bluuebunny/crossref_metadata_2025 huggingface dataset:
Deterministic actin waves as generators of cell polarization cues
Authors: Stankevicins Luiza , Ecker Nicolas , Terriac Emmanuel , Maiuri Paolo , Schoppmeyer Rouven , Vargas Pablo , Lennon-Duménil Ana-Maria , Piel Matthieu , Qu Bin , Hoth Markus , Kruse Karsten , Lautenschläger Franziska
Published: December 2019

Significance

Dendritic cells are immune cells that migrate within the human body in search of pathogens. This search is performed by a random walk, which combines persistent and diffuse movements. The mechanism underlying this random walk is currently not known. We analyzed very long trajectories of dendritic cells ex vivo, and we describe here their characteristic persistent and diffusive patterns. Together with theoretical analysis, we provide evidence that the random walk of dendritic cells could be a consequence of the intrinsic actin dynamics without need for molecular noise or external polarization cues. Our results hint at the possibility that these cells can adapt their random search strategies by changing the spontaneous dynamics of their actin cytoskeleton.
Revisiting the tumorigenesis timeline with a data-driven generative model
Authors: Lahouel Kamel , Younes Laurent , Danilova Ludmila , Giardiello Francis M. , Hruban Ralph H. , Groopman John , Kinzler Kenneth W. , Vogelstein Bert , Geman Donald , Tomasetti Cristian
Published: December 2019

Cancer is driven by the sequential accumulation of genetic and epigenetic changes in oncogenes and tumor suppressor genes. The timing of these events is not well understood. Moreover, it is currently unknown why the same driver gene change appears as an early event in some cancer types and as a later event, or not at all, in others. These questions have become even more topical with the recent progress brought by genome-wide sequencing studies of cancer. Focusing on mutational events, we provide a mathematical model of the full process of tumor evolution that includes different types of fitness advantages for driver genes and carrying-capacity considerations. The model is able to recapitulate a substantial proportion of the observed cancer incidence in several cancer types (colorectal, pancreatic, and leukemia) and inherited conditions (Lynch and familial adenomatous polyposis), by changing only 2 tissue-specific parameters: the number of stem cells in a tissue and its cell division frequency. The model sheds light on the evolutionary dynamics of cancer by suggesting a generalized early onset of tumorigenesis followed by slow mutational waves, in contrast to previous conclusions. Formulas and estimates are provided for the fitness increases induced by driver mutations, often much larger than previously described, and highly tissue dependent. Our results suggest a mechanistic explanation for why the selective fitness advantage introduced by specific driver genes is tissue dependent.
Improvement of refill friction stir spot welds by auxiliary material addition
Authors: Chen Shujun , Shi Jiaxu , Yuan Tao , Jiang Xiaoqing
Published: December 2019

An innovative technology to improve the bonding of refill friction stir spot welding by auxiliary material addition was proposed. The annular groove was eliminated and the energy absorption was increased. Weld bonding was enhanced because the improved technology affected the hook, retractable line and stir zone (SZ) shape significantly: (1) the effective bearing thickness of the welds increased as the hook penetration through the sheet thickness was reduced significantly, (2) the retractable line was eliminated as the dynamic recrystallisation was enhanced along the path of the sleeve moving and (3) fracture propagation was impeded by the bending interface between the SZ and the base materials.
Relationship between age-hardening by continuous precipitation and damping capacity in AZ91 alloy
Authors: Han Jin-Gu , Jun Joong-Hwan
Published: December 2019

The strain-amplitude-dependent and strain-amplitude-independent damping capacities of a cast AZ91 magnesium alloy as functions of its age-hardening response induced by continuous precipitation have been investigated. The damping capacities of the AZ91 alloy exhibited a decreasing tendency in the order of solutionised, underaged, overaged, and peak aged states in the strain-amplitude-dependent region, whereas they increased continuously with aging time in the strain-amplitude-independent region. In view of the microstructural evolution during aging, the lower Al concentration in the α-(Mg) matrix and the lower number density of continuous precipitates are thought to be responsible for the better damping capacities of the AZ91 alloy in the strain-amplitude-independent and strain-amplitude-dependent regions, respectively.
The Chinese diaspora’s ‘imaginary’ homeland in the novels by four Chinese-American and Chinese-Indonesian writers
Authors: Kusumaningtyas Purwanti , Cohen James
Published: December 2019

Studies on Chinese diaspora and their connections with their homeland have focused on various perspectives, such as historical, socio-cultural, and economic, however, rarely discussed through literary works. This study aims to elaborate on the representations of the Chinese diaspora’s homeland in novels by two Chinese-American authors, Maxine Hong Kingston and Amy Tan, and two Chinese-Indonesian authors, Marga T. and Mira W. By employing Salman Rushdie’s memory-based imaginary homeland and Benedict Anderson’s creation-based imagined communities, the authors of this essay discuss the Chinese- American and Chinese-Indonesian people’s views of their homeland in their present contexts in their respective countries. The Chinese-American novels present their imaginary homeland through the utilization of fragmented legends and distorted myths. On the other hand, the Chinese-Indonesian novels present their imagined homeland by foregrounding the image of modernity through the exposure of wealthy families’ lifestyles and the picture of Western-oriented education and religious affiliations. The different experiences demonstrate that the notion of ‘homeland’ needs to be widened and pluralized to be able to embrace the heterogeneity of the diaspora.
Study on microstructure of NiAl matrix high temperature lubricating composites containing BaO/TiO2 metallic oxide
Authors: Li Bo , Gao Yimin , Li Cong , Kang Yunchuan , Zheng Qiaoling , Zhao Siyong
Published: December 2019

The microstructure of NiAl matrix high temperature lubricating composites containing BaO/TiO2 metallic oxides were investigated. The NiAl-BaO/TiO2 composites were fabricated by vacuum hot-pressing sintering. The diffraction peaks of NiAl slightly shifted to the left with the addition of BaO/TiO2 metallic oxide. The crystal plane distance of NiAl phase in the composite was bigger than that in NiAl material according to the Bragg equation. Meanwhile, the lattice distortion and dislocation occurred in the composite structure, which is probably due to the Ti element dissolve in the NiAl matrix during sintering. The cohesive energy and formation enthalpy of NiAl were improved with the incremental of Ti solution contents through density functional theory calculations, which was indicated that the Ti element could dissolve in the NiAl and was in good accordance with the results of XRD and TEM.
High wear resistance hypoeutectic Fe–C–B alloy by hot rolling
Authors: Li Feng , Li Zhenhua
Published: December 2019

A novel high wear resistance hypoeutectic Fe–C–B alloy by hot rolling with isolated hard lumps distributed in matrix is reported. The effect of deformation on microstructure and properties of the alloy during hot rolling process was systematically investigated. The results showed that with the increase of deformation, the continuous hard phase network in the alloy was crushed into isolated hard lumps, and the properties of the alloy were improved significantly. The alloy with 66.7% deformation displayed excellent mechanical properties with the impact value of 12.6 J while its hardness was still kept at 58.6 HRC. And the wear resistance of the alloy with 66.7% deformation was 1.21 times as that of the commercial Cr20Mo high chromium cast iron.
Changes in physical activity of adolescent girls in the context of their perception of the Healthy Me programme
Authors: Mazur Joanna , Dzielska Anna , Kleszczewska Dorota , Oblacińska Anna , Fijałkowska Anna
Published: December 2019

Background

An assumption was made that results of programme evaluation lead to better understanding for whom this intervention may work. The aim of the article is to compare the changes in physical activity of the intervention programme participants depending on subjective assessment of its impact.

Methods

The data were obtained from 14- to15-year-old Polish girls (N = 1120) from 48 random selected secondary schools participating in the 1-year Healthy Me programme in the 2017/2018. Schools were randomly assigned to one of two types of intervention or to a control (null) group. Satisfaction with the programme according to 21 criteria was measured retrospectively just after the intervention. Change in MVPA (moderate-to-vigorous physical activity) during the programme implementation was assessed in relation to satisfaction level, and adjusted for initial MVPA.

Results

In total, the MVPA did not change significantly comparing pre- and post-intervention surveys (3.94 ± 1.94 vs. 3.87 ± 1.93)—P = 0.093. However, the perceived notable improvement of functioning in 10 out of 21 areas was related to the unquestionable increase in MVPA (P ≤ 0.001). With respect to the four impact areas, an interaction was demonstrated between an intervention group and an improvement in the domain-specific functioning. The beneficial impact of the programme on these areas was associated with the improvement of physical activity only in case of full and null intervention.

Conclusions

Indicators related to the implementation process and the results obtained during the Healthy Me programme evaluation could represent a change in motivational and environmental factors that indirectly affects adolescent girl’s physical activity.
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

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

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 <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 < 0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 y + non-TYR; 5-y OS = 0%), intermediate risk (<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

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

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

Determining 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.]
The Top Health Care Stories of 2019: Cyberattacks and Hospital Data Security
Authors: Brodhead Frank
Published: December 2019

Responses to a growing threat fall short.
The Top Health Care Stories of 2019: A Changing Climate and the Elimination of Protections
Authors: McSpedon Corinne
Published: December 2019

The health consequences could be significant and long lasting.
The Top Health Care Stories of 2019: Society in Distress
Authors: Halpern Lucy Wang
Published: December 2019

A year marked by upheaval and increasing social disparities.
Concentration and Volume: Understanding Sodium and Water in the Body
Authors: Bertschi Lydia A.
Published: December 2019

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

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

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

Background:

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

Objectives:

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

Objectives:

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.
Effect of Alternative Pasteurization Techniques on Human Milk's Bioactive Proteins
Authors: Aceti Arianna , Cavallarin Laura , Martini Silvia , Giribaldi Marzia , Vitali Francesca , Ambretti Simone , Zambrini Vittorio , Corvaglia Luigi
Published: December 2019

Objectives:

Human milk (HM) feeding leads to improved outcome for preterm infants. When mother's milk is unavailable, pasteurized donor HM (DHM) is the recommended alternative over formula. The Holder pasteurization (HoP) method is universally performed in HM banks; however, it is known to impair several functional HM components. The aim of this study was to compare the efficacy of HoP with 2 innovative processing methods (high‐temperature short‐time [HTST] pasteurization and high‐pressure processing [HPP]) in preserving some bioactive HM protein components.

Methods:

HM samples from donors of the Bologna HM bank were collected and divided into 4 subsamples: 1 was kept raw, and each of the others was processed using a different technique (HoP, HTST, and HPP at 600 MPa for 3 minutes). Total protein content, secretory immunoglobulin A (sIgA), and lactoferrin contents were compared.

Results:

Both HM lactoferrin and sIgA content were negatively affected, but to a different extent, by each method: sIgA was preserved by HTST, with only HPP leading to a significant reduction (−38.8%); lactoferrin content was strongly reduced by HoP (−87.5%) and HTST (‐83.5%), and preserved by HPP. Variations in protein profile were seen for all processing methods, being more relevant for HoP, followed by HTST and, finally, by HPP. All the 3 methods lowered the untreated HM microbial counts to undetectable levels, in accordance with national guidelines.

Conclusions:

Both HTST and HPP better preserved the original HM protein profile, compared to HoP. They, however, affected differently some bioactive HM components involved in immune response and antibacterial activity.
Welfare Checks and Therapeutic Risk Management
Authors: WORTZEL HAL S. , BARNES SEAN M. , CANNIZZARO KAILY A. , VILLARREAL EDGAR J. , MATARAZZO BRIDGET B. , ALLEN MICHAEL H.
Published: December 2019

In clinical practice, welfare checks have become a fairly common aspect of suicide prevention. At the same time, the medical literature provides almost no guidance to inform clinicians under what circumstances welfare checks should be requested, how best to go about placing those requests, or how to document decision-making related to this important subject. Literature searches spanning both PubMed and Google Scholar failed to yield any applicable results. Performed correctly, welfare checks have the potential to be life-saving interventions for persons in suicidal crises. Performed incorrectly, welfare checks may become an overly defensive practice that damages therapeutic relationships, violates patients’ rights, and consumes important and limited community resources. The need for thoughtful guidance to assist clinicians in navigating these difficult clinical scenarios is long overdue. This column, the second in a 2-part series, offers an approach to welfare checks informed by the tenets of therapeutic risk management.
Effect of Mild Hypothermia on the Diaphragmatic Microcirculation and Function in A Murine Cardiopulmonary Resuscitated Model
Authors: Li Shao-Ping , Zhou Xian-Long , Li Qi , Zhao Yu-Qian , Zhao Zhi-Gang , Zhao Yan
Published: December 2019

Objective:

Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model.

Methods:

Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed.

Results:

Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group.

Conclusion:

MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.
Five-year Outcomes of Pulmonary Hypertension With and Without Elevated Left Atrial Pressure in Patients Evaluated for Kidney Transplantation
Authors: Caughey Melissa C. , Detwiler Randal K. , Sivak Joseph A. , Rose-Jones Lisa J. , Kshirsagar Abhijit V. , Hinderliter Alan L.
Published: December 2019

Background.

Pulmonary hypertension (PH) is frequently reported in patients with advanced chronic kidney disease and is associated with early allograft failure and death. However, the causes of PH are heterogeneous, and patient prognosis may vary by etiologic subtype.

Methods.

Data from the University of North Carolina Cardiorenal Registry were examined to determine associations between PH, with or without elevated left atrial pressure (eLAP), and mortality in candidates for kidney transplantation. PH and eLAP were determined by Doppler echocardiography and by tissue Doppler imaging, respectively.

Results.

From 2006 to 2013, 778 registry patients were screened preoperatively by echocardiography. Most patients were black (64%) and men (56%); the mean age was 56 years. PH was identified in 97 (12%) patients; of these, eLAP was prevalent in half. During a median follow-up of 4.4 years, 179 (23%) received a kidney transplant, and 195 (25%) died. After adjustments for demographics, comorbidities, dialysis vintage, and kidney transplantation, PH was associated with twice the 5-year mortality (hazard ratio [HR] = 2.11; 95% confidence interval [CI]: 1.48-3.03), with stronger associations in the absence of eLAP (HR = 2.87; 95% CI: 1.83-4.49) than with eLAP (HR = 1.11; 95% CI: 0.57-2.17), P for interaction = 0.01.

Conclusions.

The mortality risk associated with PH among patients with advanced chronic kidney disease appears to differ by etiology. Patients with PH in the absence of eLAP are at high risk of death and in need of focused attention. Future research efforts should investigate potential strategies to improve outcomes for these patients.
Bilateral Proximal Forearm Transplantation: Case Report at 7 Years
Authors: Iglesias Martín , Villanueva-Castro Eliezer , Macias-Gallardo Julio , Alberú-Gómez Josefina , Leal-Villalpando Rafael P. , Zamudio-Bautista Jorge , Acosta Victor , Butrón Patricia , Sierra-Madero Juan G. , Cuellar-Rodriguez Jennifer , Espinosa-Cruz Verónica , Gómez-Camargo Claudia , Mayorquín-Ruiz Mariana , Vázquez-Lamadrid Jorge , Toussaint-Caire Sonia , Domínguez-Cherit Judith , Dorantes-García Joel , Furuzawa-Carballeda Janette , Hernandez-Castillo Carlos R. , Guzmán González Juan M. , Castelan-Carmona Natalia , López-Mártinez Mayra , González-Tableros Norma , Arvizu-Hernández Adriana , De Santiago-Zárate Adrián
Published: December 2019

Background.

Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT.

Case Presentation.

A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force.

Results.

Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year.

Conclusions.

Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.
High Content Screening, a reliable system forCoxiella burnetiiisolation from clinical samples
Authors: Francis Rania , Mioulane Maxime , Bideau Marion Le , Mati Marie-Charlotte , Fournier Pierre-Edouard , Raoult Didier , Khalil Jacques Yaacoub Bou , Scola Bernard La
Published: December 2019

Q fever, caused byCoxiella burnetii, is a worldwide zoonotic disease that may cause severe forms in humans and requires a specific and prolonged antibiotic treatment. Although the current serological and molecular detection tools enable a reliable diagnosis of the disease, culture ofC. burnetiistrains is mandatory to evaluate their antibiotic susceptibility and sequence their genome in order to optimize patient management and epidemiological studies. However, cultivating this fastidious microorganism is difficult and restricted to reference centers as it requires biosafety-level 3 laboratories and relies on cell culture performed by experienced technicians. In addition, the culture yield is low, which results in a small number of isolates being available. In this work, we developed a novel high content screening (HCS) isolation strategy based on optimized high-throughput cell culture and automated microscopic detection of infected cells with specifically-designed algorithms targeting cytopathic effects. This method was more efficient than the shell-vial assay when applied to both frozen specimens (7 isolates recovered by HCS only, sensitivity 91%vs78% for shell-vial) and fresh samples (1 additional isolate using HCS, sensitivity 7%vs5% for shell-vial). In addition, detecting positive cultures by an automated microscope reduced the need for expertise and saved 24% of technician working time. Application of HCS to antibiotic susceptibility testing of 12 strains demonstrated that it was as efficient as the standard procedure that combines shell-vial culture and quantitative PCR. Overall, this high-throughput HCS system paves the way to the development of improved cell culture isolation of human viruses.
The Two Amino Acids Proximate to the Renin Cleavage Site of Human Angiotensinogen Do Not Affect Angiotensin II-mediated Functions in Mice
Authors: Wu Chia-Hua , Wu Congqing , Howatt Deborah A. , Moorleghen Jessica J. , Cassis Lisa A. , Daugherty Alan , Lu Hong S.
Published: December 2019

Objective

Renin cleavage of angiotensinogen (AGT) has species specificity. Since the residues at positions 11 and 12 of AGT are different between human and mouse AGT, we determined whether these two residues in AGT affect renin cleavage and angiotensin II-mediated functions using an adeno-associated viral (AAV) approach for manipulating AGT in vivo.

Approach and Results

Hepatocyte-specific AGT deficient (hepAGT-/-) mice in an LDL receptor -/- background were infected with AAVs containing a null insert, human AGT, or mouse AGT expressing the same residues of the human protein at positions 11 and 12 [mouse AGT (L11V;Y12I)]. Expression of human AGT in hepAGT-/- mice led to high plasma human AGT concentrations without changes in plasma mouse endogenous AGT, plasma renin concentrations, blood pressure, or atherosclerosis. This is consistent with human AGT not being cleaved by mouse renin. To determine whether the residues at positions 11 and 12 in human AGT lead to the inability of mouse renin to cleave human AGT, hepAGT-/- mice were injected with AAV encoding mouse AGT (L11V;Y12I). Expression of mouse AGT (L11V;Y12I) resulted in increased plasma mouse AGT concentrations, reduced renin concentrations, and increased renal AngII concentrations that were comparable to their concentrations in hepAGT+/+ mice. This mouse AGT variant increased blood pressure and atherosclerosis in hepAGT-/- mice to the magnitude of hepAGT+/+ mice.

Conclusion

Replacement of L11 and Y12 to V11 and I12, respectively, in mouse AGT does not affect renin cleavage and AngII-mediated functions in mice.

HIGHLIGHTS

Human AGT is not cleaved by mouse renin and does not change AngII-mediated functions in hepatocyte-specific AGT -/- mice.

Replacement of the N-terminal amino acids at 11 and 12 positions from mouse to human AGT does not affect renin cleavage and AngII-mediated functions in hepatocyte-specific AGT -/- mice.