bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of miR-484 is associated with poor prognosis and tumor progression of gastric cancer
Authors: Li Ying , Liu Yusong , Yao Jie , Li Rui , Fan Xiaocheng 
Published: March 2020

Abstract
Background
Gastric cancer is one of the most common cancers leading to high cancer mortality. MicroRNA-484 (miR-484) has been evaluated as a biomarker for various types of cancers. The subject of this study is to investigate the functional role of miR-484 in gastric cancer.

Methods
The expression of miR-484 in gastric cancer was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Kaplan-Meier survival and Cox regression analyses were employed to explore the prognostic significance of miR-484 in gastric cancer. The functional role of miR-484 in gastric cancer was determined by CCK-8 and Transwell assays.

Results
The results showed that miR-484 was significantly downregulated in gastric cancer tissues and cell lines. The downregulation of miR-484 was closely related to differentiation, lymph node metastasis, TNM stage, and poor prognosis. Cox regression analyses demonstrated that miR-484 was an independent prognosis indicator for gastric cancer patients. Additionally, the downregulation of miR-484 enhanced cell proliferation, migration, and invasion in gastric cancer cells.

Conclusion
These data demonstrated that miR-484 can serve as a potential prognostic biomarker and therapeutic target for gastric cancer and it may be involved in the progression of gastric cancer.
High frequency optogenetic activation of inputs to the lateral amygdala forms distant association with foot-shock
Authors: Li Fei , Jia Chun-Hui , Huang Jun , Bi Guo-Qiang , Lau Pak-Ming 
Published: March 2020

Abstract
Aim
A hallmark of classical conditioning is that conditioned stimulus (CS) must be tightly coupled with unconditioned stimulus (US), often requiring temporal overlap between the two, or a short gap of several seconds. In this study, we investigate the temporal requirements for fear conditioning association between a strong artificial CS, high-frequency optogenetic activation of inputs into the lateral amygdala of rats, and a foot-shock to the animal with delays up to many minutes.

Methods
AAV-oChIEF-tdTomato viruses were injected into the auditory cortex and the medial geniculate nucleus of rats. An optical fiber was implanted just above the lateral amygdala of the animal. Optogenetic high-frequency stimuli (oHFS; containing five 1-s trains of 100 Hz laser pulses) were delivered to the lateral amygdala, before or after (with varying intervals) a foot-shock that elicits fear responses in the animal. Pre-trained lever-press behavior was used to assess the degree of fear recall by optogenetic test stimuli (OTS; 10 Hz for 2 min) 24 h after the association experiment.

Results
In contrast to the tight temporal requirement for classical conditioning with paired optogenetic moderate-frequency stimuli (oMFS; 10 Hz for 20 s) and foot-shock, oHFS followed by foot-shock with a 5-min or even 1-h (but not 3-h) interval could successfully establish an association to be recalled by OTS the next day. Meanwhile, foot-shock followed by oHFS with a 5-min (but not 1-h) interval could also establish the conditioning. Thus, distant association may be formed between temporally distant stimuli when the CS is strong.
A mutant vesicular stomatitis virus with reduced cytotoxicity and enhanced anterograde trans-synaptic efficiency
Authors: Lin Kunzhang , Zhong Xin , Ying Min , Li Lei , Tao Sijue , Zhu Xutao , He Xiaobin , Xu Fuqiang 
Published: March 2020

AbstractUnderstanding the connecting structure of brain network is the basis to reveal the principle of the brain function and elucidate the mechanism of brain diseases. Trans-synaptic tracing with neurotropic viruses has become one of the most effective technologies to dissect the neural circuits. Although the retrograde trans-synaptic tracing for analyzing the input neural networks with recombinant rabies and pseudorabies virus has been broadly applied in neuroscience, viral tools for analyzing the output neural networks are still lacking. The recombinant vesicular stomatitis virus (VSV) has been used for the mapping of synaptic outputs. However, several drawbacks, including high neurotoxicity and rapid lethality in experimental animals, hinder its application in long-term studies of the structure and function of neural networks. To overcome these limitations, we generated a recombinant VSV with replication-related N gene mutation, VSV-NR7A, and examined its cytotoxicity and efficiency of trans-synaptic spreading. We found that by comparison with the wild-type tracer of VSV, the NR7A mutation endowed the virus lower rate of propagation and cytotoxicity in vitro, as well as significantly reduced neural inflammatory responses in vivo and much longer animal survival when it was injected into the nucleus of the mice brain. Besides, the spreading of the attenuated VSV was delayed when injected into the VTA. Importantly, with the reduced toxicity and extended animal survival, the number of brain regions that was trans-synaptically labeled by the mutant VSV was more than that of the wild-type VSV. These results indicated that the VSV-NR7A, could be a promising anterograde tracer that enables researchers to explore more downstream connections of a given brain region, and observe the anatomical structure and the function of the downstream circuits over a longer time window. Our work could provide an improved tool for structural and functional studies of neurocircuit.
Coexistence of cerebral hypometabolism and neuroinflammation in the thalamo-limbic-brainstem region in young women with functional somatic syndrome
Authors: Matsudaira Takashi , Terada Tatsuhiro , Obi Tomokazu , Yokokura Masamichi , Takahashi Yukitoshi , Ouchi Yasuomi 
Published: March 2020

Abstract
Background
Functional somatic syndrome (FSS) is a disorder characterized by clusters of medically unexplained symptoms. Some women suffer from persistent FSS after human papillomavirus (HPV) vaccination. However, a causal relationship has not been established, and the pathophysiology of FSS remains elusive. Here, we aimed to identify the brain regions showing altered cerebral metabolism and neuroinflammation in patients with FSS and to correlate the measures of positron emission tomography (PET) with clinical data. Twelve women diagnosed with FSS following HPV vaccination (FSS group) underwent both [18F]FDG-PET to measure glucose metabolism and [11C]DPA713-PET to measure neuroinflammation. [18F]FDG standardized uptake value ratio (SUVR) and [11C]DPA713 binding potential (BPND) values were compared voxel-wise between the FSS and control groups (n = 12 for [18F]FDG, n = 16 for [11C]DPA713). A region-of-interest (ROI)-based analysis was performed to correlate PET parameters with clinical scores. Statistical significance was set at p < 0.05 corrected for multiple comparisons.

Results
Statistical parametric mapping revealed a concomitant significant decrease of [18F]FDG SUVR and increase of [11C]DPA713 BPND in the regions covering the thalamus, mesial temporal area, and brainstem in the FSS group. Correlation analysis revealed that intelligence and memory scores were significantly positively correlated with [18F]FDG SUVR and negatively so with [11C]DPA713 BPND in these regions. A direct comparison between [18F]FDG SUVR and [11C]DPA713 BPND revealed a significant positive correlation in the right hippocampus and amygdala.

Conclusions
Cerebral hypometabolism with neuroinflammation occurring in the thalamo-limbic-brainstem region may reflect the pathophysiology of FSS.
Effects of siRNA silencing on the susceptibility of the fish cell line CHSE-214 to Yersinia ruckeri
Authors: Menanteau-Ledouble Simon , Schachner Oskar , Lawrence Mark L. , El-Matbouli Mansour 
Published: March 2020

AbstractYersinia ruckeriis a facultative intracellular enterobacterium mostly known as the causative agent of enteric redmouth disease in salmonid fish. In the present study, we applied RNA inhibition to silence twenty pre-selected genes on the genome of a fish cell line (CHSE-214) followed by a gentamicin assay to quantify the effect of silencing on the cells’ susceptibility to infection and found that silencing of 18 out of 20 genes significantly reduced the number ofY. ruckerirecovered. These findings improve our understanding of the infection process byY. ruckeriand of the interactions between this bacterial pathogen and host cells.
New approaches for the solution of space-time fractional Schrödinger equation
Authors: Demir Ali , Bayrak Mine Aylin , Ozbilge Ebru 
Published: March 2020

AbstractThe aim of this study is to establish the solution of the time-space fractional Schrödinger equation subject to initial and boundary conditions which has many applications in science such as nonlinear optics, plasma physics, super conductivity, based on the residual power series method (RPSM). We first apply suitable transformations to make the order of one of the fractional derivatives integer to implement the RPSM easily to construct the fractional power series solution. The method proposed in this article gives highly encouraging results. Illustrative examples show that this method is compatible with solving such fractional differential equations.
Shannon type inequalities via time scales theory
Authors: Ansari Iqrar , Khan Khuram Ali , Nosheen Ammara , Pečarić Ðilda , Pečarić Josip 
Published: March 2020

AbstractThe aim of present paper is to obtain Shannon type inequalities using the extended version of Jensen’s inequality in time scales settings. The concept of differential entropy of a continuous random variable on time scales is introduced, and its bounds for some particular distributions are also estimated.
Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial communities
Authors: Böhm Maria-Elisabeth , Razavi Mohammad , Marathe Nachiket P. , Flach Carl-Fredrik , Larsson D. G. Joakim 
Published: March 2020

Abstract
Background
New antibiotic resistance determinants are generally discovered too late, long after they have irreversibly emerged in pathogens and spread widely. Early discovery of resistance genes, before or soon after their transfer to pathogens could allow more effective measures to monitor and reduce spread, and facilitate genetics-based diagnostics.

Results
We modified a functional metagenomics approach followed by in silico filtering of known resistance genes to discover novel, mobilised resistance genes in class 1 integrons in wastewater-impacted environments. We identified an integron-borne gene cassette encoding a protein that conveys high-level resistance against aminoglycosides with a garosamine moiety when expressed in E. coli. The gene is named gar (garosamine-specific aminoglycoside resistance) after its specificity. It contains none of the functional domains of known aminoglycoside modifying enzymes, but bears characteristics of a kinase. By searching public databases, we found that the gene occurs in three sequenced, multi-resistant clinical isolates (two Pseudomonas aeruginosa and one Luteimonas sp.) from Italy and China, respectively, as well as in two food-borne Salmonella enterica isolates from the USA. In all cases, gar has escaped discovery until now.

Conclusion
To the best of our knowledge, this is the first time a novel resistance gene, present in clinical isolates, has been discovered by exploring the environmental microbiome. The gar gene has spread horizontally to different species on at least three continents, further limiting treatment options for bacterial infections. Its specificity to garosamine-containing aminoglycosides may reduce the usefulness of the newest semisynthetic aminoglycoside plazomicin, which is designed to avoid common aminoglycoside resistance mechanisms. Since the gene appears to be not yet common in the clinics, the data presented here enables early surveillance and maybe even mitigation of its spread.
Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer
Authors: English Krystal , Shepherd Andrew , Uzor Ndidi-Ese , Trinh Ronnie , Kavelaars Annemieke , Heijnen Cobi J. 
Published: March 2020

AbstractNeurodegenerative disorders, including chemotherapy-induced cognitive impairment, are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.We used an in vitro system in which astrocytes containing mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons damaged by cisplatin. Culture of primary cortical neurons with cisplatin reduced neuronal survival and depolarized neuronal mitochondrial membrane potential. Cisplatin induced abnormalities in neuronal calcium dynamics that were characterized by increased resting calcium levels, reduced calcium responses to stimulation with KCl, and slower calcium clearance. The same dose of cisplatin that caused neuronal damage did not affect astrocyte survival or astrocytic mitochondrial respiration. Co-culture of cisplatin-treated neurons with astrocytes increased neuronal survival, restored neuronal mitochondrial membrane potential, and normalized neuronal calcium dynamics especially in neurons that had received mitochondria from astrocytes which underlines the importance of mitochondrial transfer. These beneficial effects of astrocytes were associated with transfer of mitochondria from astrocytes to cisplatin-treated neurons. We show that siRNA-mediated knockdown of the Rho-GTPase Miro-1 in astrocytes reduced mitochondrial transfer from astrocytes to neurons and prevented the normalization of neuronal calcium dynamics.In conclusion, we showed that transfer of mitochondria from astrocytes to neurons rescues neurons from the damage induced by cisplatin treatment. Astrocytes are far more resistant to cisplatin than cortical neurons. We propose that transfer of functional mitochondria from astrocytes to neurons is an important repair mechanism to protect the vulnerable cortical neurons against the toxic effects of cisplatin.
Low incidence of maxillary hypoplasia in isolated cleft palate
Authors: Azouz Vitali , Ng Marilyn , Patel Niyant , Murthy Ananth S. 
Published: March 2020

Abstract
Background
The cause of maxillary growth restriction in patients with cleft lip and palate remains controversial. While studies have investigated the effects surgical technique and timing have on maxillary growth, few focus on patients with isolated cleft palate (ICP). The purpose of this study was to determine the impact palate repair and its associated complications may have on maxillary growth.

Methods
A retrospective chart review of ICP patients who underwent palatoplasty from 1962 to 1999 at Akron Children’s Hospital was performed. Patient demographics, Veau type, age at primary repair, closure technique, presence of fistula or velopharyngeal insufficiency (VPI), number of palatal operations, maxillary hypoplasia (MH) frequency, and follow-up were recorded. Exclusion criteria included patients with cleft lip, submucous cleft, or syndromes.

Results
Twenty-nine non-syndromic ICP patients were identified; 62% (n = 18) had Veau type 1 and 38% (n = 11) had Veau type 2. All patients underwent 2-flap or Furlow palatoplasty with mobilization of mucoperiosteal flaps. Vomerine flaps were used in all Veau 2 cleft palate closures. Palatoplasty was performed at a mean age of 19.9 ± 8.2 months. Average follow-up was 209 ± 66.5 months. The rate of VPI was 59% (n = 17) and the rate of oronasal fistula was 14% (n = 4).

Conclusions
There was a low incidence of MH despite complications after initial palate closure. Our results seem to suggest that age at palate closure, type of cleft palate, and type of surgical technique may not be associated with MH. Additionally, subsequent procedures and complications after primary palatoplasty such as VPI and palatal fistula may not restrict maxillary growth.
Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma
Authors: Rodríguez-Cid Jeronimo Rafael , Campos-Gomez Saul , García-Montes Vanessa , Magallanes-Maciel Manuel , Flores-Mariñelarena Rodrigo Rafael , Fernández-Garibay Valeria Michelle , González-Espinoza Iván Romarico , Ceja-García Juan Paulo , Cázarez-Price Juan Carlos , Martínez-Barrera Luis , Barriguete-Parra Leopoldo , Zuloaga-Fernandez Carlos Jose , Kuri-Exsome Roberto , Suárez-García David , Gonzalez-Villanueva Jorge Ignacio , Flores-Anaya Noé , Acevedo-Delgado Jose Antonio , Astorga-Ramos Alma Magdalena , Gerson-Cwilich Raquel , Villalobos-Prieto Alberto , Rodríguez-Silva Claudia , Noriega-Iriondo Maria Fernanda , Vázquez-Cortés Leticia , Perales-Rodríguez Eusebio , Acosta-Espinoza Alicia , Perez-Lozano Yareni , Capdeville-García Daniel , Alatorre-Alexander Jorge Arturo 
Published: March 2020

PURPOSE The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.
Comparative Safety and Health Care Expenditures Among Patients With Chronic Myeloid Leukemia Initiating First-Line Imatinib, Dasatinib, or Nilotinib
Authors: Cole Ashley L. , Wood William A. , Muluneh Benyam , Lund Jennifer L. , Elston Lafata Jennifer , Dusetzina Stacie B. 
Published: March 2020

PURPOSE: Tyrosine kinase inhibitors (TKIs) have dramatically improved survival for patients with chronic myeloid leukemia (CML). No overall survival differences were observed between patients initiating first- and second-generation TKIs in trials; however, real-world safety and cost outcomes are unclear. We evaluated comparative safety and health care expenditures between first-line imatinib, dasatinib, and nilotinib among patients with CML. PATIENTS AND METHODS: Eligible patients had one or more fills for imatinib, dasatinib, or nilotinib in the MarketScan Commercial and Medicare Supplemental databases between January 1, 2011, and December 31, 2016 (earliest fill is the index date), 6 months pre-index continuous enrollment, CML diagnosis, and no TKI use in the pre-index period. Hospitalizations or emergency department visits (safety events) were compared across treatment groups using propensity-score-weighted 1-year relative risks (RRs) and subdistribution hazard ratios (HRs). Inflation-adjusted annual health care expenditures were compared using quantile regression. RESULTS: Eligible patients included 1,417 receiving imatinib, 1,067 receiving dasatinib, and 647 receiving nilotinib. The 1-year risk of safety events was high: imatinib, 37%; dasatinib, 44%; and nilotinib, 40%, with higher risks among patients receiving dasatinib (RR, 1.17; 95% CI, 1.06 to 1.30) and nilotinib (RR, 1.07; 95% CI, 0.93 to 1.23) compared with those receiving imatinib. Over a median of 1.7 years, the cumulative incidence of safety events was higher among patients receiving dasatinib (HR, 1.23; 95% CI, 1.10 to 1.38) and nilotinib (HR, 1.08; 95% CI, 0.95 to 1.24) than among those receiving imatinib. One-year health care expenditures were high (median, $125,987) and were significantly higher among patients initiating second-generation TKIs compared with those receiving imatinib (difference in medians: dasatinib v imatinib, $22,393; 95% CI, $17,068 to $27,718; nilotinib v imatinib, $19,463; 95% CI, $14,689 to $24,236). CONCLUSION: Patients receiving imatinib had the lowest risk of hospitalization or emergency department visits and 1-year health care expenditures. Given a lack of significant differences in overall survival, imatinib may represent the ideal first-line therapy for patients, on average.
Assessing the Impact of Early Identification of Patients Appropriate for Palliative Care on Resource Use and Costs in the Final Month of Life
Authors: Look Hong Nicole J. , Liu Ning , Wright Frances C. , MacKinnon Marnie , Seung Soo Jin , Earle Craig C. , Gradin Sharon , Sati Saurabh , Buchman Sandy , Mittmann Nicole 
Published: March 2020

PURPOSE: This study evaluates whether an intervention to identify Canadian patients eligible for a palliative approach changes the use of health care resources and costs within the final month of life. METHODS: Between 2014 and 2017, physicians identified 1,187 patients in family practice units and cancer centers who were likely to die within 1 year based on diagnosis, symptom assessment, and performance status. A multidisciplinary intervention that included activation of community resources and initiation of palliative planning was started. By using propensity-score matching, patients in the intervention group were matched 1:1 with nonintervention controls selected from provincial administrative data. We compared health care use and costs (using 2017 Canadian dollars) for 30 days before death between patients who died within the 1-year follow-up and matched controls. RESULTS: Groups (n = 629 in each group) were well-balanced in sociodemographic characteristics, comorbidities, and previous health care use. In the last 30 days, there was no differences in proportions between the two groups of patients regarding emergency department visits, intensive care unit admissions, or inpatient hospitalizations. However, patients in the intervention group had greater use of palliative physician encounters, community home care visits, and/or physician home visits (92.8% v 88.4%; P = .007). In the 507 pairs with cancer, more patients in the intervention group underwent chemotherapy (44% v 33%; P < .001) and radiation (18.7% v 3.2%; P = .043) in the last 30 days. Mean cost per patient was similar for the intervention group (mean, $17,231; 95% CI, $16,027 to $18,436) and for the control group (mean, $16,951; 95% CI, $15,899 to $18,004). CONCLUSION: Even with the limitations in our observational study design, identification of palliative patients did not significantly change overall costs but may shift resources toward palliative services.