bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroimaging and Circuit Mechanisms of Schizophrenia
Authors: Woodward Neil D. , Heckers Stephan , Ongur Dost , Sheffield Julia M. 
Published: January 2025

Abstract
Neuroimaging’s unique capability at capturing pathology in brain images has transformed the understanding of schizophrenia. Numerous abnormalities in brain structure have been identified, including ventricular enlargement, smaller subcortical and hippocampal volumes, and widespread cortical thinning. Functional neuroimaging has informed the mechanisms of psychosis phenotypes and cognitive impairment. Connectivity based methods have helped develop and test neural models of schizophrenia, including network models emphasizing dysconnectivity in cortical, thalamocortical, and hippocampal circuits. Magnetic resonance spectroscopy has revealed abnormalities in glutamatergic and GABAergic neurotransmission. Studies of unaffected family members and genetic syndromes associated with elevated risk for psychosis have informed genetic mechanisms. These discoveries helped redefine schizophrenia as a brain disorder. Nevertheless, neuroimaging has yet to fundamentally alter the clinical management of individuals with schizophrenia. Greater emphasis on longitudinal and intervention studies, optimizing psychometric properties (e.g., reliability) of neuroimaging variables, and dimensional assessments of psychopathology will help reach this goal.
Neurotrophic Mechanisms of Depression and Antidepressant Action in Animal and Human Studies
Authors: Monteggia Lisa M. 
Published: January 2025

Abstract
Neurotrophic factors are required for the proliferation, maturation, and guidance of neurons during development, but they also play critical roles in the adult brain. The disruption of neurotrophic factor expression and signaling by stress has been hypothesized to contribute to an individual’s vulnerability to depression. Conversely, neurotrophic factors have been shown to be critical for antidepressant effects, including the rapid action of ketamine and scopolamine. This chapter provides an overview of neurotrophic factors, with a focus on brain-derived neurotrophic factor (BDNF), in depression and the complexity of recent findings. It also discusses the essential role of BDNF in antidepressant action, including rapid antidepressant effects of ketamine and scopolamine.
Current Treatments for Depression
Authors: Fava Maurizio , Krystal John H. 
Published: January 2025

Abstract
Major depressive disorder (MDD) is a highly prevalent and disabling medical condition, with such prevalence having markedly increased during the COVID-19 pandemic. Depression may be a predictor of later medical disease and, in the presence of comorbid medical illness, is associated with poorer medical outcomes. It is critical to provide adequate treatment of MDD. This chapter reviews the pharmacological approaches to the treatment of patients with MDD, ranging from the monoamine-based pharmacotherapies to the more recently introduced glutamatergic and GABAergic antidepressants. It also reviews the pharmacological actions of these agents and their relevance to both efficacy and tolerability, as well as the results of the STAR*D study, the largest trial ever conducted in MDD. The chapter describes the most common approaches to MDD patients who do not respond adequately to antidepressants and, in particular, the most common augmentation strategies. The roles of psychotherapy and of brain stimulation strategies are discussed.
Current Treatments for Anxiety and Trauma-Related Disorders
Authors: Szuhany Kristin L. , Feldman Benjamin , Malgaroli Matteo , Simon Naomi M. 
Published: January 2025

Abstract
Abstract: Anxiety and trauma-related disorders are some of the most commonly occurring mental health conditions and have a significant impact on quality of life and/or functioning. This chapter highlights evidence-based pharmacotherapy, psychotherapy, and integrative health interventions for common anxiety and trauma-related disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, and post-traumatic stress disorder. First-line interventions generally include selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors, as well as cognitive–behavioral therapy approaches. However, patient preference, resources, access, and clinical presentation factors such as comorbidity must be considered when selecting treatment. Digital interventions also offer alternatives to increase access and scalability of evidence-based interventions. Future directions include emphasis on processes of change and mechanisms of action, including for novel interventions and augmentation strategies, to further optimize and personalize interventions for anxiety and trauma-related disorders.
The Lewy Body Dementias
Authors: Galvin James E. , Bras Jose Tomas 
Published: January 2025

Abstract
Lewy body dementia (LBD) is the second most common form of neurocognitive disorder after Alzheimer’s disease and covers two related diagnoses: dementia with Lewy Bodies and Parkinson’s disease dementia. Despite being a common disorder, diagnosis outside expert academic centers remains a significant challenge. The core pathological feature of LBD is the cortical Lewy body; however, many cases will have coexistent Alzheimer’s disease pathology. Genetic risk factors for LBD include mutations in genes for apolipoprotein E (APOE), α-synuclein (SNCA), and galactocerebrosidase (GBA). Dopamine transporter imaging remains the most sensitive, but platforms for measuring α-synuclein are being developed. Current therapies focus on symptomatic relief, but experimental cell and animal models are providing new insights for the development of disease-modifying therapeutics.
Novel Approaches for Treating Alzheimer’s Disease and Other Dementias
Authors: Silva M. Catarina , Butler David C. , Temple Sally , Haggarty Stephen J. 
Published: January 2025

Abstract
Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) are associated with memory and reasoning impairment caused by progressive brain cell death. A common disease feature is the accumulation of pathological aggregating proteins in neurons and glia of the affected brain regions, such as extracellular deposition of amyloid plaques and intracellular tau neurofibrillary tangles. Despite substantial research and investment efforts, there are no effective disease-modifying or preventative therapeutics for AD/ADRD. Challenges include insufficient understanding of pathogenic mechanisms, poor target validation/binding, poor drug delivery to the brain, and weak drug-modifier effects. Repeated AD/ADRD clinical trial failures underscore the need for innovative human cellular and preclinical animal models, novel therapeutic modalities, and new ways to stratify patient populations. In this chapter, progress toward these goals is reviewed, including innovations in small molecules, biologics, immunotherapies, and gene therapies that target protein–protein interactions and aggregation, promote protein degradation, lessen neuroinflammation, and improve blood–brain barrier accessibility.
Neuroimaging in Pediatric Psychiatric Disorders
Authors: Roberts Timothy P. L. , Bloy Luke 
Published: January 2025

Abstract
Noninvasive imaging and electrophysiological techniques have been developed to probe specific aspects of brain function and dysfunction, providing spatial maps of functional centers and temporal activity characteristics. These techniques have evolved from single-modality methods identifying functional localization, specialization, and segregation, through real-time measures of neuronal activity, toward multimodality integration of structural, functional, and spectrotemporal approaches. While imaging makes an immediate impact in neurologic conditions where physical brain lesions are clearly evident, to make a commensurate contribution within neuropsychiatry is substantially more complex; nonetheless by combining concepts of morphology, neurochemistry, neural signal propagation, and regional connectivity, there appears to be ample opportunity to contribute not only to the diagnosis of patients with mental illness but also to the stratification and subtyping across behavioral phenotypes and, ultimately, to patient management. This chapter present an overview of the most common noninvasive neuroimaging methodologies, as well as their applications to pediatric neurodevelopmental disorders.
Neurobiology of Tic Disorders and Obsessive–Compulsive Disorder
Authors: Pittenger Christopher 
Published: January 2025

Abstract
Obsessive–compulsive disorder (OCD) and Tourette syndrome (TS), along with other tic disorders, involve pathophysiological alterations in the corticostriatal circuitry. Both are neurodevelopmental conditions, although OCD can also have adult onset. They are frequently comorbid and often run together in families. Genetic studies suggest shared risk factors, especially in the case of early onset OCD. Because of these shared characteristics, they are treated together in this chapter. Structural and functional neuroimaging studies are refining understanding of the abnormalities in corticostriatal connectivity that accompany symptomatology. Advances in animal models that may capture aspects of pathophysiology have allowed testing of specific etiological hypotheses and have established several systems in which more precise mechanistic studies of pathophysiology are proceeding. Finally, growing evidence suggests that immune dysregulation may contribute to a subset of cases.
Digital Therapies of Psychiatric Disorders
Authors: Biagianti Bruno , Nahum Mor , Yitzhak Neta , Vinogradov Sophia 
Published: January 2025

Abstract
The field of digital mental health is rapidly expanding. This chapter focuses on digital interventions for depression, emphasizing that only a limited number of adequately powered and rigorously designed randomized clinical trials have investigated their efficacy in well-defined participant groups. Digital cognitive–behavioral theory (dCBT) is the most commonly used scientific paradigm studied to date, and the data indicate that for mild depression, self-guided dCBT interventions are efficacious, whereas for moderate or severe symptoms, assisted dCBT and blended treatments are preferable. Digital behavioral activation and cognitive training programs have also been explored. In the near future, it is likely that multiple aspects of digital technology will be able to be harnessed to create precision phenotyping and to deliver and monitor individualized digital interventions in real time via closed-loop systems. Digital mental health formularies are already available and being further developed to support clinicians in understanding patient engagement, efficacy, and safety.
Quo Vadis
Authors: Lawrence Ryan E. , Lieberman Jeffrey A. 
Published: January 2025

Abstract
In the course of its history, psychiatry has faced many challenges and controversies, including an ongoing search for biomarkers, a need for more effective treatments, difficulties in enabling access to care, questions surrounding the appropriateness of involuntary treatment, and ongoing stigma. These challenges are not unique to the present age. Each has historical precedent and exists in a historical context that has profoundly shaped how psychiatry has evolved over decades and sometimes over centuries. Understanding this historical context provides perspective on how these challenges developed into their current shape and offers hints of the future. This chapter provides a historical review of the field of psychiatry.
Discrimination, Bias, and Their Effects on Professionalism Standards for Underrepresented Groups
Authors: Chawla Vanika , Alexander Amy 
Published: January 2025

Abstract
This chapter explores unique considerations of the applications of professionalism for those underrepresented in medicine groups, including first-generation physicians, international medical graduates, LGBTQ+ physicians, physicians with disabilities, Asian medical trainees, and physicians and racial and ethnic minorities (e.g., Black, Latinx, and Native American) medical students and physicians. Bias is reviewed in the constructs and applications of professionalism that may negatively disadvantage these groups, and the importance of identifying, acknowledging, and challenging these notions to operationalize professionalism is discussed in a manner that is inclusive and encourages diversity. This chapter explores research with a focus on qualitative studies and narratives to illustrate the experiences of diverse physicians and their experiences with professionalism.
Low-Dose Neuroleptics for Treating Delirium
Authors: Araya Deborah 
Published: January 2025

Abstract
“A Double-Blind Trial of Haloperidol, Chlorpromazine, and Lorazepam in the Treatment of Delirium in Hospitalized AIDS Patients” compares the efficacy and side effects of 3 drugs commonly used to treat delirium. The researchers gained consent from 244 nondelirious hospitalized patients with AIDS. Thirty patients subsequently developed delirium while in the hospital setting and were randomized to 1 of 3 treatment arms. The results were measured using the Delirium Rating Scale, Mini-Mental State scores, and the Extrapyramidal Symptoms Rating Scale. Both haloperidol and chlorpromazine were found effective in low doses with minimal side effects. Lorazepam worsened delirium symptoms and had treatment-limiting side effects.
The Use of Very Low-Dose Methadone for Palliative Pain Control
Authors: Davis Mellar P. 
Published: January 2025

Abstract
Methadone is a unique opioid analgesic with high-efficacy binding to mu receptors. In a study by Salpeter and colleagues, patients on potent opioids were placed on a loading dose (2.5–15 mg/day) depending on whether opioid naïve or tolerant and then the potent opioid in the opioid-tolerant patient was tapered. Haloperidol was used as an adjuvant. The median pain intensity score on methadone was 0 (range 0–6), similar in cancer and noncancer patients. Haloperidol was used in 40% of those receiving methadone and 70% of those who converted from long-acting opioids to methadone. The median dose of haloperidol was 3 mg (interquartile range 2–6 mg).
Lorazepam and Haloperidol Versus Haloperidol Monotherapy for the Treatment of Agitated Delirium
Authors: Juba Katherine M. , Svengsouk Jefferson S. 
Published: January 2025

Abstract
Agitated delirium is a common symptom in patients with a limited life expectancy. The objective of this single-center, double-blind, randomized controlled trial was to assess the efficacy of 3 mg intravenous (IV) lorazepam + 2 mg IV haloperidol versus placebo + 2 mg IV haloperidol for the treatment of agitated delirium in adult patients with advanced cancer. Ninety patients were enrolled, and 52 patients completed the study (n = 26 lorazepam and n = 26 placebo). Patients who received lorazepam + haloperidol had a greater decrease in agitation (Richmond Agitation-Sedation Scale [RASS] = –4.1 points) than haloperidol alone (RASS = –2.3 points) (P &lt; .001). This study suggests that the addition of 3 mg IV lorazepam to IV haloperidol versus haloperidol alone resulted in a significantly greater reduction in agitation at 30 minutes and at 8 hours with a lower risk of hyperactivity.
Treatment of Cancer-Related Fatigue With Dexamethasone
Authors: Mis Lydia , Kamal Arif 
Published: January 2025

Abstract
Clinicians frequently prescribe corticosteroids to patients with advanced cancer for the management of cancer-related fatigue (CRF), pain, nausea, and anorexia/cachexia based on small randomized trials that have shown benefit. This trial was undertaken to examine the benefit of short-term dexamethasone (14 days) versus placebo on CRF and other symptoms using validated, patient assessment instruments. At the conclusion of the trial period (day 15), there was a significant improvement in CRF and other patient-related symptom scores except for overall symptom distress or psychological distress scores. There was no difference in the frequency of adverse effects between the 2 groups. More studies are needed to evaluate the safety and efficacy of corticosteroids for CRF for longer durations of time as many patients are living many months with advanced cancer.
Efficacy of Levetiracetam, Fosphenytoin, and Valproate for Established Status Epilepticus by Age Group (ESETT)
Authors: Yeh Angela , Martin Emily J. 
Published: January 2025

Abstract
In this multicenter, double-blind, response-adaptive, randomized controlled trial, investigators found that levetiracetam, fosphenytoin, and valproate were equally effective and safe in the treatment of benzodiazepine-refractory status epilepticus among children (&lt; 18 years), adults (18–65 years), and older adults (&gt; 65 years).
Treatment of Malodorous Tumors With Topical Metronidazole
Authors: Mis Lydia 
Published: January 2025

Abstract
Malodorous tumors cause emotional distress due to the appearance of fungating wounds, exudate, pain, constant bleeding risk, low self-esteem, social isolation, and low quality of life (QOL). Family and caregivers may avoid such patients. This study showed that once- to twice-daily application of metronidazole (MTZ) 0.75% gel successfully decreased odor (measured on a scale of 0 to 5) by day 14 to a score of 0 to 1 in 95.5% of patients and that 71.4% of patients were satisfied with results. Treatment was well tolerated except for 2 cases of tumoral bleeding (1 each of mild and moderate). The use of MTZ 0.75% gel should be considered as part of fungating wound care management protocols.
The Effect of Cannabis on Appetite and Quality of Life in Patients With Cancer-Related Anorexia-Cachexia Syndrome
Authors: Natarajan Balakrishnan , Bhagavat Bavna 
Published: January 2025

Abstract
“Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients With Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial From the Cannabis-In-Cachexia-Study-Group,” is a randomized controlled trial which studied 243 patients with cancer-related anorexia-cachexia syndrome (CACS) over a 6 week period. This trial investigated the effects of cannabis extract (CE), THC (delta-9-tetrahydrocannabinol), and placebo on appetite and quality of life (QOL). Results revealed no significant differences between the CE, THC, and placebo arms in QOL, appetite, nausea, mood, and cannabinoid-related toxicity. There was early closure of the trial due to insufficient differences between study arms. Increase in appetite was noted in other studies3, however THC dosing was variable. No strong recommendation of cannabinoids for palliation of appetite and QOL can be made on the basis of this study. Further studies on larger sample sizes are needed to characterize the palliative and adverse effects of cannabinoids.
Role of Paracetamol (Acetaminophen) for Cancer Pain Requiring High-Dose Opioids
Authors: Pandey Shila 
Published: January 2025

Abstract
Cancer pain is a common symptom managed by palliative care clinicians that may require high-dose opioids. The use of paracetamol (acetaminophen) as an adjuvant to an opioid regimen was studied in this randomized, controlled, crossover trial. Thirty-one patients received paracetamol and placebo for 5 days. The primary outcome was effect on pain and number of breakthrough medications used. Secondary outcomes included adverse effects and overall well-being. There were no statistically significant differences in any of these variables. Palliative care providers should question the role of paracetamol as an adjuvant to an opioid regimen &gt; 200 mg/day.
Treatment of Painful Wounds With Topical Morphine
Authors: Protus Bridget McCrate , Brinker Joni 
Published: January 2025

Abstract
Opioid receptors are present on peripheral nerve terminals and are believed to play a role in pain modulation at the site of pressure injuries, malignant lesions, and other wound types. The authors present a case series to illustrate treatment of painful wounds with application of a compounded morphine-hydrogel topical wound dressing. All but 1 of the patients obtained pain relief after topical morphine applications. Additional research is needed to determine definitive benefit of topical opioid application for painful wounds. Based on subjective patient reporting of pain control, topical morphine appears to be effective at reducing pain in open wounds.
Efficacy and Safety of Valproic Acid Versus Haloperidol in Patients With Acute Agitation
Authors: Vanston Vincent Jay , Langi Alyssa 
Published: January 2025

Abstract
The objective was to compare the efficacy of valproate versus haloperidol in decreasing agitation in affected patients in the emergency department. A total of 160 acutely agitated patients were assigned to receive intravenous sodium valproate (20 mg/kg) or intramuscular haloperidol (5 mg/1 mL). Agitation was measured at baseline and 30 minutes after the first injection using 3 agitation scales. A larger proportion of patients in the haloperidol group experienced intense sedation and extrapyramidal symptoms compared with the valproate group. Findings suggest that in the clinical practice setting of emergency psychiatry, intravenous valproate is as effective as haloperidol in reducing agitation, with a better safety profile.
Migraine in women
Authors: Macgreggor Anne 
Published: January 2025

Abstract
Around 4 of every 10 women will experience migraine at some point during their lives, with most having their first attack by age 35 years. This chapter deals with the influence of the hormonal effects of menstruation and menopause and the implications for contraception and pregnancy. It covers pathophysiology, diagnosis and management options full these areas of Women’s Health.
bpass stellar evolution models incorporating α-enhanced composition – I. Single star models from 0.1 to 316 M⊙
Authors: Byrne Conor M , Eldridge Jan J , Stanway Elizabeth R 
Published: January 2025

ABSTRACT
Stellar evolution modelling is fundamental to many areas of astrophysics including stellar populations in both nearby and distant galaxies. It is heavily influenced by chemical composition. Observations of distant galaxies and nucleosynthesis calculations show that $\alpha$-process elements are enriched faster than iron group elements. We present a dense grid of single-star models calculated using the bpass stellar evolution code and covering masses ($0.1\le \mathrm{\mathrm{ M}}/$M$_\odot$$\le 316$), metallicity mass fractions ($10^{-5} \le Z \le 0.04$), and $\alpha$-to-iron abundance ratios ($-0.2\le$$[\alpha /\rm {Fe}]$$\le +0.6$). By comparing solar-scaled models to ones enriched in $\alpha$-process elements, we find that stellar radii, surface temperatures, Main Sequence lifetimes, supernova progenitor properties and supernova rates are all sensitive to changes in $[\alpha /\rm {Fe}]$. Lifetimes of low-mass stars differ by up to 0.4 dex, while surface temperatures of massive stars at the end of the Main Sequence also differ by around 0.4 dex. Inferred supernova rates when $[\rm {Fe}/\rm {H}]$ is unknown can be highly uncertain. Models with different $[\alpha /\rm {Fe}]$ but comparable iron abundances show smaller variations, indicating that while iron primarily defines the course of evolution; $\alpha$-enhancement none the less has an impact of up to 0.1 dex on stellar properties. Such changes are small for individual stars, but have a large cumulative effect when considering an entire stellar population as demonstrated by isochrone fitting to nearby clusters. Changes in radii and lifetimes have further consequences for a stellar population including binary stars, as they influence the timing, nature, and occurrence rate of mass transfer events.