bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suboptimal Immune Recovery Despite Sustained HIV Suppression Among a Yi Ethnic Population in Southwest China
Authors: Chen Liyu , Liu Chang-Hai , Kang Shuang , Du Lingyao , Ma Fanghua , Li Changmin , Bai Lang , Li Hong , Tang Hong 
Published: June 2021

Abstract
Objectives: Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of non-AIDS-related and AIDS-related events. The aim of this study was to investigate the potential determinants associated with suboptimal CD4+ T cell count recovery during free ART with sustained viral suppression among a HIV-infected Yi ethnic population in Liangshan Prefecture, an area with high HIV prevalence in China.Method: This retrospective study included all HIV-infected Yi adults (≥ 18 years and with baseline CD4+ T cell count less than 500 cells/μL) who initiated ART supported by NFATP between January 2015 and December 2018 in Zhaojue county, Liangshan Prefecture (Figure 1), and achieved virological suppression (viral load < 50 copies/mL) within 12 months after ART initiation and maintained sustained virological suppression. Univariate and multivariate log-binomial regression models were used to assess determinants of suboptimal immune recovery, producing adjusted odds ratios (aORs) and confidence intervals (CIs).Results: A total of 277 HIV-infected Yi patients (male/female, 140/137) with a mean age of 36.57 ± 7.63 years and a mean baseline CD4+ T cell count of 284.49 ± 117.11 cells/μL were included. Nearly half of the Yi patients were infected through injection drug use (48.7%, 135/277), and the prevalence of anti-HCV antibody was high (43.7%, 121/277). The free ART regimens were 91% efavirenz-based, 5.1% nevirapine-based, and 3.9% lopinavir/ritonavir-based. After a mean 3.77 ± 1.21 years of ART, optimal immune recovery (CD4+ T cell count ≥ 500 cells/μL), intermediate immune recovery (350≤CD4 < 500 cells/μL), and suboptimal immune recovery (CD4 < 350 cells/μL) occurred in 32.9%, 31%, and 36.2% of the included patients, respectively. After adjustments, multivariable analysis revealed that low pre-ART CD4+ cell count, WHO clinical stage III and IV, and coinfection with HCV were associated with suboptimal immune recovery. Conclusions: Our study support prompt ART initiation after HIV diagnosis, and curative HCV treatment in HCV/HIV co-infected patients for improving the immunological effectiveness of ART among HIV-infected Yi patients in Liangshan Prefecture.Trial registration: None
Efficacy of Single-site Radiotherapy Plus PD-1 Inhibitors vs PD-1 Inhibitors for Oligometastatic Non-Small Cell Lung Cancer
Authors: Wang Peiliang , Yin Tianwen , Zhao Kaikai , Yu Jinming , Teng Feifei 
Published: June 2021

Abstract
Purpose: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aim to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods: We retrospectively identified oligometastatic NSCLC (≤4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS) . Results: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of radiotherapy to ICI therapy significant increased the best ORR from 31.2% to 50.8%, p=0.015). The out-of-field (abscopal`) response rate could reach 41.3% (95% CI, 26.5%-56.1%) in the ICI plus RT group. Median progression-free survival was 8.9 months (95%CI, 4.7-13.1 months) with ICI alone versus 13.8 months (95% CI, 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.568; p=0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients with aged <65 years (p=0.016), patients with ECOG PS=0 (p=0.048), patients with 1-2 metastatic sites (p=0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm.Conclusion: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.
A375 Melanoma Cells are Sensitized to Cisplatin-Induced Toxicity by a Synthetic Nitro-Flavone Derivative 2-(4-Nitrophenyl)-4H-Chromen-4-one Through Inhibition of PARP1
Authors: Mitra Anindita , Ghosh Rita 
Published: June 2021

Abstract
Background: Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. Methods and Results: In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. Conclusion: The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
A New Hendra Virus Genotype Found in Australian Flying Foxes
Authors: Wang Jianning , Anderson Danielle E , Halpin Kim , Hong Xiao , Chen Honglei , Walker Som , Valdeter Stacey , Heide Brenda van der , Neave Matthew J , Bingham John , O’Brien Dwane , Eagles Debbie , Wang Lin-Fa , Williams David T 
Published: June 2021

Abstract
Background

Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Pteropid bats (flying foxes) are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequent surveillance of Australian flying foxes for this novel virus over a nine year period using qRT-PCR testing of bat tissues submitted primarily for Australian bat lyssavirus (ABLV) diagnosis. Genome sequencing and characterisation of the novel HeV variant was also undertaken.
Methods

Spleen and kidney samples harvested from flying fox carcasses were initially screened with two real-time qRT-PCR assays specific for the prototype HeV. Two additional qRT-PCR assays were developed specific for the HeV variant first detected in samples from a flying fox in 2013. Next-generation sequencing and virus isolation was attempted from selected samples to further characterise the new virus.
Results

Since 2013, 98 flying foxes were tested and 11 were positive for the new HeV variant. No samples were positive for the original HeV. Ten of the positive samples were from grey-headed flying foxes (GHFF, Pteropus poliocephalus), however this species was over-represented in the opportunistic sampling (83% of bats tested were GHFF). The positive GHFF samples were collected from Victoria and South Australia and one positive Little red flying fox (LRFF, Pteropus scapulatus) was collected from Western Australia. Immunohistochemistry (IHC) confirmed the presence of henipavirus antigen, associated with an inflammatory lesion in cardiac blood vessels of one GHFF. Positive samples were sequenced and the complete genome was obtained from three samples. When compared to published HeV genomes, there was 84% sequence identity at the nucleotide level. Based on phylogenetic analyses, the newly detected HeV belongs to the HeV species but occupies a distinct lineage. We have therefore designated this virus HeV genotype 2 (HeV-G2). Attempts to isolate virus from PCR positive samples have not been successful.
Conclusions

A novel HeV genotype (HeV-G2) has been identified in two flying fox species submitted from three states in Australia, indicating that the level of genetic diversity for HeV is broader than first recognised. Given its high genetic relatedness to HeV, HeV-G2 should be considered a zoonotic pathogen.
Blinking Patterns in Calves and Changes Following Restraint and Disbudding
Authors: Ugwu Nnenna , Love Emma , Murrell Jo , Whay Helen R. , Knowles Toby G , Hockenhull Jo 
Published: June 2021

Abstract
The use of spontaneous eye blink rate [EBR] as a non-invasive stress measure is well documented in humans and is gleaning research attention in animal studies. Thus, this study investigated the EBR patterns and changes associated with two known stressful conditions, crush-restraint and disbudding, in dairy calves. Fifty-four female Holstein dairy calves were studied. EBR patterns were assessed in two separate studies (n = 10 in first study; n = 25 in replicate study) four times daily for 4-5 days. Additionally, the EBR of 19 calves divided into two groups (disbudded group = 13; sham group = 6) was recorded following crush-restraint and disbudding (under anaesthesia)/sham-disbudding (without anaesthesia). EBR was consistent across days and times in the first study but in the replicate study, it varied across days. The disbudded group had lower EBR following crush-restraint but was comparable with the sham group following disbudding. Findings suggest that spontaneous blinking may potentially serve as an instant measure of stress in dairy calves based on the elevations associated with crush-restraint and disbudding. However, blink rates may vary across days, and this should be considered when utilizing this measure to assess stress.
Comparison of Endoscopic Brush And Net Catheters As Sampling Tools To Analyze Lower Rectum Intestinal Mucus Samples of Patients With Ulcerative Colitis
Authors: Nakamura Masanao , Maeda Keiko , Yamamoto Kenta , Yamamura Takeshi , Sawada Tsunaki , Mizutani Yasuyuki , Ishikawa Eri , Kakushima Naomi , Furukawa Kazuhiro , Iida Tadashi , Ishikawa Takuya , Ohno Eizaburo , Honda Takashi , Kawashima Hiroki , Ishigami Masatoshi , Fujishiro Mitsuhiro 
Published: June 2021

Abstract
Background and aims: The pathophysiology of ulcerative colitis remains unclear, but early lesions on the colorectal mucosal surface may play an important role in its etiology. Intestinal mucus samples, including inner and outer layers, are collected by net or brush catheters, but the quality of the samples obtained by each method has not been fully investigated. The aim of this study was to compare the microbiome and protein content of Intestinal mucus collected by net and brush catheters during colonoscopy.Methods: Intestinal mucus samples from the lower rectum of four patients with ulcerative colitis were collected using a net catheter, a brush catheter, and intestinal fluid suction. Microbiome and protein content were analyzed using 16S rRNA gene sequencing and mass spectrometry.Results: The patients demonstrated significant differences in microbiome alpha diversity (p <0.05), but this difference was not observed between the sampling methods. Net catheter samples demonstrated higher total protein concentrations than brush catheter samples. Mucus-associated proteins (Mucin-2, Mucin-5B, Mucin-13, and IgGFc-binding protein) were more abundantly collected by nets in three patients with active ulcerative colitis, but more abundant by brushes in patients with inactive ulcerative colitis.　Bifidobacterium and some oral bacteria were similarly associated with ulcerative colitis activity.Conclusions: Brush catheters are more likely to collect the intestinal mucus of inner layer, whereas net catheters are more likely to collect larger samples that include the outer mucus layer, as well as intestinal fluid. Two sampling methods with different types of work on the mucosa may lead different results among patients with mucosal vulnerabilities.
Multiple Bronchiolar Adenomas With Malignant Transformation and CCNE1 Mutation: a Case Report and Literature Review
Authors: Li Xiaojun , Wu Yonghui , Hui Dayang , Luo Xiaoxuan , Wu Weibin , Zhang Jian , Chen Huiguo 
Published: June 2021

Abstract
Background: Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors (CMPT). BA is considered to be a benign neoplasm, but a few previous cases have been reported with the possibility of malignant transformation. Therefore，the genetic and histological nature of BA is controversial so far. We describe a rare case of multiple BAs with malignant transformation and CCNE1（cyclin E1）mutation to increase the understanding of this disease.Case description: A 56-year-old woman was admitted to our hospital due to two ground-glass nodules (GGNs) in the left lung detected by chest CT without symptom. The pure GGN located in the upper lingual segment about 6 mm in diameter and another mixed GGN located in the dorsal segment about 7 mm. The two GGNs have been found a year ago without treatment, and the mixed GGN become larger to 8 mm with vacuole sign in the next year health checkup. We performed a wedge resection of the two nodules completely by video-assisted thoracoscopy (VATS). Postoperative pathology indicated that the pure GGN was atypical bronchial adenoma, while the mixed GGN was atypical bronchial adenoma with malignant transformation which was missed in frozen section. Gene mutations analysis by next-generation sequencing (NGS) showed CCNE1 gene mutation in both lesions, and her-2 mutation was identified in the mixed GGN. The programmed cell death 1 ligand 1 (PD-L1) expression analysis of tumor cells showed 0% and less than 1% in the pure GGN and the mixed GGN, respectively. Conclusion: BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic in atypical cases with some driver genes mutation and we should be vigilant for its potentiality of malignant transformation in clinical practice.
Coarsening Behavior of Bulk Nanobubbles in Water
Authors: Lee Jeong Il , Huh Han Sol , Park Joong Yull , Han Jung-Geun , Kim Jong-Min 
Published: June 2021

Abstract
In recent years, extremely small gas bubbles called bulk nanobubbles (BNBs) have drawn great attention due to their impressive effects and their wide applicability in a variety of technological fields, including biomedical engineering, water treatment, and nanomaterials. However, unsolved questions remain regarding the stability and behavior of BNBs. In the present work, BNBs were generated in water using a gas-liquid mixing method. To investigate the coarsening behavior of BNBs in water over time, particle analysis was performed using a nanoparticle tracking analysis (NTA) method. Over time, the BNB diameter continuously increased (from 88.50 nm to 201.00 nm), and its cubic radius increased linearly (r3 ~ t). While the concentration of BNBs decreased (from 3.47 ×108 particles/mL to 0.61 ×108 particles/mL), the total volume of BNBs remained the same. Moreover, the size distribution broadened over time, and the concentration of larger BNBs gradually increased over time. These results indicate that relatively small BNBs disappear and larger BNBs grow through mass transfer between BNBs instead of dissolution of the gas and coalescence. In other words, BNBs underwent Oswald ripening; that is, gas molecules detached from smaller BNBs, diffused into the continuous phase, and then were absorbed into larger BNBs.
An in vitro study regarding an animal model for the attenuation of SARS-CoV-2: Are cats possible candidates?
Authors: Oguzoglu Tuba Cigdem , Hanifehnezhad Alireza , Özkul Aykut 
Published: June 2021

Abstract
Although the origin of the SARS-CoV-2 pandemic is not definitively known, this virus is seen that adapted to human. It is known yet, several animal species are naturally susceptible for SARS-CoV-2, including pets. In this in vitro study, it was investigated whether cats could have a host status in this infection. It was also following questioned, whether cats could be an animal model for vaccine attenuation. Felis catus whole fetus 4 (FCWF-4) and Vero cells were used in this study for propagation of SARS-CoV-2-Ank1 strain. Virus replication was controlled by immunohistochemistry and real time pcr techniques. While an increase in virus titer was detected in the serious passages made in Vero cells, no increase was observed in the FCWF-4 cell. The results were confirmed by immunohistochemistry. Due to the fact that SARS CoV 2 is a zoonotic potential, its presence in domestic animals frequently investigated in current studies. Cats can get this virus from infected owners with whom they share the same habitat. The results of this study also showed that cats are not candidates to be a natural source of infection for SARS-CoV-2.
Using the QI Maturity Tool – Modified Ontario Version to Assess the State of QI Maturity in Ontario’s Public Health Units
Authors: Law Madelyn , Berry Alex , Clarke Nicole , Hay Graham , Muhl Caitlin , Pilato Kelly , Hunter Danielle , Larson Anna 
Published: June 2021

Abstract
Background

Implementation of quality improvement (QI) practices varies considerably among public health units (PHUs) in Ontario. With the emphasis on continuous quality improvement (CQI) in the revised Ontario Public Health Standards (OPHS), there is a need to understand the level of quality improvement (QI) maturity in Ontario’s PHUs. The objective of this research was to establish a baseline understanding of QI maturity in Ontario’s PHUs.
Methods

The QI Maturity Tool - Modified Ontario Version was used to assess the state of QI maturity in 34 PHUs across Ontario. QI maturity was assessed through 23 questions across three dimensions: QI Organizational Culture; QI Capacity and Competency; and QI Perceived Value. QI maturity scores were classified into five stages: Beginning; Emerging; Progressing; Achieving; and Excelling. QI maturity scores were calculated for each of the 34 participating PHUs to determine their stage of QI maturity. Each PHU’s score was then used to determine the provincial average for QI maturity. Participants were also asked to answer three questions related to core CQI organizational structures.
Results

Across the 34 PHUs, 3,503 staff participated in the survey. A review of individual PHU scores indicates that Ontario’s PHUs are at varying stages of QI maturity. The average QI maturity score of 4.94 for the 34 participating PHUs places the provincial average in the “Emerging” stage of QI maturity. By QI dimensions, the participating PHUs scored in the “Emerging” stage for QI Organizational Culture (5.09), the “Beginning” stage for QI Competency and Capacity (4.58), and the “Achieving” stage for QI Perceived Value (6.00).
Conclusion

There is an urgent need for Ontario’s PHUs to progress to higher stages of QI maturity. Participants place a high value on QI, but collectively are at less “mature” stages of QI in relation to QI organizational culture and the competency and capacity to engage in QI activities. PHUs should leverage the value that staff place on QI to foster the development of a culture of QI and provide staff with relevant knowledge and skills to engage in QI activities.
A Novel Three-MicroRNA Signature for Predicting Survival in Patients with Nasopharyngeal Carcinoma
Authors: Zhang Shan-Qiang , Liu Jun , Chen Hai-Bin , Dai Wen-Jie , Zhou Li-Qing , Xie Chong-Wei , LI Ji-Cheng 
Published: June 2021

Abstract
This study aims to use integrated bioinformatics technology to dig a predictive miRNA-signature correlated with the prognosis of Nasopharyngeal carcinoma (NPC). Initially, 94 up-regulated and 91 down-regulated differentially expressed microRNAs (DEMs) of NPC were identified in the GEO dataset, and univariate COX regression analysis showed their abnormal expression were significantly associated with poor prognosis of NPC, respectively (P=0.002, P<0.001 and P<0.001). Subsequently, hsa-miR-29c, hsa-miR-30e and hsa-miR-93 identified by random forest algorithm were used to construct a predictive signature through multivariate COX regression analysis. Moreover, PCA, Kaplan-Meier analysis, time-dependent ROC analysis, and univariate and multivariate COX regression analysis demonstrated that there were significant differences in risk score, survival time and the expression of 3 DEMs between the high-risk group and the low-risk group (P< 0.001), and the high-risk group had worse OS (P<0.001). Furthermore, the average AUC values of 1- to 5-year OS, DFS and DMFS predicted by the signature were all above 0.7, and showed better clinical independence than other commonly used indexes. Eventually, 295 differentially expressed mRNAs were obtained by the intersection of the predicted results of TargetScan and the differentially expressed mRNAs in the datasets. Among them, 56 differentially expressed mRNAs were related to PFS. GO and KEGG enrichment analysis indicated that the poor prognosis of NPC was related to the abnormality of chromosomes, cytokines, and chemokines. Collectively, we constructed a 3-miRNA signature with better independent performance in predicting the prognosis for NPC, which may provide a basis for finding new therapeutic targets of NPC patients.