bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arenobufagin Inhibits the Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin Pathway and Induces Apoptosis and Autophagy in Pancreatic Cancer Cells
Authors: Wei Xiaolu , Yang Jian , Mao Yingqiu , Zhao Haiyu , Si Nan , Wang Hongjie , Bian Baolin 
Published: February 2020

Objective
The aim of the study was to investigate the effects of arenobufagin on pancreatic carcinoma in vitro and in vivo and its molecular mechanism.

Methods
The proliferation of pancreatic cancer cells was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Transmission electron microscopy was used to observe the formation of autophagic vacuoles after arenobufagin treatment. Hoechst 33258 and monodansylcadaverine fluorescence staining were performed to evaluate cell apoptosis and autophagy. Annexin V–fluorescein isothiocyanate/propidium iodide double-staining and JC-1 staining assays were used to evaluate apoptosis-related changes. Reverse-transcription polymerase chain reaction and western blotting were carried out to examine the expression of apoptosis- and autophagy-related markers after arenobufagin treatment. A tumor xenograft nude mouse model was established to evaluate arenobufagin efficacy in vivo.

Results
Arenobufagin effectively inhibited the proliferation of SW1990 and BxPC3 cells and induced cell arrest, apoptosis, and autophagy. Arenobufagin upregulated the expression of apoptotic- and autophagy-related proteins while downregulated the expression of phosphatidylinositol 3-kinase family proteins. Furthermore, arenobufagin also exerted inhibitory effects on tumor growth in xenograft nude mice.

Conclusions
Arenobufagin inhibits tumor growth in vivo and in vitro. The mechanism underlying arenobufagin action may involve induction of autophagy and apoptosis through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway.
Real-World Dosing Patterns and Outcomes of Patients With Metastatic Pancreatic Cancer Treated With a Liposomal Irinotecan Regimen in the United States
Authors: Barzi Afsaneh , Miksad Rebecca , Surinach Andy , Corvino Frank A. , Wang Siqi , Torres Aracelis Z. , Mamlouk Khalid , Pulgar Sonia , Valderrama Adriana , Bekaii-Saab Tanios , Ahn Daniel 
Published: February 2020

Objectives
Liposomal irinotecan (nal-IRI) is a topoisomerase inhibitor proven to improve survival in metastatic pancreatic cancer (mPC). This study describes real-world characteristics of patients treated with nal-IRI for mPC.

Methods
Patients 18 years or older diagnosed with stage IV mPC and treated with nal-IRI were selected retrospectively from a deidentified electronic health record database of more than 2 million US cancer patients. Demographics, clinical and dosing characteristics, and treatment outcomes were collected.

Results
Of 257 total patients, 145 (57%) received nal-IRI as first- or second-line therapy. Median nal-IRI treatment duration was 51 days, longer when nal-IRI was used as first/second versus as third-line therapy or later (62 vs 44.5 days). Seventy patients (27.2%) experienced dose modification. Median time to treatment discontinuation was 2.3 versus 1.6 months for first-/second- versus third-line therapy or later, respectively. Median overall survival from nal-IRI initiation was 5.6 versus 4.1 months for first-/second- versus third-line therapy or later, respectively. Prior irinotecan treatment, baseline serum albumin less than 40 g/L, and baseline neutrophil-to-lymphocyte ratio greater than 5 were associated with reduced overall survival.

Conclusions
This is the first large US study of real-world US mPC patients treated with nal-IRI. These results, comparable to the NAPOLI-1 trial, can help inform future studies and the efficacy of nal-IRI in mPC therapy.
Glucose-Dependent FOXM1 Promotes Epithelial-to-Mesenchymal Transition Via Cellular Metabolism and Targeting Snail in Human Pancreatic Cancer
Authors: Kyuno Takuro , Kohno Takayuki , Konno Takumi , Yamaguchi Hiroshi , Kyuno Daisuke , Imamura Masafumi , Kimura Yasutoshi , Kojima Takashi , Takemasa Ichiro 
Published: February 2020

Objectives
Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism.

Methods
We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells.

Results
Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition–modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1.

Conclusions
Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.
Mitigating Risks of Swallowed Button Batteries
Authors: Lerner Diana G. , Brumbaugh David , Lightdale Jenifer R. , Jatana Kris R. , Jacobs Ian N. , Mamula Petar 
Published: February 2020

ABSTRACTDespite ongoing efforts of the national Button Battery Task Force (BBTF), cases of major morbidity and mortality continue to be reported at a higher rate after ingestion of higher voltage and larger button batteries. Initiation of sucralfate or honey shortly after some button battery ingestions is crucial to prevent further injury while awaiting emergent removal. Endoscopic acetic acid irrigation post removal of button battery may halt deeper injury. Gastroenterologists need to be aware of the updates to the National Capital Poison Center algorithm for button battery ingestion.
Predictors of In-Hospital Mortality in Thrombotic Thrombocytopenic Purpura in Children in the United States: A Population Analysis
Authors: Umapathi Krishna Kishore , Thavamani Aravind , Puliyel Mammen 
Published: February 2020

Background:
Despite proven efficacy and increased availability of therapeutic plasma exchange, thrombotic thrombocytopenic purpura (TTP) is associated with significant morbidity and mortality.

Study Design and Methods:
This study utilized the Kids’ Inpatient Database and National Inpatient Sample (2003 to 2016) to study predictors of in-hospital mortality in hospitalized TTP patients. Adjusted odds ratios of death with various putative risk factors were calculated using multiple regression analysis.

Results:
Among 1568 hospitalizations with TTP as primary admission diagnosis who underwent therapeutic plasma exchange, 69 deaths were identified (all-cause mortality, 0.04%; median time-to-death, 6 wk). Overall, hospitalizations rates were fairly similar across the study period. The overall incidence of TTP related hospitalizations is 1.51 per 100,000 hospitalizations. A total of 69 deaths were reported with an all-cause in-hospital mortality rate of 0.04% (69/1568). The median time-to-death was 6 weeks. The majority of deaths occurred in age 16 to 20 years (58%), females (56.5%), and African American (42.9%) as shown in Table 2. Mean age for nonsurvivors was 14 years and the mean age of 15 years for survivors (P=0.01). Younger age, male sex, African-American ethnicity, malignancy, sepsis, acute kidney injury, platelet transfusion was significantly associated with mortality in patients with TTP.

Conclusions:
Early and targeted therapy for high risk individuals should be used to guide management of TTP patients for improved survival outcomes.
Liver Stiffness Measurement by Vibration Controlled Transient Elastography Does Not Correlate to Hepatic Iron Overload in Children With Sickle Cell Disease
Authors: Costa Peter , Rudolph Bryan , Kogan-Liberman Debora , Manwani Deepa , Silver Ellen J. , Ovchinsky Nadia 
Published: February 2020

Background:
Children with sickle cell disease (SCD) are at risk of liver injury because of sickle cell hepatopathy and iron overload from chronic transfusions (CT). The authors examine the association between iron overload and liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE), which has been shown to correlate with fibrosis.

Methods:
Patients 21 years of age and less with SCD had VCTE performed; those who received CT underwent magnetic resonance imaging T2* for iron quantification.

Results:
The authors enrolled 42 patients, 17 (40%) of whom received CT. There was no difference in LSM between patients who underwent CT (5.5±1.5 kPa) and those who did not (5.2±2.3 kPa) (P=0.923). There was no correlation between iron quantification and LSM (r=−0.077, P=0.769). However, children 12 years of age and older had abnormal LSM when compared with a reference range (P=0.013).

Conclusion:
VCTE is a noninvasive technology that is feasible in children with SCD. LSM values were elevated in older children but did not correlate with iron overload, suggesting that fibrosis may not be affected by iron overload alone. Though additional data are needed, LSM may be a useful test for the progression of liver disease in SCD regardless of iron burden.
The Adverse Impact of Thalassemia Major on Adolescents’ Oral Health-related Quality of Life
Authors: Ebeid Fatma S.E. , Khan Nisreen I.H. 
Published: February 2020

Background:
Adolescents with beta-thalassemia major (βTM) had unfavorable quality of life (QOL).

Objectives:
To assess oral health status of adolescents with βTM and its impact on their oral health-related QOL (OHRQoL).

Subjects and Methods:
Forty adolescents with βTM were recruited and compared with 40 age-matched and sex-matched healthy adolescents. Intraoral examination including dental caries assessment, oral hygiene index simplified (OHI-S), and Angle classification were performed. OHRQoL questionnaires were filled-out using child perception questionnaire-short form16.

Results:
Although the majority of adolescents with βTM had dental problems and convinced by their need for dental treatment, nearly half of them never brushed their teeth nor visited dental office. Patients showed higher frequency of class II malocclusion (P=0.017) and higher percentage of poor simplified debris index (DI-S) and OHI-S grade (P=0.008, 0.037, respectively). The median of DI-S and OHI-S were significantly higher in adolescents with βTM (P=0.009, 0.037, respectively). Adolescents with βTM had worse emotional well-being total score (P=0.049) than controls. Patients with poor oral hygiene had the worse total OHRQoL score (P=0.03). The total OHRQoL score showed significant positive correlation with oral hygiene; DI-S, calculus index-S, and OHI-S (P=0.028, 0.038, and 0.045, respectively).

Conclusion:
βTM had a negative impact on the emotional well-being aspect.
Characteristics of Blood Transfusion During Induction Remission in Children With Acute Lymphoblastic Leukemia: A Single-Center Retrospective Investigation
Authors: Sun Jun-Bo , Lu Ying-Yu , Huang Ling-Ling , Yu Qian-Qian , Tu Song-Ji , Xie Zhi-Wei 
Published: February 2020

Objective:To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission.Subjects and Methods:By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed.Results:One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day.Conclusions:Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.
Trajectories of Self-reported Physical Functioning and Symptoms in Lung Cancer Survivors
Authors: Medysky Mary E. , Dieckmann Nathan F. , Winters-Stone Kerri M. , Sullivan Donald R. , Lyons Karen S. 
Published: February 2020

Background
Lung cancer survivors are at risk of accelerated declines in physical functioning attributed to cancer treatment. However, it is unknown whether patients experience the same rate of functional decline and how symptoms may contribute to different trajectories.

Objectives
The aims of this study were to identify interindividual differences in the pattern and rate of change in self-reported functioning in lung cancer survivors and examine whether and how symptoms are related to physical functioning over time.

Methods
This was a secondary data analysis in 72 lung cancer survivors. Multilevel modeling was used to estimate trajectories of self-reported physical functioning over 1 year and assess the relation between functioning, fatigue, depressive symptoms, and pain severity across time.

Results
Within the sample, average physical functioning did not significantly decrease (coefficient, −0.46; 95% confidence interval [CI] = −2.85 to 0.94) over time. However, among individual lung cancer survivors, baseline physical functioning varied significantly (SD, 20.76; 95% CI, 16.84–25.59) and changed at significantly different rates over 1 year (SD, 3.50; 95% CI, 2.13–5.68). Fatigue, assessed over 1 year, was the only significant symptom predictor of physical functioning changes over time (coefficient = 1.03; 95% CI, 0.79–1.27).

Conclusions
In this sample of lung cancer survivors, not all survivors experienced the same rate of self-reported functional decline and those with lower levels of fatigue reported better physical functioning.

Implications for Practice
Nurses should recognize that some lung cancer survivors may have faster rates of functional declines than others, which may be related to fatigue severity. Early identification and management of fatigue could help avoid or delay future disability.
Symptom Clusters Change Over Time in Patients With Lung Cancer During Perichemotherapy
Authors: Li Nannan , Wu Jing , Zhou Jie , Wu Caiqin , Dong Lu , Fan Wenjing , Zhang Jinyu 
Published: February 2020

BackgroundLung cancer has become the leading cause of cancer-related deaths in China, and patients often experience multiple symptoms and substantial discomfort. Understanding and managing concurrent symptoms of patients with lung cancer are crucial during perichemotherapy.ObjectiveTo determine the types and components of symptom clusters according to the severity dimension and to understand how they change over time during perichemotherapy in a homogeneous population of patients with lung cancer.MethodsPatients were recruited using convenience sampling. The Chinese version of the MD Anderson Symptom Inventory and the revised lung cancer module were used to measure multiple symptoms at the following 3 separate points: 2 weeks before chemotherapy (T1), chemotherapy cycle 1 (T2), and chemotherapy cycle 4 (T3). Symptom clusters were identified by exploratory factor analysis.ResultsA total of 144 patients with non–small cell lung cancer participated in the study. Six symptom clusters were identified at the 3 time points. Among the 6 symptom clusters, 3 symptom clusters remained stable at all time points, and differences were found in symptom clusters before and after chemotherapy.ConclusionsSymptom clusters can change during perichemotherapy, showing some stability and differences over time.Implications for PracticeAn improved understanding of symptom cluster trajectories in patients with lung cancer may facilitate effective assessment, prevention, and management of multiple concurrent symptoms. These findings will help clinicians to develop predictive interventions and reduce the symptom burden of patients undergoing chemotherapy.
Addressing Challenges to Coordinating the Implementation of Place-Based Chronic Disease Prevention Interventions in Los Angeles
Authors: Green Gabrielle , DeFosset Amelia R. , Gase Lauren N. , Kuo Tony 
Published: February 2020

Context:
Chronic disease prevention initiatives have traditionally been structured to address a single disease, potentially limiting the scope of health impacts. In the past decade, initiatives have increasingly adopted a coordinated approach, in which multiple interventions are intended to work synergistically—often in a bounded geographic area—to address interrelated risk factors and diseases. However, despite increased interest in this coordinated approach, few examples exist of how coordination has been operationalized in local public health practice.

Implementation:
In 2014, the Los Angeles County Department of Public Health launched the 4-year Chronic Disease Prevention Strategy (CDPS). Through CDPS, the Los Angeles County Department of Public Health implemented a range of environmental, lifestyle change, and health system interventions intended to collectively reduce chronic disease among adults in Los Angeles, with concentrated implementation occurring in 1 high-need neighborhood.

Evaluation:
This case study examined the activities undertaken to coordinate across CDPS interventions and documented challenges to these efforts. Data were collected via a document review of programmatic materials and structured conversations with staff leading implementation of CDPS interventions.

Results:
Document review and structured conversations with staff identified 3 primary coordination activities: (1) collaborating on outreach materials to unify messaging, (2) developing a network of common partners, and (3) investing in shared data collection. Operational challenges identified were disparate short-term objectives across interventions, minimal alignment between clinical practice and CDPS goals, restrictions around bidirectional referrals between organizations, and limited bandwidth among new partners to engage with multiple CDPS interventions. Contextual challenges identified were competing social and political issues, and geographic fluidity regarding where community members sought health resources.

Conclusion:
Developing an initiative-specific coordination plan prior to implementation may help reduce challenges to coordination. Modifications in how health initiatives are funded and structured may be needed: greater flexibility in how funding is administered, and the inclusion of coordination-specific metrics, may enable more robust coordination.
Using the Collaborative Requirements Development Methodology to Build Laboratory Capacity for Timely Diagnosis During the Zika Epidemic in Puerto Rico
Authors: Rembert Juneka H. , Zometa Carlos S. , O'Carroll Patrick W. , Licier Anabelle L. , McPhillips-Tangum Carol , Hale Piper M. 
Published: February 2020

Introduction:
In 2016, Puerto Rico became the focal point of the Zika epidemic, with more than 36 000 laboratory-confirmed cases before August. The Puerto Rico Department of Health (PRDH) responded by providing tests to symptomatic and asymptomatic pregnant women. The increased demand for Zika testing placed unprecedented strain on the laboratory capacity and information management processes used within the PRDH. The PRDH recognized the need to have an updated informatics system that securely manages, stores, and transmits digital data. The Centers for Disease Control and Prevention funded the Public Health Informatics Institute to collaborate with the PRDH to assess and improve the informatics capability to respond to the ongoing Zika virus transmission in Puerto Rico.

Approach:
The team employed a 4-component approach to assess the informatics system and improve the information management processes for laboratory testing and reporting of arboviral diseases (Zika, chikungunya, and dengue). The method consisted of a (1) needs assessment, (2) business process analysis and requirements definition, (3) vendor analysis, and (4) solution implementation.

Results:
The needs assessment determined that the PRDH's procedures for arbovirus testing and reporting were highly complex and paper-based and thus did not maximize the use of existing technology. The solution was to build a Web portal. The business process analysis yielded information to create a map of the flow of specimens, an arbovirus context diagram, and more than 200 requirements. The requirements identified in this process guided the design and creation of the Web portal.

Discussion:
This report describes the process to build a Web portal to enhance laboratory testing and electronic reporting of Zika cases during the 2016 epidemic in Puerto Rico. We demonstrate the utility of applying the Collaborative Requirements Development Methodology, a proven informatics method, to the development of a Web portal for managing arboviruses in a health department.
Exploring Reimbursement Options for the National Diabetes Prevention Program: Lessons Learned From a Pilot Project in Los Angeles, 2014-2018
Authors: Mosst Jennifer Torres , DeFosset Amelia , Sivashanmugam Megala , Kuo Tony 
Published: February 2020

Context:
Although Medicare and several state Medicaid programs are beginning to cover the cost of delivering the National Diabetes Prevention Program (National DPP), little is known about the logistical challenges to establishing reimbursement options for these services.

Objective:
To describe Los Angeles' experience working with payers to identify and establish reimbursement pathways for National DPP providers.

Design:
A case study was conducted to identify regional options for covering the costs of the National DPP.

Setting:
Los Angeles.

Participants:
A managed care organization along with selected National DPP providers (those that provide in-person and/or online services) participated in this regional pilot project.

Intervention:
The Los Angeles County Department of Public Health explored and prototyped reimbursement options for the National DPP, using input from and participation by target health plans (payers) and program providers.

Main Outcome Measure:
The establishment of a regional reimbursement approach for the National DPP.

Results:
Pilot project participants weighed the pros and cons of billing (Medicare/Medicaid)/reimbursing for program services directly, ultimately choosing to go with a third-party integrator that worked with payers to handle the administrative process of reimbursing program providers for their services. The integrator negotiated and obtained reimbursements on the behalf of the National DPP providers.

Conclusions:
Lessons from this case study suggest an emerging need to build further capacity among National DPP providers, as they are often community-based organizations that are not equipped to bill Medicare/Medicaid directly for services. A third-party integrator represents a viable approach for addressing this logistical issue.