bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multistability in the epithelial-mesenchymal transition network
Authors: Xin Ying , Cummins Bree , Gedeon Tomáš 
Published: February 2020

Abstract
Background
The transitions between epithelial (E) and mesenchymal (M) cell phenotypes are essential in many biological processes like tissue development and cancer metastasis. Previous studies, both modeling and experimental, suggested that in addition to E and M states, the network responsible for these phenotypes exhibits intermediate phenotypes between E and M states. The number and importance of such states is subject to intense discussion in the epithelial-mesenchymal transition (EMT) community.

Results
Previous modeling efforts used traditional bifurcation analysis to explore the number of the steady states that correspond to E, M and intermediate states by varying one or two parameters at a time. Since the system has dozens of parameters that are largely unknown, it remains a challenging problem to fully describe the potential set of states and their relationship across all parameters. We use the computational tool DSGRN (Dynamic Signatures Generated by Regulatory Networks) to explore the intermediate states of an EMT model network by computing summaries of the dynamics across all of parameter space. We find that the only attractors in the system are equilibria, that E and M states dominate across parameter space, but that bistability and multistability are common. Even at extreme levels of some of the known inducers of the transition, there is a certain proportion of the parameter space at which an E or an M state co-exists with other stable steady states.

Conclusions
Our results suggest that the multistability is broadly present in the EMT network across parameters and thus response of cells to signals may strongly depend on the particular cell line and genetic background.
Successful control of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae ST307 outbreak in a neonatal intensive care unit
Authors: Baek Eun-Hwa , Kim Se-Eun , Kim Sunjoo , Lee Seungjun , Cho Oh-Hyun , In Hong Sun , Shin Jeong Hwan , Hwang Inyeong 
Published: February 2020

Abstract
Background
In this study, we evaluated the genetic relatedness of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KPN) isolates from an outbreak in a neonatal intensive care unit (NICU) in August 2017, We implemented an active countermeasure to control this outbreak successfully.

Methods
The incidence of healthcare-associated ESBL-KPN bacteremia was evaluated before and after initiating enhanced infection control (IC) practices in January 2018. Surveillance cultures were set up and monitored for neonates, medical personnel, and NICU environments. Molecular analyses, including pulse-field gel electrophoresis (PFGE), sequence typing, and ESBL genotyping, were performed for the isolated KPN strains.

Results
After implementing the enhanced IC procedures, the healthcare-associated bacteremia rate decreased from 6.0 to 0.0 per 1000 patient-days. Samples from neonates (n = 11/15, 73.3%), medical personnel (n = 1/41, 2.4%), and medical devices and the environments (6/181, 3.3%) tested positive for ESBL-KPN in the surveillance cultures in December 2017. Active surveillance cultures revealed that 23 of 72 neonates who were screened (31.9%) were colonized with ESBL-KPN between January and March 2018. All the isolates demonstrated closely related PFGE patterns and were identified as ST307 strain carrying the CTX-M-15 gene.

Conclusions
Contaminated NICU environments and medical devices, as well as transmission by medical personnel, appeared to be the source of the outbreak of ESBL-KPN infection. We employed an enhanced IC strategy during January–March 2018 and successfully controlled the clonal outbreak of CTX-M-15-positive KPN. ST307 has emerged as an important bacteremia-causing pathogen in the NICU and should be carefully monitored.
A case of Tinea Faciei caused by Trichophyton benhamiae: first report in China
Authors: Tan Jingwen , Liu Xiaoping , Gao Zhiqin , Yang Hong , Yang Lianjuan , Wen Hai 
Published: February 2020

Abstract
Background
Trichophyton benhamiae is a zoophilic dermatophyte that can cause tinea in humans and animals. Lesions caused by T. benhamiae tend to be highly inflammatory, and patients are often infected by animals or other patients infected with T. benhamiae. In this paper, we report the first case of tinea faciei caused by T. benhamiae in a Chinese girl who might be transmitted from a fox.

Case presentation
A 4-year-old girl from HaiNing city developed an itchy, erythematous, and annular plaque on her right face for the past 2 months. Before the lesion appeared, she was in close contact with the fur of a fox for almost 1 week. Septate hyaline hyphae were detected by direct mycological examination of the scales. Cultures grew on Sabouraud’s dextrose agar (SDA) at 26 °C for 2 weeks revealed the presence of T. mentagrophytes. A molecular sequencing test confirmed that the isolate was consistent with reference strains to T. benhamiae. Then, the diagnosis of tinea faciei due to T. benhamiae was made. Treatment with terbinafine (oral 125 mg/d) and sertaconazole nitrate cream (topical, twice daily) for 4 weeks was initiated and achieved significant improvement of the skin lesions.

Conclusions
This rare dermatophytosis case highlights the importance of ITS sequencing in helping to recognize rare pathogenic fungi that can be easily misdiagnosed with a conventional morphological diagnosis.
The impact of 18F-FDOPA-PET/MRI image fusion in detecting liver metastasis in patients with neuroendocrine tumors of the gastrointestinal tract
Authors: Barachini O. , Bernt R. , Mirzaei S. , Pirich C. , Hergan K. , Zandieh S. 
Published: February 2020

Abstract
Background
This study assesses the value of image fusion using 18F-fluoro-L-DOPA (18F-DOPA) positron emission tomography (PET) and magnetic resonance imaging (MRI) for examining patients with neuroendocrine tumors (NETs) and a suspicion of metastasis of the liver.

Methods
Eleven patients (five women and six men aged between 20 and 81, with a mean age of 54.6 years) were included in the study. All patients underwent whole-body 18F-DOPA PET examinations and contrast-enhanced MRI with diffusion-weighted sequences (DWS). Image fusion was performed using a semiautomatic voxel-based algorithm. Images obtained using PET and MRI were assessed separately. Side-by-side evaluations of fused PET/MRI images were also performed.

Results
In total, 55 liver lesions (52 liver metastases and 3 benign lesions) were detected in the 11 patients. Sensitivity detection for liver lesions was higher when using PET/CT than when using contrast-enhanced MRI without DWSs and lower than using MRI with DWSs. The sensitivity of PET/MRI image fusion in the detection of liver metastasis was significantly higher than that of MRI with DWSs (P < 0.05).

Conclusion
Images of the liver obtained using PET and MRI in patients with NETs exhibited characteristic features. These findings suggest that an appropriate combination of available imaging modalities can optimize patient evaluations.
Stereotactic radiotherapy on brain metastases with recent hemorrhagic signal: STEREO-HBM, a two-step phase 2 trial
Authors: Lesueur Paul , Kao William , Leconte Alexandra , Geffrelot Julien , Lequesne Justine , Lacroix Joëlle , Brachet Pierre-Emmanuel , Hrab Ioana , Royer Philippe , Clarisse Bénédicte , Stefan Dinu 
Published: February 2020

Abstract
Background
Brain metastases often occur in cancer evolution. They are not only responsible for death but also for disorders affecting the quality of life and the cognitive functions.
Management of brain metastases usually consists in multi-modality treatments, including neurosurgery, whole brain radiotherapy (WBRT), and more recently radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), systemic treatment (chemotherapy or targeted therapy), combined or not with corticosteroids. Almost 20% of brain metastases can present recent (within 15 days) bleeding signs on neuro-imagery. In these conditions, WBRT is the usual treatment. Yet, patients may benefit from a more aggressive strategy with SRT or FSRT. However, these options were suspected to possibly major the risk of brain haemorrhage, although no scientifically proven. Radiation oncologists therefore usually remain reluctant to deliver SRS/FSRT for bleeding brain metastases.
It is therefore challenging to establish a standard of care for the treatment of bleeding brain metastases.
We propose a phase II trial to simultaneously assess safety and efficacy of FSRT to manage brain metastases with hemorrhagic signal.

Methods
The STEREO-HBM study is a multicenter two-step non-randomised phase II trial addressing patients with at least one bleeding brain metastasis out of a maximum of 3 brain metastases. Each brain metastasis will be treated with 30 Gy in 3 fractions for 1 week.
The main endpoint is based on both safety and efficacy endpoints as proposed by Bryant and Day’s design. Safety endpoint is defined as the rate of bleeding complications 4 months post-FSRT while efficacy endpoint is defined as the 6-month local control rate. Multi-modal MRI will be used to assess intra-tumoral hemorrhagic events before and after treatment. Patients’ quality of life will also be assessed.

Discussion
Management of bleeding brain metastases is still debated and poorly explored in clinical trials. There is sparse and weak data on the signification of pretreatment intra-tumour haemorrhagic signs or on the risk of brain bleeding complications after FSRT.
We expect this first prospective phase 2 trial in this particular setting will allow to clarify the place of FSRT to optimally manage bleeding brain metastases.

Trial registration
NCT 03696680, registered October, 4, 2018.

Protocol version
Version 2.1 dated from 2018/11/09.
Reduced doses of dabrafenib and trametinib combination therapy for BRAF V600E-mutant non-small cell lung cancer prevent rhabdomyolysis and maintain tumor shrinkage: a case report
Authors: Adachi Yuta , Yanagimura Naohiro , Suzuki Chiaki , Ootani Sakiko , Tanimoto Azusa , Nishiyama Akihiro , Yamashita Kaname , Ohtsubo Koushiro , Takeuchi Shinji , Yano Seiji 
Published: February 2020

Abstract
Background
A BRAF V600E mutation is found as driver oncogene in patients with non-small cell lung cancer. Although combined treatment with dabrafenib and trametinib is highly effective, the efficacy of reduced doses of the drugs in combination therapy has not yet been reported.

Case presentation
A Japanese man in his mid-sixties was diagnosed with unresectable lung adenocarcinoma and was unresponsive to cytotoxic chemotherapy and immune checkpoint inhibitors. The BRAF V600E mutation was detected by next generation sequencing, and the patient was subjected to treatment with dabrafenib and trametinib in combination. Although the treatment reduced the tumor size, he experienced myalgia and muscle weakness with elevated serum creatine kinase and was diagnosed with rhabdomyolysis induced by dabrafenib and trametinib. After the patient recovered from rhabdomyolysis, the treatment doses of dabrafenib and trametinib were reduced, which prevented further rhabdomyolysis and maintained tumor shrinkage.

Conclusion
The reduction of the doses of dabrafenib and trametinib was effective in the treatment of BRAF V600E-mutant NSCLC, and also prevented the incidence of rhabdomyolysis.
Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study
Authors: Westphalen C. Benedikt , Kukiolka Tobias , Garlipp Benjamin , Hahn Lars , Fuchs Martin , Malfertheiner Peter , Reiser Marcel , Kütting Fabian , Heinemann Volker , Beringer Andreas , Waldschmidt Dirk T. 
Published: February 2020

Abstract
Background
Gemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash.

Methods
This multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade ≥ 2), duration of erlotinib treatment (≤8 weeks, > 8 weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0–1, 2) and age (≤65 years, > 65 years).

Results
Within the full analysis set (FAS; N = 270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade ≥ 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11 months with an OS of 9.93 months in rash-positive and 8.68 months in rash-negative patients. Median PFS was 5.06 months for rash-positive and 4.11 months for rash-negative patients. PFS was longer in patients with rash grade ≥ 2 and in older patients (> 65 years). Examination using a multivariate Cox proportional model revealed that an age > 65 years was associated with longer OS (hazard ratio 0.640; p = 0.0327) and PFS (hazard ratio 0.642; p = 0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3.

Conclusions
Comparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade ≥ 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals.

Trial registration
ClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013.
Child characteristics and early intervention referral and receipt of services: a retrospective cohort study
Authors: McManus Beth M. , Richardson Zachary , Schenkman Margaret , Murphy Natalie J. , Everhart Rachel M. , Hambidge Simon , Morrato Elaine 
Published: February 2020

Abstract
Background
Early Intervention (EI) is a federally mandated, state-administered system of care for children with developmental delays and disabilities under the age of three. Gaps exist in the process of accessing EI through pediatric primary care, and low rates of EI access are well documented and disproportionately affect poor and minority children. The aims of this paper are to examine child characteristics associated with gaps in EI (1) referral, (2) access and (3) service use. To our knowledge, this is the first study to leverage linked safety net health system pediatric primary care and EI records data to follow EI-referred children longitudinally to understand EI service use gaps from EI referral to EI service utilization.

Methods
In a retrospective cohort design (14,710 children with developmental disability or delay), we linked pediatric primary care records between a large, integrated safety net health system in metro Denver and its corresponding EI program (2014–2016). Using adjusted marginal effects [ME, (95% CI)], we estimated gaps in EI referral, access, and service type (i.e., physical [PT], occupational [OT], speech therapy [ST] and developmental intervention [DI]). Analyses accounted for child characteristics including socio-demographics, diagnosis, condition severity, and baseline function.

Results
Only 18.7% of EI-eligible children (N = 2726) received a referral; 26% of those (N = 722) received services for a net enrollment rate of 5% among EI-eligible children. Having the most severe developmental condition was positively associated with EI referral [ME = 0.334 [0.249, 0.420]) and Individualized Family Services Plan (IFSP) receipt [ME = 0.156 [0.088, 0.223]). Children less likely to be EI-referred were Black, non-Hispanic (BNH) [ME = -0.029 (− 0.054, − 0.004)] and had a diagnosed condition ([ME = − 0.046 (− 0.087, − 0.005)]. Children with a diagnosis and those with higher income were more likely to receive PT or OT. Higher baseline cognitive and adaptive skills were associated with lower likelihood of PT [ME = -0.029 (− 0.054, − 0.004)], OT [ME = -0.029 (− 0.054, − 0.004)], and ST [ME = -0.029 (− 0.054, − 0.004)].

Conclusions
We identified and characterized gaps in EI referral, access, and service use in an urban safety-net population of children with high rates of developmental delay. Interventions are needed to improve integrated systems of care affecting primary care and EI processes and coordination.
The use of long-acting Aripiprazole in a multi-center, prospective, uncontrolled, open-label, cohort study in Germany: a report on global assessment of functioning and the WHO wellbeing index
Authors: Schöttle Daniel , Janetzky Wolfgang , Luedecke Daniel , Beck Elmar , Correll Christoph U. , Wiedemann Klaus 
Published: February 2020

Abstract
Background
In this non-interventional study, the functionality and well-being of patients with schizophrenia with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic population.

Methods
This non-interventional, prospective, multicenter 6-month study included 242 predominantly symptomatically stable patients (mean age 43.1 ± 15.1 years, 55% male) who switched their treatment to AOM after 9.7 (± 22.3) months of oral treatment. Outcome parameters included functionality (Global Assessment of Functioning, GAF), patient’s wellbeing (WHO-5 Well-Being Index, WHO-5), and both patient’s and clinician’s assessment of efficacy and tolerability of AOM. Treatment emergent adverse events (TRAE) were also recorded.

Results
At baseline, the mean GAF score was 47.0 (±13.9), indicating that patients experienced serious impairment in functioning. A continuous increase to 60.2 (±17.0) during treatment was found, with a robust and significant increase already after 4 weeks. At study start, patients reported diminished wellbeing, with a mean score of 10.6 (±5.6) on the WHO-5 scale. During treatment, patient wellbeing increased continuously with strong and significant improvements even after 4 weeks and an overall improvement of 4.8 (±6.9) over the course of 6 months with an endpoint of 15.4 (±5.5). Stratification of these results showed that more pronounced effects were achieved in younger patients ≤35 years (p<0.05 for GAF). The effectiveness and tolerability of AOM was rated good/very good by most patients (89.2 and 93.7%) and physicians (91.4 and 96.8%). Only few TRAEs occurred.

Conclusions
Our results show a significant positive effect after initiation of AOM treatment in predominantly stable patients with schizophrenia on their functioning and wellbeing, which was even more pronounced in patients aged ≤35 years, thereby supporting previous randomized controlled findings under routine conditions in clinical practice.
Prevalence and risk factors of post-traumatic stress disorder among elderly survivors six months after the 2008 Wenchuan earthquake in China
Authors: Li Lan , Reinhardt Jan D. , Van Dyke Craig , Wang Heng , Liu Maoqiong , Yamamoto Aiko , Chen Qian , Hu Xiuying 
Published: February 2020

Abstract
Background
Several studies indicate that older age is a risk factor for probable post-traumatic stress disorder (PTSD). However, evidence on the prevalence and risk factors for elderly disaster survivors is limited.

Methods
Multi-stage stratified sampling was applied in this cross-sectional study. The Revised Version of the Impact of Event Scale (IES-R) was used to evaluate symptoms of PTSD. Chi-squared test was used for univariable analysis of prevalence of probable PTSD by possible determinants. Multivariable logistic regression analysis was utilized to further explore risk factors for PTSD.

Results
427 elderly survivors age 60 or older participated. The prevalence of probable PTSD was 40.5, 36.3, and 21.5% according to a cut off score of the IES-R of 33, 35, and 2 points on average across items, respectively. In multivariable logistic regression, elderly survivors with a higher number of diagnosed chronic illnesses were more likely to be screened positive for PTSD and those with a greater number of family members living in the same home were less likely to be classified as having probable PTSD for all cut off scores. Elderly survivors with improved economic status and those with primary school or lower education were more often estimated to have probable PTSD with a cut off score of 35 and 2 points on average.

Conclusions
Elderly survivors in a high impact area following a major earthquake are at high risk for developing PTSD. Those who live alone and report pre-existing chronic illness are particularly vulnerable.
Impact of mother’s education on full immunization of children aged 12–23 months in Eritrea: population and health survey 2010 data analysis
Authors: Kibreab Fitsum , Lewycka Sonia , Tewelde Andebrhan 
Published: February 2020

Abstract
Background
Although vaccination coverage in Eritrea has improved in recent years, some children are still missing out, and it’s important to identify risk factors for lower coverage in order to target campaigns and interventions. The objective of this study was to assess: (1) the impact of maternal education on full immunization of children aged 12–23 months, and (2) whether the association was confounded or modified by other factors.

Methods
This study was a secondary data analysis of the Eritrean Population and Health Survey 2010 (EPHS 2010). In this analysis 1323 mothers of children aged 12–23 months were included. The outcome of the study was full immunization, defined as receiving all the WHO recommended basic vaccines: one dose of Bacillus Calmette-Gué rin (BCG), three doses of diphtheria-pertussis-tetanus(DPT), three doses of polio, and one dose of measles vaccine. The primary exposure was maternal education. Data on immunization coverage came from vaccination cards and from mothers’ or caretakers’ verbal reports. Bivariate and multivariable logistic regression analyses were performed.

Result
Full vaccination coverage among children aged 12–23 months was 83%. Most children received BCG (95%), DPT1 (97%), DPT2 (96%), DPT3 (93%), polio1 (97%), polio2 (97%), polio3 (91%) and measles (92%). In unadjusted analyses, children of mothers with primary (OR = 2.75, 95% CI 1.74–4.37), and middle or above (OR = 3.16, 95% CI 2.09–4.78) education were more likely to be fully immunised. However, after adjusting for wealth, region, ANC visit, and vaccination card ownership, only the effect for primary education remained significant (OR = 2.34, 95% CI 1.30–4.21).

Conclusion
The result of this study suggested that children of mothers who attained primary level were more likely to be fully vaccinated than children of mothers with no education. The association was influenced by wealth index of household, mothers ANC visit, region, and possession of vaccination card. The Expanded Program on Immunization of the Ministry of Health should target strategies to enhance full immunization among children of mothers with no education.