bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal growth factor receptor mutations in non–small cell lung cancer undetected by high-sensitivity allele-specific real-time polymerase chain reaction–based assays
Authors: Shen Chia-I , Ho Hsiang-Ling , Yeh Yi-Chen , Chiu Chao-Hua , Chou Teh-Ying 
Published: February 2020

Background:
Identifying epidermal growth factor receptor (EGFR) mutation status is critical for planning lung cancer treatment. Sanger sequencing detects both known and novel mutations but shows poor sensitivity. High-sensitivity allele-specific real-time polymerase chain reaction (ASRP)-based assays offer quick and reliable results, but may overlook uncommon mutations. We aimed to define the rate at which high-sensitivity ASRP-based assays missed uncommon EGFR mutations.

Methods:
Non–small cell lung cancer specimens that were diagnosed as EGFR wild-type (EGFR-WT) by high-sensitivity ASRP-based assays and had residual DNA samples were sent for Sanger sequencing. Patient characteristics and clinical features were evaluated by chart review, and outcomes of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy were studied.

Results:
Hundred DNA specimens diagnosed by high-sensitivity ASRP-based assays as EGFR-WT were rechecked by Sanger sequencing. Two samples which were re-biopsy specimens from patients with EGFR mutations were excluded from the analysis. Sanger sequencing was failed in 24 samples. Among the remaining 74 samples, 6 (8.1%) had EGFR mutations—one exhibited exon 19 deletion (delT751_I759insS), two exhibited substitution mutations (S768I+V769L and L861Q), and three exhibited exon 20 insertions (N771_P772insN, P772_H773insHP, and H773_V774insAH). Only the patient with the exon 19 deletion had received EGFR-TKI therapy. Although the best tumor response was only stable disease, this was maintained for >10 months.

Conclusion:
High-sensitivity ASRP-based assays can overlook uncommon mutations. This detection failure rate is worth noting, especially when treating patients from regions known to have a high prevalence of EGFR mutation. Patients carrying uncommon mutations may still benefit from EGFR-TKI therapy.
Efficacy of Using Available Data to Examine Nurse Staffing Ratios and Quality of Care Metrics
Authors: Carlisle Byron , Perera Anjali , Stutzman Sonja E. , Brown-Cleere Shelley , Parwaiz Aatika , Olson DaiWai M. 
Published: February 2020

ABSTRACT

BACKGROUND: Nurse staffing ratios impact both the quality and safety of care on a particular unit. Most hospitals have access to a large volume of nurse-sensitive outcomes. We hypothesized that these data could be used to explore the impact of changing the nurse-to-patient ratio on patient-reported outcomes, nurse satisfaction scores, and quality of care metrics. METHODS: Retrospective data from hospital resources (eg, Press Ganey reports) were linked to daily staffing records (eg, assignment sheets) in a pre-post study. Before September 2017, the nurse-to-patient ratio was 1:1.75 (pre); afterward, the ratio was reduced to 1:1.5 (post). RESULTS: Press Ganey National Database of Nursing Quality Indicators scores were improved, staffing turnover rates were reduced, and falls were linked to periods of high nurse-to-patient ratios. CONCLUSION: This study shows the efficacy of using readily available metrics to explore for associations between nurse staffing and nurse-sensitive outcomes at the nursing care unit level. This provides a unique perspective to optimize staffing ratios based on personalized (unit-level) metrics.
Clinical impression for identification of vulnerable older patients in the emergency department
Authors: Calf Agneta H. , Lubbers Sonja , van den Berg Annemarie A. , van den Berg Else , Jansen Carolien J. , van Munster Barbara C. , de Rooij Sophia E. , ter Maaten Jan C. 
Published: February 2020

Objectives:
To investigate whether the clinical impression of vulnerability and the Dutch Safety Management Program (VMS), a screening instrument on four geriatric domains (activities in daily living, falls, malnutrition, delirium) are useful predictors of 1-year mortality in older patients in the emergency department.

Methods:
This was a prospective observational study in the emergency department of a tertiary care teaching hospital. Patients aged 65 years and older visiting the emergency department, and their attending physicians and nurses were included. Clinical impression of vulnerability appraised by physician and nurse and the VMS-screening were recorded.

Results:
We included 196 patients of whom 64.8%, 61.7%, and 52.6% were considered vulnerable based on the clinical impression of vulnerability of physicians, nurses, and VMS-screening, respectively. Agreement between clinical impression of vulnerability of physicians and nurses, and VMS-screening were both fair (overall agreement 63.3% for both, and respectively kappa 0.32 and kappa 0.31). Clinical impression of vulnerability of physicians, nurses, and VMS-screening had a sensitivity of respectively 94%, 86%, and 73% for predicting 1-year mortality. A positive clinical impression of vulnerability was associated mostly with factors which can be observed directly during first patient contact after arrival to the emergency department, such as age, nutritional status, and functional impairment.

Conclusion:
The clinical impression of vulnerability is a simple dichotomous question which can be used as a first step in the identification of vulnerable older emergency department patients, whereas the more time-consuming VMS-screening is more specific for detection of vulnerability. The clinical impression of vulnerability is therefore useful in a busy emergency department environment where time and resources are limited.
The use of 3D virtual surgical planning and computer aided design in reconstruction of maxillary surgical defects
Authors: Glas Haye H. , Vosselman Nathalie , de Visscher Sebastiaan A.H.J. 
Published: February 2020

Purpose of reviewThe present review describes the latest development of 3D virtual surgical planning (VSP) and computer aided design (CAD) for reconstruction of maxillary defects with an aim of fully prosthetic rehabilitation. The purpose is to give an overview of different methods that use CAD in maxillary reconstruction in patients with head and neck cancer.Recent findings3D VSP enables preoperative planning of resection margins and osteotomies. The current 3D VSP workflow is expanded with multimodal imaging, merging decision supportive information. Development of more personalized implants is possible using CAD, individualized virtual muscle modelling and topology optimization. Meanwhile the translation of the 3D VSP towards surgery is improved by techniques like intraoperative imaging and augmented reality. Recent improvements of preoperative 3D VSP enables surgical reconstruction and/or prosthetic rehabilitation of the surgical defect in one combined procedure.SummaryWith the use of 3D VSP and CAD, ablation surgery, reconstructive surgery, and prosthetic rehabilitation can be planned preoperatively. Many reconstruction possibilities exist and a choice depends on patient characteristics, tumour location and experience of the surgeon. The overall objective in patients with maxillary defects is to follow a prosthetic-driven reconstruction with the aim to restore facial form, oral function, and do so in accordance with the individual needs of the patient.
Health Literacy Assessment of Detained Individuals and Correctional Officers Within a Large Urban Jail
Authors: Welvers Alecia , Rosenberger Kelly D. , Corbridge Susan J. 
Published: February 2020

Background:
Little research has been done to address the health literacy level of detained individuals and correctional officers.

Purpose:
The aim of this pilot project was to describe the health literacy of individuals detained or working within a large urban jail to inform their health education.

Methods:
Health literacy assessments were conducted using the Rapid Estimate of Adult Literacy in Medicine–Short Form (REALM-SF) and the Newest Vital Sign (NVS) tools.

Results:
Of the 48 participants, 17% (n = 8) exhibited low health literacy on the REALM-SF, whereas 38% (n = 18) demonstrated the need for improved health literacy when assessed with the NVS. Detained individuals from the women's tiers were more likely to have lower health literacy than the detained veterans or correctional officers.

Conclusions:
Results indicate that tailored health education programming, using evidence-based health literacy improvement techniques, should be offered to the individuals detained or working within a correctional facility.
Angiotensin II Type-1 Receptor Antibodies Are Associated With Active Allograft Dysfunction Following Pediatric Liver Transplantation
Authors: Wozniak Laura J. , Hickey Michelle J. , Chan Alvin P. , Venick Robert S. , Farmer Douglas G. , Busuttil Ronald W. , Reed Elaine F. , McDiarmid Sue V. 
Published: February 2020

Background.
Angiotensin II type-1 receptor (AT1R) antibodies have been associated with rejection and allograft loss in solid organ transplantation and may act synergistically with HLA donor-specific antibodies (DSA). Our aims were to assess the prevalence of AT1R antibodies and determine if they were associated with allograft dysfunction in pediatric liver transplant recipients.

Methods.
We performed a retrospective, cross-sectional study of HLA DSA and AT1R antibodies in 2 cohorts of pediatric liver transplant recipients: a stable control cohort with normal allograft function (n = 70) who consented to have serum samples collected for research purposes during a routine clinic visit and a cohort with active allograft dysfunction (n = 9) whose serum samples were collected as part of clinical care.

Results.
AT1R antibodies >17 U/mL were detected in 29% of stable control patients and 89% of patients with active allograft dysfunction (P = 0.001). In stable control patients, AT1R antibodies were associated with younger age at transplant (P = 0.010), younger age at time of sample collection (P < 0.001), shorter interval since transplant (P = 0.090), and presence of HLA DSA (P = 0.003). AT1R antibodies in stable control patients were not associated with rejection or allograft loss. However, AT1R antibodies combined with HLA DSA in patients with active allograft dysfunction were associated with rejection and allograft loss.

Conclusions.
Our results suggest that AT1R antibodies are more common in patients with active allograft dysfunction and may be a risk factor for worse outcomes. Further research is needed to longitudinally assess the clinical impact of HLA DSA and AT1R antibodies.
In silico chemical profiling and identification of neuromodulators fromCurcuma amadatargeting Acetylcholinesterase
Authors: Ali Md. Chayan , Munni Yeasmin Akter , Das Raju , sultana Marium , Akter Nasrin , Rahman Mahbubur , Uddin Md. Nazim , Das Kantu , Hossen Md. , Hannan Md. Abdul , Dash Raju 
Published: February 2020

AbstractCurcuma amada or Mango ginger, a member of the Zingiberaceae family, has been revealed as a beneficiary medicinal plant having diverse pharmacological activities against a wide range of diseases. Due to having neuromodulation properties of this plant, the present study characterized the secondary metabolites of Curcuma amada for their drug-likeness properties, identified potent hits by targeting Acetylcholinesterase (AChE) and revealed neuromodulatory potentiality by network pharmacology approaches. Here in silico ADMET analysis was performed for chemical profiling, and molecular docking and molecular dynamics simulations were used to hit selection and binding characterizations. Accordingly, ADMET prediction showed that around 87.59% of compounds processed drug-likeness activity, where four compounds have been screened out by molecular docking. Guided from induced-fit docking, molecular dynamics simulations revealed phytosterol and curcumin derivatives as the most favorable AChE inhibitors with the highest binding energy, as resulted from MM-PBSA analysis. Furthermore, all of the four hits were appeared to modulate several signaling molecules and intrinsic cellular pathways in network pharmacology analysis, which are associated with neuronal growth survival, inflammation, and immune response, supporting their capacity to revert the condition of neuro-pathobiology. Together, the present in silico based characterization and system pharmacology based findings demonstrate Curcuma amada, as a great source of neuromodulating compounds, which brings about new development for complementary and alternative medicine for the prevention and treatment of neurodegenerative disorders.
A targeted folate receptor-α near-infrared fluorescent agent used for in vitro diagnosis of endometrial cytology
Authors: Liang Dongxin , Tuo Xiaoqian , Zhao Lanbo , Zhang Kailu , Wang Yiran , Feng Xue , Yin Panyue , Guo Lin , Jing Wei , Wang Qing , Sun Chao , Zou Junkai , Han Lu , Li Qiling 
Published: February 2020

AbstractThe aim of this study is to perform the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions.
A novel germline EGFR variant p.R831H causes predisposition to familial CDK12-mutant prostate cancer with tandem duplicator phenotype
Authors: Qian Kaiyu , Wang Gang , Ju Lingao , Liu Jiyan , Zheng Hang , Zhang Yingao , Chen Liang , Xiong Yaoyi , Luo Yongwen , Wang Yejinpeng , Peng Tianchen , Chen Fangjin , Liu Dongmei , Liu Xuefeng , Zhang Yi , Xiao Yu , Wang Xinghuan 
Published: February 2020

Abstract5-10% of total prostate cancer (PCa) cases are hereditary. Particularly, immunocheckpoint inhibitor-sensitive tandem duplicator phenotype (TDP) accounts for 6.9% PCa cases, whereas genetic susceptibility genes remain completely unknown. We identified a Chinese family with two PCa patients, in which the PCa phenotype co-segregated with a rare germline variant EGFRR831H. Patient-derived conditionally reprogrammed cells (CRC) exhibited increased EGFR and AKT phosphorylation, and a sensitivity to EGFR antagonist Afatinib in migration assays, suggesting the EGFR allele was constitutively active. Both EGFRR831H-mutant tumors contained biallelic CDK12 inactivation, together with prominent tandem duplication across the genome. These somatic mutations could be detected in urine before surgery. Analysis of public databases showed a significant correlation between mutation status of EGFR and CDK12. Taken together, our genetic and functional analyses identified a previously undescribed link between EGFR and prostate cancer.
Partitioning the colonization and extinction components of beta diversity: Spatiotemporal species turnover across disturbance gradients
Authors: Tatsumi Shinichi , Strengbom Joachim , Čugunovs Mihails , Kouki Jari 
Published: February 2020

ABSTRACTChanges in species diversity often result from species losses and gains. The dynamic nature of beta diversity (i.e., spatial variation in species composition) that derives from such temporal species turnover, however, has been largely overlooked. Here, we disentangled extinction and colonization components of beta diversity by using the sets of species that went locally extinct and that newly colonized the given sites. We applied this concept of extinction and colonization beta diversity to plant communities that have been repeatedly measured in experimentally disturbed forests. We first found no difference in beta diversity across disturbance gradients when it was analyzed for communities at a single point in time. From this result, we might conclude that disturbance caused no impact on how species assemble across space. However, when we analyzed the extinction and colonization beta diversity, both measures were found to be significantly lower in disturbed sites compared to undisturbed sites. These results indicate that disturbance removed similar subsets of species across space, making communities differentiate, but at the same time induced spatially uniform colonization of new species, causing communities to homogenize. Consequently, the effects of these two processes canceled each other out. The relative importance of extinction and colonization componentsper sealso changed temporally after disturbance. Analyses using extinction and colonization beta diversity allowed us to detect nonrandom dis- and re-assembly dynamics in plant communities. Our results suggest that common practices of analyzing beta diversity at one point in time can mask significant variation driven by disturbance. Acknowledging the extinction–colonization dynamics behind beta diversity is essential for understanding the spatiotemporal organization of biodiversity.
Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in Sugar Porter family
Authors: Custódio Tânia Filipa , Paulsen Peter Aasted , Frain Kelly May , Pedersen Bjørn Panyella 
Published: February 2020

AbstractThe human glucose transporters GLUT1 and GLUT3 have a central role in glucose uptake as canonical members of the Sugar Porter (SP) family. GLUT1 and GLUT3 share a fully conserved substrate-binding site with identical substrate coordination, but differ significantly in transport affinity in line with their physiological function. Here we present a 2.4 Å crystal structure of GLUT1 in an inward open conformation and compare it with GLUT3 using both structural and functional data. Our work shows that interactions between a cytosolic “Sugar Porter motif” and a conserved “A motif” stabilize the outward conformational state and increases substrate apparent affinity. Furthermore, we identify a previously undescribed Cl-ion site in GLUT1 and an endofacial lipid/glucose binding site which modulate GLUT kinetics. The results provide a possible explanation for the difference between GLUT1 and GLUT3 glucose affinity, imply a general model for the kinetic regulation in GLUTs and suggest a physiological function for the defining SP sequence motif in the Sugar Porter family.Summary BlurbNew structure of GLUT1 compared to GLUT3 explain different substrate affinities. The result provide a functional rationale for key structural motifs that define the universal Sugar Porter family.
First record of a Nathusius’ pipistrelle (Pipistrellus nathusii) overwintering at a latitude above 60°N
Authors: Blomberg AS , Vasko V , Salonen S , Pētersons G , Lilley TM 
Published: February 2020

AbstractHighly mobile species are considered to be the first to respond to climate change by transforming their ranges of distribution. There is evidence suggesting thatPipistrellus nathusii, a long-distance migrant, is expanding both its reproduction and overwintering ranges to the North. We recorded the echolocation calls of bats at 16 sites in South-Western Finland on two consecutive winters, and detected calls ofP. nathusiiat one of the sites throughout the latter winter. To our knowledge, this is the northernmost observation of an overwinteringP. nathusii, and further evidence that the species is already responding to climate change.
Identification of Immunological Features Enables Survival Prediction of Muscle-Invasive Bladder Cancer Patients Using Machine Learning
Authors: Gavriel Christos G , Dimitriou Neofytos , Brieu Nicolas , Nearchou Ines P , Arandjelović Ognjen , Schmidt Günter , Harrison David J , Caie Peter D 
Published: February 2020

AbstractClinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insights into patient prognosis. In this paper, we apply multiplex immunofluorescence on MIBC tissue sections to capture whole slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1. We propose a machine learning based approach for the prediction of 5 year prognosis with different combinations of image, clinical, and spatial features. An ensemble model comprising several functionally different models successfully stratifies MIBC patients into two risk groups with high statistical significance (pvalue < 1e− 05). Critical to improving MIBC survival rates, our method classifies correctly 71.4% of the patients who succumb to MIBC within 5 years, significantly higher than the 28.6% of the current clinical gold standard, the TNM staging system.
SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression
Authors: Traughber C. Alicia , Opoku Emmanuel , Brubaker Gregory , Major Jennifer , Lu Hanxu , Lorkowski Shuhui Wang , Neumann Chase , Hardaway Aimalie , Chung Yoon-Mi , Gulshan Kailash , Sharifi Nima , Brown J. Mark , Smith Jonathan D. 
Published: February 2020

ABSTRACTHigh density lipoprotein (HDL) metabolism, in part, is facilitated by scavenger receptor class B, type 1 (SR-B1) that mediates its uptake into cells. SR-B1 is upregulated in prostate cancer tissue. Here, we report that knockout (KO) of SR-B1 via CRISPR/Cas9 editing led to reduced HDL uptake into prostate cancer cells, and reduced their proliferation in response to HDL.In vivostudies using syngeneic SR-B1 wildtype (SR-B1+/+) and SR-B1 KO (SR-B1−/−) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice showed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1−/−prostate cancer cells formed smaller tumors in WT hosts, than SR-B1+/+cells in same host model. Tumor volume data was overall similar to survival data. We conclude that tumoral SR-B1 KO reduced HDL-mediated increases in prostate cancer cell proliferation and disease progression.