bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroimaging in Addiction
Authors: Williams Tim M , Srivastava Shrikant , Lingford-Hughes Anne R , Nutt David J 
Published: November 2023

Abstract
Dependence on and harmful use of substances have wide reaching public health implications. In 2004, 19.1 million people in the United States (7.9% of the population aged 12 and over) were current illicit drug users, with marijuana being the most commonly used substance (SAMHSA, 2004). Recently there has been a significant increase in the nonmedical use of painkillers among young adults (aged 18–25 years). Alcohol is used regularly by the majority of the population in the United States; however, young adults report the highest prevalence of binge and heavy drinking (41.2 and 15.1%, respectively). Furthermore, 22.5 million people in the United States were classified with past-year substance dependence or abuse (9.4% of the population), 3.8 million of whom had received treatment in the 12 months prior to survey.
Adjuvants for Pain
Authors: Chang Craig K , Pappagallo Marco 
Published: November 2023

Abstract
An adjuvant for pain is a pharmacological agent that is added to a primary analgesic agent, for example, an opioid, to increase or aid its effect (see Table 25.1). Although adjuvants usually have treatment indications other than pain, advances in molecular biology and neuroscience have generated new strategies to treat pain with these medications.
Interventional Pain Medicine
Authors: Dubois Michel Y , Patel Roshni 
Published: November 2023

Abstract
Interventional pain medicine is an important part of pain management. Although there are many interventional approaches available for treating pain (Box 28.1), the expression ‘‘interventional pain medicine’’ is usually reserved for all procedures done with the use of a needle. Nerve blocks, a prime example, have been used for more than a century for both diagnostic and therapeutic purposes. Many minimally invasive interventions may be effective in diagnosing or managing chronic pain from a variety of sources. Performing these procedures requires an understanding of the relevant anatomy, physiology, and pharmacology, as well as the ability to interpret the results. Most of these techniques should be practiced only after special advanced training.
Behavioral Medicine Treatment in the Management of the Chemically Dependent Patient
Authors: Wootton Joshua 
Published: November 2023

Abstract
Where pharmacological approaches to chemical dependency are concerned, addiction is frequently considered essentially a brain disease, but no medication is likely ever to control addiction on its own, without treatment applied to the social and behavioral dimensions of chemical dependency (Leshner, 1997; NIDA, 1999). Even when immediate physiological dependency has been addressed and overcome, there will always remain those environmental and emotional cues that, when encountered, may tend to reawaken the craving and result in relapse (Beck et al., 2001). Visiting a certain neighborhood or location, pursuing activities with a particular group of people, or just being alone and experiencing feelings of boredom, emptiness, or anxiety can all trigger powerful and familiar cravings, even after prolonged periods of abstinence (Franken et al., 2001; Leshner, 1997).
Managing Pain and Substance Abuse in the Patient With HIV/AIDS
Authors: Breitbart William , Dhingra Lara K 
Published: November 2023

Abstract
In the past decade, adults in the United States diagnosed with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) have benefited from profound advances in treatment and access to care. However, despite these improvements in survival and care, pain in HIV/AIDS patients continues to be a major problem affecting quality of life outcomes for the majority of patients diagnosed. Pain rates in HIV/AIDS patients are high (30% to 93%), with patients who have a history of substance abuse particularly underserved in pain management. HIV/ AIDS patients with a history of substance abuse are more likely to have their pain underassessed and undertreated than patients without a history of substance abuse. It is well-documented that current or past substance abuse is a formidable barrier to adequate pain management in HIV/AIDS care.
Abuse Liability Assessmentof Prescription Opioids in Chronic Nonmalignant Pain Patients
Authors: Zacny James P 
Published: November 2023

Abstract
The purpose of this chapter is to introduce the reader to the concept of abuse liability assessment (ALA) of opioids; how ALA of prescription opioids might be done in chronic nonmalignant pain (CNMP) patients; some of the problems that need to be addressed when designing ALA studies in this population and interpreting the results of the studies; and research questions that might be addressed in the conduct of such studies. Given the paucity of studies that have addressed issues of abuse liability of opioids in CNMP patients (Moulin et al. 1996; Tassain et al. 2003), this chapter is meant to serve as a catalyst to stimulate discussion between pain researchers, pain clinicians, addiction medicine specialists, and abuse liability researchers on this topic.
Beyond the Baton
Authors: Wittry Diane 
Published: November 2023

Abstract
Seasoned conductor Diane Wittry draws a comprehensive roadmap to a successful career in Beyond the Baton. With first-hand understanding of how the role of the conductor has changed across the years, she expertly examines the new set of duties--both on and off of the podium--that now fall upon the shoulders of the music director. From getting a job to fundraising and educational outreach, Wittry’s comprehensive tips and strategies guide students and professional conductors alike through the leadership and organizational skills necessary for success. Numerous real-life examples illustrate vital skills for artistic leadership such as programming subscription, pops, and educational concerts; understanding the budget and the music director’s role in funding the artistic vision; and presenting speeches, and radio and televised interviews. In informative conversations with the author, successful conductors Leonard Slatkin, Robert Spano, and JoAnn Falletta offer tips from personal experience on how music directors can work successfully with orchestras, and what their roles are with the board and the community. With up-to-date information and extensive listings, the resource section provides valuable information that conductors use every day in a convenient and practical format. Wittry gives conductors easy access to contact information for national musical organizations, guest artist managers, music publishers, internet sources, conducting competitions, summer festivals, grants, and scholarships. Programming lists and sample contracts and resumes can also be found within these pages. A comprehensive, step-by-step guide to success in the conducting world, Beyond the Baton is an indispensable companion, and its advice will help all aspiring and practicing conductors make the most of their talent and training.
Evaluation of Sleep, and Sleep Disorders
Authors: Lee-Chiong Teofilo 
Published: November 2023

Abstract
Inquiry should be made into the patient’s history of medical, surgical, or psychiatric disorders; family history of sleep conditions; medication and substance use; and nighttime activities.
The interview should include a thorough family history. Many disorders tend to be more prevalent among children, siblings, and other close relatives of patients. These include snoring, restless legs syndrome, narcolepsy, obstructive sleep apnea, enuresis, sleepwalking, sleep terrors, familial fatal insomnia, mood disorders, and schizophrenia. A positive family history is present in up to 30% of patients with narcolepsy or restless legs syndrome.
A complete medication list must be obtained. Many medications can cause insomnia or excessive sleepiness, or they can precipitate or aggravate parasomnias or restless legs syndrome.
Model Organisms in the Study of Development and Disease
Authors: Bier Ethan , Mcginnis William 
Published: November 2023

Abstract
The past two decades have brought major breakthroughs in our understanding of the molecular and genetic circuits that control a myriad of developmental events in vertebrates and invertebrates. These detailed studies have revealed surprisingly deep similarities in the mechanisms underlying developmental processes across a wide range of bilaterally symmetric metazoans (bilateralia). Such phylogenetic comparisons have de7ned a common core of genetic pathways guiding development and have made it possible to reconstruct many features of the most recent common ancestor of all bilateral animals, which most likely lived 600–800 million years ago (Shubin et al., 1997; Knoll and Carroll, 1999). As Meshed out in more detail below and reiterated as a major unifying theme throughout the book, the common metazoan ancestor already had in place many of the genetic pathways that are present in modern-day vertebrates and invertebrates. This ancestor can be imagined as an advanced worm-like or primitive shrimp-like creature that had a few distinct body specializations along the nose-to-tail axis and was subdivided into three distinct germ layers (ectoderm, mesoderm, and endoderm). It also had evolved an inductive signaling system to partition the ectoderm into neural versus nonneural components and is likely to have possessed appendages or outgrowths from its body wall with de7ned anterior–posterior, dorsal– ventral, and proximal–distal axes, as well as light-sensitive organs, a sensory system for detecting vibrations, a rudimentary heart, a molecular guidance system for initiating axon outgrowth to the midline of the nervous system, ion channels for conducting electrical impulses, synaptic machinery required for neural transmission, trachea, germ cells, and an innate immune system.
Molecular Regulation of Cardiogenesis
Authors: Nigam Vishal , Srivastava Deepak 
Published: November 2023

Abstract
Congenital heart malformations, the most common of all human birth defects, occur in almost 1% of the population worldwide, regardless of race (Hoffman and Kaplan, 2002). An additional 1%–2% of the population harbor more subtle cardiac developmental anomalies that only become apparent as age-dependent phenomena reveal the underlying pathology. With more than 1 million survivors of congenital heart disease (CHD) in the United States, it is becoming apparent that genetic disruptions which predispose to developmental defects can have ongoing consequences in the maintenance of speci7c cell types and cellular processes over decades (Srivastava, 2004). A more precise understanding of the causes of CHD is imperative for the recognition and potential intervention of progressive degenerative conditions among the survivors of CHD.
The Sex Determination Pathway
Authors: Erickson Robert P 
Published: November 2023

Abstract
Sexual differentiation is a dynamic process that is subject to a sequential program. This program is so ordered that it can be carried to completion in consecutive stages, often described in the literature as (1) the establishment of chromosomal sex at fertilization, (2) the development of gonadal sex, and (3) the development of secondary sexual characteristics, collectively called the sexual phenotype. However, recent research has shown that sex differences are present immediately after fertilization, thus suggesting that sexual development should be considered to include a stage of pregonadal sexual dimorphism (Erickson and Blecher, 2004). This paradigm of a developmental cascade constitutes the central dogma of sexual differentiation, formulated in principle by A. Jost at the end of the 1940s to explain the results of his experiments on fetal castration in rabbits. He observed that the extirpation of the gonads (ovaries or testes) before sexual differentiation had occurred invariably resulting in the development of fetuses in a female-type pattern (Jost, 1953).
STK11 (LKB1) and Peutz–Jeghers Syndrome
Authors: Antonarakis Stylianos E 
Published: November 2023

Abstract
A family with intestinal polyposis and mucocutaneous pigmentation was first described by the Dutch physician Johannes Peutz from Hague in 1921 (Peutz, 1921). Harold Jeghers from Boston also described additional patients (Jeghers, 1944). He, along with Victor McKusick and Katz, provided a definitive description of the syndrome in 1949 (Jeghers et al., 1949). For an extensive historical account see Keller et al. (2001). This autosomal dominant disease was probably first described in twin sisters with “ink-black pigmentation of the lips and mouth” by Johnathan Hutchinson in 1896 (Hutchinson, 1896). Francis Giardello in 1987 pointed out that patients with this syndrome have an increased risk for the development of cancer at gastrointestinal and other sites (Giardiello et al., 1987). The genomic interval on chromosome 19p13.3 that harbors a responsible gene was mapped by Akseli Hemminki and Lauri Aaltonen in Helsinki in 1997 using comparative genomic hybridization, loss of heterozygosity, and linkage analysis (Hemminki et al., 1997). A year later Hemminki, and independently Dieter Jenne from Martinsried Germany, identified the gene responsible for PJS and characterized several pathogenic mutations (Hemminki et al., 1998; Jenne et al., 1998). The gene that encodes STK11 was first cloned and its sequence deposited in Genbank (U63333) by Jun-ichi Nezu of Chugai Pharmaceuticals in 1996 after a screen to isolate new kinases and was named LKB1 (liver kinase B1). Suggestive evidence for additional PJS-causing genomic regions has been provided (Mehenni et al., 1998).
The RAS Pathway
Authors: Swensen Jeffrey , Viskochil David 
Published: November 2023

Abstract
In the early 1960s, at the London Hospital Research Laboratories, plasma filtrate collected from a leukemic rat during the routine passage of Moloney leukemia retrovirus was injected into newborn mice. Rather than developing signs of leukemia as expected, the mice grew tumors that proved to be sarcomas. Additional mice inoculated with filtrates of these tumors rapidly developed sarcomas themselves (Harvey, 1964). The tumors resulted from an unknown oncogenic virus that was later named Harvey murine sarcoma virus. A group at the University of Chicago obtained similar results while passing Kirsten murine erythroblastosis virus through rats (Kirsten and Mayer, 1967). Their virus became known as Kirsten murine sarcoma virus.
RAS Signaling Defects and Noonan Syndrome
Authors: Tartaglia Marco , Gelb Bruce D 
Published: November 2023

Abstract
Moonan syndrome (OMIM 163950) is a pleomorphic disorder affecting the cardiovascular, craniofacial, skeletal, hematopoietic, lymphatic, and central nervous systems. It can result from mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase (PTP), Src homology 2 (SHP-2), or the KRAS gene, which encodes a RAS GTPase. The disorder is generally transmitted as an autosomal dominant trait, although many cases result from de novo mutations. Defects in the PTPN11 gene, which resides at chromosomal band 12q24.1, account for approximately 50% of cases. The more than 60 mutations that have been reported are mostly missense changes, with the vast majority affecting residues clustering at the interface between the N-terminal SH2 and PTP domains. Mutant SHP-2 proteins have a gain of function, usually through effects on the molecular switching mechanism important for activating/inactivating this enzyme. Missense PTPN11 mutations also recur in LEOPARD syndrome (MIM 151100), which is clinically related to Noonan syndrome. These mutations cause loss of catalytic activity of the phosphatase and are hypothesized to have dominant-negative effect on the wild-type protein. Defects in the KRAS gene account for approximately 2% of Noonan syndrome cases and engender gain of function in RAS signaling through reduced KRAS GTPase activity or increased GDP/GTP dissociation rate. Clinical manifestations of Noonan syndrome include a typical dysmorphic appearance, congenital heart defects [particularly pulmonic stenosis (PS)] or hypertrophic cardiomyopathy (HCM), webbing of the neck, short stature, cryptorchidism, eye abnormalities, and skeletal anomalies such as pectus deformities, cubitus valgus, and vertebral anomalies. A minority of affected individuals has bleeding diathesis, hearing loss, and mental retardation. Diagnosis is made by clinical examination. Prenatal diagnosis of Noonan syndrome may be suspected in the presence of ultrasonographic findings such as nuchal edema or cystic hygroma. Therapy in the neonatal period and infancy involves discovering and treating the cardiac disease and managing the feeding problems. Orchidopexy is indicated for undescended testes. Growth hormone (GH) therapy has been used to ameliorate the short stature. Preventive pediatric care is appropriate for the hematologic and developmental issues.
RASA1 and Capillary Malformation– Arteriovenous Malformation
Authors: Revencu Nicole , Boon Laurence M , Mulliken, John B , Vikkula Miikka 
Published: November 2023

Abstract
RASA1 encodes p120RasGTPase-activating protein (p120RasGAP), an important RAS inhibitor. Mutations in this gene result in capillary malformation–arteriovenous malformation (CM–AVM; OMIM 608354), a newly recognized autosomal dominant disorder (Eerola et al., 2003). Small, multifocal and randomly distributed CMs are the hallmark of the disorder. In addition, about one-third of patients have a fast-How lesion. Forty-seven mutations have been identified until now and most of them would lead to a truncated protein if translated. Thus, the most likely pathogenic mechanism is loss of function.
PAX6 and Aniridia and Related Phenotypes
Authors: Heyningen Veronica Van , Williamson Kathleen 
Published: November 2023

Abstract
The PAX6 gene on chromosome 11p13 was isolated by positional cloning (Ton et al., 1991) as a strong candidate gene for the human eye anomaly aniridia (OMIM 106210) (Fig. 86–1). The gene was identi(ed within the aniridia subregion of the Wilms’ tumor, aniridia, genitourinary abnormalities, and mental retardation (WAGR, OMIM 194072) contiguous deletion site. Its expression pattern, assessed by RNA in situ hybridization in human and mouse development, is consistent with a role for PAX6 in developmental eye disease, although it is broader than the spectrum of tissues affected in aniridia.
PAX9 and Hypodontia
Authors: Patel Pragna I , Brown Donald T 
Published: November 2023

Abstract
The most common abnormality affecting the formation of the dentition is deviation from the usual number of the human permanent dentition (a total of 32 teeth in both jaws) or the deciduous dentition (20 total teeth in both jaws). When the number of teeth is less than the normal complement of dentition, the condition is known as hypodontia. Other anomalies seen in association with hypodontia include small tooth size (microdontia) and anomalies in tooth shape, most commonly tapering or “peg-shaped” teeth (McKeown et al., 2001; Brook et al., 2002). Frameshift, nonsense, and missense mutations in the human paired box gene 9 (PAX9) gene have been associated with hypodontia involving primarily posterior teeth. Severe hypodontia associated with a submicroscopic deletion involving loss of the entire gene in one family supports a model implicating haploinsuf)ciency of PAX9 as the primary cause for hypodontia involving molar teeth. Both primary and permanent dentitions are affected, with the effects being more prominent in the case of permanent teeth. PAX9 is a member of a family of transcription factors characterized by a common DNAbinding domain called the paired domain. It is highly homologous to PAX1, with which it shares an overlapping pattern of expression. PAX9 is a 342–amino acid protein encoded by a single gene mapping to human chromosome 14q21. Homozygous Pax9 mutant mice die shortly following birth. They lack a thymus, parathyroid glands, and ultimobranchial bodies. Mutant mice have a cleft secondary palate at birth, and tooth development is arrested at the bud stage, resulting in the absence of all teeth. Heterozygous mutants display no discernible defects.
SOX3 and Infundibular Hypoplasia
Authors: Kelberman Daniel , Dattani Mehul T 
Published: November 2023

Abstract
duplications of Xq26–27 encompassing SOX3 [sex-determining region Y (SRY)-box 3] have previously been associated with variable hypopituitarism and learning difculties. More recently, lossof-function polyalanine tract expansion mutations within SOX3 have been associated with essentially similar phenotypes of infundibular hypoplasia and midline defects of the central nervous system (CNS), with anterior pituitary hypoplasia and varying degrees of hypopituitarism. Variable mental retardation or learning difficulties are observed in some cases. Targeted disruption of Sox3 in mice reveals a somewhat analogous phenotype, with mutant mice exhibiting abnormal development of the infundibulum and hypothalamus, which subsequently disrupts necessary inductive signals for correct anterior pituitary development. Correct gene dosage of SOX3 is therefore critical for normal development of the diencephalon and infundibulum and, consequently, the anterior pituitary in humans and mice. The role of SOX3 in the etiology of X-linked hypopituitarism needs further investigation.
SOX18 and the Hypotrichosis–Lymphedema–Telangiectasia Syndrome
Authors: Ghalamkarpour Arash , Devriendt, Koen , Vikkula Miikka 
Published: November 2023

Abstract
The hypotrichosis–lymphedema–telangiectasia syndrome (HLTS; OMIM 607823) is a rare syndrome with autosomal dominant or recessive pattern of inheritance. It is characterized by the triad of sparse hair, (2) lymphatic edema, and (3) cutaneous telangiectasias. The hair has usually a normal appearance at birth but becomes sparse during infancy. Eyebrows and eyelashes are missing and the patients do not develop axillary or pubic hair. Lymphedema mostly affects lower limbs and has a variable age at onset from congenital to puberty. Telangiectasias can be present at palms, soles, scalp, scrotum, or legs; however, it is not observed in all patients. The molecular basis of HLTS was established by considering the murine ragged phenotype as a putative counterpart of the human disorder. Sex determining Y-box 18 (SOX18), the human ortholog of the murine ragged gene, was found to be mutated in patients with HLTS, accounting for both recessive and dominant forms of the disease.