bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caregiver support and positive airway pressure therapy adherence among adolescents with obstructive sleep apnea
Authors: Parmar Arpita , Messiha Sandra , Baker Adele , Zweerink Allison , Toulany Alene , Narang Indra 
Published: August 2019

AbstractIntroductionPositive airway therapy (PAP) adherence rates are suboptimal among adolescents with obstructive sleep apnea (OSA) and strategies to increase PAP adherence is a clinical priority. This study evaluates if caregiver support is associated with PAP adherence rates among adolescents with OSA.MethodsWe conducted a retrospective study and evaluated PAP adherence rates among adolescents with OSA from 2012 to 2017. Adherence was measured as continuous variables: average PAP usage (minutes per night) and average PAP usage &gt;4 hours/night (% of all nights). We evaluated if adolescents with OSA who were receiving practical caregiver support with PAP had higher adherence than adolescents with OSA without caregiver support.ResultsOne hundred and seven adolescents with OSA (mean age=14.1±2.5 years, 64.5% male, mean BMI percentile=89.0±21.8) seen between January 2012 and August 2017 at our institution were included. In this study, 60.7% (n=65) of adolescents with OSA were receiving practical caregiver support with PAP therapy. Adolescents with OSA receiving practical caregiver support with PAP used therapy for a significantly greater duration each night compared to adolescents who were not receiving practical caregiver support (298.5±206.7 versus 211.9±187.2 minutes; P=0.02). Greater time since the initial PAP prescription was independently associated with PAP adherence.ConclusionFocusing on PAP adherence early may help adolescents with OSA incorporate therapy into their nightly routine, which may improve adherence and lead to improved health outcomes in adolescents with OSA. Practical caregiver support may be an essential component of ensuring optimal PAP adherence among adolescents with OSA.
Development of a novel prostate apoptosis response-4 (Par-4) protein entity with an extended duration of action for therapeutic treatment of cancer
Authors: Kim Kyungbo , Araujo Pereira , Hebbar Nikhil , Zhou Ziyuan , Zheng Xirong , Zheng Fang , Rangnekar Vivek M , Zhan Chang-Guo 
Published: August 2019

Abstract
Prostate apoptosis response-4 (Par-4) is a tumor suppressor which protects against neoplastic transformation. Remarkably, Par-4 is capable of inducing apoptosis selectively in cancer cells without affecting the normal cells. In this study, we found that recombinant Par-4 protein had limited serum persistence in mice that may diminish its anti-tumor activity in vivo. To improve the in vivo performance of the short-lived Par-4 protein, we aimed to develop a novel, long-lasting form of Par-4 with extended sequence, denoted as Par-4Ex, without affecting the desirable molecular function of the natural Par-4. We demonstrate that the Par-4Ex protein entity, produced by using the Escherichia coli expression system suitable for large-scale production, fully retains the desirable pro-apoptotic activity of Par-4 protein, but with ~7-fold improved biological half-life. Further in vivo tests confirmed that, due to the prolonged biological half-life, the Par-4Ex protein is indeed more potent in suppressing metastatic tumor growth in mice.
$S$
-matrix unitarity and renormalizability in higher-derivative theories
Authors: Abe Yugo , Inami Takeo , Izumi Keisuke , Kitamura Tomotaka , Noumi Toshifumi 
Published: August 2019

Abstract
We investigate the relation between $S$-matrix unitarity ($SS^\dagger=1$) and renormalizability in theories with negative-norm states. The relation has been confirmed in many field theories, including gauge theories and Einstein gravity, by analyzing the unitarity bound, which follows from the $S$-matrix unitarity and the norm positivity. On the other hand, renormalizable theories with a higher-derivative kinetic term do not necessarily satisfy the unitarity bound because of the negative-norm states. In these theories it is not known whether the $S$-matrix unitarity provides a nontrivial constraint related to the renormalizability. In this paper, by relaxing the assumption of norm positivity we derive a bound on scattering amplitudes weaker than the unitarity bound, which may be used as a consistency requirement for $S$-matrix unitarity. We demonstrate in scalar field models with a higher-derivative kinetic term that the weaker bound and the renormalizability imply identical constraints.
Different seniority states of $^{119-126}$Sn isotopes: shell-model description
Authors: Srivastava Praveen C , Bhoy Bharti , Ermamatov M J 
Published: August 2019

Abstract
In the present work, available experimental data up to high-spin states of $^{119-126}$Sn isotopes with different seniority ($v$), including $v = 4$, 5, 6, and 7, are interpreted with the shell model, by performing shell-model calculations in the 50–82 valence shell composed of $1g_{7/2}$, $2d_{5/2}$, $1h_{11/2}$, $3s_{1/2}$, and $2d_{3/2}$ orbitals. The results are compared with the available experimental data. These states are described in terms of broken neutron pairs occupying the $h_{11/2}$ orbital. Possible configurations of seniority isomers in these nuclei are discussed. The breaking of three neutron pairs is responsible for generating high-spin states. The isomeric states $5^-$, $7^-$, $10^+$, and $15^-$ of even Sn isotopes, and isomeric states $19/2^+$, $23/2^+$, $27/2^-$, and $35/2^+$ of odd Sn isotopes, are described in terms of different seniority. For even Sn isotopes, the isomeric states $5^-$, $7^-$, and $10^+$ are due to seniority $v = 2$; the isomeric state $15^-$ is due to seniority $v = 4$, and, in the case of odd Sn isotopes, the isomeric states $19/2^+$, $23/2^+$, and $27/2^-$ are due to seniority $v = 3$, and the isomeric state $35/2^+$ in $^{123}$Sn is due to seniority $v = 5$. These are maximally aligned spins, which involve successive pair breakings in the $\nu (h_{11/2})$ orbital.
An update on X-Linked agammaglobulinaemia: clinical manifestations and management
Authors: Shillitoe Benjamin Martin James , Gennery Andrew R. 
Published: August 2019

Purpose of review
X-linked agammaglobulinaemia (XLA) is a congenital defect of development of B lymphocytes leading to agammaglobulinaemia. It was one of the first primary immunodeficiencies described, but treatment has remained relatively unchanged over the last 60 years. This summary aims to outline the current outcomes, treatments and future research areas for XLA.

Recent findings
Immunoglobulin therapy lacks IgA and IgM, placing patients at theoretical risk of experiencing recurrent respiratory tract infections and developing bronchiectasis despite best current therapy. Recent cohort studies from Italy and the USA conform that bronchiectasis remains a major burden for this group despite best current efforts. However, gene therapy offers a potential cure for these patients with proven proof of concept murine models.

Summary
The potential limitations of current immunoglobulin therapy appear to be confirmed by recent cohort studies, and therefore further work in the development of gene therapy is warranted. Until this is available, clinicians should strive to reduce the diagnostic delay, regularly monitor for lung disease and individualize target immunoglobulin doses to reduce infection rates for their patients.
Anesthesia-induced immune modulation
Authors: Rossaint Jan , Zarbock Alexander 
Published: August 2019

Purpose of review
Surgery, invasive procedures and anesthesia itself may induce an inflammatory response in the patient. This represents an evolutionary inherited and conserved response of the host to environmental stimuli and may lead to both beneficial and potentially harmful effects. This review highlights the mechanisms of anesthesia-induced and perioperative immune modulation.

Recent findings
The innate and adaptive immune system serve the host in protection against invading pathogens. Yet, an inflammatory immune response may also be induced by different noninfectious stimuli, for example invasive perioperative procedures and the surgical trauma itself. These stimuli may lead to the activation of the immune system with the consequence of perturbation of cell, tissue of even organ functions in cases of an overshooting immune response. Several perioperative factors have been identified that modulate the immune response, for example different anesthetic drugs and surgical tissue injury, but their impact on immune system modulation may also vary with respect to the procedural context and include both pro-inflammatory and anti-inflammatory effects.

Summary
The current review will highlight the current knowledge on the perioperative anesthesia-induced and surgery-induced modulation of the immune response and also address possible intervention strategies for the development of future therapeutic approaches.
Update on pregnancy complications in systemic lupus erythematosus
Authors: Marder Wendy 
Published: August 2019

Purpose of review
This review summarizes recent research in the field of systemic lupus erythematosus (SLE) and pregnancy with focus on clinical and biochemical predictors of adverse pregnancy outcomes (APOs), accumulating evidence for the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy, and the importance of preconception counseling.

Recent findings
Ongoing research from PROMISSE investigators (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) adds to the understanding of risk factors for APOs in SLE pregnancies, including aberrant complement activation, incomplete downregulation of lupus-associated transcription factors, and lower socioeconomic status. Evidence supporting numerous advantages for continuing HCQ in pregnancy, as well as support for low-dose aspirin in preeclampsia prevention is reviewed. Practice gaps exist among rheumatologists in ensuring effective contraception when women of childbearing age are undergoing therapy with potentially fetotoxic medications. The publication of organizational guidelines provides evidence-based recommendations on lupus pregnancy management.

Summary
Outcomes of lupus pregnancies continue to improve with understanding of risk factors that predict APOs as well as improvements in disease management. Rheumatologists caring for women with SLE should be familiar with the most up-to-date research in order to optimize pregnancy outcomes in this population.
Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection
Authors: Metsemakers Willem-Jan , Fragomen Austin T. , Moriarty T. Fintan , Morgenstern Mario , Egol Kenneth A. , Zalavras Charalampos , Obremskey William T. , Raschke Michael , McNally Martin A. ,   on behalf of the Fracture-Related Infection (FRI) consensus group
Published: August 2019

Summary:
Fracture-related infection (FRI) remains a challenging complication that imposes a heavy burden on orthopaedic trauma patients. The surgical management eradicates the local infectious focus and if necessary facilitates bone healing. Treatment success is associated with debridement of all dead and poorly vascularized tissue. However, debridement is often associated with the formation of a dead space, which provides an ideal environment for bacteria and is a potential site for recurrent infection. Dead space management is therefore of critical importance. For this reason, the use of locally delivered antimicrobials has gained attention not only for local antimicrobial activity but also for dead space management. Local antimicrobial therapy has been widely studied in periprosthetic joint infection, without addressing the specific problems of FRI. Furthermore, the literature presents a wide array of methods and guidelines with respect to the use of local antimicrobials. The present review describes the scientific evidence related to dead space management with a focus on the currently available local antimicrobial strategies in the management of FRI.

Level of Evidence:
Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
Lycorine Induces Apoptosis and G1 Phase Arrest Through ROS/p38 MAPK Signaling Pathway in Human Osteosarcoma Cells In Vitro and In Vivo
Authors: Ning Lei , Wan Shuanglin , Jie Zhiwei , Xie Ziang , Li Xiang , Pan Xin , Wan Xinyu , Chen Wenxiang , Huang Hai , Wang Jiying , Qin An , Fan Shunwu , Zhao Xiangde 
Published: August 2019

Study Design.
Xenograft osteosarcoma mouse model.

Objective.
We determined the effect of lycorine on osteosarcoma.

Summary of Background Data.
Osteosarcoma is an aggressive malignant neoplasm, is most prevalent in teenagers and adults and current treatment approaches have reached a survival plateau and attempts to improve osteosarcoma prognosis have proven unsuccessful. Thus there is clear evidence that development of new agents with high efficacy and fewer side effects to provide better prognostic outcome is urgently needed.

Methods.
The toxicity, function and mechanism of lycorine (LY) on osteosarcoma were accessed in vitro by CCK-8 assay, flow cytometry, and western blotting and in vivo by the xenograft osteosarcoma mouse model.

Results.
In this study, we found that LY exhibited dose-dependent and time-dependent cytotoxic effects on human osteosarcoma cell-lines SJSA-1 and U2OS, inducing G1 phase cell cycle arrest and cellular death via apoptosis. Mechanistically, LY treatment elevated ROS generation that activates the p38 mitogen-activated protein kinases (MAPKs) and p53-dependent apoptotic program. Inhibition of ROS generation by NAC or p38 MAPK signaling by SB203580 attenuated the p53-mediated cell cycle arrest and apoptosis induced by LY. In vivo administration of LY markedly reduced tumor growth with little organ-related toxicity in a mouse xenograft model of osteosarcoma.

Conclusion.
Collectively, our data suggests that LY exhibit therapeutic potential for the treatment of osteosarcoma.

Level of Evidence: N/A
Percutaneous Unilateral Biportal Endoscopic Spine Surgery Using a 30-Degree Arthroscope in Patients With Severe Lumbar Spinal Stenosis
Authors: Kim Nackhwan , Jung Seok Bong 
Published: August 2019

Background:
Unilateral biportal endoscopic surgery (UBESS) for severe lumbar central canal stenosis (LCCS) remains challenging.

Objective:
To describe the use of UBESS with a 30-degree arthroscope in patients with severe LCCS.

Materials and Methods:
Working and viewing portals were created in each unilateral paravertebral area at the target interlaminar level. After ensuring the visual field with a 30-degree arthroscope, effective tissue removal was possible through safe access to the bilateral hypertrophic yellow ligament with minimal osteotomy. The authors evaluated 58 patients and analyzed the clinical outcomes using the visual analog scale, Macnab criteria, and self-predicted walking distance.

Results:
The visual analog scale scores for low back and leg pains decreased from 7.1 to 1.9 and from 7.9 to 1.6, respectively, at 18 months after the procedure. According to the Macnab criteria, “excellent,” “good,” and “fair” results were obtained in 51.7%, 41.4%, and 6.9% subjects, respectively. Before surgery, the subjects could walk a mean of 305.8±468.1 m. After surgery, 43.1% of the patients could walk for >1 hour, whereas the remaining patients could walk 1521.8±1831.1 m.

Conclusion:
UBESS using a 30-degree arthroscope can be an efficient and safe intervention in patients with severe LCCS.
Global and Regional Diagnostic Accuracy of Lung Ultrasound Compared to CT in Patients With Acute Respiratory Distress Syndrome*
Authors: Chiumello Davide , Umbrello Michele , Sferrazza Papa Giuseppe Francesco , Angileri Alessio , Gurgitano Martina , Formenti Paolo , Coppola Silvia , Froio Sara , Cammaroto Antonio , Carrafiello Gianpaolo 
Published: August 2019

Objectives:
Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound and CT scan.

Design:
A prospective, observational study.

Setting:
Intensive care and radiology departments of a University hospital.

Patients:
Thirty-two sedated, paralyzed acute respiratory distress syndrome patients (age 65 ± 14 yr, body mass index 25.9 ± 6.5 kg/m2, and Pao
2/Fio
2 139 ± 47).

Interventions:
Lung CT scan and lung ultrasound were performed at positive end-expiratory pressure 5 cm H2O. A standardized assessment of six regions per hemithorax was used; each region was classified for the presence of normal aeration, alveolar-interstitial syndrome, consolidation, and pleural effusion. Agreement between the two techniques was calculated, and diagnostic variables were assessed for lung ultrasound using lung CT as a reference.

Measurements and Main Results:
Global agreement between lung ultrasound and CT ranged from 0.640 (0.391–0.889) to 0.934 (0.605–1.000) and was on average 0.775 (0.577–0.973). The overall sensitivity and specificity of lung ultrasound ranged from 82.7% to 92.3% and from 90.2% to 98.6%, respectively. Similar results were found with regional analysis. The diagnostic accuracy of lung ultrasound was significantly higher when those patterns not reaching the pleural surface were excluded (area under the receiver operating characteristic curve: alveolar-interstitial syndrome 0.854 [0.821–0.887] vs 0.903 [0.852–0.954]; p = 0.049 and consolidation 0.851 [0.818–0.884] vs 0.896 [0.862–0.929]; p = 0.044).

Conclusions:
Lung ultrasound is a reproducible, sensitive, and specific tool, which allows for bedside detections of the morphologic patterns in acute respiratory distress syndrome. The presence of deep lung alterations may impact the diagnostic performance of this technique.
Epidemiology and Outcome of Critically Ill Pediatric Cancer and Hematopoietic Stem Cell Transplant Patients Requiring Continuous Renal Replacement Therapy: A Retrospective Nationwide Cohort Study
Authors: Raymakers-Janssen Paulien A. M. A. , Lilien Marc R. , Tibboel Dick , Kneyber Martin C. J. , Dijkstra Sandra , van Woensel Job B. M. , Lemson Joris , Cransberg Karlien , van den Heuvel-Eibrink Marry M. , Wösten-van Asperen Roelie M. 
Published: August 2019

Objective:
Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU.

Design:
A nationwide, multicenter, retrospective, observational study.

Setting:
Eight PICUs of a tertiary care hospitals in the Netherlands.

Patients:
Pediatric cancer and hematopoietic stem cell transplant patients (cancer and noncancer) who received continuous renal replacement therapy from January 2006 to July 2017 in the Netherlands.

Interventions:
None.

Measurement and Main Results:
Of 1,927 PICU admissions of pediatric cancer and hematopoietic stem cell transplant patients, 68 of 70 evaluable patients who received continuous renal replacement therapy were included. Raw PICU mortality was 11.2% (216/1,972 admissions). PICU mortality of patients requiring continuous renal replacement therapy was 54.4% (37/68 patients). Fluid overload (odds ratio, 1.08; 95% CI, 1.01–1.17) and need for inotropic support (odds ratio, 6.53; 95% CI, 1.86–23.08) at the start of continuous renal replacement therapy were associated with PICU mortality. Serum creatinine levels increased above 150% of baseline 3 days before the start of continuous renal replacement therapy. Urine production did not reach the critical limit of oliguria. In contrast, body weight (fluid overload) increased already 5 days prior to continuous renal replacement therapy initiation.

Conclusions:
PICU mortality of pediatric cancer and hematopoietic stem cell transplant patients requiring continuous renal replacement therapy is sadly high. Fluid overload at the initiation of continuous renal replacement therapy is the most important and earliest predictor of PICU mortality. Our results suggest that the most commonly used criteria of acute kidney injury, that is, serum creatinine and urine production, are not useful as a trigger to initiate continuous renal replacement therapy. This highlights the urgent need for prospective studies to generate recommendations for effective therapeutic interventions at an early phase in this specific patient population.
Window of Opportunity trials for biomarker discovery in breast cancer
Authors: Arnedos Monica , Roulleaux Dugage Matthieu , Perez-Garcia Jose , Cortes Javier 
Published: August 2019

Purpose of review
Window of Opportunity (WOO) studies have gain their place in current clinical and translational research in breast cancer patients. This review provides current information and future applications of this specific type of research.

Recent findings
So far, WOO trials in breast cancer patients have demonstrated their utility in breast cancer research as: first they allow administering a treatment for a short period of time to treatment-naïve patients whose tumors have not developed mechanisms of resistance or heterogeneity because of previous therapies. Second, it brings a unique opportunity for translational research providing easy access to tumor tissue in order to evaluate antitumor effect from initial biopsy and from surgical resection specimen. They provide the perfect scenario for biomarker discovery and validation in an efficient and timely manner and valuable information about drug pharmacodynamics. Several issues need to be contemplated when designing and performing this type of trials including choice of a biological surrogate endpoint of efficacy as standard clinical activity endpoints are not feasible.

Summary
Despite some limitations like the absence of information about secondary mechanisms of resistance, WOO trials represent an important support for drug development and biomarker discovery in breast cancer patients.