categories. The focus for advancing diagnostic practices shifted from descriptive to reliability and validity in the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Related Health Problems. Because these categorical diagnoses did not advance knowledge of disease mechanisms, the chapter describes the introduction of dimensional assessments of symptom domains by the National Institute of Mental Health as the Research Domain Criteria. An unresolved current clinical proposal would combine all psychotic conditions into a “primary psychosis” category with continuous ratings of illness features. Finally, the chapter highlights some epidemiology, genetic, and population features of the psychoses and their clinical and etiological heterogeneity.
Model Building for the Study of Schizophrenia
Authors: Gordon Joshua A. 
Published: January 2025

Abstract
The complexity of schizophrenia begs the question as to what can be learned from preclinical models. Neither animal nor human cellular models can mimic the full complexity of symptoms and signs that is schizophrenia. Guided by specific hypotheses, however, model systems can and do provide important insights into neurobiological pathways of relevance to the disorder and can identify novel targets for therapeutic development. Considering models that test etiological hypotheses has led to the recognition that specific brain mechanisms play important roles in the pathways of risk for the disorder. Models of pathophysiological hypotheses support the notion that these processes could play a causal role in the signs and symptoms of the disorder. In addition, models of pharmacological hypotheses give rise to plausible mechanisms by which drugs mimic the disorder. The findings reviewed in this chapter provide powerful examples of the importance of model building for the study of schizophrenia.
Neural and Circuit Mechanisms of Cognitive Dysfunction in Schizophrenia
Authors: Dienel Samuel J. , Lewis David A. 
Published: January 2025

Abstract
Cognitive dysfunction, including disturbances in working memory, is a core feature of schizophrenia and the best predictor of long-term functional outcome. Although working memory depends on a distributed circuit involving multiple cortical and subcortical regions, the prefrontal cortex (PFC) is a critical node within the working memory network. Therefore, the neural substrate for impaired working memory in schizophrenia appears to reflect, at least in part, alterations in PFC glutamatergic, GABAergic, and dopaminergic signaling in persons with schizophrenia. This chapter reviews the basic circuitry of the primate PFC responsible for working memory and the alterations to this circuitry in individuals with schizophrenia. These alterations are revealed through both in vivo imaging studies and postmortem studies of PFC circuitry in schizophrenia. The convergence of findings suggests multiple avenues for novel therapeutic interventions targeted at ameliorating the cognitive burden and improving the functional outcome in this patient population.
Genetics of Bipolar Disorder
Authors: Liu Dongjing , Mullins Niamh 
Published: January 2025

Abstract
This chapter provides an overview of the genetics of bipolar disorder and its clinical subtypes. Bipolar disorder is highly polygenic and shows substantial genetic overlap with other mental illnesses. In recent years, the number of genome-wide significant loci identified through consortium efforts has increased from a handful to 64, and the first bipolar disorder gene implicated through rare protein-truncating variants has emerged from large-scale sequencing efforts. Translating these discoveries into biological and etiological understanding will require further developments of high-throughput experimental methods that can address large numbers of genes within genome-wide association study loci, as well as sophisticated computational approaches that can integrate genetic associations with multi-omics data. These future advances, combined with expanding collaboration and increasing sample sizes, will inevitably lead to biologically meaningful risk genes and pathways underlying disease risk, thus paving the way to actionable diagnostic and therapeutic knowledge.
Neuroimaging and Network Mechanisms in Bipolar Disorder
Authors: Edmiston E. Kale , Bertocci Michele A. , Ghane-Ezabadi Merage , Phillips Mary L. 
Published: January 2025

Abstract
Bipolar disorder is characterized by episodic depression and periods of elevated mood. This mood lability is thought to arise from altered brain structure and function. Neuroimaging has identified alterations in several large-scale networks in the disorder. Dysfunction of these networks may lead to altered task-based engagement of their hubs. Another key focus of the functional neuroimaging literature in bipolar disorder is reward anticipation. These studies also show altered function in reward-associated regions. Consistent with these findings, reduced gray matter volume and cortical thickness are observed in regions associated with reward anticipation and emotion regulation. Similarly, diffusion imaging methods have identified reduced white matter integrity in tracts that form the structural basis of these functional networks. Taken together, these findings contribute to an emerging neuroanatomic model of bipolar disorder that has the potential to aid in the development of novel approaches to prevention and treatment.
Diagnosis and Epidemiology of Depression
Authors: Murrough James W. 
Published: January 2025

Abstract
Depression is a leading cause of disability worldwide and is observed to occur in all geographical and socio-demographic contexts. Depression is common, and onset of illness tends to occur early in adulthood, contributing to its burden of illness. Risk factors for depression include early childhood adversity, low socioeconomic status, psychosocial stressors, and the presence of certain medical and psychiatric illnesses. The diagnosis of depression can be challenging, and the diagnosis relies of establishing the presence of a collection of characteristic symptoms and illness course. The illness is highly co-morbid with both other psychiatric illnesses as well as with non-psychiatric medical conditions. Emerging approaches to the diagnosis of depression consider dimensional approaches, as well as the role of objective biological and behavioural aspects of the illness, in diagnosis and in the identification of potential subtypes of the disorder.
Neuroendocrine Mechanisms of Depression
Authors: Binder Elisabeth B. , Deussing Jan M. 
Published: January 2025

Abstract
Major depressive disorder (MDD) is among the most common psychiatric disorders. This chapter summarized the evidence for neuroendocrine changes in the pathophysiology of MDD from both human and animal studies. The focus lies on the hypothalamus–pituitary–adrenal (HPA) axis, which is central for the response to stress and adversity. Altered function of the HPA axis has been linked to MDD at different levels, from measured endocrine changes to altered receptor function. Moderation by genetic variants and epigenetic mechanisms are discussed. Finally, the evidence for using measures of the HPA axis as biomarkers for MDD is presented, and pharmacological studies targeting this system are summarized.
Diagnosis and Epidemiology of Anxiety, Obsessive–Compulsive, and Trauma and Stressor-Related Disorders
Authors: Stein Murray B. , Keough Meghan E. , Roy-Byrne Peter P. 
Published: January 2025

Abstract
This chapter discusses the diagnosis and epidemiology of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, anxiety disorders, obsessive–compulsive and related disorders, and trauma- and stressor-related disorders. These disorders are among the most common experienced by individuals on a 12-month and lifetime basis. Panic attacks can occur across many anxiety disorders, and they can co-occur with depressive disorders. Anxiety and related disorders tend to occur early in life and almost always chronologically precede depressive disorders, with which they are frequently comorbid. Studies have shown that the prevalence of anxiety disorders has increased during the COVID-19 pandemic era. Accurate differential diagnosis, including recognition of medical disorders that may be contributing to symptoms, is critical for optimal prognostic determination and treatment planning.
Neuroimaging and Circuit Mechanisms of Anxiety and Trauma-Related Disorders
Authors: Fonzo Gregory A. 
Published: January 2025

Abstract
Functional neuroimaging of anxiety and trauma-related disorders has substantially enhanced neurobiological understanding of these conditions in humans. This chapter summarizes neuroimaging studies examining emotional reactivity, defensive learning, and emotion regulation in anxiety and trauma-related disorders. Across diagnoses, anxiety is characterized by not only a propensity toward facilitated fear learning and deficient ability to overwrite this learning but also elevated reactivity to threatening and emotionally provocative cues and difficulty adaptively regulating emotional states. These processes generally implicate elevated activity in defensive threat circuitry. However, specific diagnoses differ in the stimuli eliciting such responses and the relative predominance of each component to the neural phenotype. This chapter synthesizes a conceptual and neurobiological framework through which existing findings can be contextualized. This framework highlights abnormal limbic and prefrontal function during response to, learning about, and regulation of emotion-eliciting stimuli as a unifying construct for understanding the neurobiology of anxiety and trauma-related disorders.
Biological Mechanisms of Anxiety Disorders
Authors: Gerhard Danielle M. , Anfei Li , Lee Francis S. , Meyer Heidi C. 
Published: January 2025

Abstract
Abstract: Anxiety disorders are characterized by persistent and debilitating feelings of worry stemming from difficulty assessing threats and inhibiting fear responding. However, heterogeneity of symptom profiles across anxiety disorders, and even within the same diagnoses, has complicated treatment because treatment success varies widely across patients. Improved mechanistic understanding of the disparate symptoms of anxiety disorders is needed to help inform the development of new treatments. There is a growing understanding that psychiatric disease, including anxiety disorders, results from perturbation of key brain regions and their complex local and regional circuitries. Increasing attention has also been given to the influence of specific genetic polymorphisms and their effects on circuit activity and behavior. This chapter highlights human neuroimaging and rodent studies that parallel one another and illustrate how an integrated approach has advanced understanding of neural circuits implicated in anxiety disorders.
Biological Mechanisms of Stress Resilience
Authors: Seeley Saren H. , Boukezzi Sarah , DePierro Jonathan , Charney Dennis S. , Feder Adriana 
Published: January 2025

Abstract
Abstract: Resilience is the ability to adapt successfully in the face of severe stress, trauma, or adversity. Best conceptualized as existing on a continuum, resilience is shaped by genetic makeup and environmental factors. The developmental years are critical for the shaping of stress response systems and brain circuits underlying emotion regulation, yet resilience can also be enhanced throughout an individual’s lifetime. This chapter presents an overview of the complex interactions between neurotransmitters, neuropeptides, hormones, and other biological systems that mediate stress resilience, as well as functional differences in neural circuitry function underlying key resilience-promoting psychological factors. The growing understanding of genetic, epigenetic, developmental, psychological, and neurobiological resilience factors continues to lead to the development of interventions to enhance stress resilience. Examples of preventive and treatment interventions are discussed, along with recent developments in the field.
Novel Approaches for Treating Substance Use Disorders
Authors: Banks Matthew L. 
Published: January 2025

Abstract
Clinical substance use disorder (SUD) treatment goals are to not only decrease drug-taking behavior but also promote allocation of behavior toward nondrug reinforcers. Preclinical drug self-administration procedures have demonstrated utility in candidate SUD medication evaluation. Decades of research has validated experimental design attributes that facilitate translation of preclinical-to-clinical results when evaluating candidate therapeutic effects. These experimental design considerations include repeated candidate therapeutic treatment to model clinical chronic dosing regimens, candidate therapeutic evaluation on self-administered abused drug dose–effect functions, and assessment of behavioral selectivity for drug- versus nondrug-maintained behaviors. Sophisticated drug “choice” self-administration procedures allow for a simplified assessment of these clinical treatment goals in a preclinical setting while also incorporating assessment of behavioral selectivity. The infrequent incorporation of these rigorous experimental design attributes has hindered preclinical SUD medication development research efforts. Future directions include the inclusion of active negative control comparator treatments to facilitate interpretation of candidate medication effects.
Current Treatments for Alzheimer’s Disease
Authors: Sano Mary , Neugroschl Judith 
Published: January 2025

Abstract
In 2023, the U.S. Food and Drug Administration (FDA) fully approved the first drug for the treatment of Alzheimer’s disease that targeted amyloid accumulation in the brain and provided evidence of clinical benefit. This chapter describes the approach that led to new drugs that are potentially disease modifying. Drug treatments provide symptomatic benefit to patients with Alzheimer’s disease and related dementias (ADRD) are also described. Up-to-date data that continue to support their use are reviewed. Effective mechanisms for managing cardiovascular risk have been tested for potential benefit in ADRD treatment or prevention, with little success. The breadth of pathologies now recognized as relevant to ADRD provides many new pathways for therapeutic development, and novel biomarkers which may revolutionize the diagnostic process and provide opportunities to ensure target engagement. New interventions are needed for all stages of disease as well as for disease prevention.
Genetics of Pediatric-Onset Psychiatric Disorders
Authors: Levy Tess , Buxbaum Joseph D. 
Published: January 2025

Abstract
Pediatric-onset psychiatric disorders are substantially heritable, with various types of genomic changes contributing to risk. Extensive research, including genome-wide association studies, has shed light on the involvement of common genetic variation with modest effect sizes. In addition, sequencing studies have identified rare genetic variation within specific genes, which contributes to higher risk. The size of genetic changes associated with pediatric psychiatric disorders varies considerably, ranging from minute alterations involving a single base pair (most commonly as single nucleotide variation/polymorphism) to more substantial chromosomal changes such as aneuploidy or copy number changes. This chapter provides a comprehensive review of the genetics and heritability of several conditions, including autism spectrum disorder, attention-deficit/hyperactivity disorder, obsessive–compulsive disorder, and Tourette and chronic tic disorders. Significant advancements have been made in this field during the past decade, and the pace of this progress is projected to continue.
Neurobiology of Autism Spectrum Disorder and Intellectual Disability
Authors: Massa Alexandra , Costales Jesse , Rubeis Silvia De , Foss-Feig Jennifer , Hof Patrick R. , Kolevzon Alexander 
Published: January 2025

Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that first manifests in early childhood and is characterized by impairments in social communication and the presence of restricted and repetitive behaviors. Approximately one-third of affected children also experience intellectual disability (ID). The current understanding of the neurobiology of ASD and ID revolves around a few central findings, including synaptic dysfunction and imbalance between excitatory and inhibitory neurotransmission. This understanding relies heavily on genetic factors; studies have revealed that 500–1,000 genes may contribute to ASD risk. Many of the known ASD genes are also associated with ID without ASD. In addition to genetic studies, imaging and histopathological studies have contributed significantly to knowledge about the neurobiology of ASD and ID. This chapter integrates findings from human and animal studies using genetic, imaging, and histopathological methods to describe emerging themes in the understanding of ASD and ID.
Socialization and the Hidden Curriculum in Medical Professionalism
Authors: Lam Justin , Martimianakis M. A. , Hafferty F. W. 
Published: January 2025

Abstract
This chapter proposes a relational framework to explicate how the formal, informal, and hidden curricula socialize medical students to dueling professionalisms. Highlighted is how these curricula can often function as mechanisms for reproducing existing white, androcentric, and Eurocentric medical culture due to the way power circulates through medical education as a part of an enculturation process. Finally, the chapter demonstrates how the hidden curriculum—in the context of the framework—can be a powerful analytic tool for medical educators and researchers alike to anticipate and analyze curricular misalignments. By examining the implications for learner socialization through phenomena like learner mistreatment policies, evaluation of professionalism, and burnout, it is demonstrated how attention to hidden curriculum effects can connect individual experiences to issues at the level of structure and culture.
Professionalism of Solidarity and the Social Contract
Authors: de Carvalho Filho Marco Antonio , Franco Renato Soleiman , de Oliveira Vidal Edison Iglesias 
Published: January 2025

Abstract
The social contract metaphor brought to light the relationship between the medical profession and society with its reciprocity of duties and obligations. This enlightening allowed medical educators and professionals to debate the values of our profession while rescuing our social responsibility and accountability. It also allowed medical students to grip their learning trajectories toward becoming doctors. However, this metaphor may be insufficient to problematize an ever-evolving relationship in a dynamic, complex, and ever-evolving society by suggesting that our relationship with society is rigid with fixed rules and boundaries. This chapter expands this metaphor by bringing the critical pedagogy concepts of liberation, critical consciousness, full citizenship, education for change, and dialogue as connection and love and combine these concepts with cultural humility to suggest a professionalism of solidarity.
Professionalism and Conscientious Objection in Medicine
Authors: Wicclair Mark 
Published: January 2025

Abstract
This chapter examines conscientious objection from the perspective of medical professionals who have, or believe they have, a conscientious objection to a medical service; contemplate requesting an accommodation; and want to know whether conscientious objection is consistent with their professional obligations. The focus is on physicians and the medical profession. It provides answers to several important questions about conscientious objection in medicine. The following questions are addressed: (1) What does it mean for physicians to conscientiously object to a medical service? (2) What should members of the medical profession consider when deciding whether to conscientiously object and request an accommodation? (3) Should members of the medical profession be willing to inform and refer? (4) Should physicians be willing to explain their objections? (5) To whom, when, and how should members of the medical profession communicate their conscientious objections?
Spirituality and Professionalism
Authors: Merlo Gia 
Published: January 2025

Abstract
Being able to address a patient’s spiritual care needs and learning the tools for engaging in the provision of spiritual care can improve patient health outcomes and quality of life and help reduce the capacity for burnout while providing holistic, patient-centered care. Learning how to provide spiritual care to patients is—or should be—a domain of medical professionalism education. The high demands of spiritual care often pose difficulties for physicians during clinical interaction due to their perceived lack of competence and confidence in appropriately and effectively addressing the topic. This chapter discusses how and why spiritual care is an integral part of medical practice and medical professionalism education; different intervention models are provided to help physicians develop this aspect of their clinical practices.