bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of cerebrospinal fluid-derived circular RNAs in lung adenocarcinoma patients with brain metastases
Authors: Wang Zhen , Yu Ruoying , Chen Xiaoxi , Bao Hua , Cao Ran , Li An-Na , Ou Qiuxiang , Tu Hai-Yan , Zhou Qing , Wu Xue , Lin Zhi-Bo , Wu Yi-Long 
Published: February 2022

AbstractBackgroundFree circular RNAs(circRNAs) escaping from primary lesion of cancer to brain are strictly regulated by blood–brain barrier and therefore cerebrospinal fluid (CSF) circRNAs have potential advantage in exploring biomarkers and mechanism of brain metastasis in lung cancer.MethodsWe collected paired cerebrospinal fluid, plasma and tumor tissues from 21 lung adenocarcinoma (ADC) patients with brain metastases (BM) and performed RNA sequencing.ResultsCompared to tumor tissue and plasma, circRNAs in CSF were characterized by lower number of spieces but higher abundance. Notably, CSF-circRNAs displayed high heterogeneity among different BM lung ADC patients. A total of 60 CSF-circRNAs was identified and associated with shorten overall survival. The circRNA-miRNA-mRNA network analysis revealed that the 60 CSF-circRNAs involved in cancer-associated pathways, and five of them showed strong association with WNT signaling pathway. Validation by RT-PCR of CSF and in vitro experiments of the five candidate circRNAs support their potential roles in cell proliferation and invasion.ConclusionsIn summary, our results depicted the heterogenous CSF-circRNAs profiles among BM lung ADC and implied that CSF-circRNAs may be promising prognosis-related biomarkers.
Macitentan attenuates cardiovascular remodelling in infant rats with chronic lung disease
Authors: Baumann Philipp , Greco Francesco , Wiegert Susanne , Wellmann Sven , Pellegrini Giovanni , Cannizzaro Vincenzo 
Published: February 2022

Abstract
Background
Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling.

Methods
In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO2) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed.

Results
FiO2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p < 0.001). Macitentan treatment significantly increased pulmonary vessel count (p = 0.004) and decreased right to left ventricular wall diameter ratios (p = 0.002). Endothelin-1 plasma concentrations were higher compared to placebo (p = 0.015). Alveolar number and size, α-smooth muscle actin, and the cardiomyocyte cross-sectional area remained unchanged (all p > 0.05).

Conclusion
The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease.
Number of antenatal care utilization and associated factors among pregnant women in Ethiopia: zero-inflated Poisson regression of 2019 intermediate Ethiopian Demography Health Survey
Authors: Arefaynie Mastewal , Kefale Bereket , Yalew Melaku , Adane Bezawit , Dewau Reta , Damtie Yitayish 
Published: February 2022

AbstractBackgroundThe frequency of antenatal care utilization enhances the effectiveness of the maternal health programs to maternal and child health. The aim of the study was to determine the number of antenatal care and associated factors in Ethiopia by using 2019 intermediate EDHS.MethodsSecondary data analysis was done on 2019 intermediate EDHS. A total of 3916.6 weighted pregnant women were included in the analysis. Zero-inflated Poisson regression analysis was done by Stata version 14.0. Incident rate ratio and odds ratio with a 95% confidence interval were used to show the strength and direction of the association.ResultAbout one thousand six hundred eighty eight (43.11%) women were attending four and more antenatal care during current pregnancy. Attending primary education (IRR = 1.115, 95% CI: 1.061, 1.172), secondary education (IRR = 1.211, 95% CI: 1.131, 1.297) and higher education (IRR = 1.274, 95% CI: 1.177, 1.378), reside in poorer household wealth index (IRR = 1.074, 95% CI: 1.01, 1.152), middle household wealth index (IRR = 1.095, 95% CI: 1.018, 1.178), rich household wealth index (IRR = 1.129, 95% CI: 1.05, 1.212) and richer household wealth index (IRR = 1.186, 95% CI: 1.089, 1.29) increases the number of antenatal care utilization. The frequency of antenatal care was less likely become zero among women attending primary (AOR = 0.434, 95% CI: 0.346, 0.545), secondary (AOR = 0.113, 95% CI: 0.053, 0.24), higher educational level (AOR = 0.052, 95% CI: 0.007, 0.367) in the inflated part.ConclusionThe number of antenatal care utilization is low in Ethiopia. Being rural, poorest household index, uneducated and single were factors associated with low number of antenatal care and not attending antenatal care at all. Improving educational coverage and wealth status of women is important to increase the coverage and frequency of antenatal care.
The molecular determinants of antigenic drift in a novel avian influenza A (H9N2) variant virus
Authors: Zheng Yiqing , Guo Yanna , Li Yingfei , Liang Bing , Sun Xiaoyuan , Li Shijia , Xia Huizhi , Ping Jihui 
Published: February 2022

AbstractBackgroundIn early 2020, a novel H9N2 AIV immune escape variant emerged in South China and rapidly spread throughout mainland China. The effectiveness of the current H9N2 vaccine is being challenged by emerging immune escape strains. Assessing key amino acid substitutions that contribute to antigenic drift and immune escape in the HA gene of circulating strains is critical for understanding virus evolution and in selecting more effective vaccine components.MethodsIn this study, a representative immune escape strain, A/chicken/Fujian/11/2020 (FJ/20), differed from current H9N2 vaccine strain, A/chicken/Anhui/LH99/2017 (AH/17) by 18 amino acids in the head domain in HA protein. To investigate the molecular determinants of antigenic drift of FJ/20, a panel of mutants were generated by reverse genetics including specific amino acids changes in the HA genes of FJ/20 and AH/17. The antigenic effect of the substitutions was evaluated by hemagglutination inhibition (HI) assay and antigenic cartography.ResultsFujian-like H9N2 viruses had changed antigenicity significantly, having mutated into an antigenically distinct sub-clade. Relative to the titers of the vaccine virus AH/17, the escape strain FJ/20 saw a 16-fold reduction in HI titer against antiserum elicited by AH/17. Our results showed that seven residue substitutions (D127S, G135D, N145T, R146Q, D179T, R182T and T183N) near the HA receptor binding sites were critical for converting the antigenicity of both AH/17 and FJ/20. Especially, the combined mutations 127D, 135G, 145N, and 146R could be a major factor of antigenic drift in the current immune escape variant FJ/20. The avian influenza A (H9N2) variant virus need further ongoing epidemiological surveillance.ConclusionsIn this study, we evaluated the relative contributions of different combinations of amino acid substitutions in the HA globular head domain of the immune escape strain FJ/20 and the vaccine strain AH/17. Our study provides more insights into the molecular mechanism of the antigenic drift of the H9N2 AIV immune escape strain. This work identified important markers for understanding H9N2 AIV evolution as well as for improving vaccine development and control strategies in poultry.
Prolonged culturing of iPSC-derived brain endothelial-like cells is associated with quiescence, downregulation of glycolysis, and resistance to disruption by an Alzheimer’s brain milieu
Authors: Williams Lindsey M. , Fujimoto Takashi , Weaver Riley R. , Logsdon Aric F. , Evitts Kira M. , Young Jessica E. , Banks William A. , Erickson Michelle A. 
Published: February 2022

Abstract
Background
Human induced pluripotent stem cell (hiPSC)-derived brain endothelial-like cells (iBECs) are a robust, scalable, and translatable model of the human blood–brain barrier (BBB). Prior works have shown that high transendothelial electrical resistance (TEER) persists in iBECs for at least 2 weeks, emphasizing the utility of the model for longer term studies. However, most studies evaluate iBECs within the first few days of subculture, and little is known about their proliferative state, which could influence their functions. In this study, we characterized iBEC proliferative state in relation to key BBB properties at early (2 days) and late (9 days) post-subculture time points.

Methods
hiPSCs were differentiated into iBECs using fully defined, serum-free medium. The proportion of proliferating cells was determined by BrdU assays. We evaluated TEER, expression of glycolysis enzymes and tight and adherens junction proteins (TJP and AJP), and glucose transporter-1 (GLUT1) function by immunoblotting, immunofluorescence, and quantifying radiolabeled tracer permeabilities. We also compared barrier disruption in response to TNF-α and conditioned medium (CM) from hiPSC-derived neurons harboring the Alzheimer’s disease (AD)-causing Swedish mutation (APPSwe/+).

Results
A significant decline in iBEC proliferation over time in culture was accompanied by adoption of a more quiescent endothelial metabolic state, indicated by downregulation of glycolysis-related proteins and upregulation GLUT1. Interestingly, upregulation of GLUT1 was associated with reduced glucose transport rates in more quiescent iBECs. We also found significant decreases in claudin-5 (CLDN5) and vascular endothelial-cadherin (VE-Cad) and a trend toward a decrease in platelet endothelial cell adhesion molecule-1 (PECAM-1), whereas zona occludens-1 (ZO-1) increased and occludin (OCLN) remained unchanged. Despite differences in TJP and AJP expression, there was no difference in mean TEER on day 2 vs. day 9. TNF-α induced disruption irrespective of iBEC proliferative state. Conversely, APPSwe/+ CM disrupted only proliferating iBEC monolayers.

Conclusion
iBECs can be used to study responses to disease-relevant stimuli in proliferating vs. more quiescent endothelial cell states, which may provide insight into BBB vulnerabilities in contexts of development, brain injury, and neurodegenerative disease.
k-Shape clustering for extracting macro-patterns in intracranial pressure signals
Authors: Martinez-Tejada Isabel , Riedel Casper Schwartz , Juhler Marianne , Andresen Morten , Wilhjelm Jens E. 
Published: February 2022

Abstract
Background
Intracranial pressure (ICP) monitoring is a core component of neurosurgical diagnostics. With the introduction of telemetric monitoring devices in the last years, ICP monitoring has become feasible in a broader clinical setting including monitoring during full mobilization and at home, where a greater diversity of ICP waveforms are present. The need for identification of these variations, the so-called macro-patterns lasting seconds to minutes—emerges as a potential tool for better understanding the physiological underpinnings of patient symptoms.

Methods
We introduce a new methodology that serves as a foundation for future automatic macro-pattern identification in the ICP signal to comprehensively understand the appearance and distribution of these macro-patterns in the ICP signal and their clinical significance. Specifically, we describe an algorithm based on k-Shape clustering to build a standard library of such macro-patterns.

Results
In total, seven macro-patterns were extracted from the ICP signals. This macro-pattern library may be used as a basis for the classification of new ICP variation distributions based on clinical disease entities.

Conclusions
We provide the starting point for future researchers to use a computational approach to characterize ICP recordings from a wide cohort of disorders.
Comparison of the distribution of lymph node metastases compared to healthy lymph nodes in breast cancer
Authors: Borm Kai J. , Ernst Lucia , Voppichler Julia , Oechsner Markus , Düsberg Mathias , Buschner Gabriel , Weber Wolfgang , Combs Stephanie E. , Duma Marciana N. 
Published: February 2022

Abstract
Background
Current literature lacks a comparison of lymph node metastases and non-pathological lymph nodes distribution in breast cancer patients. The aim of the current retrospective study was to generate a comprehensive atlas of the lymph node system.

Methods
143 breast cancer patients underwent F-18-FDG-PET/CT (PET/CT) imaging for staging purposes and were diagnosed with regional lymph node metastases. Based on the PET/CT data set a total of 326 lymph node metastases and 1826 non-pathological lymph nodes were detected and contoured manually in the patient collective. Using rigid and deformable registration algorithms all structures were transferred to a template planning CT of a standard patient. Subsequently, a 3D-atlas of the distribution of lymph node metastases and non-pathological lymph nodes were generated and compared to each other.

Results
Both, lymph node metastases and non-pathological lymph nodes, accumulated in certain areas (“hot-spots”) within the lymphatic drainage system. However large differences regarding the distribution patterns were detected: lymph node metastases hot spots occurred in close proximity to the subclavian vein in level I-III, whereas the non-pathological lymph nodes accumulated mostly (within a wider range) in level I. In level II and III lymph node metastases exceeded clearly the areas in which non-pathological lymph nodes occurred.

Conclusion
Lymph node metastases and non-pathological lymph node distribution within the lymph node system differ clearly. Based on our results, an individual adjustment of the CTV in order to include visible lymph nodes in level II and III should be discussed.
Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging
Authors: Lim Yu Jin , Song Changhoon , Kim Hak Jae ,   Korean Association for Lung Cancer,   Korea Central Cancer Registry
Published: February 2022

Abstract
Background
In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI.

Methods
Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI.

Results
Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up.

Conclusions
In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.
Utility of next-generation sequencing in genetic testing and counseling of disorders involving the musculoskeletal system—trends observed from a single genetic unit
Authors: Iyer Gayatri R. , Kumar Roshan , Poornima Subhadra , Kamireddy Aruna Priya , Juturu Keerthi Konda , Bhatnagar Lekhangda , Arora Srinka , Suresh Vaishnavi , Utage Prashant R. , Bailur Sarah , Pujar Akhilesh N. , Hasan Qurratulain 
Published: February 2022

Abstract
Background
Disorders involving the musculoskeletal system are often identified with short stature and a range of orthopedic problems. The clinical and genetic heterogeneity of these diseases along with several characteristic overlaps makes definitive diagnosis difficult for clinicians. Hence, using molecular testing in addition to conventional tests becomes essential for appropriate diagnosis and management.

Methods
Comprehensive clinical examination, detailed pretest and posttest counseling, molecular diagnosis with next-generation sequencing (NGS), genotype–phenotype correlation and Sanger sequencing for targeted variant analysis.

Results
This manuscript reports a molecular spectrum of variants in 34 orthopedic cases referred to a single genetic unit attached to a tertiary care hospital. The diagnostic yield of NGS-based tests coupled with genetic counseling and segregation analysis was 79% which included 7 novel variants. In about 53% (i.e. 18/34 cases), molecular testing outcome was actionable since 8 of the 18 underwent prenatal diagnosis, as they were either in their early gestation or had planned a pregnancy subsequent to molecular testing, while ten cases were premaritally/prenatally counseled for the families to take informed decisions as they were in the reproductive age.

Conclusions
The report highlights the importance of NGS-based tests even in a low resource setting as it helps patients, families and healthcare providers in reducing the economic, social and emotional burden of these disorders.
Patients’ access to rare neuromuscular disease therapies varies across US private insurers
Authors: Margaretos Nikoletta M. , Bawa Komal , Engmann Natalie J. , Chambers James D. 
Published: February 2022

Abstract
Background
The extent to which different US private insurers require their enrollees to meet the same coverage criteria before gaining access to treatment is unclear. Our objective was to scrutinize the patient access criteria imposed by US private insurers for a set of rare neuromuscular disease (NMD) disease-modifying therapies (DMTs).

Methods
We examined coverage policies issued by 17 large US private insurers for the following NMD treatments: nusinersen and onasemnogene abeparvovec for spinal muscular atrophy, edaravone for amyotrophic lateral sclerosis, and eteplirsen for Duchenne muscular dystrophy. We reviewed the plans’ coverage policies and identified the patient access criteria, including clinical prerequisites, step therapy protocols, and prescriber requirements. We compared the plans’ patient access criteria with the therapies’ US Food and Drug Administration (FDA)-labeled indications.

Results
The included insurers issued 65 coverage policies for the included therapies. Plans imposed coverage restrictions beyond the FDA-approved indications in 60 coverage policies; plans did not cover eteplirsen in five policies. No therapy was covered the same way by all insurers. Plans applied clinical criteria beyond the FDA label indication in 56 policies and step therapy protocols in three policies. Plans required that a neurologist prescribe the therapy in 37 policies, 22 of which required the neurologist to have expertise in the particular disease. Plans often required patients to suffer from symptoms of particular severity; e.g. for eteplirsen, plans differed in their 6-min walk test requirements; for edaravone, some plans required that patients had normal respiratory function, while others required only that patients did not require ventilation; for nusinersen and onasemnogene abeparvovec, plans differed in the number of SMN2 gene copies they required patients to have (SMN2 copy number is correlated with disease severity).

Conclusions
The evaluated large US private insurers tended to impose coverage restrictions beyond the FDA label indication for the included set of rare NMD DMTs. Plans rarely applied the same patient access criteria in their coverage policies for the same products. Inconsistent coverage criteria mean that patients with different insurers have variable access to the same therapies across insurers.
Effectiveness of non-specialist delivered psychological interventions on glycemic control and mental health problems in individuals with type 2 diabetes: a systematic review and meta-analysis
Authors: Oyedeji Ayodeji D. , Ullah Ibrahim , Weich Scott , Bentall Richard , Booth Andrew 
Published: February 2022

Abstract
Background
Typically, specialist mental health professionals deliver psychological interventions for individuals with poorly controlled type 2 diabetes mellitus (T2DM) and related mental health problems. However, such interventions are not generalizable to low- and middle-income countries, due to the dearth of trained mental health professionals. Individuals with little or no experience in the field of mental health (referred to as non-specialists) may have an important role to play in bridging this treatment gap.

Aim
To synthesise evidence for the effectiveness of non-specialist delivered psychological interventions on glycaemic control and mental health problems in people with T2DM.

Methods
Eight databases and reference lists of previous reviews were systematically searched for randomized controlled trials (RCTs). Outcome measures were glycated hemoglobin (HbA1c), diabetes distress and depression. The Cochrane Collaboration Risk of Bias Tool was used for risk of bias assessment. Data from the included studies were synthesized using narrative synthesis and random effects meta-analysis.

Results
16 RCTs were eligible for inclusion in the systematic review. The 11 studies that were pooled in the meta-analysis demonstrated a reduction in HbA1c in favor of non-specialist delivered psychological interventions when compared with control groups (pooled mean difference = − 0.13; 95% CI − 0.22 to − 0.04, p = 0.005) with high heterogeneity across studies (I2 = 71%, p = 0.0002). The beneficial effects of the interventions on diabetes distress and depression were not consistent across the different trials.

Conclusion
Non-specialist delivered psychological interventions may be effective in improving HbA1c. These interventions have some promising benefits on diabetes distress and depression, although the findings are inconclusive. More studies of non-specialist delivered psychological interventions are needed in low- and middle-income countries to provide more evidence of the potential effectiveness of these interventions for individuals living with T2DM.