bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women
Authors: Sun Wei , Qin Xueyun , Zhou Jing , Xu Mingjing , Lyu Zhangyan , Li Xin , Zhang Kai , Dai Min , Li Ni , Hang Dong 
Published: July 2020

Abstract
Background
Although human papillomavirus (HPV) infection has been regarded as the cause of cervical cancer in over 99% of cases, only a small fraction of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains undetermined.

Methods
The current study included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to compute odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.

Results
HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.

Conclusions
In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.
Pharmacovigilance in healthcare education: students’ knowledge, attitude and perception: a cross-sectional study in Saudi Arabia
Authors: Alwhaibi Monira , Alhindi Ghaida , Alshamrani Majd , Essa Maryam Bin , A. Al Aloola Noha , Alhawassi Tariq M. 
Published: July 2020

Abstract
Background
Medication safety and pharmacovigilance (PV) remains as an important discipline worldwide. However, there is a significant lack of knowledge of PV and adverse drug reaction (ADR) reporting among students in the healthcare field. Thus, this study is aimed to measure knowledge, attitude, and perceptions and compares it between healthcare students (i.e., medicine, dentistry, and nursing).

Methods
A cross-sectional study involving 710 undergraduate healthcare students from different universities in Saudi Arabia was conducted. A validated structured pilot-tested questionnaire was administered to the participants to assess their knowledge, attitude, and perceptions towards PV and ADRs reporting. Descriptive statistics were used to describe the study findings. Data were analyzed using SPSS version 21.

Results
Overall, the study found that 60.8 and 40.0% of healthcare students correctly defined PV and ADRs respectively. Most students showed positive attitudes and perceptions towards PV and ADRs reporting. PV knowledge, attitude, and perceptions towards PV were significantly higher among pharmacy students as compared to other healthcare students. Only 39% of healthcare students revealed that they have received any form of PV education and 49% of them indicated that PV is well covered in their school curriculum. Pharmacy students are more trained in their schools to report and have performed ADRs reporting in their school as compared to other healthcare students.

Conclusions
Pharmacy students have better knowledge, attitude, and perception towards PV and ADR reporting in comparison to other healthcare students. The study clearly describes the need for integrating pharmacovigilance education in Saudi healthcare schools’ curriculums to prepare them for real-world practices and workplaces.
Relationship between oxygen consumption and neuronal activity in a defined neural circuit
Authors: Özugur Suzan , Kunz Lars , Straka Hans 
Published: July 2020

Abstract
Background
Neuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O2 consumption. Therefore, O2 levels in the brain are a critical parameter that influences neuronal function. Measurements of O2 consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges.

Results
We used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O2 levels in the brain under in vivo-like conditions. We measured O2 concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O2 levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O2 concentration to bath levels, indicating that the brain tissue consumed the available O2. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O2 concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O2 consumption by ~ 50%, illustrating the substantial O2 amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O2 consumption with parameters that correlated with burst magnitude and duration.

Conclusions
Controlled experimental manipulations of both the O2 level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O2 consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O2-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O2 dynamics in relation to neuronal computations.
Assessment of dynamic balancing responses following perturbations during slow walking in relation to clinical outcome measures for high-functioning post-stroke subjects
Authors: Zadravec Matjaž , Olenšek Andrej , Rudolf Marko , Bizovičar Nataša , Goljar Nika , Matjačić Zlatko 
Published: July 2020

Abstract
Background
Generating appropriate balancing reactions in response to unexpected loss of balance during walking is important to prevent falls. The purpose of this study was to assess dynamic balancing responses following pushes to the pelvis in groups of post-stroke and healthy subjects.

Methods
Forty-one post-stroke subjects and forty-three healthy subjects participated in the study. Dynamic balancing responses to perturbations triggered at heel strike of the left or right leg, directed in the forward, backward, inward and outward directions during slow treadmill walking were assessed. Responses of the healthy group provided reference values used to classify responses of the post-stroke group into two subgroups; one within the reference responses (“inside” subgroup) and the other that falls out (“outside” subgroup). A battery of selected clinical outcome measures (6-Minute Walk Test, 10-Meter Walk Test, Timed-Up-and-Go test, Four Square Step Test, Functional Gait Assessment, Functional Independence Measure and One-legged stance test) was additionally assessed in the post-stroke group.

Results
The “inside” subgroup of post-stroke subjects was able to appropriately modulate centre-of-pressure and ground-reaction-force both under the impaired and non-impaired leg in response to perturbations. The “outside” subgroup of post-stroke subjects showed limited modulation of centre-of-pressure and ground-reaction-force under the impaired leg; instead stepping strategy was used in which the non-impaired leg was placed such as to make a longer step (forward perturbation), to make a shorter step (backward perturbation) or to make a cross-step (outward perturbation). Consequently, peak centre-of-mass displacements following perturbations were significantly higher in the “outside” subgroup compared to the “inside” subgroup. Responses in both subgroups following inward perturbations did not differ. Majority of clinical outcome measures moderately correlated with the peak centre-of-mass displacements for forward perturbations and exhibited weak correlations for other perturbation directions.

Conclusions
Substantial number of post-stroke subjects, that were considered to be independent walkers, have reduced capabilities to execute appropriate balancing responses following perturbations commencing on the hemiparetic leg and may thus benefit from perturbation-based training. Timed-Up-and-Go and Functional Independence Measure tests may provide an indication on the abilities of each subject to counteract unexpected loss of balance. However, a reliable assessment should be done through perturbation-based measures.
Recent advances in CAR-T cell engineering
Authors: Huang Ruihao , Li Xiaoping , He Yundi , Zhu Wen , Gao Lei , Liu Yao , Gao Li , Wen Qin , Zhong Jiang F. , Zhang Cheng , Zhang Xi 
Published: July 2020

AbstractChimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CAR-T therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CAR-T cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CAR-T cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CAR-T cells. Paired with an immune modifier, the use of fourth-generation and next-generation CAR-T cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CAR-T cell therapy.
meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes
Authors: Ciuculete Diana M. , Voisin Sarah , Kular Lara , Jonsson Jörgen , Rask-Andersen Mathias , Mwinyi Jessica , Schiöth Helgi B. 
Published: July 2020

Abstract
Background
Little is known about how genetics and epigenetics interplay in depression. Evidence suggests that genetic variants may change vulnerability to depression by modulating DNA methylation (DNAm) and non-coding RNA (ncRNA) levels. Therefore, the aim of the study was to investigate the effect of the genetic variation, previously identified in the largest genome-wide association study for depression, on proximal DNAm and ncRNA levels.

Results
We performed DNAm quantitative trait locus (meQTL) analysis in two independent cohorts (total n = 435 healthy individuals), testing associations between 102 single-nucleotide polymorphisms (SNPs) and DNAm levels in whole blood. We identified and replicated 64 SNP-CpG pairs (padj. < 0.05) with meQTL effect. Lower DNAm at cg02098413 located in the HACE1 promoter conferred by the risk allele (C allele) at rs1933802 was associated with higher risk for depression (praw = 0.014, DNAm = 2.3%). In 1202 CD14+ cells sorted from blood, DNAm at cg02088412 positively correlated with HACE1 mRNA expression. Investigation in postmortem brain tissue of adults diagnosed with major depressive disorder (MDD) indicated 1% higher DNAm at cg02098413 in neurons and lower HACE1 mRNA expression in CA1 hippocampus of MDD patients compared with healthy controls (p = 0.008 and 0.012, respectively). Expression QTL analysis in blood of 74 adolescent revealed that hsa-miR-3664-5p was associated with rs7117514 (SHANK2) (padj. = 0.015, mRNA difference = 5.2%). Gene ontology analysis of the miRNA target genes highlighted implication in neuronal processes.

Conclusions
Collectively, our findings from a multi-tissue (blood and brain) and multi-layered (genetic, epigenetic, transcriptomic) approach suggest that genetic factors may influence depression by modulating DNAm and miRNA levels. Alterations at HACE1 and SHANK2 loci imply potential mechanisms, such as oxidative stress in the brain, underlying depression. Our results deepened the knowledge of molecular mechanisms in depression and suggest new epigenetic targets that should be further evaluated.
Socio-economic disparities and returning to work following an injury
Authors: Savitsky Bella , Radomislensky Irina , Goldman Sharon , Gitelson Natalia , Frid Zhanna , Peleg Kobi 
Published: July 2020

Abstract
Background
Traumatic injury is one of the main reasons for temporary and permanent occupational disability.
The objective of this study was to define the role of socio-economic position on post-injury occupational absenteeism.

Methods
This was a nationwide retrospective cohort study, based on linking The Israeli National Trauma Registry (INTR) and the National Insurance Institute (NII) databases.
The study population included 44,740 injured workers (residents of Israel, aged 21–67, hospitalized between 2008 and 2013 and employed prior to injury as salaried workers). Logistic-regression models tested the probability of not returning to work (RTW).

Results
The majority of the study population (61%) RTW within 1 month following the injury event. Income prior to injury was significantly associated with longer out of work stay, explaining 9% variance. A significant interaction (p value < 0.0001) was found between age and income on out of work stay more than 1 month, 1 year and 2 years. Logistic regression models of out of work stay were conducted separately for all age groups. Lower income was associated with greater chance for out of work stay for more than 1 month; and the gap between the lowest and highest income quartiles was greater among older workers (age 55+), where there was an elevenfold increase in probability of not RTW among casualties from the lowest vs. highest income quartile. In comparison to other population groups, Arabs were at greater odds of longer out of work stay following an injury. Among injured persons recognized by the NII as having occupational injuries, the odds for not RTW within a month, a year and 2 years were respectively 3.9, 2.5 and 2.2 times significantly greater in comparison to employees injured outside the workplace.

Conclusions
This study identified population groups with a high probability of not RTW following an injury requiring hospitalization. Intervention programs for injured employees should promote early rehabilitation and aim to shorten out of work stay. These programs should be ethnically adapted and focus on underprivileged and disadvantaged populations.
Controllability of fractional evolution systems of Sobolev type via resolvent operators
Authors: Yang He , Zhao Yanjie 
Published: July 2020

AbstractIn this paper, we consider the nonlocal controllability of $\alpha\in (1,2)$
α
∈
(
1
,
2
)
-order fractional evolution systems of Sobolev type in abstract spaces. By utilizing fixed point theorems and the theory of resolvent operators we establish some sufficient conditions for the nonlocal controllability of Sobolev-type fractional evolution systems.
A specialised finite element for simulating self-healing quasi-brittle materials
Authors: Freeman Brubeck L. , Bonilla-Villalba Pedro , Mihai Iulia C. , Alnaas Waled F. , Jefferson Anthony D. 
Published: July 2020

AbstractA new specialised finite element for simulating the cracking and healing behaviour of quasi-brittle materials is presented. The element employs a strong discontinuity approach to represent displacement jumps associated with cracks. A particular feature of the work is the introduction of healing into the element formulation. The healing variables are introduced at the element level, which ensures consistency with the internal degrees freedom that represent the crack; namely, the crack opening, crack sliding and rotation. In the present work, the element is combined with a new cohesive zone model to simulate damage-healing behaviour and implemented with a crack tracking algorithm. To demonstrate the performance of the new element and constitutive models, a convergence test and two validation examples are presented that consider the response of a vascular self-healing cementitious material system for three different specimens. The examples show that the model is able to accurately capture the cracking and healing behaviour of this type of self-healing material system with good accuracy.
A call to protect patients, correctional staff and healthcare professionals in jails and prisons during the COVID-19 pandemic
Authors: Oladeru Oluwadamilola T. , Tran Nguyen-Toan , Al-Rousan Tala , Williams Brie , Zaller Nickolas 
Published: July 2020

AbstractThis editorial describes why surge planning in the community must account for potential infection outbreaks in jails and prisons, and why incarcerated people and those in contact with them, including over 450,000 correctional officers and thousands of healthcare staff working in prisons, are at significant risk of COVID-19 exposure. We then explain how our nation’s jails and prisons will continue to serve as breeding grounds for devastating COVID-19 outcomes and offer specific guidance and a call to action for the immediate development of correctional healthcare strategies designed to protect the health and safety of patients and correctional and healthcare staff and the communities in which they are situated. Correctional officers and correctional healthcare professionals need the nation’s reassurance during this dire time that they will not be abandoned and further stigmatized for responding to the needs of incarcerated people. Our collective health depends on it.
When testing stakes are no longer high: impact on the Chinese College English learners and their learning
Authors: Chen Qiuxian , Hao Chenxian , Xiao Yangyu 
Published: July 2020

AbstractIt is now a consensus that high-stakes testing exerts powerful impact in controlling curriculum and pedagogy, and shaping students’ learning. The power of testing is especially strong in contexts where testing culture prevails. The Chinese educational context is such a context which is dominated by competitive tests. The language testing results from large-scale tests, such as CET-4 (College English Test—Band 4), used to be included as a compulsory prerequisite for undergraduates to get their bachelor’s degree. Such a requirement has been removed recently to reduce testing stakes for leverage purposes. Thus, it is worthwhile to investigate whether the change will possibly help to impact students and their learning in a positive way.Our study aimed to explore the impact of changes in the stakes of a language test in the Chinese university context. Data were collected through questionnaires from 544 College English students at a university in north-western China. Our analysis via SPSS 2.3 showed that test-taking was still well accepted and practiced; while reducing the stakes helped to redirect the students towards English learning, it had less impact on their English learning motivation and approaches. The findings also show that the test-dominated environment that is deep-rooted in the macro- and micro-contexts decided the students’ responses to this policy change.
A comprehensive survey of anomaly detection techniques for high dimensional big data
Authors: Thudumu Srikanth , Branch Philip , Jin Jiong , Singh Jugdutt 
Published: July 2020

AbstractAnomaly detection in high dimensional data is becoming a fundamental research problem that has various applications in the real world. However, many existing anomaly detection techniques fail to retain sufficient accuracy due to so-called “big data” characterised by high-volume, and high-velocity data generated by variety of sources. This phenomenon of having both problems together can be referred to the “curse of big dimensionality,” that affect existing techniques in terms of both performance and accuracy. To address this gap and to understand the core problem, it is necessary to identify the unique challenges brought by the anomaly detection with both high dimensionality and big data problems. Hence, this survey aims to document the state of anomaly detection in high dimensional big data by representing the unique challenges using a triangular model of vertices: the problem (big dimensionality), techniques/algorithms (anomaly detection), and tools (big data applications/frameworks). Authors’ work that fall directly into any of the vertices or closely related to them are taken into consideration for review. Furthermore, the limitations of traditional approaches and current strategies of high dimensional data are discussed along with recent techniques and applications on big data required for the optimization of anomaly detection.
Trees of Panama: A complete checklist with every geographic range
Authors: Condit Richard , Aguilar Salomón , Pérez Rolando 
Published: July 2020

AbstractBackgroundCentral America is one of the most diverse floristic provinces in the world, but comprehensive plant lists for the region are incomplete and need frequent updating. Full geographic ranges of individual species are seldom known. Our detailed forest inventory plots of Panama thus lack a global geographic perspective. In order to provide one, we assembled a thoroughly vetted checklist of all tree species of Panama, along with an estimate of each one’s range size based on published specimen records.Results1) Panama has 3043 tree species in 141 families and 752 genera; 57.6% were ≥ 10 m tall and 16.9% were 3-5 m tall.2) The widest ranges were >1.5×107km2, covering the entire neotropics and reaching >30∘latitude; 12.4% of the species had ranges exceeding 107km2. The median range was 6.9×105km2.3) At the other extreme, 16.2% of the species had a range <20,000 km2, a criterion suggesting endangered status.4) Range size increased with a tree species’ height and varied significantly among families.5) Tree census plots, where we mapped and measured all individuals, captured 27.5% of the tree species, but a biased selection relative to range size; only 4.5% of the species in plots had ranges <20,000 km2.ConclusionsOur checklist of the trees of Panama, based on rigorous criteria aimed at matching plot censuses, is 20% larger than previous. By recording species’ maximum heights, we allow comparisons with other regions based on matching definitions, and the range sizes provide a quantitative basis for assessing extinction risk. Our next goal is to merge population density from plot censuses to add rigor to predictions of extinction risk of poorly-studied tropical tree species.