bluuebunny/crossref_metadata_2025_split huggingface dataset:
MKKS and the McKusick–Kaufman and Bardet–Biedl Syndromes
Authors: Biesecker Leslie G 
Published: November 2023

Abstract
McKusick–Kaufman syndrome (MKS) is a rare developmental anomaly syndrome originally described among the Amish that comprises polydactyly, hydrometrocolpos, and congenital heart disease (CHD) (Kaufman et al., 1972) (Fig. 132–1). Bardet–Biedl syndrome (BBS) is more common and manifests wider pleiotropy, comprising polydactyly, retinal degeneration, obesity, mental retardation, renal anomalies, and a wide array of other less common malformations (Beales et al., 1999). Both of these developmental anomaly syndromes can be caused by mutations in the MKKS gene (also known as BBS6) (Katsanis et al., 2000; Slavotinek et al., 2000; Stone et al., 2000) and are inherited in an autosomal recessive pattern, although rare families with BBS have evidence of more complex inheritance (Katsanis et al., 2001; Badano and Katsanis, 2002). BBS is genetically heterogeneous, and the MKS phenotype may be considered to be a mild form of BBS (see Chapter 155 for a complete discussion of BBS). The MKKS gene encodes a putative group II chaperonin similar to an archebacterial thermosome (Stone et al., 2000). Interestingly, another recently described BBS gene, BBS10, shows evidence of homology to the group II chaperonin family as well (Stoetzel et al., 2006). These data suggest that the pathogenesis of BBS and MKS are related to protein folding or misfolding.
PQBP1 and the Renpenning, Sutherland-Haan, Golabi-Ito-Hall, and Hamel Cerebropalatocardiac and XLMR Syndromes and Nonsyndromic XLMR
Authors: Schwartz Charles 
Published: November 2023

Abstract
The assumption was that proteins identified by the screen would be involved in the pathology of polyglutamine diseases. Indeed, subsequent studies clearly showed that PQBP1 interacts with ataxin-1 through its polar amino acid domain (Okazawa et al., 2002). This interaction apparently stimulates apoptosis leading to cell death. But the PQBP1 protein has another important role in developmental disorders beyond its involvement in polyglutamine diseases. Mutations in the gene result in numerous X-linked mental retardation (XLMR) syndromes: Renpenning (OMIM 309500, Renpenning et al., 1962; Stevenson et al., 1998), Golabi–Ito–Hall (Golabi et al., 1984), Sutherland–Haan (OMIM 309500, Sutherland et al., 1988), Hamel cerebropalatocardiac (OMIM 300463, Hamel et al., 1994), as well as MRX55 nonsyndromic XLMR (Deqaqi et al., 1998). That mutations in PQBP1 give rise to syndromic XLMR conditions is not surprising since it contains several important domains: a WW domain, which probably regulates gene expression by binding to RNA polymerase II (Komuro et al., 1999b; Okazawa et al., 2002; Llorian et al., 2004, 2005); a polar amino acid rich domain (PRD), which not only interacts with huntingtin (Busch et al., 2003) and ataxin 1 (Okazawa et al., 2002) but also inhibits the transcriptional activation of Brn2, a member of the family of POU domain containing transcription factors (Waragai et al., 1999); a nuclear localization signal (NLS) and a C-terminal domain (CTD) that binds to the small ribonucleoprotein, U5-15KD, which is a component of the U5 spliceosome complex (Reuter et al., 1999; Waragai et al., 2000; Okazawa et al., 2001).
TBCE and the Hypoparathyroidism–Retardation–Dysmorphism (HRD) Syndrome
Authors: Diaz George A , Parvari, Ruti , Hershkovitz Eli 
Published: November 2023

Abstract
Mutations in a tubulin-specific chaperone, TBCE, which encodes tubulin cofactor E, cause the syndrome of hypoparathyroidism, retardation, and dysmorphism [HRD; also known as Sanjad–Sakati or autosomal recessive Kenny–Caffey syndrome (KCS)]. Tubulin cofactors are essential for the biogenesis of native tubulin heterodimers, the basic unit of microtubules. On the basis of its established role in tubulin biogenesis, loss of TBCE function should be lethal, but mutation of the gene results instead in a pleiotropic disorder of growth failure, parathyroid gland aplasia, and neurological disease. In contrast, mutations in genes important for the regulation of microtubule growth primarily cause neurological diseases. The HRD disease phenotype is more global than predicted by the established role of the cofactor in tubulin biogenesis and highlights the existence of novel TBCE functions in the organization and regulation of the microtubule cytoskeleton.
LMNA and LBR and the Hutchinson–Gilford Progeria Syndrome and Associated Laminopathies
Authors: Gordon Leslie B , Brown, W Ted , Rothman Frank G 
Published: November 2023

Abstract
Hutchinson–Gilford Progeria Syndrome (HGPS), also referred to as childhood progeria, is an extremely rare, uniformly fatal, segmental “premature aging” disease in which children exhibit some phenotypes of aging in their early years. All children die as a consequence of severe atherosclerosis at an average age of 13 years (range 8–21 years) (DeBusk, 1972; Hennekam, 2006). There is no known treatment or cure. Until recently, no progress was made on the genetics of this disease. Then, in 2003, the genetic basis for HGPS was uncovered (Cao and Hegele, 2003; De Sandre-Giovannoli et al., 2003; Eriksson et al., 2003), and HGPS joined a family of genetic dis- eases known as the laminopathies, whose causal mutations lie along the LMNA gene (Capell and Collins, 2006; Mattout et al., 2006; Rankin and Ellard, 2006). Lamin proteins produced by this gene act as key structural and cell signaling elements of the inner nuclear membrane of most differentiated cells (reviewed in Gruenbaum et al., 2003).
An Introduction to Guanine Nucleotide–Binding Proteins
Authors: Newey Sarah E , Aelst Linda Van 
Published: November 2023

Abstract
Guanine nucleotide–binding proteins (GNBPs) regulate a vast array of physiological processes from cell growth and differentiation to sensory perception. There are two major families. First, the small, monomeric GTPases, whose founder member, Ras, is known to be important in regulating cell growth. Second, the heterotrimeric G proteins that are coupled to G protein–coupled receptors (GPCRs), through which many physiological and developmental processes are regulated. These families of proteins act as molecular switches, cycling between an inactive guanosine diphosphate (GDP) bound state and an active guanosine triphosphate (GTP) bound state, transducing extracellular signals to downstream signaling components. Here we give an introduction to the monomeric and heterotrimeric protein superfamilies and consider how these proteins are regulated, the signaling pathways in which they participate, and, ultimately, how these signals from multiple family members are integrated to generate a biological response.
Microtubule Motors: Intracellular Transport, Cell Division, Ciliary Movement, and Nuclear Migration
Authors: Youn Yong-Ha , Pramparo, Tiziano , Wynshaw-Boris Anthony 
Published: November 2023

Abstract
Intracellular motility in eukaryotic cells is generated by motor proteins, which drive directional transport along cytoskeletal filaments such as microtubules, the primary intracellular rail system. These cytoplasmic cytoskeletal elements provide not only structure and support to the cell but also an intracellular directional railway that allows components of the cell to be transported outside of organelles (Hirokawa and Takemura, 2005). This railway system transports molecular complexes and organelles after synthesis in the cell body to their proper peripheral location. Similarly, endocytic vesicles are transported from the cell surface to the center of the cell. In the cell, microtubule plus ends are directed toward the cell membrane and minus ends are anchored at the centrosome, one type of the microtubule-organizing center (MTOC) in a cell.
Lissencephaly with Cerebellar Hypoplasia
Authors: Olson Eric C , Walsh Christopher A 
Published: November 2023

Abstract
Lissencephaly with cerebellar hypoplasia (LCH) is characterized by abnormal development of both the cerebral cortex and cerebellum. LCH is distinguished from classical lissencephaly (Chapter 150) by profound cerebellar hypoplasia and less severe cortical malformations. The cortical malformation in LCH is described by the term “pachygria”, (thick gyri), a term that contrasts with agyria found in severe forms of lissencephaly. LCH is inherited in an autosomal recessive fashion, and is associated with profound neurological disability, including ataxia, hypotonia, mental retardation and seizures. One form of LCH is associated with mutations in the Reelin gene (RELN), the human ortholog of the murine Reln gene, which was originally discovered as mutated in the mutant reeler mouse. Using the reeler mouse model, a great deal of progress has been made in understanding the signaling mechanisms triggered by Reelin, and other members of the Reelin signaling pathway are candidate genes for additional forms of human LCH.
The Bardet–Biedl Syndromes
Authors: Sheffield Val C , Zhang Qihong , Heon Elise , Stone, Edwin M , Carmi Rivka 
Published: November 2023

Abstract
BARDET–BIEDL SYNDROME
Bardet–Biedl syndrome (BBS) (OMIM 209900) is a heterogeneous autosomal recessive disorder characterized by a combination of clinical findings that include obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay (Ammann, 1970; Alton and McDonald, 1973; Harnett et al., 1988; Green et al., 1989). Clinical characterization and the nomenclature describing this syndrome have evolved over time. In 1866, Laurence and Moon reported a syndrome consisting of mental retardation, retinal degeneration, hypogonadism, ataxia, and spas- tic paraplegia. Nearly six decades later, Bardet (1920) and Biedl (1922) independently described patients with the additional clinical features of polydactyly and obesity (Bardet, 1920; Biedl, 1922). Subsequently, Solis-Cohen and Weiss (1924) reported a single fam- ily that had features that overlapped those described by Laurence and Moon (1866), Bardet (1920), and Biedl (1922), suggesting the name Laurence–Moon–Biedl syndrome (Bardet, 1920; Biedl, 1922; Solis-Cohen, 1924). The disorder was later referred to in the scienti2c and medical literature as Laurence–Moon–-Bardet–Biedl syndrome (McLoughlin and Shanklin, 1967; Klein and Ammann, 1969). The Laurence–Moon–Bardet–Biedl syndrome has in general been viewed as two distinct clinical disorders. BBS is used to refer to patients and families that have the minimum findings of retinopathy, obesity, and polydactyly without spastic paraplegia. Patients affected with Laurence–Moon syndrome do not have polydactyly (Ammann, 1970). Although BBS is considered to be rare, it is the more common of the two syndromes. The incidence in the general population is often cited as being less than 1:100,000 (Klein and Ammann, 1969; Lofterod et al., 1990; Croft et al., 1995; Beales et al., 1997).
SNAP29 and Cerebral Dysgenesis, Neuropathy, Ichthyosis, and Palmoplantar Keratoderma syndrome
Authors: Mandel Hannah , Sprecher Eli , Rapaport, Debora , Horowitz Mia 
Published: November 2023

Abstract
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK) is an autosomal recessive neurocutaneous syndrome recently described in Northern Israel and resulting from aberrant function of SNAP29, a protein involved in the regulation of vesicle trafficking.
GJA1 (Connexin 43) and the Oculodentodigital Syndrome
Authors: Richardson Rebecca J , Dixon Michael J 
Published: November 2023

Abstract
Oculodentodigital syndrome (ODD; OMIM 164200) is a congenital disorder that is characterized by abnormalities of the face, eyes, dentition, and limbs (Fig. 173–1). ODD is inherited as an autosomal dominant trait and displays high penetrance but variable expression (Fig. 173–1). The ODD locus was initially mapped to a 28 cM region of human chromosome 6q22–q24 (Gladwin et al., 1997), which was subsequently refined to a 1.9 cM interval defined by the polymorphic markers D6S266/D6S261 proximally and D6S1639 distally (Boyadjiev et al., 1999). Recently, using a candidate gene approach, Paznekas and coworkers reported that ODD arises as the result of heterozygous mutations in GJA1, the gene encoding the gap junction protein connexin 43 (Paznekas et al., 2003). These findings have been confirmed and extended by a series of studies, which demonstrate clearly that the pleiotropic features observed in ODD result from predominantly missense mutations in connexin 43 (Pizzuti et al., 2004; Richardson et al., 2004; Honkaniemi et al., 2005; Vasconcellos et al., 2005; Vitiello
et al., 2005).
KCNJ2 and the Andersen–Tawil Syndrome
Authors: Renner David R , Tawil Rabi , Tristani-Firouzi, Martin , Ek Louis J Ptácˇ 
Published: November 2023

Abstract
Andersen–Tawil syndrome (ATS) (OMIM 170390) is a rare auto- somadominant disorder characterized by the triad of dysmorphic features, prolonged QT intervals with ventricular dysrhythmias, and episodic paralysis (Tawil et al., 1994; Sansone et al., 1997; Canún et al., 1999). Prior studies excluded linkage to the hyperkalemic periodic paralysis SCN4A locus on chromosome 17, the long QT syndrome (LQTS) locus on chromosome 11 (KCNQ1), and the CACNA1S locus on chromosome 1. An ATS gene was linked to markers on chromo- some 17q23 near the inward rectifying potassium channel gene KCNJ2, encoding Kir2.1. Sequencing KCNJ2 in the linked family identified a mutation D71V in the N terminus of the protein. To date, nearly 30 additional mutations were identified in highly conserved regions of the channel. This disorder is the first to illustrate a direct link between skeletal and cardiac muscle excitability, as well as a link between paroxysmal cell hyperexcitability and developmental phenotypes. More recently, based on expression of KCNJ2 in brain, study of ATS mutation carriers has elucidated a neurocognitive phenotype (Yoon et al., 2006b).
EVC and EVC2 and the Ellis–van Creveld Syndrome and Weyers Acrofacial Dysostosis
Authors: Galdzicka Marzena , Egeland, Janice A , Ginns Edward I 
Published: November 2023

Abstract
Ellis–van Creveld syndrome, EvC, is an inherited, autosomal recessive, chondrodysplastic dwarfism, frequently associated with congenital heart disease. The consistently observed clinical manifestations include short-limbed disproportionate dwarfism, shortened ribs, postaxial polydactyly, and dysplastic nails and teeth. Weyers acrofacial dysostosis is an autosomal dominant disorder sharing the hallmark manifestations of EvC, but with a less severe presentation and without cardiac abnormalities. Weyers acrofacial dysostosis and EvC syndrome are allelic and genetically heterogeneous conditions. Homozygous or compound heterozygote mutations in EVC or EVC2 result in EvC syndrome, while a heterozygous, dominant mutation in either EVC or EVC2 leads to Weyers acrofacial dysostosis. Other than predicted transmembrane domains, no obvious homologies or motifs give clues regarding the functions of the EVC2 protein. It is clear that EVC and EVC2 have a tightly linked genomic organization, are divergently transcribed, and have multiple start sites and numerous splice variants. These genomic features may reMect a transcriptional regulatory scheme that coordinates the expression of these two genes in a way that is critical to normal skeletal and cardiac development. Sonography, radiologic findings, and fetoscopy have been used for prenatal diagnosis of EvC syndrome, while DNA mutation analyses still do not generally provide genotype–phenotype correlations that are useful for genetic counseling. The finding that mutations affecting the expression of the EVC or EVC2 genes can result in either EvC syndrome or Weyers acrofacial dysostosis adds another dimension not only to the clinical diagnosis of these disorders but also to the interpretation of genetic information used for prenatal diagnosis and genetic counseling.
TRIM37 and Mulibrey Nanism
Authors: Hämäläinen Riikka , Karlberg Niklas , Kallijärvi Jukka , Lipsanen-Nyman, Marita , Lehesjoki Anna-Elina 
Published: November 2023

Abstract
Mulibrey nanism (muscle-liver-brain-eye nanism; OMIM 253250) is a rare prenatal-onset growth restriction disorder with progressive cardiopathy and dysmorphic facial features. It was first described in Finland in the early 1970s (Perheentupa et al., 1970, 1973). The first suspected mulibrey nanism patients from outside of Finland were described in 1976 (Cumming et al., 1976; Voorhess et al., 1976). Molecular genetic studies on mulibrey nanism were initiated in the mid 1990s and resulted in the identification of the underlying TRIM37 gene in 2000 (Avela et al., 2000). At present, a total of 90 Finnish and 14 nonFinnish patients with a molecularly confirmed diagnosis of mulibrey nanism are known.
Deletion of 7q11.23 Genes and Williams Syndrome
Authors: Korenberg Julie R , Dai Li , Bellugi Ursula , Järvinen-Pasley Anna , Mills Debra L , Galaburda Albert , Reiss, Allan , Pober Barbara R 
Published: November 2023

Abstract
Williams syndrome [WS; also Williams–Beuren syndrome (WBS)] is a neurodevelopmental condition that is caused by a hemizygous deletion of about 1.5–1.8 megabases, a region of chromo- some band 7q11.23 that contains about 28 genes (Ewart et al., 1993; Osborne, 1999; Osborne et al., 1999). Found in 1 in 7500–20,000 live births (Stromme et al., 2002), persons with WS have characteristic facial features, congenital and adult cardiovascular disease, and distinctive cognitive and behavioral characteristics. WS is a compelling genetic model for understanding human cognition, chromosome organization, and evolution.
Cells and Selves the Training of Jakob Henle and Theodor Schwann
Authors: Lab Mullers 
Published: November 2023

Abstract
An assistant who presides so long in the class and laboratory ends up as the most In the previous chapter, I described Müller’s scientific aims, methods, and values and the conditions under which he and his students worked. In this and the next five chapters, I will present the students’ viewpoints, emphasizing each pupil’s relationship with Müller, Müller’s influence on his science, and his motivation for depicting Müller in a particular way.
Ernst Haeckel’s Evolving Narratives
Authors: Lab Mullers 
Published: November 2023

Abstract
Anyone who is beginning to suspect that scientists define themselves by rejecting their mentors’ ideas should look hard at the career of Ernst Haeckel. Haeckel’s best-selling books belie the notion that each scientific generation establishes its identity by rebelling against the previous one.1 Unlike du Bois-Reymond, Haeckel built his scientific reputation by showing his likeness to Müller—but he had to re-create Müller in order to do it.
Naturalism and Evil
Authors: Layman C Stephen 
Published: November 2023

Abstract
So far we’ve considered the problem of evil just as a problem for Theism. In this respect, our discussion has been typical. Anthologies in the philosophy of religion commonly treat the problem of evil simply as a problem for Theism, the main question being II Are Theistic replies adequate?” One seldom sees arguments to the effect that non-Theistic views have difficulty accounting for evil. Moreover, Naturalists commonly regard the problem of evil as a special problem for Theism and not as a problem for Naturalism at all. I think this is a mistake.
Botanical Medicine in Integrative Oncology*
Authors: Standish Leanna J , Alschuler Lise N , Ready Ann B , Torkelson Carolyn , Sivam Gowsala , Wenner Cynthia 
Published: November 2023

Abstract
Many of our best chemotherapy drugs originally came from plants (e.g., paclitaxel from the yew tree, vincristine, vinblastine, vinorel- bine from the red periwinkle plant, camptothecin from the Chinese tree Camptotheca accuminata, podophyllin from mayapple). It is likely that there are still antineoplastic and immunomodula-tory plant medicines to be discovered.
Physical Activity and Cancer
Authors: stevinson Clare , Courneya kerry s. 
Published: November 2023

Abstract
Research has established that physical activity plays an important role in the prevention and management of many chronic medical conditions. Physical activity helps to protect against colon and breast cancer, and possibly endometrial, lung, and prostate cancer. Physical activity is essential for maintaining a healthy body weight, which is important since obesity is a major risk factor for many cancers. Some preliminary data suggest that postdiagnosis physical activity may be associated with increased survival in colon and breast cancer.
Energy Medicine and Cancer
Authors: Lutgendorf Susan k. , Mullen Elizabeth 
Published: November 2023

Abstract
Energy medicine is a complementary and alternative medicine (CAM) modality whose practitioners purport to restore the flow of energy fields associated with the human body for symptom relief, disease prevention, and health restoration. Experimental evidence of the health benefits of energy medicine has been mixed, with many studies suffering from methodological weaknesses. Preclinical trials suggest that energy medicine may enhance immunity and decrease both growth and activity of cancer cells.
Integrative Medicine and Breast Cancer
Authors: Tripathy Debu 
Published: November 2023

Abstract
Many forms of complementary and alternative medicine (CAM) are widely used in breast cancer. Very few controlled clinical trials have been performed to evaluate the safety and effectiveness of CAM for either symptom management or the prevention and treatment of breast cancer. A low-fat diet with ample vegetable and fruit and a high level of physical activity shows the most promise in improving recurrence and mortality for early-stage breast cancer in retrospective and prospective trials.
Radiation Therapy and Integrative Oncology
Authors: Mumber Matthew p. 
Published: November 2023

Abstract
Radiation oncology is a rapidly evolving field, with new technology helping to increase the probability of tumor cell kill while decreasing toxicity to normal tissue structures. The addition of complementary therapies to radiation must be evaluated with an individualized risk to benefit analysis that includes several factors: overall goal of care (curative versus palliative), category of use for the complementary intervention (antineoplastic, supportive care, or prevention), and the timing of the combination (before, during, or after radiation). Several supportive intent complementary therapies can now be considered as a part of the standard of care in combination with conventional cancer therapies that include radiation as a part of the treatment plan.
Optic Neuritis
Authors: Vaphiades Michael S , Kline Lanning B 
Published: November 2023

Abstract
The term optic neuritis denotes primary inflammation of the optic nerve, usually from demyelinating disease. The term can also be used in describing an optic neuropathy due to the contiguous spread of inflammation from meninges, orbital tissues, or paranasal sinuses. When there is swelling of the optic disc, the term papillitis is sometmes used. When the clinical history and examination suggest optic neuritis but the optic disc appears normal, the term retrobulbar optic neuritis is used. The diagnosis of optic neuritis is based on clinical criteria. Critical elements in establishing the diagnosis are a detailed history and an accurate examination. For this reason, the ophthalmologist must be familiar with the clinical profile of optic neuritis.
Ischemic Optic Neuropathy
Authors: Buono Lawrence M 
Published: November 2023

Abstract
I schemic optic neuropathy is the most common nonglaucomatous optic nerve disorder encountered in patients above 50 years of age. This disorder has been classified by the presence (anterior ischemic optic neuropathy) or absence (posterior ischemic optic neuropathy) of optic disc edema at the onset of visual loss. The former is common, while the latter is rare and established only as a diagnosis of exclusion. This chapter focuses primarily on anterior ischemic optic neuropathy, emphasizing current thinking on diagnosis, patient evaluation, and management.