bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Essays of Julia C. Collins, 1864–1865
Authors: Collins Julia C 
Published: November 2023

Abstract
It is a faulty and indolent humility that makes some of our people sit still and learn nothing, because they cannot learn everything. We are born with faculties and power, capable of almost anything. Who can measure our capacity, or set bounds to our progression in knowledge? Destitute alike of knowledge, the children of the white race have, in this respect, no advantage over the black; both have everything to learn. All must begin with the simplest elements of knowledge, and advance from step to step, in nearly the same manner. Much time and skill are requisite to mould the mind in strength and beauty, by proper exercise of its faculties. The mind is formed, gradually expanded and strengthened into vigorous action. We must subject ourselves to severe, and sometimes painful discipline, for this very exercise will enrich and embellish the mind with new and important ideas. We must feel that there is nothing too hard for industry and perseverance to accomplish. We must scale the rugged hill of science, by dint of powerful effort and great self-reliance, and at last reward ourselves by drinking at the richest streams of science and literature.
The Moral Significance of Early Human Embryos in Religious Thought
Authors: Cohen Cynthia B 
Published: November 2023

Abstract
In a pluralistic democratic society such as that in the United States, no exploration of the moral significance of early human embryos would be complete it if were to consider only secular views of this matter. The views of those who adhere to religious traditions within that polity also need to be taken into account if we are to gain a more complete picture of the reasoning of many citizens about contentious issues as we develop public policy. That is especially the case today, when the views of active and influential religious adherents about whether stem cells derived from human embryos should be used in research have been playing a prominent role in public policy decisions about this research.
Sleep In The Medical Disorders
Authors: Lee-Chiong Teofilo 
Published: November 2023

Abstract
Many medical disorders can give rise to disturbances of sleep and alter sleep architecture. Sleep can be impaired by the medical conditions themselves or by the medications used to treat them. Several symptoms associated with medical disorders, such as pain, dyspnea, nocturia, and pruritus can potentially disturb sleep, with the severity of sleep complaints waxing and waning in relation to the course of the medical illness. More than one sleep pathology may be present in a particular patient. The sleep disturbance causes distress and functional impairment, and requires independent clinical management. Conversely, sleep impairment can alter the presentation and adversely affect the symptoms of a variety of medical conditions, including respiratory, cardiac, gastrointestinal, renal, rheumatologic and infectious disorders.
Asthma is a disease characterized by episodic dyspnea and wheezing, reversible episodes of bronchoconstriction, and airway hyperreactivity to a variety of specific and nonspecific stimuli.
Sleep disturbance in patients with asthma can result in complaints of insomnia (including early morning awakenings) or excessive sleepiness. In one study, three of every four asthmatics reported nocturnal awakenings occurring at least once weekly, whereas two-thirds had nocturnal awakenings at least three times a week. Sleep in patients with nocturnal asthma is characterized by poor sleep quality with frequent arousals. They may awaken repeatedly due to coughing, dyspnea, wheezing, and chest discomfort. Complaints of insomnia and/or excessive daytime sleepiness are not infrequent.
Sleep in Neurologic Disorders
Authors: Lee-Chiong Teofilo 
Published: November 2023

Abstract
Alzheimer disease is the most common degenerative disorder of the central nervous system that causes dementia. Fragmentation and repetitive arousals/awakenings characterize the sleep of persons with dementia. Confusion, agitation, and wandering can occur at night (“sun downing”), further contributing to sleep disruption (Box 10–1). Sleep complaints may be due primarily to the underlying dementia or to related sleep-disordered breathing, periodic limb movements of sleep, or secondary depression. Reversal of the sleep-wake rhythms can be seen with patients complaining of nocturnal insomnia and excessive daytime sleepiness. Polysomnography may demonstrate decreases in rapid eye movement (REM) sleep time and REM density. Sleep efficiency is reduced.
Management includes proper sleep hygiene practices (eg, avoiding caffeine, maintaining a regular sleep schedule, and eliminating daytime naps), and treatment of concurrent depression and medical disorders, including pain syndromes, that might contribute to sleep disturbance. Short-term use of hypnotics, such as zolpidem, zaleplon, or eszopiclone, may be tried for insomnia.
Psychiatric and Behavioral Disorders
Authors: Lee-Chiong Teofilo 
Published: November 2023

Abstract
Acomplicated interface exists between psychiatric and sleep disorders—psychiatric symptoms are amplified and aggravated by sleep disruption, and the pathology of psychiatric disorders may contribute to worsening sleep quality. In addition, persons with insomnia are at higher risk of developing a new psychiatric disorder, particularly major depression, within a year of the onset of insomnia.
Psychiatric disorders can give rise to insomnia, excessive sleepiness, or parasomnias (eg, nightmares or sleep terrors) (Boxes 11–1 and 11–2).. It has been estimated that a third to a half of cases of chronic insomnia are associated with a psychiatric condition. Changes in sleep architecture include a decrease in rapid eye movement (REM) sleep latency that is seen with depressive episodes, schizophrenia, and borderline personality disorder.
Schizophrenia (psychosis) is a chronic psychiatric disorder characterized by both “positive symptoms” (eg, hallucinations, delusions, and disorganized speech and behavior) and “negative symptoms” (eg, affective flattening, avolition [limited goal-directed behavior], and alogia [restricted thought and speech production]). This disabling condition has a median age of onset between 15 and 25 years of age. Course is chronic with significant impairments in self-care, interpersonal interactions, and work performance.
Being Deposed
Authors: Shuy Roger W 
Published: November 2023

Abstract
After the report is submitted, American linguistic expert witnesses can expect to be deposed by the other side, whose lawyers will go through each point with a finetoothed comb. (The deposition does not exist in the United Kingdom, where experts can be questioned at trial about their written reports.) The U.S. deposition is structured so that the opposing lawyers can try to find out (discover) what you will say at trial and to provide a record of your work that can be addressed if you do testify. Their third agenda is to discover what kind of witness you’ll be, whether you can be rattled, how well you handle tough questions, and how the jury or judge may regard you as an expert. The deposition is taken under oath and is usually held in the office of the opposing attorney. The attorney you work with will be there to object whenever necessary. Depositions are recorded by a court reporter, often with an accompanying videotape recording.
Giving Testimony in the Direct Examination
Authors: Shuy Roger W 
Published: November 2023

Abstract
Most civil and criminal cases never go to trial. It is estimated, in fact, that some 90 percent of criminal and criminal cases end before any testimony has to be given. Criminal cases can end with a plea of guilty, a negotiated plea agreement, or a dismissal of charges. Civil cases are often settled with agreements by both parties, often involving the exchange of sums of money. My own experience bears this out. I have testified in only 10 percent of all the cases I’ve worked on over the past 30 years.
Muscle and Somite Development
Authors: anderson Douglas , Rhee, jerry m. , rawls alan 
Published: November 2023

Abstract
Vertebrate skeletal muscle is derived from paraxial and head mesoderm that appears on either side of the neural tube during gastrulation. A fundamental understanding of the cellular events associated with myogenesis has been well established through classic embryological studies in the chicken and mouse model systems. The 7rst appearance of myogenic cells is within individual somites derived from paraxial mesoderm. During embryonic development, these cells must undergo rapid expansion, migration, differentiation, and remodeling in order to generate the morphologically and functionally diverse perinatal muscles groups. Myogenic cells must also respond to spatial and temporal cues that lead to differences in cell fate along the anterior/posterior (A/P) and dorsal/ventral (D/V) axes. In addition, development of the skeletal muscle must be coordinated with the development of bone and cartilage, tendon, the peripheral nerves, and vasculature. During the past 15 years, gain-of-function and loss-of-function approaches have been used to reveal the complex genetic network that integrates these processes. In this chapter, we will review the embryonic development of somites and muscle and focus on our current understanding of the genetic regulation of somitogenesis and skeletal muscle development.
IHH and Acrocapitofemoral Dysplasia and Brachydactyly A1
Authors: Hellemans Jan , Mortier Geert R 
Published: November 2023

Abstract
The 7rst steps in skeletal morphogenesis involve the induction of undifferentiated mesenchyme and its differentiation into condensed mesenchyme. In the human skeleton, only the membranous bones of the skull and part of the clavicle are formed by direct ossi7cation of condensed mesenchyme (intramembranous ossi7cation). For the large majority of bones, bone formation and growth proceed through an intermediate cartilaginous template or anlage in a process called endochondral ossi7cation. These cartilaginous models are formed by further differentiation of condensed mesenchymal cells into chondrocytes that produce hyaline cartilage instead of mesenchymal matrix. In the center of these cartilaginous templates, chondrocytes will form columns of proliferating cells and subsequently enlarge to become hypertrophic chondrocytes, producing type X collagen. In parallel with the cellular differentiation, the extracellular cartilage matrix will be altered through the actions of carbonic anhydrase and alkaline phosphatase. Finally, the hypertrophic chondrocytes disintegrate and die with simultaneous calci7cation of the modi7ed matrix. The newly formed spaces with calci7ed cartilage are invaded by periosteal blood vessels and osteogenic cells, which soon differentiate into osteoblasts. The latter deposit a bony matrix on the calci7ed cartilage, resulting in the formation of the primary center of ossi7cation. This ossi7cation center is formed within the central portion of the cartilage template and will expand both proximally and distally toward the ends (epiphyses) of the developing bone. Also, secondary ossi7cation centers start appearing in the epiphyseal regions. As these ossi7cation centers enlarge, they replace almost all the cartilage by bone except, 7rstly, for a layer of specialized hyaline cartilage at the joint surfaces (articular cartilage) and, secondly, a thicker zone between the diaphysis and the epiphysis, representing the growth plate.
An Introduction to TGF-J3-related Signaling
Authors: Descotte Veronica , O’connor, Michael B , Jadrich Joy 
Published: November 2023

Abstract
Members of the transforming growth factor-β (TGF-β) superfamily of secreted polypeptides play diverse roles in regulating numerous biological processes in a wide variety of organisms. These factors have been implicated in mediating embryonic development, cell proliferation and differentiation, apoptosis, organogenesis, and wound healing; and when misregulated, they can contribute to the etiology of disease. Phylogenetic considerations suggest that this family is one of the oldest signaling pathways, having arisen before the divergence of a common ancestor of arthropods and vertebrates approximately 1.3 billion years ago (Newfeld et al., 1999). In this chapter, we will provide an overview of the signal-transduction pathway utilized by these factors and the mechanisms by which the activities of these pathways are regulated. Much of our understanding of the biology of these factors derives from a multidisciplinary experimental approach using biochemical, genetic, and embryological methods as well as numerous model systems such as Drosophila, Caenorhabditis elegans, Xenopus, zebrafish, and mice. We will give only selected examples here, and the reader is encouraged to examine other reviews (Shi and Massagué, 2003; Massagué et al., 2005; Moustakas and Heldin, 2005) for supplementary information on specific aspects of the biology of these factors. In addition, other chapters in this volume will focus on various human pathologies and developmental disorders that have been linked to defects in different components of this pathway (see Chapters 32–40).
GDF5 (CDMP1) and Chondrodysplasia (Grebe, Hunter–Thompson, and Du Pan Types), and Brachydactyly, Type C
Authors: Kilpatrick Michael W , Tsipouras Petros 
Published: November 2023

Abstract
The human osteochondrodysplasias comprise a large and heterogeneous group of inherited disorders affecting skeletal morphogenesis. Grebe-type chondrodysplasia (OMIM 200700) is characterized by a normal axial skeleton and severely shortened and deformed extremities exhibiting a proximo-distal gradient of severity. This condition is classi%ed as a form of acromesomelic dysplasia. Two other phenotypically similar conditions are the Hunter–Thompson (OMIM 201250) and Du Pan (OMIM 228900) types of chondrodysplasia. Brachydactyly type C (BTC) (OMIM 113100) is characterized primarily by shortening and hypersegmentation of phalangeal and metacarpal bones, and occasionally polydactyly and other skeletal abnormalities. In contrast to the autosomal recessive Grebe, Hunter– Thompson, and Du Pan types of chondrodysplasia, BTC is inherited as autosomal dominant. These conditions are caused by mutations in the gene encoding growth differentiation factor 5 (GDF5), otherwise known as cartilage-derived morphogenetic protein-1 (CDMP1) (OMIM 601146), and they together comprise the spectrum of CDMP1 morphopathies. CDMP1 encodes a signaling molecule, which is a member of the transforming growth factor-β (TGF-β) superfamily.
ENG, ACVRL1, and SMAD4 and Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu Syndrome)
Authors: Srinivasan Sudha , Berg, Jonathan N , Marchuk Douglas A 
Published: November 2023

Abstract
Hereditary hemorrhagic telangiectasia (HHT) or Osler–Weber–Rendu syndrome is an autosomal-dominant vascular disorder characterized by the presence of focal arteriovenous malformations (AVMs) and telangiectases. AVMs are direct communications between arteries and veins without an intervening capillary bed. Telangiectases are clusters of abnormally dilated thin-walled vessels. Penetrance of HHT is age dependent and nearly complete by age 50. There is a high variability of symptoms among affected individuals even in the same family with respect to the age of onset, severity, and organs affected (reviewed in Guttmacher et al., 1995; Marchuk et al., 2003; Abdalla and Letarte, 2006). Symptoms include recurrent epistaxis (nosebleeds), mucocutaneous telangiectases, and AVMs, particularly in the lung, brain, and liver. The primary symptoms can lead to secondary complications such as high-output cardiac failure and stroke.
RUNX2 and Cleidocranial Dysplasia
Authors: Fonseca Patricia , Lee, Brendan , Napierala Dobrawa 
Published: November 2023

Abstract
Runt-related transcription factor 2 (RUNX2) is a RUNT-domain transcription factor required for osteoblast cell fate commitment and chondrocyte maturation. Hence, it serves as a central regulator of intramembranous and endochondral ossification during embryonic skeletogenesis and during the postnatal development. Runx2 directs the expression of multiple genes, including matrix components of bone and hypertrophic cartilage, and regulates the transition of hypertrophic chondrocytes to primary spongiosa. It acts in a context-dependent fashion, specified by both upstream transcriptional regulators of Runx2 expression and direct protein–protein interactions regulating its transactivation of target genes. Haploinsufficiency of RUNX2 in humans causes a dominantly inherited skeletal disorder: cleidocranial dysplasia (CCD). CCD is characterized by delayed intramembranous ossification and defective chondrocyte maturation in some (but not all) skeletal elements. The classic form of CCD is characterized by the triad of delayed closure of the fontanel, hypoplastic clavicles, and dental anomalies. However, genotype–phenotype studies show that RUNX2 mutations can also result in a range of phenotypes from mild CCD predominated by dental features to severe CCD, complicated by significant osteoporosis. The clinical diagnosis can usually be confirmed by pathognomonic findings from radiographic studies. Management is conservative for the skeletal complications, but the significant morbidity associated with dental anomalies dictates an aggressive multidisciplinary approach. Both in vitro and mouse model studies have identified regulators of RUNX2 function, whereas the description of CCD-related conditions raises interesting questions about the potential relationship of these conditions to components of the RUNX2 transcriptional network.
FLT4 (VEGFR3) and Milroy Disease
Authors: Ferrell Robert E , Finegold David 
Published: November 2023

Abstract
The vascular endothelial growth factor receptor-3 (VEGFR3) is a member of the VEGF receptor family, which binds both vascular endothelial growth factors C and D. VEGFR3 is expressed on lymphatic endothelia, and is required for normal development of the lymphatic system. Mutations in VEGFR1 (now designated FLT4 for fms-related tyrosine kinase 4) have been found to cause Milroy disease, an inherited abnormality of the lymphatic system. This autosomal dominant disorder is characterized by swelling of the extremities, the lower usually being affected to a greater degree than the upper. Imaging studies reveal hypoplasia or aplasia of the lymphatics. The management is symptomatic, currently limited to manual massage and compression. Multiple, independent, nonconservative mutations in the tyrosine kinase domains of VEGFR3 have been identified, which segregate with the lymphedema phenotype in families, and show defective protein kinase activity and altered stability in in vitro expression studies. The Chy mouse, a chemically mutagenized model, demonstrates a comparable mutation in the kinase domain of the mouse homolog of VEGFR3, and the dermal lymphatic phenotype is corrected by VEGFC gene therapy. This and early human studies make VEGFR3 an attractive target for the treatment of human lymphedema.
Signaling Pathways of Glial Cell–Derived Neurotrophic Factor
Authors: Reichardt Louis F 
Published: November 2023

Abstract
Glial cell–derived neurotrophic factor (GDNF), a distant relative of transforming growth factor-β (TGF-β), was purified as a factor that promotes the survival and differentiation of embryonic mesencephalic dopaminergic neurons (Lin et al., 1993). A closely related protein, neurturin, was purified as a factor that promotes the survival of sympathetic neurons (Kotzbauer et al., 1996). Subsequently, two additional members of the GDNF family of ligands, artemin and persephin, were identified in expressed sequence tag (EST) databases (Baloh et al., 1998; Milbrandt et al., 1998; Masure et al., 1999). Each of these proteins has been shown to function as a survival and differentiation factor for subpopulations of cultured neurons (reviewed in Baloh et al., 2000a; Takahashi, 2001; Sariola and Saarma, 2003).
The PI3K-LKB1 Pathway
Authors: Shaw Reuben J , Cantley lewis C 
Published: November 2023

Abstract
Rrowth control in all metazoans is regulated by a number of conserved signal transduction pathways. These pathways govern the timing and developmental speci&gt;city of cell growth and differentiation in response to external cues including presence and location of growth factors, morphogens, nutrients, and neighboring cells. The phosphoinositol 3-kinase (PI3K) pathway is one of the central signaling pathways governing cell growth, cell survival, and cell migration. Studies in the past few years have revealed that activation of PI3K underlies the development of a large number of human cancers. One of the main downstream targets of PI3K activity is the protein serine/ threonine kinase mTOR (mammalian target of rapamycin). Recent studies have revealed that hyperactivation of mTOR signaling is a common biochemical thread underlying a handful of inherited familial cancer syndromes including those with phosphatase and tensin homolog deleted on chromosome ten (PTEN), TSC1, TSC2, NF1, and LKB1 (STK11) mutations. Here we illuminate what is known about the detailed circuitry of these signaling pathways, and discuss potential points for therapeutic intervention (Fig. 57–1).
PTEN and the Cowden and Bannayan–Riley–Ruvalcaba Syndromes
Authors: Zbuk Kevin M , Eng Charis 
Published: November 2023

Abstract
The PTEN Hamartoma Tumor Syndrome (PHTS) includes not only the entities Cowden Syndrome (CS; MIM 158350) and Bannayan–Riley–Ruvalcaba syndrome (BRRS; MIM 153480), which are the focus of this chapter, but also Proteus syndrome (PS; MIM 176920), and Proteus-like syndrome (PSL), and perhaps other developmental disorders. These heterogeneous groups of disorders are all, to varying degrees, associated with germline mutations of the PTEN [for phosphatase and tensin homolog, deleted on chromosome 10 (ten)] tumor suppressor gene. PTEN, localized to 10q23.3 is a dual specicity phosphatase. Its lipid phosphatase is crucial in down-regulating the Akt pathway through dephosphorylation of phosphoinositol-3,4,5triphosphate (PIP3) thus facilitating G1 cell cycle arrest and/or apoptosis. It’s protein phosphatase down-regulates cyclin D1 and prevents the phosphorylation of mitogen-activated protein kinase (MAPK), playing important roles in inhibition of cell growth and spreading, in addition to mediating, cell cycle arrest. The importance of PTEN localization to different subcellular compartments is increasingly recognized and will undoubtedly offer insight into novel mechanisms of PTEN dysfunction. CS is an underrecognized and underdiagnosed autosomal dominant disorder. Patients with CS are at increased risk of developing breast, thyroid, and endometrial cancers, in addition to benign neoplasias of these same organs, and have characteristic cutaneous manifestations including papillomatous papules and trichilemmomas. BRRS is characterized by macrocephaly, lipomas, hemangiomas, and speckled penis.