bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed Tomography and Health Study of Using Erlotinib and Apatinib for Advanced Non-Small Cell Lung Cancer
Authors: Cao Hua , Yan Mao-Sheng , Zheng Tao , Kong Cheng , Deng Quan-Tong , Xu Rui-Lian
Published: March 2020

Purpose: Maintenance on TKIs is still of clinical value. VEGF inhibitors have shown promise for treating advanced NSCLC that is refractory to other treatments, though their duration of efficacy is often short. Few reports have documented combination therapeutic options for patients
with resistance to EGFR-TKIs using biostatistical analysis. Methods: We examine the case of experimental human subject with resistance to EGFRTKIs treated with erlotinib and apatinib, a novel TKI targeting vascular EGFR-2. This paper uses statistical methods of mean estimation to process
data. Many clinical trials were conducted to determine the therapeutic index of target therapy in the treatment of NSCLC. This allows us to learn more about the side effects of target therapy. We have also implemented Computed Tomography(CT) pre- and post-treatment to confirm our bioanalysis.
Results: Our experimental subject has this type of disease. After 12 months of treatment with erlotinib (150 mg/d), the patient showed slow progression. In the absence of a TM790 gene mutation, she received combination therapy with erlotinib and apatinib and the daily dose is 500 mg.
4 months later, we reduce the dose of apatinib to 250 mg/d because of grade 3 proteinuria, grade 2 hypertension, and diarrhea. After 19 months, her primary and metastatic lesions remained stable. The patient is in good condition except for occasional grade 1 diarrhea. Conclusion: The
combination erlotinib with apatinib may provide long-term progression-free survival in patients with mutant EGFR who have acquired resistance to EGFR-TKIs.
A Comparison of Each Sleep Stage Autonomic Nervous System Activity in Different Sleep Apnea Severity Levels
Authors: Chung Yung-Ming , Lou Shyh-Liang , Tsai Peng-Zhe , Wang Ming-Chen , Hang Liang-Wen
Published: March 2020

Sleep apnea has increasingly become a public health issue. To further elucidate the physiological changes in different sleep apnea severity levels, we analyzed the autonomic nervous system (ANS) activity in each sleep stage by heart rate variability (HRV), moreover, we clarified how
sleep apnea severity affects hypnogram and sleep quality. Subjects used in this study was obtained from PhysioNet, and the patient data were grouped into mild, moderate, and severe levels of sleep apnea according to apnea–hypopnea index (AHI). The electrocardiogram readings during the
period of free apnea were extracted and evaluated by HRV and represented to the sleep stages as follows: Awake, rapid eye movement (REM), and nonrapid eye movement (NREM) in different sleep apnea levels, respectively. The results indicated that the severe group (AHI ≥ 30 events per hour)
has higher sympathetic nervous system (SNS) activity and lower parasympathetic nervous system (PNS) activity in NREM. This elevates the ANS tone in NREM similar to Awake, making the ANS activity between NREM and Awake indistinguishable. Furthermore, we evaluated the effects both with (w/)
and without (w/o) apnea events in REM and NREM separately. Apnea events that occurred in REM (w/) were not different compared to those in REM (w/o). On the other hand, apnea events occurring in NREM (w/) activated SNS and suppressed PNS activity. This altered the ANS tone, which suggested
an early sleep stage transition to REM or Awake. This study indicates how sleep apnea severity correlates to the imbalance of ANS activity and it might disrupt the normal hypnogram. Consequently, from the ANS point of view that patients with severe apnea do not get appropriate rest from sleeping,
these patients need some medical interventions or treatment to prevent the development of chronic diseases.
Drought Monitoring in the Middle East and North Africa (MENA) Region: Participatory Engagement to Inform Early Warning Systems
Authors: Fragaszy Stephen Russell , Jedd Theresa , Wall Nicole , Knutson Cody , Fraj Makram Belhaj , Bergaoui Karim , Svoboda Mark , Hayes Michael , McDonnell Rachael
Published: March 2020

When drought hits water-scarce regions, there are significant repercussions for food and water security, as well as serious issues for the stability of broader social and environmental systems. To mitigate these effects, environmental monitoring and early warning systems aimed at detecting the onset of drought conditions can facilitate timely and effective responses from government and private sector stakeholders. This study uses multistage, participatory research methods across more than 135 interviews, focus groups, and workshops to assess extant climatic, agricultural, hydrological, and drought monitoring systems; key cross-sector drought impacts; and drought monitoring needs in four countries in the Middle East and North Africa (MENA) region: Morocco, Tunisia, Lebanon, and Jordan. This extensive study of user needs for drought monitoring across the MENA region is informing and shaping the ongoing development of drought early warning systems, a composite drought indicator (CDI), and wider drought management systems in each country. Overarching themes of drought monitoring needs include technical definitions of drought for policy purposes; information-sharing regimes and data-sharing platforms; ground-truthing of remotely sensed and modeled data; improved data quality in observation networks; and two-way engagement with farmers, organizations, and end-users of drought monitoring products. This research establishes a basis for informing enhanced drought monitoring and management in the countries, and the broad stakeholder engagement can help foster the emergence of effective environmental monitoring coalitions.
Variations in Precipitating Convective Feature Populations with ITCZ Width in the Pacific Ocean
Authors: Wodzicki Kyle R. , Rapp Anita D.
Published: March 2020

Many recent studies have aimed to better understand changes in the characteristics of the intertropical convergence zone (ITCZ), including ITCZ location, width, and precipitation intensity. However, very few studies have looked at the relationship between characteristics of convection within the ITCZ and ITCZ width. The present work uses information from an ITCZ identification database and Tropical Rainfall Measuring Mission (TRMM) precipitation feature (PF) database to quantify variations in convective characteristics across the ITCZ in the Pacific Ocean. Data are partitioned into wide and narrow ITCZ regimes to quantify differences in convection between different ITCZ regimes. Under the wide regime, convection deeper than 5 km, with areas greater than 100 km2, or stratiform rain fractions greater than 0.5 is, on average, 24%, 23%, and 12% more frequent, respectively. In the narrow regime, the signal is reversed, with average increases in the frequency of convection with heights below 5 km, areas less than 100 km2, or stratiform rain fractions less than 0.5 of 15%, 4%, and 6%, respectively. Positive and negative anomalies in columnar water vapor (CWV) and sea surface temperature (SST) across the ITCZ are observed in the wide and narrow regimes, respectively. There is also a strong positive correlation between an El Niño–Southern Oscillation (ENSO) index and ITCZ width anomalies, with wide (narrow) ITCZs occurring during warm (cold) phases of ENSO. This implies that the strengthening and weakening of the Walker circulation associated with ENSO may play a role in modulating the convective populations that contribute to the Pacific ITCZ width variations.
Perceptions of Mental Health Conditions in Criminal Cases: A Survey Study Involving Swedish Lay Judges
Authors: Sörman Karolina , Cox Jennifer , Rimsten Charlotte Eklund , Stanziani Marissa , Lernestedt Claes , Kristiansson Marianne , Howner Katarina
Published: March 2020

Perceptions of mental health conditions influence how individuals with psychiatric diagnoses are treated within the community, in the legal system, and at different institutions. We examined perceptions of mental health conditions among lay judges ( N = 643), working at district and appellate courts throughout Sweden. Participants read a web-based survey including a crime vignette in which the person charged with a crime was described as having schizophrenia ( n = 186), antisocial personality disorder (ASPD) with psychopathic traits ( n = 219), or intellectual disability ( n = 238). Participants’ perceptions of schizophrenia were largely in line with Swedish legislation regarding the medicolegal concept of severe mental disturbance (SMD). Findings were more varied for the other two conditions, however. Perceptions of individuals with ASPD with psychopathic traits were not consistent with the Swedish SMD legislation. The results highlight the complexity of legislation addressing mental illness and criminality.
When Tonight Is Not the Night: Sexual Rejection Behaviors and Satisfaction in Romantic Relationships
Authors: Kim James J. , Muise Amy , Sakaluk John K. , Rosen Natalie O. , Impett Emily A.
Published: March 2020

In most long-term romantic relationships, partners experience sexual conflicts of interest in which one partner declines the other partner’s sexual advances. We investigated the distinct ways people reject a partner’s advances (i.e., with reassuring, hostile, assertive, and deflecting behaviors) in Studies 1 and 2. Using cross-sectional (Study 3) and daily experience methods (Study 4), we investigated how perceptions of a partner’s rejection behaviors are linked with the rejected partner’s relationship and sexual satisfaction. We found robust evidence that perceived partner reassuring behaviors were associated with greater satisfaction, whereas perceived partner hostile behaviors were associated with lower levels of satisfaction. Perceived partner responsiveness was a key mechanism underlying the effects. Findings for assertive and deflecting behaviors were limited, but the effect of deflecting behaviors was qualified by levels of hostile behaviors for sexual satisfaction. Findings provide the first empirical investigation of the specific ways partners can decline one another’s advances to preserve satisfaction.
Modeling dynamic processes with panel data: An application of continuous time models to prevention research
Authors: Deboeck Pascal R. , Cole David A. , Preacher Kristopher J. , Forehand Rex , Compas Bruce E.
Published: March 2020

Many interventions are characterized by repeated observations on the same individuals (e.g., baseline, mid-intervention, two to three post-intervention observations), which offer the opportunity to consider differences in how individuals vary over time. Effective interventions may not be limited to changing means, but instead may also include changes to how variables affect each other over time. Continuous time models offer the opportunity to specify differing underlying processes for how individuals change from one time to the next, such as whether it is the level or change in a variable that is related to changes in an outcome of interest. After introducing continuous time models, we show how different processes can produce different expected covariance matrices. Thus, models representing differing underlying processes can be compared, even with a relatively small number of repeated observations. A substantive example comparing models that imply different underlying continuous time processes will be fit using panel data, with parameters reflecting differences in dynamics between control and intervention groups.
Optimal Relocation Strategy for Public Bike System with Selective Pick-Up and Delivery
Authors: Lee Euntak , Son Bongsoo , Han Youngjun
Published: March 2020

Public bike-sharing systems in many countries provide convenience as users can rent or return a bike freely at any station, but this may cause a demand–supply imbalance of the bike inventory for certain stations. To solve this issue, this research develops a bike-relocation strategy including both demand prediction and relocating route optimization. First, the bike demand is estimated by a least-square boosting algorithm, and numbers of relocating bikes are decided comparing bike inventories at each station. Second, based on predicted demand, the number of transporting vehicles and relocating routes are optimized by genetic algorithm. The strategy aims to minimize service vehicle numbers and relocating time with selective pick-up and delivery. The proposed strategy is evaluated by applying it to a real-world public bike system in Gangnam-district in Seoul, South Korea, and the results show the system can be improved significantly. Specifically, the bike demand satisfaction ratio increases from 0.87 to 1.00 in the morning peak hour, which shows that the proposed strategy better satisfies the bike demand. The uniformity of spare inventory is also improved, as a coefficient of variation decreases from 0.73 to 0.56. The reasonableness index, which reflects a sufficient number of bike stands, indicates 87% and 92% stations have a proper number of stands at morning peak hour and 24 h, respectively, with respect to predicted demand. The results show that the bike system with the proposed strategy has more reliability with stable inventory, and the operating cost could decrease with fewer relocating vehicles and optimized vehicle routes.
Interactive Video Authoring of Instruction for the Mentally Handicapped
Authors: Thorkildsen Ron , Hofmeister Alan
Published: March 2020

The article describes the development and field testing of a Microcomputer/Videodisc computer assisted instruction system for mentally handicapped students with primary emphasis on the authoring system, which is a set of computer programs designed to allow noncomputer programmers to write instructional programs for use with the Microcomputer/Videodisc system. The objectives of the authoring system were evaluated as part of the overall field tests. Evaluation results are reported along with details on the operational aspects of the authoring system.
Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron
Authors: Ma C-L , Li L , Yang G-M , Zhang Z-B , Zhao Y-N , Zeng X-F , Zhang D-X , Yu Y , Shi Z-J , Yan Q-W , Li L-H , Hong S-J
Published: March 2020

Objective:

Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism.

Methods:

The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot.

Results:

The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity ( p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins ( p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased ( p < 0.05).

Conclusion:

Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.
Leininger’s Ethnonursing Research Method: Historical Retrospective and Overview
Authors: Wehbe-Alamah Hiba , McFarland Marilyn
Published: March 2020

A historical overview and evolution of Leininger’s ethnonursing research method (ERM) is presented along with descriptions of the method’s purpose, goal, terminology, and enablers. A succinct guide to using ERM is provided to assist novice and seasoned researchers, as well as mentors and educators, in teaching, mentoring, advising, and/or conducting ethnonursing research studies. Criteria for evaluation of qualitative research studies, such as the ERM, are highlighted.
The Origins of Trust Asymmetry in International Relationships: An Institutional View
Authors: Wang Mengyang , Zhang Qiyuan , Zhou Kevin Zheng
Published: March 2020

Trust is key to relationship marketing. Although trust is bilateral, studies on the dispersion of trust among exchange parties remain limited, leaving the antecedents and outcomes of trust asymmetry largely underexplored. To fill the gaps, this study empirically examines the effects of different types of trust asymmetry on exchange performance and then investigates the institutional origins of trust asymmetry in international interfirm exchanges. Drawing on a survey of 134 international buyer–supplier relationships in China, the study finds that both calculative trust asymmetry and relational trust asymmetry have negative influences on exchange performance. The study also finds that formal institutional distance constrains calculative trust asymmetry and informal institutional distance increases relational trust asymmetry. Moreover, prior interactions and expectations of continuity significantly moderate the effects of formal and informal institutional distance. This study advances trust studies in cross-border settings.
Substance use, affective symptoms, and suicidal ideation among Russian, Somali, and Kurdish migrants in Finland
Authors: Salama Essi , Castaneda Anu E. , Suvisaari Jaana , Rask Shadia , Laatikainen Tiina , Niemelä Solja
Published: March 2020

Comorbidity of substance use with affective symptoms and suicidality has been well documented in the general population. However, population-based migrant studies about this association are scarce. We examined the association of affective symptoms and suicidal ideation with binge drinking, daily smoking, and lifetime cannabis use among Russian, Somali, and Kurdish migrants in comparison with the Finnish general population. Cross-sectional data from the Finnish Migrant Health and Wellbeing Study (Maamu, n = 1307) and comparison group data of the general Finnish population ( n = 860) from the Health 2011 Survey were used. Substance use included self-reported current binge drinking, daily smoking, and lifetime cannabis use. Affective symptoms and suicidal ideation were measured using the Hopkins Symptom Checklist-25 (HSCL-25). We performed multivariate logistic regression analyses, including age, gender, and additional socio-demographic and migration-related factors. Suicidal ideation (OR 2.4 95% CI 1.3–4.3) was associated with binge drinking among Kurds and lifetime cannabis use among Russians (OR 5.6, 95% CI 1.9–17.0) and Kurds (OR 5.5, 95% CI 1.9–15.6). Affective symptoms were associated with daily smoking (OR 1.6, 95% CI 1.02–2.6) and lifetime cannabis use (OR 6.1, 95% CI 2.6–14.5) among Kurdish migrants. Our results draw attention to the co-occurrence of suicidal ideation, affective symptoms, and substance use, especially among Kurdish migrants. These results highlight the variation of comorbidity of substance use and affective symptoms between the different populations. This implies that screening for substance use in mental healthcare cannot be neglected based on presumed habits of substance use.
Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS
Authors: Akimoto Hayato , Negishi Akio , Oshima Shinji , Wakiyama Haruna , Okita Mitsuyoshi , Horii Norimitsu , Inoue Naoko , Ohshima Shigeru , Kobayashi Daisuke
Published: March 2020

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.
BESI: Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment—Phases 1 and 2
Authors: Bankole Azziza , Anderson Martha S. , Homdee Nutta , Alam Ridwan , Lofton Ashley , Fyffe Nykesha , Goins Hilda , Newbold Temple , Smith-Jackson Tonya , Lach John
Published: March 2020

Background and Objectives:

Caregiver burden associated with dementia-related agitation is one of the commonest reasons a community-dwelling person with dementia (PWD) transitions to a care facility. Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment (BESI) is a system of body-worn and in-home sensors developed to provide continuous, noninvasive agitation assessment and environmental context monitoring to detect early signs of agitation and its environmental triggers.

Research Design and Methods:

This mixed methods, remote ethnographic study is explored in a 3-phase, multiyear plan. In Phase 1, we developed and refined the BESI system and completed usability studies. Validation of the system and the development of dyad-specific models of the relationship between agitation and the environment occurred in Phase 2.

Results:

Phases 1 and 2 results facilitated targeted changes in BESI, thus improving its overall usability for the final phase of the study, when real-time notifications and interventions will be implemented.

Conclusion:

Our results show a valid relationship between the presence of dementia related agitation and environmental factors and that persons with dementia and their caregivers prefer a home-based monitoring system like BESI.
HiCoACR: A reconfiguration decision-making model for reconfigurable security protocol based on hierarchically collaborative ant colony
Authors: Yi Zhuo , Liao Ying , Du Xuehui , Lu Xin , Cao Lifeng
Published: March 2020

Reconfigurable security protocols, with dynamic protocol configuration and flexible resource allocation, have become a state-of-the-art technology to guarantee the security of space-ground integrated network. However, reconfiguration decision-making for reconfigurable security protocols remains a major challenge in order to adapt to diverse secure service requirements and deploy higher security level but more complicated security strategies in nodes with limited resources and computing abilities. To handle this problem commendably, a hierarchically collaborative ant colony–based reconfiguration decision-making model called HiCoACR is proposed. This model, inspired by the ideas of hierarchical reinforcement learning and population collaboration, decomposes the reconfiguration decision-making problem into two sub-problems by introducing a two-level hierarchy ant colony consisting of the Explorer and the Worker. The Explorer controls directions of protocol reconfiguration and generates abstract scheduling sub-goals which are conveyed from the Worker. While the Worker schedules most suitable cryptogram resources for each sub-goal received and produces the optimal reconfiguration solution which is verified and re-optimized by a Lévy process–based stochastic gradient descent algorithm. Both the Explorer and the Worker adopt a modified version of ant colony algorithm to fulfill its targets, where a hierarchical pheromone is defined to reinforce positive behaviors of each ant colony. Experiment results suggest that HiCoACR outperforms baseline algorithms and possesses well model transferability.
Investigating the effects of ongoing-task bias on prospective memory
Authors: Strickland Luke , Loft Shayne , Heathcote Andrew
Published: March 2020

Event-based prospective memory (PM) refers to the cognitive processes required to perform a planned action upon encountering a future event. Event-based PM studies engage participants in an ongoing task (e.g., lexical decision-making) with an instruction to make an alternative PM response to certain items (e.g., items containing “tor”). The Prospective Memory Decision Control (PMDC) model, which provides a quantitative process account of ongoing-task and PM decisions, proposes that PM and ongoing-task processes compete in a race to threshold. We use PMDC to test whether, as proposed by the Delay Theory of PM costs, PM can be improved by biasing decision-making against a specific ongoing-task choice, so that the PM process is more likely to win the race. We manipulated bias in a lexical decision task with an accompanying PM intention. In one condition, a bias was induced against deciding items were words, and in another, a bias was induced against deciding items were non-words. The bias manipulation had little effect on PM accuracy but did affect the types of ongoing-task responses made on missed PM trials. PMDC fit the observed data well and verified that the bias manipulation had the intended effect on ongoing-task processes. Furthermore, although simulations from PMDC could produce an improvement in PM accuracy due to ongoing-task bias, this required implausible parameter values. These results illustrate the importance of understanding event-based PM in terms of a comprehensive model of the processes that interact to determine all aspects of task performance.
Theoretical studies of reaction mechanisms for potential reactions of HNCO with HO2 radicals
Authors: An Beibei , Huang Fuhua , Chen Ke , Jiang Jiamin , Xu Jianbin , Wang Li
Published: March 2020

The reaction mechanism of HNCO with HO2 radicals is investigated by means of the B3PW91/6-311+G(d,p) method to determine a more reasonable pathway. Four possible entrance patterns are designed; however, only three situations are finally confirmed. When HNCO and HO2 are close to each other, they first form an intermediate a2. Then, the terminal O atom in HO2 connects with the C atom of HNCO along with the H atom transferring from HO2 to the O atom of HNCO. After that the C–O bond ruptures again to form i. Finally, product P6(NCO + HOOH) is generated from i via H atom transfer. P6 is the most accessible product with the simplest steps and lowest barrier height. In addition, the energy of several of the routes is refined at the CCSD(T)/6-311+G(d,p) level based on the optimized geometries. Although there are some differences, the most favorable product is still P6. It is expected that this study would be helpful in further studies on HNCO and in understanding its reactions.
Inhibition of ornithine decarboxylase restores hypoxic pulmonary vasoconstriction in endotoxemic mice
Authors: Gebauer P.H. , Turzo M. , Lasitschka F. , Weigand M.A. , Busch C.J.
Published: March 2020

Endotoxemia impairs hypoxic pulmonary vasoconstriction which leads to systemic hypoxemia. This derogation is attributable to increased activity of nitric oxide synthase 2 and arginase metabolism. Gene expression analysis has shown increased expression of ornithine decarboxylase in lungs of endotoxemic mice, a downstream enzyme of arginase metabolism. The aim of this study was to investigate whether inhibition of ornithine decarboxylase increases hypoxic pulmonary vasoconstriction in lungs of endotoxemic mice. Mice received lipopolysaccharides or saline intraperitoneal, and hypoxic pulmonary vasoconstriction was measured using an isolated perfused mouse lung model. Additional mice with and without endotoxemia were pretreated with the ornithine decarboxylase‐inhibitor difluoromethylornithine before examination of hypoxic pulmonary vasoconstriction. Hypoxic pulmonary vasoconstriction was defined as the difference of pulmonary arterial pressure between normoxic and hypoxic ventilation. In addition, lung tissue was analyzed using real‐time quantitative polymerase chain reaction, Western blot and immunohistochemistry. Lipopolysaccharides caused an up‐regulation of ornithine decarboxylase mRNA level (2.73 ± 0.19‐fold increase, p < 0.05) as well as ornithine decarboxylase protein level (4.05 ± 0.37‐fold increase, p < 0.05). Endotoxemia attenuated hypoxic pulmonary vasoconstriction when compared with untreated control mice (26.3 ± 9.7% vs. 67.0 ± 17.5%). Difluoromethylornithine (20, 100, 500 mg kg−1 body weight intraperitoneal) restored hypoxic pulmonary vasoconstriction in lungs of endotoxemic mice in a dose‐dependent way (25.8 ± 9.9%, 57.3 ± 17.2%, 62.3 ± 12.4%) and decreased hypoxic pulmonary vasoconstriction in control mice (53.6 ± 13.6%, 40.0 ± 14.9%, 35.9 ± 12.4%). These results show that endotoxemia induces ornithine decarboxylase expression and suggest that ornithine decarboxylase contributes to the endotoxemia‐induced impairment of hypoxic pulmonary vasoconstriction. Inhibition of ornithine decarboxylase might be a target in the therapy of diseases with inflammation impaired hypoxic pulmonary vasoconstriction, like the sepsis‐associated acute respiratory distress syndrome (ARDS).
Why Black Adolescents Are Vulnerable at School and How Schools Can Provide Opportunities to Belong to Fix It
Authors: Gray DeLeon L. , Hope Elan C. , Byrd Christy M.
Published: March 2020

This article discusses factors contributing to the belonging vulnerability of Black adolescents as well as educational policy considerations for providing Black adolescents with opportunities to belong at school. Scholarship at the intersection of educational psychology and teacher education provides cultural interpretations for why and how Black adolescents are vulnerable to issues of belonging when educators are not in their corner, and when curricula do not reflect their cultures. Policy recommendations include (a) strategic investments in principal preparation, (b) information and human resources to develop culturally relevant learning opportunities, and (c) substantive roles for students as school and community leaders who can help address structural causes of belonging vulnerability among this population.
Cytomegalovirus Retinitis in a Patient Taking Tocilizumab: A Case Report
Authors: Ong Erin S. , Thompson John T.
Published: March 2020

Purpose:

This report discusses a case of cytomegalovirus (CMV) retinitis in a patient taking tocilizumab for maintenance and remission of giant cell arteritis (GCA).

Methods:

A case report is presented.

Results:

A 78-year-old African American woman with no significant past medical history and an ocular history of primary open-angle glaucoma presented to the retina clinic with vitritis in the right eye. Four months earlier, she had been diagnosed with biopsy-proven GCA and prescribed 30 mg of prednisone daily and 162 mg tocilizumab subcutaneously weekly. Diagnostic vitrectomy with polymerase chain reaction of the vitreous was positive for CMV. Her retinitis gradually resolved after 3 months of treatment with valganciclovir, with no recurrence 4 months after discontinuing the valganciclovir.

Conclusions:

Physicians should be aware of the potential to develop CMV retinitis in the setting of tocilizumab use for GCA treatment.
Reliability and reproducibility of the new AO/OTA 2018 classification system for proximal humeral fractures: a comparison of three different classification systems
Authors: Marongiu Giuseppe , Leinardi Lorenzo , Congia Stefano , Frigau Luca , Mola Francesco , Capone Antonio
Published: March 2020

Background

The classification systems for proximal humeral fractures routinely used in clinical practice include the Neer and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) 2007 systems. Currently used systems have low inter- and intraobserver reliability. In 2018, AO/OTA introduced a new classification system with the aim of simplifying the coding process, in which the Neer four-part classification was integrated into the fracture description. The aim of the present work is to assess the inter- and intraobserver agreement of the new AO/OTA 2018 compared with the Neer and AO/OTA 2007 classifications.

Materials and methods

A total of 116 radiographs of consecutive patients with proximal humeral fracture were selected and classified by three observers with different levels of experience. All three observers independently reviewed and classified the images according to the Neer, AO/OTA 2007, and new AO/OTA 2018 systems. To determine the intraobserver agreement, the observers reviewed the same set of radiographs after an interval of 8 weeks. The inter- and intraobserver agreement were determined through Cohen’s kappa coefficient analysis.

Results

The new AO/OTA 2018 classification showed substantial mean inter- (k = 0.67) and intraobserver (k = 0.75) agreement. These results are similar to the reliability observed for the Neer classification (interobserver, k = 0.67; intraobserver, k = 0.85) but better than those found for the AO/OTA 2007 system, which showed only moderate inter- (k = 0.57) and intraobserver (k = 0.58) agreement. The two more experienced observers showed better overall agreement, but no statistically significant difference was found. No differences were found between surgical experience and agreement regarding specific fracture types or groups.

Conclusions

The results showed that the Neer system still represents the more reliable and reproducible classification. However, the new AO/OTA 2018 classification improved the agreement among observers compared with the AO/OTA 2007 system, while still maintaining substantial descriptive power and simplifying the coding process. The universal modifiers and qualifications, despite their possible complexity, allowed a more comprehensive fracture definition without negatively affecting the reliability or reproducibility of the classification system.

Level of evidence: Level III, diagnostic studies
PD-L1 monoclonal antibody-decorated nanoliposomes loaded with Paclitaxel and P-gp transport inhibitor for the synergistic chemotherapy against multidrug resistant gastric cancers
Authors: Yu Jinling , Hu Fengli , Zhu Qiankun , Li Xiaodong , Ren Haiyang , Fan Shengjie , Qian Bo , Zhai Bo , Yang Dongdong
Published: March 2020

Multidrug resistance (MDR) based on ATP-dependent efflux transporters (p-glycoprotein (p-gp)) remains a major obstacle in successful chemotherapy treatment. Herein, we have investigated the potential of PD-L1 mAb-conjugated nanoliposome to serve as a targeted delivery platform for the co-delivery of paclitaxel (PTX) and p-gp specific transport inhibitor (TQD, tariquidar) in drug-resistant gastric cancers. Two drugs, PTX and TQD, were co-loaded in a single vehicle in a precise ratio to enhance the prospect of combination chemotherapeutic effect. Cellular uptake study indicated that PD-PTLP had higher internalization efficiency in PD-L1 receptor overexpressing SGC7901/ADR cells than non-targeted PTLP. Highest synergy was observed at a weight fraction of 1/0.5 (PTX/TQD) and the combination of PTX and TQD resulted in obvious synergistic effect compared to that of individual drugs alone. Our in vitro results showed that TQD was effective in reversing the multidrug resistance in SGC7901/ADR cells. The IC50 value of PD-PTLP was 0.76 μg/ml compared to 6.58 μg/ml and 7.64 μg/ml for PTX and TQD, respectively. PD-TPLP triggered significantly higher levels of reactive oxygen species (ROS) and cell apoptosis compared to that of free PTX or TQD. Furthermore, the in vivo antitumor study showed that the combination chemotherapy of PD-PTLP displayed a significant inhibition of tumor burden of drug-resistant xenograft tumors with significantly higher terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Furthermore, free PTX resulted in significant increase in the levels of AST and ALT while PD-PTLP insignificantly different compared to that of control indicating the safety index. Overall, we believe that combination of anticancer drug with a p-gp inhibitor could provide a potential direction toward the treatment of drug-resistant gastric tumors.
A machine learning approach on multiscale texture analysis for breast microcalcification diagnosis
Authors: Fanizzi Annarita , Basile Teresa M. A. , Losurdo Liliana , Bellotti Roberto , Bottigli Ubaldo , Dentamaro Rosalba , Didonna Vittorio , Fausto Alfonso , Massafra Raffaella , Moschetta Marco , Popescu Ondina , Tamborra Pasquale , Tangaro Sabina , La Forgia Daniele
Published: March 2020

Background

Screening programs use mammography as primary diagnostic tool for detecting breast cancer at an early stage. The diagnosis of some lesions, such as microcalcifications, is still difficult today for radiologists. In this paper, we proposed an automatic binary model for discriminating tissue in digital mammograms, as support tool for the radiologists. In particular, we compared the contribution of different methods on the feature selection process in terms of the learning performances and selected features.

Results

For each ROI, we extracted textural features on Haar wavelet decompositions and also interest points and corners detected by using Speeded Up Robust Feature (SURF) and Minimum Eigenvalue Algorithm (MinEigenAlg). Then a Random Forest binary classifier is trained on a subset of a sub-set features selected by two different kinds of feature selection techniques, such as filter and embedded methods. We tested the proposed model on 260 ROIs extracted from digital mammograms of the BCDR public database. The best prediction performance for the normal/abnormal and benign/malignant problems reaches a median AUC value of 98.16% and 92.08%, and an accuracy of 97.31% and 88.46%, respectively. The experimental result was comparable with related work performance.

Conclusions

The best performing result obtained with embedded method is more parsimonious than the filter one. The SURF and MinEigen algorithms provide a strong informative content useful for the characterization of microcalcification clusters.
Network hub-node prioritization of gene regulation with intra-network association
Authors: Chang Hung-Ching , Chu Chiao-Pei , Lin Shu-Ju , Hsiao Chuhsing Kate
Published: March 2020

Background

To identify and prioritize the influential hub genes in a gene-set or biological pathway, most analyses rely on calculation of marginal effects or tests of statistical significance. These procedures may be inappropriate since hub nodes are common connection points and therefore may interact with other nodes more often than non-hub nodes do. Such dependence among gene nodes can be conjectured based on the topology of the pathway network or the correlation between them.

Results

Here we develop a pathway activity score incorporating the marginal (local) effects of gene nodes as well as intra-network affinity measures. This score summarizes the expression levels in a gene-set/pathway for each sample, with weights on local and network information, respectively. The score is next used to examine the impact of each node through a leave-one-out evaluation. To illustrate the procedure, two cancer studies, one involving RNA-Seq from breast cancer patients with high-grade ductal carcinoma in situ and one microarray expression data from ovarian cancer patients, are used to assess the performance of the procedure, and to compare with existing methods, both ones that do and do not take into consideration correlation and network information. The hub nodes identified by the proposed procedure in the two cancer studies are known influential genes; some have been included in standard treatments and some are currently considered in clinical trials for target therapy. The results from simulation studies show that when marginal effects are mild or weak, the proposed procedure can still identify causal nodes, whereas methods relying only on marginal effect size cannot.

Conclusions

The NetworkHub procedure proposed in this research can effectively utilize the network information in combination with local effects derived from marker values, and provide a useful and complementary list of recommendations for prioritizing causal hubs.
MHiC, an integrated user-friendly tool for the identification and visualization of significant interactions in Hi-C data
Authors: Khakmardan Saman , Rezvani Mohsen , Pouyan Ali Akbar , Fateh Mansoor , Alinejad-Rokny Hamid
Published: March 2020

Background

Hi-C is a molecular biology technique to understand the genome spatial structure. However, data obtained from Hi-C experiments is biased. Therefore, several methods have been developed to model Hi-C data and identify significant interactions. Each method receives its own Hi-C data structure and only work on specific operating systems.

Results

We introduce MHiC (Multi-function Hi-C data analysis tool), a tool to identify and visualize statistically signifiant interactions from Hi-C data. The MHiC tool (i) works on different operating systems, (ii) accepts various Hi-C data structures from different Hi-C analysis tools such as HiCUP or HiC-Pro, (iii) identify significant Hi-C interactions with GOTHiC, HiCNorm and Fit-Hi-C methods and (iv) visualizes interactions in Arc or Heatmap diagram. MHiC is an open-source tool which is freely available for download on https://github.com/MHi-C.

Conclusions

MHiC is an integrated tool for the analysis of high-throughput chromosome conformation capture (Hi-C) data.
Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis
Authors: Villa Gianluca , Amass Timothy , Giua Rosa , Lanini Iacopo , Chelazzi Cosimo , Tofani Lorenzo , McFadden Rory , De Gaudio A. Raffaele , OMahony Sean , Levy Mitchell M. , Romagnoli Stefano
Published: March 2020

Background

The “END-of-Life ScorING-System” (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients.

Materials and methods

Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient’s ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis.

Results

Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort.

Conclusions

ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care.

Trial registration

Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.
Diagnostic accuracy and utility of three dengue diagnostic tests for the diagnosis of acute dengue infection in Malaysia
Authors: Chong Zhuo Lin , Sekaran Shamala Devi , Soe Hui Jen , Peramalah Devi , Rampal Sanjay , Ng Chiu-Wan
Published: March 2020

Background

Dengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute - a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo - a commercially available RDT, and SD Dengue NS1 Ag enzyme-linked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection.

Methods

This prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12.

Results

The sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6–68.7) and 95.0% (95%CI 91.7–97.3), versus 66.5% (95%CI 60.0–72.6) and 95.4% (95%CI 92.1–97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7–59.1) and 97.7% (95%CI 95.1–99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8–87.1) with corresponding decrease in specificity to 87.4% (95%CI 82.8–91.2). Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0–29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% (95%CI 11.4–18.6) if SD Bioline NS1/IgM/IgG combo was negative.

Conclusions

The performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies.