bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palatal Measurements Pre- and Post-Furlow Cleft Palate Repair: Analysis of Palatal Lengthening and Comparison Within Cleft Types
Authors: Chang Brian L. , Yu Jason W. , Nikonova Elena , Low David W. , Taylor Jesse A. , Jackson Oksana 
Published: October 2018

Objective: The purpose of this study was to characterize intraoperative palatal lengthening with the modified Furlow cleft palatal repair and to determine whether lengthening correlated with preoperative cleft width, cleft type, or operating surgeon. Design: Retrospective study. Setting: Academic tertiary care pediatric hospital. Patients: One hundred eighty pediatric patients undergoing primary or secondary palatoplasty using the Furlow technique. Interventions: Cleft and palatal lengths and widths were measured pre- and post-Furlow cleft palatal repair. Main Outcome Measures: Immediate postoperative percentage change in surface palate length, straight palate length, and soft palate length. Results: The average cleft widest width and width at the hard–soft palate junction were 10.2 and 9.5 mm, respectively, and varied with Veau cleft type. Following Furlow palatoplasty, lengths of the curved, straight, and soft palate increased by 7.5%, 15.8%, and 30.6%, respectively. Degree of palatal lengthening varied among surgeons and Veau cleft type but was not related to cleft width. Seven (4.0%) patients developed postoperative oronasal fistulas. Patients with a Veau IV cleft and larger cleft widths were at an increased risk for fistula formation. Conclusions: This study demonstrates that overall palatal lengthening occurs with the modified Furlow technique. Long-term follow-up studies are needed to determine the clinical relevance of these findings.
Public knowledge of late-life cognitive decline and dementia in an international sample
Authors: Van Patten Ryan , Tremont Geoffrey 
Published: October 2018

Background and objectives One method of mitigating global increases in dementia prevalence involves assessing public knowledge and then educating laypeople. We measured knowledge of late-life pathological cognitive decline in a diverse, international sample using a standardized, validated instrument. Research design and methods: We assessed 3619 international respondents recruited through Amazon’s Mechanical Turk with a 44-item dementia knowledge survey and 18 sociodemographic items. Results Results suggested that the following sociodemographic variables are associated with less overall knowledge: young age, male gender, low educational attainment, born in a developing nation, of ethnic minority status, not married, and less prior dementia experience. Specific knowledge gaps emerged in cerebrovascular disease, delirium versus dementia, treatment of behavioral dementia symptoms, Alzheimer’s disease genetics, Parkinson’s disease symptoms, and characteristics of chronic traumatic encephalopathy and subjective cognitive decline. Discussion and implications: Findings may facilitate effective multinational dementia education initiatives by providing specific recommendations as to which sociodemographic populations and content knowledge domains will benefit the most from limited resources.
Health care providers’ roles and responsibilities in management of polypharmacy: Results of a modified Delphi
Authors: Farrell Barbara , Thompson Wade , Black Cody D. , Archibald Douglas , Raman-Wilms Lalitha , Grassau Pamela , Patel Tejal , Weaver Lynda , Eid Khaled , Winslade Nancy 
Published: October 2018

Background: Little is known about the roles that allow interprofessional teams to effectively manage older patients experiencing polypharmacy. Objectives: To identify and examine the consensus on salient interprofessional roles, responsibilities and competencies required in managing polypharmacy. Methods: Four focus groups with 35 team members practising in geriatrics were generated to inform survey development. The sessions generated 63 competencies, roles or responsibilities, which were categorized into 4 domains defined by the Canadian Interprofessional Health Collaborative. The resulting survey was administered nationally to geriatric health care professionals who were asked to rate the importance of each item in managing polypharmacy; we sought agreement within and across professions using a confirmatory 2-round Delphi method. Results: Round 1 was completed by 98 survey respondents and round 2 by 72. There was high intra-professional and interprofessional consensus regarding the importance of competencies among physicians, nurses and pharmacists; though pharmacists rated fewer competencies as important. Less consensus was observed among other health care professionals or they indicated the nonimportance of competencies despite focus group discussion to the contrary. Discussion: Although there is a strong consensus of polypharmacy management competencies across team members who have been more traditionally involved in medication management, there continue to be health care providers with differing understandings of competencies that may contribute to reduced reliance on medication. Lower importance ratings suggest pharmacists may not acknowledge or recognize their own potential roles in interprofessional polypharmacy management. Conclusion: Further exploration to understand the underutilization of professional expertise in managing polypharmacy will contribute to refining role clarity and translating competencies in practical settings, as well as guiding educators regarding curricular content.
Shift models for dose-finding in partially ordered groups
Authors: Horton Bethany Jablonski , Wages Nolan A , Conaway Mark R 
Published: October 2018

Background Limited options are available for dose-finding clinical trials requiring group-specific dose selection. While conducting parallel trials for groups is an accessible approach to group-specific dose selection, this approach allows for maximum tolerated dose selection that does not align with clinically meaningful group order information. Methods The two-stage continual reassessment method is developed for dose-finding in studies involving three or more groups where group frailty order is known between some but not all groups, creating a partial order. This is an extension of the existing continual reassessment method shift model for two ordered groups. This method allows for dose selection by group, where maximum tolerated dose selection follows the known frailty order among groups. For example, if a group is known to be the most frail, the recommended maximum tolerated dose for this group should not exceed the maximum tolerated dose recommended for any other group. Results With limited alternatives for dose-finding in partially ordered groups, this method is compared to two alternatives: (1) an existing method for dose-finding in partially ordered groups which is less computationally accessible and (2) independent trials for each group using the two-stage continual reassessment method. Simulation studies show that when ignoring information on group frailty, using independent continual reassessment method trials by group, 30% of simulations would result in maximum tolerated dose selection that is out of order between groups. In addition, the two-stage continual reassessment method for partially ordered groups selects the maximum tolerated dose more often and assigns more patients to the maximum tolerated dose compared to using independent continual reassessment method trials within each group. Simulation results for the proposed method and the less computationally accessible approach are similar. Conclusion The proposed continual reassessment method for partially ordered groups ensures appropriate maximum tolerated dose order and improves accuracy of maximum tolerated dose selection, while allowing for trial implementation that is computationally accessible.
Temporal autoregulation during human PU.1 locus SubTAD formation
Authors: Schuetzmann Daniel , Walter Carolin , van Riel Boet , Kruse Sabrina , König Thorsten , Erdmann Tabea , Tönges Alexander , Bindels Eric , Weilemann Andre , Gebhard Claudia , Wethmar Klaus , Perrod Chiara , Minderjahn Julia , Rehli Michael , Delwel Ruud , Lenz Georg , Gröschel Stefan , Dugas Martin , Rosenbauer Frank 
Published: October 2018

Abstract
Epigenetic control of gene expression occurs within discrete spatial chromosomal units called topologically associating domains (TADs), but the exact spatial requirements of most genes are unknown; this is of particular interest for genes involved in cancer. We therefore applied high-resolution chromosomal conformation capture sequencing to map the three-dimensional (3D) organization of the human locus encoding the key myeloid transcription factor PU.1 in healthy monocytes and acute myeloid leukemia (AML) cells. We identified a dynamic ∼75-kb unit (SubTAD) as the genomic region in which spatial interactions between PU.1 gene regulatory elements occur during myeloid differentiation and are interrupted in AML. Within this SubTAD, proper initiation of the spatial chromosomal interactions requires PU.1 autoregulation and recruitment of the chromatin-adaptor protein LDB1 (LIM domain–binding protein 1). However, once these spatial interactions have occurred, LDB1 stabilizes them independently of PU.1 autoregulation. Thus, our data support that PU.1 autoregulates its expression in a “hit-and-run” manner by initiating stable chromosomal loops that result in a transcriptionally active chromatin architecture.
Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway
Authors: Peng Yulin , Wang Yan , Tang Ning , Sun Dongdong , Lan Yulong , Yu Zhenlong , Zhao Xinyu , Feng Lei , Zhang Baojing , Jin Lingling , Yu Fabiao , Ma Xiaochi , Lv Chuanzhu 
Published: October 2018

Abstract
Background
Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear.

Methods
Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice.

Results
The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo.

Conclusion
In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
From Diagnosis to Survivorship: Using Cancer Support Group as an Advocacy and Support Tool for Cancer Care
Authors: Orji Gloria M. , Chidebe Runcie C.W. , Igbokwe Chuks , Banwo-Fatai Khadijat , Gimba Swatkasa , Agbi Rose , Emezue Peace , Dantsoho Sarah A. , Nwagboso Emeka J. , Abdulazeez Jemilat , Okoro Nkechi , Orjiako Tochukwu Charles , Okoye Ifeoma , Aruah Chinedu S. 
Published: October 2018

Purpose Cancer diagnosis comes with many challenges. Diagnosis is a huge burden to the patient, family, and community that subjects them to financial crisis, emotional distress, a dearth of self-esteem, and physiologic deformations. From a patient’s perspective, the treatment of cancer is complex and complicated with a weak health care system, attitude of health care workers, lack of insurance, lack of trust in orthodox medicine, and stigmatization. Patients with cancer are constantly seeking solace, people to listen to them, and people who understand their state of mind and can be a source of inspiration. Studies have shown that peer cancer support groups result in psychological benefit and improve relationships. The 2016 World Cancer Congress patient’s pavilion inspired us to start cancer support group for patients with cancers, survivors, and caregivers, known as the Abuja Breast Cancer Support Group, through the Union for International Cancer Control SPARC Metastatic Breast Cancer Challenge project. The cancer support group was primarily founded for only patients with breast cancer, survivors, caregivers, and for peer support. As of today the group has transitioned from being a patient group to also being an advocacy group with a number of activities and programs that are aimed at guiding all patients with cancer from diagnosis to survivorship. Methods This study reviewed the 1 year activities of the Abuja Breast Cancer Support Group and surveyed the impact of peer support on the 36 members of the group using a mixed-methods approach. Results Cancer support groups have the potential to revolutionize cancer care in sub-Saharan Africa, as we have seen with HIV/AIDs support groups. Use of technological tools is helpful to build connectedness. Conclusion There was an improvement in the psychological states of patients as well as in their physiologic understanding of their diagnosis by meeting together, networking, and interacting through a WhatsApp group. Our qualitative findings also indicate that patients with cancer need platforms through which to speak out, to advocate, and to change the course of cancer care if provided with the necessary training and support. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . No COIs from the authors.
Management of Nasopharyngeal Carcinoma: Is Adjuvant Therapy Needed?
Authors: Lee Victor H. , Lam Ka-On , Chang Amy T. , Lam Tai-Chung , Chiang Chi-Leung , So Tsz-Him , Choi Cheuk-Wai , Lee Anne W. 
Published: October 2018

Nasopharyngeal carcinoma of the undifferentiated histologic subtype is endemic and prevalent in southeast Asia. The dramatic improvement of treatment outcomes and overall prognosis during the past few decades has been attributed to advances in disease screening and diagnosis, diagnostic imaging, radiotherapy techniques, use of combination systemic therapy, and dedicated clinical and biomarker surveillance. The current practice of treating patients with advanced locoregional disease using cisplatin concurrent with conventional fractionated radiotherapy, followed by adjuvant cisplatin and fluorouracil, was established in 1998 when the landmark Intergroup-0099 Study demonstrated a survival benefit with the addition of systemic therapy. There is little doubt regarding the need for concurrent chemotherapy, but there has been uncertainty about the magnitude of the benefit attributed to the adjuvant phase. Furthermore, instead of one-size-fits-all recommendations, it will be ideal if we can tailor adjuvant therapy to high-risk patients only to avoid unnecessary toxicities. In addition, recent evidence suggests that induction chemotherapy before concurrent chemoradiation can achieve better outcomes, especially in distant control, even in the modern era of intensity-modulated radiation therapy. This article provides a comprehensive review of key literature on the current management of locoregionally advanced nasopharyngeal carcinoma and highlights future research directions to unravel these controversies.
Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions
Authors: Bouillon Roger , Marcocci Claudio , Carmeliet Geert , Bikle Daniel , White John H , Dawson-Hughes Bess , Lips Paul , Munns Craig F , Lazaretti-Castro Marise , Giustina Andrea , Bilezikian John 
Published: October 2018

AbstractThe etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D–deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
Physician Advocacy for Public Health
Authors: Gusmano Michael K. 
Published: October 2018

AbstractThis article documents the public positions taken by the American Academy of Pediatrics, the American College of Physicians, and the American Medical Association on five topics with implications for public health: access to care for undocumented patients, fracking, gun control, climate change, and same-sex marriage. There are stark divisions on each of these issues between political parties, and taking a strong public position on them runs the risk of alienating some members of Congress, but each of these associations has done so. At the same time, there is a clear distinction between the public positions of these organizations and the priority given to them by their offices in Washington, DC. Drawing on an organizational maintenance framework, the author argues that taking these public positions is explained, in part, by a growth in the number of women and the number of physicians that affiliate with the Democratic Party in the United States.
How the American Medical Association's Rent-Seeking Strategy Compensated for Its Loss of Members
Authors: Laugesen Miriam J. 
Published: October 2018

Abstract
Membership in the American Medical Association (AMA) has suffered a precipitous decline since the 1970s and, with it, a loss in revenue. The expansion of subsidized student memberships has bolstered its official membership number; only 12.6% of physicians who have completed their training now belong. The AMA strengthened its alliances with specialty societies and even tried to restructure the organization around organizational (rather than individual) membership: two hundred specialty societies are incentivized to encourage their members to join the AMA. Earlier federal policies supported by the AMA that gave it a central role in recommending Medicare reimbursement policies have established a membership pipeline for the AMA partly because specialty societies need to influence reimbursement policies. Commercial products have also helped subsidize AMA lobbying efforts that reinforce its historical position, despite a loss of members.
A Fluorescent Naphthalenediimide-Alkoxyfuroxan Photoinduced Nitric Oxide Donor
Authors: Seymour Christopher Peter , Nakata Akito , Tsubaki Motonari , Hayashi Masahiko , Matsubara Ryosuke 
Published: October 2018

Abstract
We describe the design and facile synthesis of a fluorescent alkoxyfuroxan naphthalenediimide (NDI) hybrid nitric oxide (NO) donor molecule which releases NO under spatiotemporal control when irradiated with visible light (420–600 nm). The hybrid also demonstrates cellular uptake made possible by its fluorescence capability. This research consolidates our recent work into visible light absorbing photosensitised furoxan NO release by addressing the limitations of previous designs. Key points of photoinduced nitric oxide donors are highlighted such as water solubility, NO release, cellular uptake, fluorescence, and longer absorption wavelengths.
Explicit interaction information from WikiPathways in RDF facilitates drug discovery in the Open PHACTS Discovery Platform
Authors: Miller Ryan A. , Woollard Peter , Willighagen Egon L. , Digles Daniela , Kutmon Martina , Loizou Antonis , Waagmeester Andra , Senger Stefan , Evelo Chris T. 
Published: October 2018

Open PHACTS is a pre-competitive project to answer scientific questions developed recently by the pharmaceutical industry. Having high quality biological interaction information in the Open PHACTS Discovery Platform is needed to answer multiple pathway related questions. To address this, updated WikiPathways data has been added to the platform. This data includes information about biological interactions, such as stimulation and inhibition. The platform's Application Programming Interface (API) was extended with appropriate calls to reference these interactions. These new methods of the Open PHACTS API are available now.
Measles: A rise in incidence and outbreaks in vulnerable groups
Authors: Keal Jo , Beckett Gail 
Published: October 2018

Jo Keal and Gail Beckett discuss measles in light of the recent rise in the number of cases in the UK and Europe, leading to outbreaks in vulnerable populations, and explore how practice nurses are in a unique position to influence the health of the wider population Measles is a highly infectious viral disease that is preventable through effective immunisation. Recent outbreaks in Europe have led to an increase in imported cases to England and Wales, leading in turn to outbreaks in some vulnerable populations. Practice nurses are in a unique position to influence the health of their population. Providing information about measles infection; the increase in UK cases; and offering opportunity for vaccination will enable patients to make an informed choice to support not only protection of their own health, but also contribute to the wider public's health protection.