bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrospinal fluid leak presented with the C1-C2 sign caused by spinal canal stenosis: a case report
Authors: Akiba Chihiro , Bandai Hideki , Ito Yoshitaka , Maeda Tsuyoshi , Yamaguchi Keisuke , Nakajima Madoka , Miyajima Masakazu 
Published: April 2020

Abstract
Background
Intracranial hypotension is a disorder characterized by low cerebrospinal fluid (CSF) pressure typically caused by loss of CSF. Although some mechanisms account for the CSF leakage have been elucidated, spinal canal stenosis has never been reported as a pathological cause of intracranial hypotension.
C1-C2 sign is a characteristic imaging feature, which indicates CSF collection between the spinous processes of C1 and C2, occasionally observed on magnetic resonance imaging (MRI) in patients with intracranial hypotension.

Case presentation
A 58-year-old man was presented to our institute with complaints of posterior cervical pain persisting for 3 months, along with numbness and muscle weakness of extremities. A fat suppression T2-weighted image of MRI illustrated fluid collection in the retrospinal region at C1-C2 level, and an 111In-DTPA cisternoscintigram clearly revealed the presence of CSF leakage into the same region. The MRI also showed stenosis in spinal canal at C3/4 level, and a computed tomography (CT) myelogram suggested a blockage at the same level. We gave a diagnosis as intracranial hypotension due to the CSF leakage, which might be caused by the spinal canal stenosis at C3/4 level. Despite 72 h of conservative therapy, a brain CT showed the development of bilateral subdural hematomas. We, therefore, performed burr-hole drainage of the subdural hematoma, blood-patch therapy at C1/2 level, and laminoplasty at C3–4 at the same time. Improvement of symptoms and imaging features which suggested the CSF leak and subdural hematoma were obtained post-operatively.

Conclusion
The present case suggested the mechanism where the CSF leakage was revealed as fluid collection in the retrospinal region at C1-C2 level. Increased intradural pressure due to the spinal canal stenosis resulted in dural tear. CSF leaked into the epidural space and subsequently to the retrospinal region at C1-C2 level, due to the presence of spinal canal stenosis caudally as well as the vulnerability of the tissue structure in the retrospinal region at C1-C2 level. Thus, our theory supports the mechanisms of previously reported CSF dynamics associated to C1-C2 sign, and also, we suggest spinal canal stenosis as a novel etiology of intracranial hypotension.
Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer
Authors: McCarthy Anne Marie , Kumar Nitya Pradeep , He Wei , Regan Susan , Welch Michaela , Moy Beverly , Iafrate A. John , Chan Andrew T. , Bardia Aditya , Armstrong Katrina 
Published: April 2020

Abstract
Introduction
The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer.

Methods
Patients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009–2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression.

Results
Among 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI:0.44–0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86–2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI:0.48–1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI:0.88–3.49 p = 0.110).

Conclusions
Among women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users. Larger studies are needed to confirm this finding and examine the relationship among aspirin use, tumor mutation profile, and the overall risk of breast cancer progression.
Influence of Nodal signalling on pluripotency factor expression, tumour cell proliferation and cisplatin-sensitivity in testicular germ cell tumours
Authors: Harpelunde Poulsen K. , Nielsen J. E. , Grønkær Toft B. , Joensen U. N. , Rasmussen L. J. , Blomberg Jensen M. , Mitchell R. T. , Juul A. , Rajpert-De Meyts E. , Jørgensen A. 
Published: April 2020

Abstract
Background
Testicular germ cell tumours (TGCTs) are characterised by an overall high cisplatin-sensitivity which has been linked to their continued expression of pluripotency factors. Recently, the Nodal signalling pathway has been implicated in the regulation of pluripotency factor expression in fetal germ cells, and the pathway could therefore also be involved in regulating expression of pluripotency factors in malignant germ cells, and hence cisplatin-sensitivity in TGCTs.

Methods
We used in vitro culture of the TGCT-derived cell line NTera2, ex vivo tissue culture of primary TGCT specimens and xenografting of NTera2 cells into nude mice in order to investigate the consequences of manipulating Nodal and Activin signalling on pluripotency factor expression, apoptosis, proliferation and cisplatin-sensitivity.

Results
The Nodal signalling factors were markedly expressed concomitantly with the pluripotency factor OCT4 in GCNIS cells, seminomas and embryonal carcinomas. Despite this, inhibition of Nodal and Activin signalling either alone or simultaneously did not affect proliferation or apoptosis in malignant germ cells in vitro or ex vivo. Interestingly, inhibition of Nodal signalling in vitro reduced the expression of pluripotency factors and Nodal pathway genes, while stimulation of the pathway increased their expression. However, cisplatin-sensitivity was not affected following pharmacological inhibition of Nodal/Activin signalling or siRNA-mediated knockdown of the obligate co-receptor CRIPTO in NTera2 cells in vitro or in a xenograft model.

Conclusion
Our findings suggest that the Nodal signalling pathway may be involved in regulating pluripotency factor expression in malignant germ cells, but manipulation of the pathway does not appear to affect cisplatin-sensitivity or tumour cell proliferation.
Patterns of access to reproductive health services in Ghana and Nigeria: results of a cluster analysis
Authors: Ogundele Oluwasegun Jko , Pavlova Milena , Groot Wim 
Published: April 2020

Abstract
Background
Inequalities in access to health care result in systematic health differences between social groups. Interventions to improve health do not always consider these inequalities. To examine access to reproductive health care services in Ghana and Nigeria, the patterns of use of family planning and maternal care by women in these countries are explored.

Methods
We used population-level data from the Ghana and Nigeria Demographic Health Surveys of 2014 and 2013 respectively. We applied a two-step cluster analysis followed by multinomial logistic regression analysis.

Results
The initial two-step cluster analyses related to family planning identified three clusters of women in Ghana and Nigeria: women with high, medium and poor access to family planning services. The subsequent two-step cluster analyses related to maternal care identified five distinct clusters: higher, high, medium, low and poor access to maternal health services in Ghana and Nigeria. Multinomial logistic regression showed that compared to women with secondary/higher education, women without education have higher odds of poor access to family planning services in Nigeria (OR = 2.54, 95% CI: 1.90–3.39) and in Ghana (OR = 1.257, 95% CI: 0.77–2.03). Compared to white-collar workers, women who are not working have increased odds of poor access to maternal health services in Nigeria (OR = 1.579, 95% CI: 1.081–2.307, p ≤ 0.01). This association is not observed for Ghana. Household wealth is strongly associated with access to family planning services and maternal health care services in Nigeria. Not having insurance in Ghana is associated with low access to family planning services, while this is not the case in Nigeria. In both countries, the absence of insurance is associated with poor access to maternal health services.

Conclusions
These differences confirm the importance of a focused context-specific approach towards reproductive health services, particularly to reduce inequality in access resulting from socio-economic status. Interventions should be focused on the categorization of services and population groups into priority classes based on needs assessment. In this way, they can help expand coverage of quality services bottom up to improve access among these vulnerable groups.
Social regulation activities in end-of-life: a qualitative study on completion of advance directives in Swiss nursing homes
Authors: Droz Mendelzweig M. 
Published: April 2020

Abstract
Background
In Switzerland as in many countries, steady trend is observed in nursing homes to promote writing of advanced directives (ADs). Implementation of ADs reflects the rise in public concern for the persons’ right to self-determination and informed decision. The issue of end-of-life conditions is particularly acute in situations with dementia. This article investigates how ADs interventions in nursing homes strive simultaneously to behave in line with the principles of care ethics and with the intention to respond to legally binding instructions. Healthcare to dying residents with dementia in nursing homes is interpreted in light of the Regulation theory.

Methods
Nursing home palliative care reference nurses were contacted through questionnaire. One hundred twenty-one addresses were reached, 69 responses were collected, giving a response rate of 57%. In order to deepen the understanding, 10 semi-directive interviews were conducted in 10 different nursing facilities with 12 palliative nurses.

Results
Presently, Swiss nursing homes are lacking a model of AD suitable to people with dementia. The study sheds light on dissimilarities in the purpose assigned to ADs’ procedure in the different facilities. Discrepancies in end-of-life care practices reveal more the influence of structural and organisational devices specific to each setting than conflicting views on end-of-life care principles. We analyse the interpretation of the Law and its implementation in the participating NHs as compromises that could be accounted for as a form of social regulation.

Conclusion
Dementia accentuates the uncertainty inherent to end-of-life trajectories. The implementation of standardised procedures aimed at collecting the wishes of the person deprived of his or her discernment is source of dissonances with regard to the multiple interests involved in these care situations. In this context, the drafting of ADs during end-of-life care in NH correspond to new normative constraints requiring new collective regulation actions.
Kinect and wearable inertial sensors for motor rehabilitation programs at home: state of the art and an experimental comparison
Authors: Milosevic Bojan , Leardini Alberto , Farella Elisabetta 
Published: April 2020

Abstract
Background
Emerging sensing and communication technologies are contributing to the development of many motor rehabilitation programs outside the standard healthcare facilities. Nowadays, motor rehabilitation exercises can be easily performed and monitored even at home by a variety of motion-tracking systems. These are cheap, reliable, easy-to-use, and allow also remote configuration and control of the rehabilitation programs. The two most promising technologies for home-based motor rehabilitation programs are inertial wearable sensors and video-based motion capture systems.

Methods
In this paper, after a thorough review of the relevant literature, an original experimental analysis is reported for two corresponding commercially available solutions, a wearable inertial measurement unit and the Kinect, respectively. For the former, a number of different algorithms for rigid body pose estimation from sensor data were also tested. Both systems were compared with the measurements obtained with state-of-the-art marker-based stereophotogrammetric motion analysis, taken as a gold-standard, and also evaluated outside the lab in a home environment.

Results
The results in the laboratory setting showed similarly good performance for the elementary large motion exercises, with both systems having errors in the 3–8 degree range. Usability and other possible limitations were also assessed during utilization at home, which revealed additional advantages and drawbacks for the two systems.

Conclusions
The two evaluated systems use different technology and algorithms, but have similar performance in terms of human motion tracking. Therefore, both can be adopted for monitoring home-based rehabilitation programs, taking adequate precautions however for operation, user instructions and interpretation of the results.
Outcome and risk of recurrence in a large cohort of idiopathic longitudinally extensive transverse myelitis without AQP4/MOG antibodies
Authors:   on behalf of the OFSEP, SFSEP, and NOMADMUS study groups, Maillart Elisabeth , Durand-Dubief Françoise , Louapre Céline , Audoin Bertrand , Bourre Bertrand , Derache Nathalie , Ciron Jonathan , Collongues Nicolas , de Sèze Jérome , Cohen Mikael , Lebrun-Frenay Christine , Hadhoum Nawel , Zéphir Hélène , Deschamps Romain , Carra-Dallière Clarisse , Labauge Pierre , Kerschen Philippe , Montcuquet Alexis , Wiertlewski Sandrine , Laplaud David , Runavot Gwenaëlle , Vukusic Sandra , Papeix Caroline , Marignier Romain 
Published: April 2020

Abstract
Background
Longitudinally extensive transverse myelitis (LETM) is classically related to aquaporin (AQP4)-antibodies (Ab) neuromyelitis optica spectrum disorders (NMOSD) or more recently to myelin oligodendrocyte glycoprotein (MOG)-Ab associated disease. However, some patients remain negative for any diagnosis, despite a large work-up including AQP4-Ab and MOG-Ab. Data about natural history, disability outcome, and treatment are limited in this group of patients.
We aimed to (1) describe clinical, biological, and radiological features of double seronegative LETM patients; (2) assess the clinical course and identify prognostic factors; and (3) assess the risk of recurrence, according to maintenance immunosuppressive therapy.

Methods
Retrospective evaluation of patients with a first episode of LETM, tested negative for AQP-Ab and MOG-Ab, from the French nationwide observatory study NOMADMUS.

Results
Fifty-three patients (median age 38 years (range 16–80)) with double seronegative LETM were included. Median nadir EDSS at onset was 6.0 (1–8.5), associated to a median EDSS at last follow-up of 4.0 (0–8). Recurrence was observed in 24.5% of patients in the 18 following months, with a median time to first relapse of 5.7 months. The risk of recurrence was lower in the group of patients treated early with an immunosuppressive drug (2/22, 9%), in comparison with untreated patients (10/31, 32%).

Conclusions
A first episode of a double seronegative LETM is associated to a severe outcome and a high rate of relapse in the following 18 months, suggesting that an early immunosuppressive treatment may be beneficial in that condition.
MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia
Authors: Plastira Ioanna , Bernhart Eva , Joshi Lisha , Koyani Chintan N. , Strohmaier Heimo , Reicher Helga , Malle Ernst , Sattler Wolfgang 
Published: April 2020

Abstract
Background
In the extracellular environment, lysophosphatidic acid (LPA) species are generated via autotaxin (ATX)-mediated hydrolysis of lysophospholipid precursors. Members of the LPA family are potent lipid mediators transmitting signals via six different G protein-coupled LPA receptors (LPAR1-6). The LPA signaling axis is indispensable for brain development and function of the nervous system; however, during damage of the central nervous system, LPA levels can increase and aberrant signaling events counteract brain function. Here, we investigated regulation of the ATX/LPA/LPAR axis in response to lipopolysaccharide-induced systemic inflammation in mice and potential neurotoxic polarization programs in LPA-activated primary murine microglia.

Methods
In vivo, LPAR1-6 expression was established by qPCR in whole murine brain homogenates and in FACS-sorted microglia. ELISAs were used to quantitate LPA concentrations in the brain and cyto-/chemokine secretion from primary microglia in vitro. Transcription factor phosphorylation was analyzed by immunoblotting, and plasma membrane markers were analyzed by flow cytometry. We used MAPK inhibitors to study signal integration by the JNK, p38, and ERK1/2 branches in response to LPA-mediated activation of primary microglia.

Results
Under acute and chronic inflammatory conditions, we observed a significant increase in LPA concentrations and differential regulation of LPAR, ATX (encoded by ENPP2), and cytosolic phospholipase A2 (encoded by PLA2G4A) gene expression in the brain and FACS-sorted microglia. During pathway analyses in vitro, the use of specific MAPK antagonists (SP600125, SB203580, and PD98059) revealed that JNK and p38 inhibition most efficiently attenuated LPA-induced phosphorylation of proinflammatory transcription factors (STAT1 and -3, p65, and c-Jun) and secretion of IL-6 and TNFα. All three inhibitors decreased LPA-mediated secretion of IL-1β, CXCL10, CXCL2, and CCL5. The plasma membrane marker CD40 was solely inhibited by SP600125 while all three inhibitors affected expression of CD86 and CD206. All MAPK antagonists reduced intracellular COX-2 and Arg1 as well as ROS and NO formation, and neurotoxicity of microglia-conditioned media.

Conclusion
In the present study, we show that systemic inflammation induces aberrant ATX/LPA/LPAR homeostasis in the murine brain. LPA-mediated polarization of primary microglia via MAPK-dependent pathways induces features reminiscent of a neurotoxic phenotype.
A hot-blast warming facility for simulating global warming in low-stature crop systems and its application case to assess elevated temperature effects on rice in Central China
Authors: Zhang Zuolin , Yang Zhiyuan , Fahad Shah , Zhang Tong , Xu Wenhao , Cui Kehui , Peng Shaobing , Huang Jianliang 
Published: April 2020

AbstractBackgroundTo study the impact of climate warming on crops, it is crucial to have a warming equipment suitable for their field environment. A facility is needed that can provide suitable combinations of different temperatures at reasonable cost for large plots.ResultsHere, an additional field warming facility option named the hot-blast warming facility (HBWF), which comprised heaters, blowers, wind breaks, and a control board was developed. An application case based on HBWF was carried out to assess elevated temperature effects on rice in Central China during 2015 and 2016. We tested four elevated temperature treatments on four rice cultivars under paddy field conditions and measured yield and its components. Heating convection air directly, the facility could increase the temperature of the rice canopy up to 1–2 °C, which could properly simulate global warming. Considering the costs, the HBWF reduced the operating costs because of its relatively lower power consumption (0.164 kW/m2), which was 80% lower than that of Free Air Temperature Increase. Our results demonstrate that the HBWF could build a 25 m2homogeneous heating area and had little effect on the relative humidity under a paddy field environment. Warming treatments significantly reduced the grain yield by 4.4–22.7% in 2015, and 30.8–61.9% in 2016, compared to the control. The main contribution to the significant decrease of the grain yields was the decrease in seed setting rate. Moreover, a reduction of 1000-grain weight led to the decline in grain yield. The increasing ranges of the temperature simulated by HBWF were stable in different years, however, whether the elevated treatments demonstrated significant difference on rice growth mainly decided by the basic atmospheric temperature (as the control) during the growth period.ConclusionsThe new warming facility is suitable for field trials to assess elevated temperature combinations and provides an extra equipment option for use in elevated temperature research in the future.
Proposal of a new shared payment model for healthcare financing in the United States: a hypothesis
Authors: Ziran Bruce H. , O’Pry E. Kathleen 
Published: April 2020

AbstractThe healthcare repayment system in America is highly flawed due to several factors such as uncontrolled costs, unequal access, varied reimbursement systems, and complex patient interfaces. In fact, it is rated the worst among the eleven developed nations analyzed in the Commonwealth Fund’s evaluation conducted every three years. We propose a novel three-tiered model for healthcare repayment designed to fulfill the needs of the patients, the providers, the payers and the nation as a whole. We hypothesized that our new plan may spread cost between multiple entities and offer better coverage and access to care. Our model uses a shared-cost approach wherein the total risk expenditure becomes the responsibility of various stakeholders including the government, insurance industry, hospitals, patients, providers as well as the nation’s economy. While there is no perfect solution to healthcare in America, we believe our three-tiered model can create an economically balanced solution to break deadlock between party lines and result in better outcomes and patient care.
Associations of CXCL1 gene 5’UTR variations with ovarian cancer
Authors: Guo Man , Xu Chao , Chen Yan-Zhe , Sun Qi-Wen , Zhao Xin-Ying , Liu Xin , Yang Yi , Hu Yi-Yan , Li Fei-Feng , Liu Shu-Lin 
Published: April 2020

Abstract
Background
There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC.

Methods
We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9).

Results
The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients.

Conclusions
Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.