bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controllability analysis of molecular pathways points to proteins that control the entire interaction network
Authors: Devkota Prajwal , Wuchty Stefan 
Published: February 2020

AbstractInputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of proteins control a high number of pathways and vice versa. Transcending different topological levels, proteins that controlled a large number of pathways also controlled a network of interactions when all pathways were combined. Furthermore, control proteins that were robust when interactions were rewired or inverted also increasingly controlled an increasing number of pathways. As for functional characteristics, such control proteins were enriched with regulatory and signaling genes, disease genes and drug targets. Focusing on evolutionary characteristics, proteins that controlled different pathways had a penchant to be evolutionarily conserved as equal counterparts in other organisms, indicating the fundamental role that control analysis of pathways plays for our understanding of regulation, disease and evolution.
Responsiveness of various reservoir species to oral rabies vaccination correlates with differences in vaccine uptake of mucosa associated lymphoid tissues
Authors: te Kamp Verena , Freuling Conrad M. , Vos Ad , Schuster Peter , Kaiser Christian , Ortmann Steffen , Kretzschmar Antje , Nemitz Sabine , Eggerbauer Elisa , Ulrich Reiner , Schinköthe Jan , Nolden Tobias , Müller Thomas , Finke Stefan 
Published: February 2020

AbstractOral rabies vaccination (ORV) is highly effective in foxes and raccoon dogs, whereas for unknown reasons the efficacy of ORV in other reservoir species is less pronounced. To investigate possible variations in species-specific cell tropism and local replication of vaccine virus, different reservoir species including foxes, raccoon dogs, raccoons, mongooses, dogs and skunks were orally immunised with a highly attenuated, high-titred GFP-expressing rabies virus (RABV). Immunofluorescence and RT-qPCR screenings revealed clear differences among species suggesting host specific limitations to ORV. While for responsive species the palatine tonsils (tonsilla palatina) were identified as a main site of virus replication, less virus dissemination was observed in the tonsils of rather refractory species. While our comparison of vaccine virus tropism emphasizes the important role that the tonsilla palatina plays in eliciting an immune response to ORV, our data also indicate that other lymphoid tissues may have a more important role than originally anticipated. Overall, these data support a model in which the susceptibility to oral live RABV vaccine infection of lymphatic tissue is a major determinant in vaccination efficacy. The present results may help to direct future research for improving vaccine uptake and efficacy of oral rabies vaccines under field conditions.
Combining transcatheter arterial embolization with iodized oil containing Apatinib inhibits HCC growth and metastasis
Authors: Zhou Chen , Yao Qi , Zhang Hongsen , Guo Xiaopeng , Liu Jiacheng , Shi Qin , Huang Songjiang , Xiong Bin 
Published: February 2020

AbstractTranscatheter arterial embolization (TAE) plays an important role in clinical liver tumor therapy. However, hypoxia after TAE limit the medium-long term efficacy of TAE. Thus, in our study, we explored the treatment effect and mechanism of combining transcatheter arterial embolization with adopted iodized oil containing Apatinib on suppressing tumor growth and metastasis. We simulated the changing of tumor microenvironment before and after TAE both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in human umbilical vein endothelial cells (HUVECs), including cell migration, invasion and apoptosis, tube formation, and wound healing. Further experiments showed that Apatinib inhibited tumor microangiogenesis to achieve the aims of inhibiting tumor growth and recurrence by means of down-regulating the phosphorylation of the RAF-mek-erk, PI3K-akt and P38MAPK pathways. The antitumor growth and anti-angiogenic effect of Apatinib was further validated by the animal experiment. Taken together, we concluded that Apatinib inhibits the angiogenesis and growth of liver cancer by down-regulating the PI3K-akt, RAF-mek-erk and P38MAPK pathways, and has a stronger inhibitory effect in hypoxic environments. Combining TAE with adopted iodized oil containing Apatinib has a stronger inhibitory effect in VX2 liver tumor growth and metastasis, which suggesting such combinations may provide a new target and strategy for interventional therapy of liver cancer.
Gemini quaternary ammonium compound PMT12-BF4 inhibits Candida albicans via regulating iron homeostasis
Authors: Hsu Li-Hang , Kwaśniewska Dobrawa , Wang Shih-Cheng , Shen Tang-Long , Wieczorek Daria , Chen Ying-Lien 
Published: February 2020

AbstractQuaternary ammonium compounds (QACs) are classified as cationic surfactants, and are known for their biocidal activity. However, their modes of action are thus far not completely understood. In this study, we synthesized a gemini QAC, PMT12-BF4 and found that it exerted unsurpassed broad-spectrum antifungal activity against drug susceptible and resistant Candida albicans, and other pathogenic fungi, with a minimal inhibitory concentration (MIC) at 1 or 2 μg/mL. These results indicated that PMT12-BF4 used a mode of action distinct from current antifungal drugs. In addition, fungal pathogens treated with PMT12-BF4 were not able to grow on fresh YPD agar plates, indicating that the effect of PMT12-BF4 was fungicidal, and the minimal fungicidal concentration (MFC) against C. albicans isolates was 1 or 2 μg/mL. The ability of yeast-to-hyphal transition and biofilm formation of C. albicans was disrupted by PMT12-BF4. To investigate the modes of action of PMT12-BF4 in C. albicans, we used an RNA sequencing approach and screened a C. albicans deletion mutant library to identify potential pathways affected by PMT12-BF4. Combining these two approaches with a spotting assay, we showed that the ability of PMT12-BF4 to inhibit C. albicans is potentially linked to iron ion homeostasis.
Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors
Authors: Amirnasr Azadeh , Verdijk Robert M. , van Kuijk Patricia F. , Kartal Pinar , Vriends Anne L. M. , French Pim J. , van Royen Martin E. , Taal Walter , Sleijfer Stefan , Wiemer Erik A. C. 
Published: February 2020

AbstractMalignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are therapy resistant and are frequently fatal. The molecular changes underlying the malignant transformation in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. MicroRNA expression profiles were determined from a series of archival, paired samples of plexiform neurofibroma and MPNST. Ninety differentially expressed microRNAs were identified between the paired samples. Three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) in MPNST were selected for functional characterization. In general, their differential expression was validated in a relevant cell line panel but only partly in a series of unpaired, fresh frozen tumor samples. As part of the validation process we also analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs. The role of microRNAs in cancer progression was examined in NF1-derived MPNST cell lines by transiently modulating microRNA levels. Our findings indicate that some microRNAs affect migratory and invasive capabilities and Wnt signaling activity but the effects are distinct in different cell lines. We conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression.
Infection in Advanced Chronic Kidney Disease and Subsequent Adverse Outcomes after Dialysis Initiation: A Nationwide Cohort Study
Authors: Chang Chih-Hsiang , Fan Pei-Chun , Kuo George , Lin Yu-Sheng , Tsai Tsung-Yu , Chang Su-Wei , Tian Ya-Chung , Lee Cheng-Chia 
Published: February 2020

AbstractIt remains unclear whether infection events before entering end stage renal disease (ESRD) have a long-term negative impact on patients with advanced chronic kidney disease (CKD) who survive to permanent dialysis. We enrolled 62,872 patients with advanced CKD who transitioned to maintenance dialysis between January 1, 2004 and December 31, 2013. We used multivariable Cox as well as Fine and Gray models to determine the association of pre-dialysis infection exposure with all-cause mortality after starting dialysis. Compared with no infection during advanced CKD, the presence of infection exposure during that period was independently associated with a higher risk of all-cause mortality in the first year of dialysis (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.27–1.42) and also during the entire follow-up period (HR 1.19, 95% CI 1.16–1.22). The increased risks of all-cause mortality increased incrementally with higher annual number of infections during advanced CKD. Similar results were found for all other adverse outcomes, e.g. post-ESRD infection-related hospitalization and major cardiac and cerebrovascular events. In conclusion, infection events during advanced CKD was associated with increased risks of adverse outcomes after dialysis has been started. Timely interventions in such a vulnerable group may help attenuate these risks.
Corticomuscular control of walking in older people and people with Parkinson’s disease
Authors: Roeder Luisa , Boonstra Tjeerd W. , Kerr Graham K. 
Published: February 2020

AbstractChanges in human gait resulting from ageing or neurodegenerative diseases are multifactorial. Here we assess the effects of age and Parkinson’s disease (PD) on corticospinal activity recorded during treadmill and overground walking. Electroencephalography (EEG) from 10 electrodes and electromyography (EMG) from bilateral tibialis anterior muscles were acquired from 22 healthy young, 24 healthy older and 20 adults with PD. Event-related power, corticomuscular coherence (CMC) and inter-trial coherence were assessed for EEG from bilateral sensorimotor cortices and EMG during the double-support phase of the gait cycle. CMC and EMG power at low beta frequencies (13–21 Hz) was significantly decreased in older and PD participants compared to young people, but there was no difference between older and PD groups. Older and PD participants spent shorter time in the swing phase than young individuals. These findings indicate age-related changes in the temporal coordination of gait. The decrease in low-beta CMC suggests reduced cortical input to spinal motor neurons in older people during the double-support phase. We also observed multiple changes in electrophysiological measures at low-gamma frequencies during treadmill compared to overground walking, indicating task-dependent differences in corticospinal locomotor control. These findings may be affected by artefacts and should be interpreted with caution.
Diagnostic Value of C-reactive Protein and Interleukin-8 in Risk Stratification of Febrile Neutropenic Children with Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Jaing Tang-Her , Chang Chih-Chen , Chang Tsung-Yen , Chen Shih-Hsiang , Wen Yu-Chuan , Tsay Pei-Kwei 
Published: February 2020

AbstractIn this analysis, the levels of CRP and IL-8 were employed as a guide for designing the duration of antibiotics administration in the condition of febrile neutropenia. The importance of laboratory biomarkers is in the early diagnosis of critical illness and adjustment of further management. IL-8 is a useful biomarker for the early identification of critically ill patients, compared to CRP in FN.
Profile of patients with penile cancer in the region with the highest worldwide incidence
Authors: Vieira Ciro Bezerra , Feitoza Laisson , Pinho Jaqueline , Teixeira-Júnior Antonio , Lages Joyce , Calixto José , Coelho Ronald , Nogueira Leudivan , Cunha Isabela , Soares Fernando , Silva Gyl Eanes Barros 
Published: February 2020

AbstractTo determine the epidemiological, histopathological, and clinical characteristics of patients diagnosed with penile cancer in the Brazilian state of Maranhão, the region with the highest incidence worldwide. One hundred and sixteen penile cancer patients were interviewed from July 2016 to October 2018. The majority of patients lived in a rural area (57%), worked in farming (58%), had a low level of schooling or no schooling (90%), and were married or in a stable relationship (74%). The mean age was 60.4 ± 16.51 years (range, 23–93 years). Phimosis (66%), poor/moderate genital hygiene (73%), history of sexually transmitted infections (55%), and zoophilia (60%) were found in the majority of patients. Most patients had their first sexual encounter at 16.2 ± 2.8 years (range, 10–25 years), and 75% had >6 sexual partners. The most common initial symptom was pruritus (37%), and most patients waited to seek treatment (average time to treatment, 18.9 months; range, 2–84 months). Human papillomavirus (HPV)-related histologies were observed in 62% of patients. Most patients had histological grades II or III (87%), stage ≥T2 disease (84%), and lymphadenopathy at admission (42%). Penectomy was performed in 96% of patients. The population with penile cancer in the region of highest incidence in the world is marked by low socioeconomic status, high prevalence of HPV infection, and phimosis. The delay in seeking treatment is related to a very high rate of advanced cancer and aggressive surgical treatment. The high prevalence of young patients was also a striking feature.
Establishment of tetracycline-regulated bimolecular fluorescence complementation assay to detect protein-protein interactions in Candida albicans
Authors: Lai Wei-Chung , Sun H. Sunny , Shieh Jia-Ching 
Published: February 2020

AbstractTo visualize protein-protein interactions in Candida albicans with the bimolecular fluorescence complementation (BiFC) approach, we created a Tet-on system with the plasmids pWTN1 and pWTN2. Both plasmids bear a hygromycin B-resistant marker (CaHygB) that is compatible with the original Tet-on plasmid pNIM1, which carries a nourseothricin-resistant marker (CaSAT1). By using GFPmut2 and mCherry as reporters, we found that the two complementary Tet-on plasmids act synergistically in C. albicans with doxycycline in a dose-dependent manner and that expression of the fusion proteins, CaCdc11-GFPmut2 and mCherry-CaCdc10, derived from this system, is septum targeted. Furthermore, to allow detection of protein-protein interactions with the reassembly of a split fluorescent protein, we incorporated mCherry into our system. We generated pWTN1-RN and pNIM1-RC, which express the N-terminus (amino acids 1–159) and C-terminus (amino acids 160–237) of mCherry, respectively. To verify BiFC with mCherry, we created the pWTN1-CDC42-RN (or pWTN1-RN-CDC42) and pNIM1-RC-RDI1 plasmids. C. albicans cells containing these plasmids treated with doxycycline co-expressed the N- and C-terminal fragments of mCherry either N-terminally or C-terminally fused with CaCdc42 and CaRdi1, respectively, and the CaCdc42-CaRdi1 interaction reconstituted a functional form of mCherry. The establishment of this Tet-on-based BiFC system in C. albicans should facilitate the exploration of protein-protein interactions under a variety of conditions.
Plausible diagnostic value of urinary isomeric dimethylarginine ratio for diabetic nephropathy
Authors: Parmar Dharmeshkumar , Bhattacharya Nivedita , Kannan Shanthini , Vadivel Sangeetha , Pandey Gautam Kumar , Ghanate Avinash , Ragi Nagarjuna Chary , Prabu Paramasivam , Pramodkumar Thyparambil Aravindakshan , Manickam Nagaraj , Mohan Viswanathan , Sripadi Prabhakar , Kuppan Gokulakrishnan , Panchagnula Venkateswarlu 
Published: February 2020

AbstractAltered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans’ Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158–0.491] and MAC [OR 0.146; 95% CI: 0.071–0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.
Palladium supported on polypyrrole/reduced graphene oxide
nanoparticles for simultaneous biosensing application of ascorbic acid, dopamine, and
uric acid
Authors: Demirkan Buse , Bozkurt Sait , Cellat Kemal , Arıkan Kubilay , Yılmaz Mustafa , Şavk Aysun , Çalımlı Mehmet Harbi , Nas Mehmet Salih , Atalar Mehmet Nuri , Alma Mehmet Hakkı , Sen Fatih 
Published: February 2020

AbstractIn this study, we report a facile and effective production process of
palladium nanoparticles supported on polypyrrole/reduced graphene oxide (rGO/Pd@PPy
NPs). A novel electrochemical sensor was fabricated by incorporation of the prepared
NPs onto glassy carbon electrode (GCE) for the simultaneous detection of ascorbic
acid (AA), dopamine (DA) and uric acid (UA). The electrodes modified with rGO/Pd@PPy
NPs were well decorated on the GCE and exhibited superior catalytic activity and
conductivity for the detection of these molecules with higher current and oxidation
peak intensities. Simultaneous detection of these molecules was achieved due to the
high selectivity and sensitivity of rGO/Pd@PPy NPs. For each biomolecule,
well-separated voltammetric peaks were obtained at the modified electrode in cyclic
voltammetry (CV) and differential pulse voltammetry (DPV) measurements.
Additionally, the detection of these molecules was performed in blood serum samples
with satisfying results. The detection limits and calibration curves for AA, DA, and
UA were found to be 4.9 × 10−8,
5.6 × 10−8, 4.7 × 10−8 M
(S/N = 3) and ranging from 1 × 10−3 to
1.5 × 10−2 M (in 0.1 M PBS, pH 3.0), respectively.
Hereby, the fabricated rGO/Pd@PPy NPs can be used with high reproducibility,
selectivity, and catalytic activity for the development of electrochemical
applications for the simultaneous detection of these biomolecules.
Cost of wind energy generation should include energy storage allowance
Authors: Boretti Alberto , Castelletto Stefania 
Published: February 2020

AbstractThe statistic of wind energy in the US is presently based on annual average capacity factors, and construction cost (CAPEX). This approach suffers from one major downfall, as it does not include any parameter describing the variability of the wind energy generation. As a grid wind and solar only requires significant storage in terms of both power and energy to compensate for the variability of the resource, there is a need to account also for a parameter describing the variability of the power generation. While higher frequency data every minute or less is needed to design the storage, low-frequency monthly values are considered for different wind energy facilities. The annual capacity factors have an average of 0.34. They vary significantly from facility to facility, from a minimum of 0.15 to a maximum of 0.5. They also change year-by-year and are subjected to large month-by-month variability. It is concluded that a better estimation of performance and cost of wind energy facilities should include a parameter describing the variability, and an allowance for storage should be added to the cost. When high-frequency data will be eventually made available over a full year for all the wind and solar facilities connected to the same grid of given demand, then it will be possible to compute growth factors for wind and solar capacity, total power and energy of the storage, cost of the storage, and finally, attribute this cost to every facility inversely proportional to the annual mean capacity factor and directly proportional to the standard deviation about this value. The novelty of the present work is the recognition of the variability of wind power generation as a performance and cost parameter, and the proposal of a practical way to progress the design of the storage and its cost attribution to the generating facilities.
DNA extraction of microbial DNA directly from infected tissue: an optimized protocol for use in nanopore sequencing
Authors: Helmersen Karin , Aamot Hege Vangstein 
Published: February 2020

AbstractIdentification of bacteria causing tissue infections can be comprehensive and, in the cases of non- or slow-growing bacteria, near impossible with conventional methods. Performing shotgun metagenomic sequencing on bacterial DNA extracted directly from the infected tissue may improve time to diagnosis and targeted treatment considerably. However, infected tissue consists mainly of human DNA (hDNA) which hampers bacterial identification. In this proof of concept study, we present a modified version of the Ultra-Deep Microbiome Prep kit for DNA extraction procedure, removing additional human DNA. Tissue biopsies from 3 patients with orthopedic implant-related infections containing varying degrees of Staphylococcus aureus were included. Subsequent DNA shotgun metagenomic sequencing using Oxford Nanopore Technologies’ (ONT) MinION platform and ONTs EPI2ME WIMP and ARMA bioinformatic workflows for microbe and antibiotic resistance genes identification, respectively. The modified DNA extraction protocol led to an additional ~10-fold reduction of human DNA while preserving S. aureus DNA. Including the DNA sequencing and bioinformatics analyses, the presented protocol has the potential of identifying the infection-causing pathogen in infected tissue within 7 hours after biopsy. However, due to low number of S. aureus reads, positive identification of antibiotic resistance genes was not possible.