bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alemtuzumab for Cytolytic Induction of Immunosuppression in Heart Transplant Recipients
Authors: Cahoon William D. , Ensor Christopher R. , Shullo Michael A. 
Published: December 2012

Objective To review available evidence about the safety and efficacy of alemtuzumab for induction of immunosuppression in heart transplant recipients. Data sources Searches of MEDLINE, EMBASE, and Cochrane databases were conducted. Key search terms included alemtuzumab, Campath-1H, CD52, lymphocyte, cytolytic, induction, immunosuppression, rejection, and cardiac transplantation. Additional pertinent data were identified through a search of abstracts from major transplant meetings. Study Selection and Data Extraction All English-language articles and abstracts identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety or efficacy of alemtuzumab for induction of immunosuppression in heart transplant patients. One retrospective cohort, 1 case series, 1 case-control series, and 1 open-label trial were identified and included for review. Data Synthesis Acute cellular rejection occurs in 40% to 70% of heart transplant recipients within the first 6 months after transplant and is associated with significant morbidity and mortality. Depleting and nondepleting antibodies have displayed positive outcomes in inducing immunosuppression; however, the ideal induction strategy that balances efficacy and toxicity remains elusive. Alemtuzumab, a cytolytic anti-CD52 antibody, has been used to induce immunosuppression in kidney, pancreas, liver, intestine, and lung transplant recipients, and its use in heart transplant has been investigated. Studies of use of alemtuzumab to induce immunosuppression in heart transplant patients have shown low rates of rejection; however, it has not been directly compared with other immunosuppression-inducing agents and safety data are limited. Conclusions Although alemtuzumab may be a practical option for inducing immunosuppression, data are insufficient to recommend its routine use in deference to more established agents. Large, randomized clinical trials with extended durations of follow-up must be conducted to characterize its efficacy and safety further.
Chronic Pain among Liver Transplant Candidates
Authors: Madan Alok , Barth Kelly S. , Balliet Wendy E. , Hernandez-Tejada Melba A. , Borckardt Jeffrey J. , Malcolm Robert , Willner Ira , Koch David , Reuben Adrian 
Published: December 2012

Context Little systematic research has been conducted to understand pain among persons with end-stage liver disease, especially among liver transplant candidates. Appropriate pain assessment and management are important areas of consideration as treatment options are limited. Objective To describe the nature of chronic pain in patients with end-stage liver disease, the extent to which pain affects daily level of functioning, and the variety and effectiveness of current treatments. Design Retrospective chart review. Setting Academic medical center in the Southeastern United States. Patients Data were collected from 108 consecutive adult liver transplant candidates. Results Most (77%) reported having experienced moderate levels of bodily pain within the past 24 hours. Patients with only alcoholic cirrhosis reported less pain than patients with cirrhosis due to other causes (alcoholism and hepatitis C, nonalcoholic steatohepatitis, only hepatitis C). Pain interfered significantly across all 10 functional domains assessed. Although 90% reported being prescribed a variety of analgesic agents (most commonly short-acting opioids), patients reported experiencing only 33% pain relief. Conclusions Pain is a significant problem among liver transplant candidates, and current pain treatments are perceived to be relatively ineffective. Increased understanding is needed to safely and effectively evaluate and treat such medically complicated patients.
The Lived Experience of Parents and Guardians Providing Care for Child Transplant Recipients
Authors: Williams Laurel , Eilers June , Heermann Judith , Smith Karen 
Published: December 2012

Context Little has been published about the caregiving experiences of the parents or guardians of children receiving liver or liver/intestinal transplants. Objective To describe the lived experiences of parents and guardians as they prepared for and provided postdischarge care to a child who received an isolated intestine or a liver/intestinal transplant and to assess the impact of transplants on parents' stress levels. Design Semistructured, audio-taped phone interviews of parents' and guardians' perceptions of their experiences preparing to and providing care to a child transplant recipient were transcribed verbatim and analyzed by the research team using established qualitative research methods. Participants Five parents or guardians (3 mothers, 1 foster mother, and 1 grandfather) of children who received a transplant between 2000 and 2008 at age 11 months to 6.7 years. Results Responses to the interviews gravitated toward 3 focal points: the parents' and guardians' perceptions of their interactions with the transplant team, their interactions with the local health care systems, and caring for themselves and their child at home. Conclusion In preparing parents and guardians to care for their children after discharge from the hospital, transplant teams need to be aware of differences between what we think we communicate and how it is interpreted by the parents and guardians, the relationships built between parents and guardians and health care teams, parents' attitudes and levels of stress, and the impact these factors have on care and the parents' and guardians' experience.
Characterization of fat distribution in Prader–Willi syndrome: Relationships with adipocytokines and influence of growth hormone treatment
Authors: Tanaka Yuriko , Abe Yoshiko , Oto Yuji , Itabashi Hisashi , Shiraishi Masahisa , Yoshino Atsunori , Obata Kazuo , Murakami Nobuyuki , Nagai Toshiro 
Published: December 2012

AbstractMarked anthropometric changes are seen in Prader–Willi syndrome (PWS). Emaciation is observed during infancy, whereas severe obesity is found in older children and adults. Growth hormone (GH) treatment modifies the anthropometric changes in PWS patients. In this study, we examined changes in the body composition of 51 PWS patients (age range, 6–54 years; median, 16.5 years), with a focus on the amount of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), VAT/SAT ratio, and serum levels of adipocytokines (adiponectin, leptin, and resistin). The relationships between VAT, SAT, and adipocytokines, and lipid abnormalities and type 2 diabetes in 24 patients with obese PWS were also evaluated. With increasing age, SAT and VAT both increased markedly, but in 18 patients receiving GH treatment, VAT remained low at ≤30 cm2. In the GH‐completed patients (n = 19), VAT and SAT increased with age to levels similar to those in non‐GH‐treated patients (n = 14). In the obese group, adiponectin decreased as VAT increased (r = –0.35, P = 0.11). Leptin (r = 0.67, P < 0.001) and resistin (r = 0.45, P = 0.04) showed positive correlations with SAT. Total cholesterol, low‐density lipoprotein, and triglyceride levels correlated negatively with adiponectin (r = –0.59, r = –0.56, r = –0.56, respectively, P < 0.05) and hemoglobin A1c (r = –0.42, P = 0.08). To maintain lower VAT and prevent cardiovascular disease risk factors, GH treatment may be advisable even in adult patients with PWS. © 2012 Wiley Periodicals, Inc.
“It's about having the choice”: Stakeholder perceptions of population‐based genetic carrier screening for fragile X syndrome
Authors: Archibald Alison D. , Hickerton Chriselle L. , Jaques Alice M. , Wake Samantha , Cohen Jonathan , Metcalfe Sylvia A. 
Published: December 2012

AbstractThis project explored, the views of key stakeholders regarding population‐based genetic carrier screening for fragile X syndrome (FXS). Interviews and focus groups were conducted with healthcare providers, relatives of individuals with FXS and members of the general population. Data were transcribed verbatim and coded into themes. 188 individuals took part in this study. Perceived benefits of carrier screening included: learning the risk of having a child with FXS; learning the risk of fragile X‐associated primary ovarian insufficiency; and the opportunity for carriers to access reproductive options. Concerns included: the emotional impact of screening and receiving a carrier result; the predictive testing nature of the carrier test with respect to fragile X‐associated tremor/ataxia syndrome; potential confusion created by receiving an intermediate result; and implications of genetic screening for society. Overall, population‐based genetic carrier screening was perceived to be acceptable provided it is optional and offered at an appropriate stage of life. With the support of the participants to promote individual choice by offering a population‐based carrier screening program for FXS, it is essential to carefully consider how screening might be offered in order to ensure broad accessibility and facilitation of decision‐making. © 2012 Wiley Periodicals, Inc.
The practice of adult genetics: A 7‐year experience from a single center
Authors: Eble Tanya N. , Nagamani Sandesh C.S. , Franco Luis M. , Plon Sharon E. , Blazo Maria , Dhar Shweta U. 
Published: December 2012

AbstractThe purpose of our study is to familiarize the reader with genetic disorders commonly seen in adults and identify challenges and barriers that limit provision of services. We conducted a retrospective chart analysis of patients seen in the adult Genetics clinics from January 2004 to December 2010 in a metropolitan medical center consisting of an academic private clinic and a county hospital clinic. During the study period, a total of 1,552 patients (n = 1,108 private clinic patients; n = 444 county clinic patients) were evaluated and managed. Of these, 790 and 280 were new patient visits at the private clinic and county clinic, respectively. Approximately 35% (374/1,070) of new patients were seen for cancer‐related indications, while neurological indications accounted for approximately 14% (153/1,070) in both clinics. Cardiology‐related indications accounted for approximately 13% (145/1,070) of patients, followed closely by chromosomal and syndromic indications for which almost 9% (96/1,070) of new patients were seen. Approximately 8% (90/1,070) of new patients were seen for musculoskeletal indications. We saw increased clinic growth during the study period and found that the most common indications for referral are: (1) Personal/family history of cancer (2) neurological (3) cardiovascular (CV) (4) chromosomal/syndromic and (5) musculoskeletal. A number of challenges were identified, including coordination of services, feasibility of testing, and an overall higher complexity of care with increased clinic scheduling time requirements. Through this review, we demonstrate the demand for adult genetics services and propose some guidelines to address the challenges of management in the adult genetics patient population. © 2012 Wiley Periodicals, Inc.
Behavior in preschool children with the 22q11.2 deletion syndrome
Authors: Klaassen Petra , Duijff Sasja , Swanenburg de Veye Henriette , Vorstman Jacob , Beemer Frits , Sinnema Gerben 
Published: December 2012

AbstractChildren with the 22q11.2 deletion syndrome (22q11DS) are at an increased risk of psychiatric problems from pre‐adolescence; little is known, however, about behavioral problems at a preschool age and the relationship between speech and behavior in this group. Parents of 90 children (aged 1.42–5.99 years) with 22q11DS filled out the Child Behavior Checklist, documenting behaviors including speech problems. Their profiles were compared with those of a comparison group consisting of 33 children with nonsyndromic orofacial clefts without 22q11DS, since both children with 22q11DS and children with clefts are expected to have speech problems. In the 22q11DS group, data on intelligence was acquired by means of formal tests. Parents of children with 22q11DS reported significantly higher mean scores on withdrawn behavior, affective problems and pervasive developmental problems compared to children with nonsyndromic clefts. Approximately 30% of children with 22q11DS had a score above the 97th percentile on at least one of the behavior subscales, indicating psychopathology. In children with 22q11DS, the reported behavioral problems were not associated with speech problems. Behavioral problems were found in 30% of young children with 22q11DS and were unlikely to be caused by speech problems. Within the 22q11DS group, behavioral problems were not related to the degree of cognitive impairment. This shows that many children with 22q11DS, known to be at an increased risk of psychiatric problems from pre‐adolescence, already show behavioral problems before the age of 6 years. © 2012 Wiley Periodicals, Inc.
Increase in central striatal dopamine transporters in patients with Shwachman–Diamond syndrome: Additional evidence of a brain phenotype
Authors: Booij Jan , Reneman Liesbeth , Alders Marielle , Kuijpers Taco W. 
Published: December 2012

AbstractPatients with Shwachman–Diamond syndrome (SDS) do not only experience well‐described physical features like skeletal abnormalities and hematological dysfunctions, but recent studies also suggested attention and working memory deficits in SDS. Indeed, a recent structural magnetic resonance imaging (MRI) study demonstrated smaller brain regions in SDS. Regarding attention and working memory, however, an important role for the neurotransmitter dopamine is well established. Therefore, in this study we assessed in vivo dopamine transporters (DATs; a specific marker of dopaminergic cells expressed in nerve terminals) and performed structural MRI in SDS. In 6 and 5 young SDS patients, respectively, we were able to acquire DAT single photon emission computed tomography (SPECT) and MRI examinations, and the data were compared to age‐matched control data. Striatal DAT binding was significantly increased in SDS patients as compared to controls. In addition, we observed significantly smaller volumes particularly posteriorly and caudally located in the brain: the corpus callosum, brainstem, and cerebellum. Also the thalamus was smaller in SDS patients than in controls. In conclusion, our data replicate earlier findings on smaller brain regions in SDS. In addition, our novel molecular imaging data suggest that SDS patients may have a dysregulated dopaminergic system. These findings may be of relevance to increase our understanding of behavioral and cognitive deficits in SDS. © 2012 Wiley Periodicals, Inc.
“Mandibulofacial dysostosis with microcephaly” caused by EFTUD2 mutations: Expanding the phenotype
Authors: Luquetti Daniela V. , Hing Anne V. , Rieder Mark J. , Nickerson Deborah A. , Turner Emily H. , Smith Joshua , Park Sarah , Cunningham Michael L. 
Published: December 2012

AbstractHeterozygous mutations in the EFTUD2 were identified in 12 individuals with a rare sporadic craniofacial condition termed Mandibulofacial dysostosis with microcephaly (MIM 610536). We present clinical and radiographic features of three additional patients with de novo heterozygous mutations in EFTUD2. Although clinical features overlap with findings of the original report (choanal atresia, cleft palate, maxillary and mandibular hypoplasia, and microtia), microcephaly was present in two of three patients and cognitive impairment was milder in those with head circumference proportional to height. Our cases expand the phenotypic spectrum to include epibulbar dermoids and zygomatic arch clefting. We suggest that craniofacial computed tomography studies to assess cleft of zygomatic arch may assist in making this diagnosis. We recommend consideration of EFTUD2 testing in individuals with features of oculo‐auriculo‐vertebral spectrum and bilateral microtia, or individuals with atypical CHARGE syndrome who do not have a CHD7 mutation, particularly those with a zygomatic arch cleft. The absence of microcephaly in one patient indicates that it is a highly variable phenotypic feature. © 2012 Wiley Periodicals, Inc.
Cardiac anomalies in Axenfeld–Rieger syndrome due to a novel FOXC1 mutation
Authors: Gripp Karen W. , Hopkins Elizabeth , Jenny Kim , Thacker Deepika , Salvin Jonathan 
Published: December 2012

AbstractAxenfeld–Rieger syndrome (ARS) is an autosomal dominant condition characterized by ophthalmologic anterior segment abnormalities and extraocular findings including dental anomalies and redundant periumbilical skin. Intragenic mutations in the homeobox gene PITX2 or the transcription factor encoding FOXC1 were identified, and genomic rearrangements encompassing either gene also cause ARS. A molecular etiology is identified in 40–60%. Extraocular anomalies occur more often with intragenic PITX2 than FOXC1 mutations. We report on a patient with infantile glaucoma presenting at age 21 months with congestive heart failure due to a dysplastic arcade mitral valve necessitating valve replacement, and mildly hypoplastic left ventricular outflow tract and aortic arch. Family history included early onset glaucoma in four relatives; congenital hip dysplasia requiring surgery in three; and an atrial septal defect in the affected maternal grandmother. Despite the absence of dental or umbilical abnormalities, anterior chamber abnormalities consistent with ARS were present in affected individuals. Molecular testing revealed a novel FOXC1 mutation (c.508C>T; p.Arg170Trp) in the proband and his affected mother; other family members were unavailable. A literature review revealed four reports of congenital heart disease associated with intragenic FOXC1 mutations, and none with intragenic PITX2 mutations. Previously, mouse studies showed Foxc1 (Mf1) expression in the developing valves and atrial septum, supporting a causal relationship of FOXC1 mutations for valvar anomalies and ASD. Hip dysplasia in three family members suggests a role for FOXC1 in the femoral head dysplasia of de Hauwere syndrome with 6p25 deletions. Further reports of clinical and molecular diagnoses will clarify genotype–phenotype correlation. © 2012 Wiley Periodicals, Inc.
A Novel Antifungal Agent with Broad Spectrum: 1‐(4‐Biphenylyl)‐3‐(1H‐imidazol‐1‐yl)‐1‐propanone
Authors: Roman Gheorghe , Mareş Mihai , Năstasă Valentin 
Published: December 2012

AbstractA series of (1‐substituted aryl)‐3‐(1H‐imidazol‐1‐yl)‐1‐propanones was synthesized through the N‐alkylation of imidazole with 3‐dimethylamino‐1‐(substituted aryl)‐1‐propanone hydrochlorides (ketonic Mannich bases). A second series of N1‐substituted imidazoles was obtained by the reduction of the carbonyl function of the imidazole–ketones in the previous series by means of NaBH4. All of the compounds were evaluated for antifungal activity against 16 strains of Candida, and 3‐(1H‐imidazol‐1‐yl)‐1‐(4‐biphenylyl)‐1‐propanone emerged as a broad‐spectrum antifungal agent. Several 3‐(1H‐imidazol‐1‐yl)‐1‐(2′‐(substituted benzyl)oxyphenyl)‐1‐propanones were also active towards Candida kefyr.
Orthogonal control of endogenous gene expression in mammalian cells using synthetic ligands
Authors: Liang Jing , McLachlan Michael J. , Zhao Huimin 
Published: December 2012

AbstractGene switches have wide utility in synthetic biology, gene therapy, and developmental biology, and multiple orthogonal gene switches are needed to construct advanced circuitry or to control complex phenotypes. Endogenous vascular endothelial growth factor (VEGF‐A) is crucial to angiogenesis, and it has been shown that multiple alternately spliced VEGF‐A isoforms are necessary for proper blood vessel formation. Such a necessity limits the utility of direct transgene delivery, which can provide only one splice variant. To overcome this limitation, we constructed a gene switch that can regulate the (VEGF‐A) locus in mammalian cells by combining an engineered estrogen receptor (ER) ligand‐binding domain (LBD), a p65 activation domain, and an artificial zinc‐finger DNA binding domain (DBD). Our gene switch is specifically and reversibly controlled by 4,4′‐dyhydroxybenzil (DHB), a small molecule, non‐steroid synthetic ligand, which acts orthogonally in a mammalian system. After optimization of the gene switch architecture, an endogenous VEGF‐A induction ratio of >100‐fold can be achieved in HEK293 cells at 1 µM DHB, which is the highest endogenous induction reported to date. In addition, induction has been shown to be reversible, repeatable, and sustainable. Another advantage is that the ligand response is tunable by varying the clonal composition of a stably integrated cell line. The integration of our findings with the technology to change ligand specificity and DNA binding specificity will provide the framework for generating a wide array of orthogonal gene switches that can control multiple genes with multiple orthogonal ligands. Biotechnol. Bioeng. 2013; 110: 1419–1429. © 2012 Wiley Periodicals, Inc.
Facile Synthesis of 4,5‐Disubstituted 2H‐1,2,3‐Triazoles by Catalyst‐free Cycloaddition between Substituted Vinyl Sulfones and Sodium Azide under Ambient Conditions
Authors: Yang Jinjin , Yin Wei , Liu Renhua , Chu Changhu 
Published: December 2012

AbstractA highly efficient method for readily preparing 4,5‐disubstituted 2H‐1,2,3‐triazoles was found. Under ambient conditions, a catalyst free cycloaddition between substituted vinyl sulfones and sodium azide could be completed in a very short time. In this cycloaddition process, sulfonyl group acts as a leaving group, while its ester group was retained.
Novel and Efficient Syntheses of Four Useful Shikimate‐derived Epoxy Chiral Building Blocks via Cyclic Sulfite Intermediates
Authors: Quan Na , Nie Liangdeng , Shi Xiaoxin , Zhu Ruiheng , Lü Xia 
Published: December 2012

AbstractAll of the four stereoisomers of methyl 4,5‐epoxy‐3‐hydroxy‐cyclohex‐1‐ene‐carboxylate (1a–1d) are useful chiral building blocks. Novel and efficient syntheses of these four epoxy chiral building blocks from naturally abundant (−)‐shikimic acid (2) via cyclic sulfite intermediates are described in this article. The targeted compound (3R,4R,5S)‐1a was synthesized via four steps from (−)‐shikimic acid in 79% overall yield. The other three targeted compounds (3S,4R,5S)‐1b, (3S,4S,5R)‐1c and (3R,4S,5R)‐1d were synthesized via seven steps from (−)‐shikimic acid in 56%, 64% and 65% overall yields, respectively.
One‐pot Three Component Synthesis of Polyfluoroarylated Arylacetates via VNSAr‐SNAr Reaction
Authors: Xiong Yang , Wu Jingjing , Xiao Senhan , Cao Song 
Published: December 2012

AbstractA series of 2‐polyfluoroaryl arylacetates were synthesized by a one‐pot three‐component VNSAr‐SNAr reaction of polyfluoroarenes, ethyl 2‐chloropropionate, and ortho‐substituted nitrobenzenes.