bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
Authors: Jaraíz-Rodríguez Myriam , Talaverón Rocío , García-Vicente Laura , Pelaz Sara G , Domínguez-Prieto Marta , Álvarez-Vázquez Andrea , Flores-Hernández Raquel , Sin Wun Chey , Bechberger John , Medina José M , Naus Christian C , Tabernero Arantxa 
Published: December 2019

Abstract

Background
Malignant gliomas are the most frequent primary brain tumors and remain among the most incurable cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor properties of this protein in in vivo glioma models.

Methods
TAT-Cx43266–283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed.

Results
While glioma stem cell malignant features were strongly affected by TAT-Cx43266–283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administered TAT-Cx43266–283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266–283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity, TAT-Cx43266–283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore, TAT-Cx43266–283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells.

Conclusion
TAT-Cx43266–283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this peptide could be considered as a new clinical therapy for high-grade gliomas.
Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors
Authors: Frühwald Michael C , Hasselblatt Martin , Nemes Karolina , Bens Susanne , Steinbügl Mona , Johann Pascal D , Kerl Kornelius , Hauser Peter , Quiroga Eduardo , Solano-Paez Palma , Biassoni Veronica , Gil-da-Costa Maria Joao , Perek-Polnik Martha , van de Wetering Marianne , Sumerauer David , Pears Jane , Stabell Niklas , Holm Stefan , Hengartner Heinz , Gerber Nicolas U , Grotzer Michael , Boos Joachim , Ebinger Martin , Tippelt Stefan , Paulus Werner , Furtwängler Rhoikos , Hernáiz-Driever Pablo , Reinhard Harald , Rutkowski Stefan , Schlegel Paul-Gerhardt , Schmid Irene , Kortmann Rolf-Dieter , Timmermann Beate , Warmuth-Metz Monika , Kordes Uwe , Gerss Joachim , Nysom Karsten , Schneppenheim Reinhard , Siebert Reiner , Kool Marcel , Graf Norbert 
Published: December 2019

Abstract

Background
Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses.

Methods
Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009–2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors.

Results
Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ± 4.5% and 30.5 ± 4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age &lt;1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission, and omission of radiotherapy were negative prognostic factors in univariate analyses (P &lt; 0.05). An adjusted multivariate model identified age &lt;1 year and a non-TYR signature as independent negative predictors of OS: high risk (&lt;1 y + non-TYR; 5-y OS = 0%), intermediate risk (&lt;1 y + ATRT-TYR or ≥1 y + non-TYR; 5-y OS = 32.5 ± 8.7%), and standard risk (≥1 y + ATRT-TYR, 5-y OS = 71.5 ± 12.2%).

Conclusions
Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.
U -duality extension of Drinfel’d double
Authors: Sakatani Yuho 
Published: December 2019

Abstract
A family of algebras $\mathcal{E}_n$ that extends the Lie algebra of the Drinfel’d double is proposed. This allows us to systematically construct the generalized frame fields $E_A{}^I$ which realize the proposed algebra by means of the generalized Lie derivative, i.e., . By construction, the generalized frame fields include a twist by a Nambu–Poisson tensor. A possible application to the non-Abelian extension of $U$-duality and a generalization of the Yang–Baxter deformation are also discussed.
The Limits of Legislative Delegation: Emergency Law in Hong Kong
Authors: Lui Edward 
Published: December 2019

Abstract
The anti-Extradition Bill saga has sparked widespread protests in Hong Kong. In a bid to quench the increasingly violent protests, the Hong Kong Government has resorted to the use of emergency legislation—the Emergency Regulations Ordinance. This use was adjudged unconstitutional by the Hong Kong Court of First Instance in Kwok Wing Hang v. Chief Executive in Council. In light of this background, this article explores the interaction between emergency law and the limits of legislative delegation under the separation of powers in Hong Kong. There are three parts to this article. First, an analytical overview of the powers given under the Ordinance will be made. Second, it will be contended that the Ordinance contravenes two limits on legislative delegation under Hong Kong’s separation of powers. The first contravention is the Ordinance allows the Chief Executive in Council to amend or suspend primary legislation. The second contravention is the Ordinance excessively empowers the Chief Executive in Council to enact subordinate legislation. The decision in Kwok is therefore correct. Third, it will be contended that the court in Kwok has rightly refused to apply a remedial interpretation to the Ordinance.
Hierarchical Hybrid Enrichment: Multitiered Genomic Data Collection Across Evolutionary Scales, With Application to Chorus Frogs (Pseudacris)
Authors: Banker Sarah E , Lemmon Alan R , Hassinger Alyssa Bigelow , Dye Mysia , Holland Sean D , Kortyna Michelle L , Ospina Oscar E , Ralicki Hannah , Lemmon Emily Moriarty 
Published: December 2019

AbstractDetermining the optimal targets of genomic subsampling for phylogenomics, phylogeography, and population genomics remains a challenge for evolutionary biologists. Of the available methods for subsampling the genome, hybrid enrichment (sequence capture) has become one of the primary means of data collection for systematics, due to the flexibility and cost efficiency of this approach. Despite the utility of this method, information is lacking as to what genomic targets are most appropriate for addressing questions at different evolutionary scales. In this study, first, we compare the benefits of target loci developed for deep- and shallow scales by comparing these loci at each of three taxonomic levels: within a genus (phylogenetics), within a species (phylogeography), and within a hybrid zone (population genomics). Specifically, we target evolutionarily conserved loci that are appropriate for deeper phylogenetic scales and more rapidly evolving loci that are informative for phylogeographic and population genomic scales. Second, we assess the efficacy of targeting multiple-locus sets for different taxonomic levels in the same hybrid enrichment reaction, an approach we term hierarchical hybrid enrichment. Third, we apply this approach to the North American chorus frog genus Pseudacris to answer key evolutionary questions across taxonomic and temporal scales. We demonstrate that in this system the type of genomic target that produces the most resolved gene trees differs depending on the taxonomic level, although the potential for error is substantially lower for the deep-scale loci at all levels. We successfully recover data for the two different locus sets with high efficiency. Using hierarchical data targeting deep and shallow levels: we 1) resolve the phylogeny of the genus Pseudacris and introduce a novel visual and hypothesis testing method that uses nodal heat maps to examine the robustness of branch support values to the removal of sites and loci; 2) estimate the phylogeographic history of Pseudacris feriarum, which reveals up to five independent invasions leading to sympatry with congener Pseudacris nigrita to form replicated reinforcement contact zones with ongoing gene flow into sympatry; and 3) quantify with high confidence the frequency of hybridization in one of these zones between P. feriarum and P. nigrita, which is lower than microsatellite-based estimates. We find that the hierarchical hybrid enrichment approach offers an efficient, multitiered data collection method for simultaneously addressing questions spanning multiple evolutionary scales. [Anchored hybrid enrichment; heat map; hybridization; phylogenetics; phylogeography; population genomics; reinforcement; reproductive character displacement.]
Concentration and Volume: Understanding Sodium and Water in the Body
Authors: Bertschi Lydia A. 
Published: December 2019

ABSTRACT
Nurses need to have a firm grasp of normal and pathophysiological mechanisms of sodium and water balance to fully understand assessment findings and establish a rationale for a patient's plan of care. While multiple mechanisms control sodium and water balance, antidiuretic hormone and aldosterone are the most important hormonal influences. This article, the first in a new series designed to improve nurses' understanding of the physiological abnormalities underlying many disorders, reviews the common etiologies and symptoms of hyponatremia and hypernatremia, as well as the role of nursing care in patients with imbalances of sodium and water. Case studies guide the reader through relevant medical history and examination findings to an understanding of both the nursing and medical plans of care.
Clinicopathological Analysis of Acquired Melanocytic Nevi and a Preliminary Study on the Possible Origin of Nevus Cells
Authors: Wang Da-guang , Huang Fei-ran , Chen Wei , Zhou Yuan , Wang Cong-yang , Zhu Feng , Shao Bing-jie , Luo Dan 
Published: December 2019

Background:
The pathogenesis of acquired melanocytic nevi (AMN) is still unclear, and the origin of nevus cells has not been clarified.

Objective:
To analyze the clinical features and pathological types of AMN and identify the possible origin of nevus cells.

Methods:
A retrospective study of 2929 cases of AMN was conducted, and 96 specimens of intradermal and junctional nevi were selected. Immunohistochemical assays were performed to detect the expression of basement membrane component receptor DDR-1 and the molecular markers on epidermal melanocytes, dermal stem cells (DSCs), and hair follicle stem cells.

Results:
Junctional nevi and compound nevi were prone to occur on glabrous skin, such as the palms, soles, and vulva, and on the extremities in children, whereas intradermal nevi tended to develop on the trunk, head, and face of adults. The immunohistochemical data revealed that both junctional nevi and intradermal nevi expressed the epidermal melanocyte surface markers E-cadherin, DDR-1, and integrin α6 and the DSC molecular markers NGFRp-75 and nestin. CD34 was expressed only in junctional nevi, whereas K19 was not expressed in any type of melanocytic nevi. There was no significant difference in molecular expression at different sites or in different ages of onset. Nestin expression was markedly stronger in the intradermal nevi than in the junctional nevi, but there was no difference between the superficial and deep nevus cell nests of intradermal nevi.

Conclusion:
AMN may have a multicellular origin that commonly follows the mode of Abtropfung. Furthermore, DSCs may partly or independently participate in the formation of nevus cells.
Writing an Evidence-based Article in Plastic Surgery: Translating Research into High-quality Care
Authors: Wood Shannon M. , Kim You J. , Chung Kevin C. 
Published: December 2019

Summary:
Evidence-based medicine (EBM) is a triad that integrates the physician’s medical expertise and the patient’s individual characteristics with the best available scientific evidence. As patients become more active in the clinical decision-making process, the application of evidence-based practice in the field of plastic surgery is more critical now than ever. As a field that is recognized by its innovation, plastic surgeons must understand the various aspects of EBM to enhance and keep the field at the top of medical discovery. Many initiatives have been implemented to guide researchers in the collection, analysis, and distribution of high-quality evidence. In particular, Plastic and Reconstructive Surgery introduced a new EBM series to provide plastic surgeons with the appropriate resources to generate and integrate high-quality evidence into their practices. As a part of this initiative, this article will assist researchers in producing an evidence-based article that is well-written, relevant, and impactful to incorporate evidence-based practice into the specialty.
The 4 Principles of Complex Abdominal Wall Reconstruction
Authors: Khansa Ibrahim , Janis Jeffrey E. 
Published: December 2019

Summary:
Abdominal wall defects are some of the most common and challenging problems encountered by plastic surgeons. A high proportion of patients with abdominal wall defects have significant comorbidities and/or contamination, putting them at high risk for complications. In addition to advanced surgical skills and precise anatomical knowledge, the plastic surgeon needs strict discipline and medical acumen, to optimize patients before and after surgery. In this paper, we discuss the goals of abdominal wall reconstruction, and the 4 steps to successful surgery: preoperative patient selection/optimization, durable and dynamic reconstruction of the musculofascial layer, careful attention to the skin and subcutaneous tissue, and meticulous postoperative management.
Air Pollution, Physical Activity, and Cardiovascular Function of Patients With Implanted Cardioverter Defibrillators: A Randomized Controlled Trial of Indoor Versus Outdoor Activity
Authors: Liu Ling , Urch Bruce , Nanthakumar Kumaraswamy , Chen Li , Smith-Doiron Marc , Brook Jeffrey R. , Speck Mary , Silverman Frances , Stieb David M. 
Published: December 2019

Objective:
To investigate whether implanted cardioverter defibrillator (ICD) patients exercising indoors on higher air pollution (AP) days had reduced adverse cardiovascular effects compared with those exercising outdoors.

Methods:
Eighteen participants were randomly divided into control or intervention groups. Blood pressure (BP), pulse rate (PR), and oxygen saturation (O2SAT) were measured daily before and after participants walked outdoors for 30 minutes. On days with higher forecast AP the intervention group exercised indoors.

Results:
AP was significantly associated with increased BP and PR, and reduced O2SAT. After adjustment for exercise levels, AP was associated with increased diastolic BP and PR in controls only. Significant improvements in cardiovascular measures over time were observed in both groups.

Conclusion:
In ICD patients, reducing AP exposure may reduce adverse cardiovascular effects, while daily mild exercise may benefit cardiovascular function.
Assessment of Work Loss Associated With Prescription-Related Opioid Use Disorder
Authors: White Alan G. , Spittle Tim , Fernan Catherine , Billmyer Emma , Marrett Elizabeth , Kwong Winghan Jacqueline , Rossiter Louis F. 
Published: December 2019

Objective:
Quantify work loss and costs associated with prescription opioid use disorder (OUD) from the employer perspective.

Methods:
Retrospective claims analysis to compare missed work days and associated costs between employees with and without an OUD diagnosis in a 12-month period.

Results:
Two thousand three hundred eleven matched-pairs of employees were compared. The mean (SD) number of days missed while waiting for disability benefits (0.24 [1.4] vs 0.17 [1.0]; P = 0.035), absenteeism due to disability claims (9.5 [40.9] vs 5.6 [30.0]; P < 0.001), and medical visits (17.8 [18.5] vs 10.0 [12.4]; P < 0.001) was higher for employees with OUD compared with those without, resulting in higher mean (SD) indirect cost estimates of $8193 ($14,694) per employee (OUD) versus $5438 ($13,683) per employee (no OUD) (P < 0.001).

Conclusions:
Prescription OUD is associated with significant work loss and may pose considerable economic burden on employers.
Projected 20‐ and 30‐Year Outcomes for Pediatric Liver Transplant Recipients in the United States
Authors: Bowring Mary G. , Massie Allan B. , Chu Nadia M. , Bae Sunjae , Schwarz Kathleen B. , Cameron Andrew M. , Bridges John F.P. , Segev Dorry L. , Mogul Douglas B. 
Published: December 2019

ABSTRACTBackground:Observed long‐term outcomes no longer reflect the survival trajectory facing pediatric liver transplant (LT) recipients today. We aimed to use national registry data and parametric models to project 20‐ and 30‐year post‐transplant outcomes for recently transplanted pediatric LT recipients.Methods:We conducted a retrospective cohort study of 13,442 first‐time pediatric (age <18) LT recipients using 1987 to 2018 Scientific Registry of Transplant Recipients data. We validated the proposed method (ie, to project long‐term patient and graft survival using parametric survival models and short‐term data) in 2 historic cohorts (1987–1996 and 1997–2006) and estimated long‐term projections among patients transplanted between 2007 and 2018. Projections were stratified by raft type, recipient age, and indication for transplant.Results:Parsimonious parametric models with Weibull distribution can be applied to post‐transplant data and used to project long‐term outcomes for pediatric LT recipients beyond observed data. Projected 20‐year patient survival for pediatric LT recipients transplanted in 2007 to 2018 was 84.0% (95% confidence interval 81.5–85.8), compared to observed 20‐year survival of 72.8% and 63.6% among those transplanted in 1997 to 2006 and 1987 to 1996, respectively. Projected 30‐year survival for pediatric LT recipients in 2007 to 2018 was 80.1% (75.2–82.7), compared to projected 30‐year survival of 68.6% (66.1–70.9) in the 1997 to 2006 cohort and observed 30‐year survival of 57.5% in the 1987 to 1996 cohort. Twenty‐ and 30‐year patient and graft survival varied slightly by recipient age, graft type, and indication for transplant.Conclusions:Projected long‐term outcomes for recently transplanted pediatric LT recipients are excellent, reflective of substantial improvements in medical care, and informative for physician‐patient education and decision making in the current era.
Parenteral Zinc Intake in Newborns With Jejunostomy or Ileostomy
Authors: D'Aniello Roberta , Terquem Elise L. , Poupon Joël , Assaf Ziad , Kermorvant‐Duchemin Elsa , Maggio Luca , Lapillonne Alexandre 
Published: December 2019

ABSTRACTObjectives:The aim of the study was to assess zinc status of newborns with parenteral nutrition with or without a small bowel stoma, to determine the incidence of zinc deficit, and to determine the clinical factors associated with plasma zinc levels.Methods:Monocentric cohort study including all liveborn infants receiving zinc parenteral intake at 500 μg · kg−1 · day−1 and who benefited from at least 1 plasma zinc assessment during hospitalization.Results:Sixty‐eight dosages of zinc were performed in 50 newborns, divided into 3 groups (no stoma = 26, jejunostomy = 11, ileostomy = 13). Thirty‐seven of the 50 infants were born preterm. The mean ± standard deviation plasma zinc was 14.9 ± 4.3 μmol/L and was similar among the 3 groups. Sixty‐four percent, 3%, and 34% of zinc values were within, below, and above the normal range, respectively. In infants with jejunostomy, only 1 plasma zinc value (5%) was below the reference range. Plasma zinc levels were negatively correlated with stoma output (r2 = −0.449; P = 0.013). In contrast to patients with limited intestinal losses (ie, no stoma and ileostomy groups) no association between zinc levels and postmenstrual age was observed in infants with a jejunostomy suggesting that 500 μg · kg−1 · day−1 was adequate not only in preterm infants but also in term infants with a jejunostomy.Conclusion:Plasma zinc levels decrease significantly with the increase of stoma output volume of newborns with small bowel stoma. Zinc deficit was prevented in newborns with a small bowel stoma receiving of 500 μg · kg−1 · day−1 of parenteral zinc.
Long‐term Outcome of Transjugular Intrahepatic Portosystemic Shunt in Children With Portal Hypertension
Authors: Di Giorgio Angelo , Nicastro Emanuele , Agazzi Roberto , Colusso Mara , D’Antiga Lorenzo 
Published: December 2019

ABSTRACTObjectives:A proportion of children with chronic liver disease have severe portal hypertension (PH) and a preserved synthetic and biliary function. In our institution these children have been managed with transjugular intrahepatic portosystemic shunts (TIPS). We aimed to evaluate the long‐term patency of TIPS placed in pediatric patients with PH.Methods:Retrospective study of children who underwent TIPS in the last 15 years. We compared patients with cirrhotic PH to those with noncirrhotic PH, and all with an historical cohort of children who underwent a surgical portosystemic shunt. Kaplan‐Meier analysis measured long‐term shunt patency.Results:Twenty‐nine patients were recorded (cirrhotic PH = 11, noncirrhotic PH  = 18, mean age 10.3 years[±4.3], mean weight 36.7 kg [±20.1], mean pediatric end‐stage liver disease score 4.1 [±7.1]); in 5 TIPS was placed after split liver transplantation. Indication for TIPS was variceal bleeding in 18, refractory ascites in 11. Primary patency rates at 6 months and at 1, 2, and 4 years were 91%, 83%, 60%, and 46%, respectively. At last follow‐up (mean of 2.8 years [±2.4, range 0.1–8.1 years]) secondary patency (after radiological revision) was 100%. The patency rate of the historical cohort of patients who underwent a surgical portosystemic shunt was 26 of 31 (82%) at a median follow‐up of 12.5 years (1.6–25.8).Conclusion:TIPS appears to have a high mid‐term patency rate, especially if monitored and revised. Its high clinical success rate, along with a minimally invasive approach, suggests that in this setting TIPS should not be regarded only as a bridge to liver transplantation.