bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study
Authors: Lee Eung Gu , Min Jinsoo , Kang Ji Young , Kim Sung Kyoung , Kim Jin Woo , Kim Yong Hyun , Yoon Hyoung Kyu , Lee Sang Haak , Kim Hyung Woo , Kim Ju Sang 
Published: June 2020

Abstract
Background
The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.

Methods
Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed.

Results
Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.

Conclusions
The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.
Systemic inflammation modulates the ability of serum ferritin to predict all-cause and cardiovascular mortality in peritoneal dialysis patients
Authors: Fu Sha , Chen Junzhe , Liu Bo , Liang Peifen , Zeng Yuchun , Feng Min , Xu Zhenjian , Zheng Guiqiong , Yang Suqiong , Xu Anping , Tang Ying 
Published: June 2020

Abstract
Background
This study aimed to ascertain whether the correlation of high serum ferritin with mortality is affected by systemic inflammation and to investigate the optimal serum ferritin level for predicting death when inflammation is considered in peritoneal dialysis (PD) patients.

Methods
We classified 221 patients into four groups according to serum ferritin concentration (100 μg/L) and high-sensitivity CRP (hs-CRP) level (3 mg/L), and followed them regularly from the date of catheterization to Dec 31, 2016, at Sun Yat-Sen Memorial Hospital, China. Clinical and biochemical data were collected at baseline, and clinical outcomes such as all-cause and cardiovascular mortality were assessed.

Results
During a median follow-up of 35 months (3 ~ 109 months), 50 (22.6%) deaths occurred. Cardiovascular disease (46.0%) was the most common cause of death, followed by infection (10.0%). The Kaplan–Meier survival analysis and log-rank test revealed significantly worse survival accumulation among PD patients with higher serum ferritin (≥100 μg/L) under elevated hsCRP levels (> 3 mg/L) (P = 0.022). A multivariate Cox regression analysis revealed that an increased serum ferritin level was independently associated with a higher risk of all-cause and cardiovascular mortality in PD patients (HR = 3.114, P = 0.021; and HR = 9.382, P = 0.032) with hsCRP above 3 mg/L after adjusting for relevant confounding factors.

Conclusion
Higher serum ferritin levels were associated with an increased risk of all-cause and cardiovascular mortality in patients undergoing PD only in the presence of elevated hsCRP levels. The correlation of serum ferritin with poor outcome should take into consideration systemic inflammation.
DNA methylation signatures of Prostate Cancer in peripheral T-cells
Authors: Mehdi Ali , Cheishvili David , Arakelian Ani , Bismar Tarek A. , Szyf Moshe , Rabbani Shafaat A. 
Published: June 2020

Abstract
Background
Prostate Cancer (PCa) is the second most common cancer in men where advancements have been made for early detection using imaging techniques, however these are limited by lesion size. Immune surveillance has emerged as an effective approach for early detection and to monitor disease progression. In recent studies, we have shown that host peripheral blood immune cells undergo changes in DNA methylation in liver and breast cancer.

Methods
In the current study, we examined the DNA methylation status of peripheral blood T cells of men with positive biopsy for PCa versus men with negative biopsy having benign prostate tissue, defined as controls. T cells DNA was isolated and subjected to Illumina Infinium methylation EPIC array and validated using Illumina amplicon sequencing and pyrosequencing platforms.

Results
Differential methylation of 449 CG sites between control and PCa T cell DNA showed a correlation with Gleason score (p < 0.05). Two hundred twenty-three differentially methylated CGs between control and PCa (∆ß +/− 10%, p < 0.05), were enriched in pathways involved in immune surveillance system. Three CGs which were found differentially methylated following DMP (Differentially methylated probes) analysis of ChAMP remained significant after BH (Benjamini-Hochberg) correction, of which, 2 CGs were validated. Predictive ability of combination of these 3 CGs (polygenic methylation score, PMS) to detect PCa had high sensitivity, specificity and overall accuracy. PMS also showed strong positive correlation with Gleason score and tumor volume of PCa patients.

Conclusions
Results from the current study provide for the first-time a potential role of DNA methylation changes in peripheral T cells in PCa. This non-invasive methodology may allow for early intervention and stratification of patients into different prognostic groups to reduce PCa associated morbidity from repeat invasive prostate biopsies and design therapeutic strategy to reduce PCa associated mortality.
Perceptions of stakeholders about the role of health system in suicide prevention in Ghizer, Gilgit-Baltistan, Pakistan
Authors: Anjum Anila , Saeed Ali Tazeen , Akber Pradhan Nousheen , Khan Murad , Karmaliani Rozina 
Published: June 2020

Abstract
Background
Suicide is a serious global public health problem, with more than 800,000 people dying by suicide worldwide every year. 79% of suicides happen in Low and Middle-Income Countries (LMICs), where lack of national suicide prevention programs coupled with inadequate MH facilities for early identification and treatment of mental disorders add to seriousness of the problems. Although there is paucity of research, studies suggest that the rate of suicide in district Ghizer, Gilgit-Baltistan (GB), in northern Pakistan may be higher compared to rest of the country.

Methods
This study aimed to explore the perceptions of stakeholders about the role of the health system at District Ghizer, GB using a qualitative descriptive exploratory research design. A total of 12 face to face in-depth interviews were conducted from the stakeholders using purposive sampling technique.

Results
The study results led to three broad themes, 1) Suicide as A Social Issue, 2) Role of Health System in Suicide Prevention, and 3) Challenges for Health System in Suicide Prevention. Theme one was sub-categorized into; a) Perceived situations contributing to suicide, b) Environmental factors. Theme two was subdivided into; a) Major hurdles for Health system, b) Lack of MH services in the available health system. Theme three was subdivided into; a) Lack of collaboration across-sectors, b) Unavailability of MH professionals, and c) Financial issues. The study findings reveal that there are multiple challenges for health system including, lack of awareness on mental issues, shortage of resources and lack of collaboration in the community. Moreover, existing policies or strategies need to be modified to overcome the existing challenges for the effective prevention.

Conclusion
This study emphasized creating awareness about MH issues, introduction of school health programs, parental counseling session and strengthening of the health system by allocating suitable budget for MH issues and suicide prevention strategies.
Changes in patient health questionnaire (PHQ-9) scores in adults with medical authorization for cannabis
Authors: Round Jessica M. , Lee Cerina , Hanlon John G. , Hyshka Elaine , Dyck Jason R. B. , Eurich Dean T. 
Published: June 2020

Abstract
Background
Legal access to medical cannabis is increasing world-wide. Despite this, there is a lack of evidence surrounding its efficacy on mental health outcomes, particularly, on depression. This study assesses the effect of medical cannabis on Patient Health Questionnaire (PHQ-9) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada.

Methods
An observational cohort study of medically authorized cannabis patients in Ontario and Alberta. Overall change in PHQ-9 scores from baseline to follow-up were evaluated (mean change) over a time period of up to 3.2 years.

Results
37,338 patients from the cohort had an initial PHQ-9 score recorded with 5103 (13.7%) patients having follow-up PHQ-9 scores. The average age was 54 yrs. (SD 15.7), 46% male, 50% noted depression at baseline. The average PHQ-9 score at baseline was 10.5 (SD 6.9), following a median follow-up time of 196 days (IQR: 77–451) the average final PHQ-9 score was 10.3 (SD 6.8) with a mean change of − 0.20 (95% CI: − 0.26, − 0.14, p-value < 0.0001). Overall, 4855 (95.1%) had no clinically significant change in their PHQ-9 score following medical cannabis use while 172 (3.4%) reported improvement and 76 (1.5%) reported worsening of their depression symptoms.

Conclusions
Although the majority showed no clinically important changes in PHQ-9 scores, a number of patients showed improvement or deteriorations in PHQ-9 scores. Future studies should focus on the parallel use of screening questionnaires to control for PHQ-9 sensitivity and to explore potential factors that may have attributed to the improvement in scores pre- and post- 3-6 month time period.
Anemia prevalence, severity and associated factors among children aged 6–71 months in rural Hunan Province, China: a community-based cross-sectional study
Authors: Li Huixia , Xiao Juan , Liao Minghui , Huang Guangwen , Zheng Jianfei , Wang Hua , Huang Qun , Wang Aihua 
Published: June 2020

AbstractBackgroundIn recent 10 years, with the rapid socioeconomic development and the extensive implementation of children nutrition improvement projects, the previous epidemiological data cannot reflect the actual level of anemia among children in China, especially in rural areas. Therefore, this study analyzed the prevalence, severity and associated factors of anemia among children aged 6–71 months in rural Hunan Province.MethodsA community-based cross-sectional study was conducted. Through multistage stratified cluster sampling, 5229 children aged 6 to 71 months and their caregivers were randomly selected from 72 villages across 24 towns in 12 counties from rural Hunan. The demographic characteristics of children and their caregivers, feeding practice, nutritional status of children, caregivers’ anemia-related feeding knowledge, and gestational conditions of mothers were acquired by using a unified questionnaire. Peripheral blood from the left-hand middle fingertip was sampled from each child, and hemoglobin concentration was measured using a HemoCue301 portable hemoglobin analyzer (Sweden). Associated factors analyses involving overall anemia and anemia severities were conducted on multivariate logistic regression models.ResultsThe overall anemia prevalence was 8.8%, and the prevalence of mild, moderate and severe anemia was 6.3, 2.5 and 0.1%, respectively. Children age groups of 6–11 months, 12–23 months and 36–47 months, exclusive breast-feeding within 6 months after birth, and maternal moderate/severe anemia were significantly associated with an increased risk of overall anemia in children. Children age groups of 6–11 months and 12–23 months were significantly associated with an increased risk of mild anemia in children. Children age groups of 6–11 months, 12–23 months and 36–47 months, low caregivers’ anemia-related feeding knowledge level, and maternal moderate/severe anemia were significantly associated with an increased risk of moderate/severe anemia in children. Children who underwent regular physical examination were less likely to have moderate/severe anemia. The common protective factor for overall, mild and moderate/severe anemia in children was high family income.ConclusionsThe anemia status of preschool children in rural Hunan Province was a mild public health problem and associated with children age group, feeding practice, regular physical examination, family income, caregivers’ anemia-related feeding knowledge level, and maternal moderate/severe anemia.
Lung and general health effects of Toll-like receptor-4 (TLR4)-interacting SPA4 peptide
Authors: Awasthi Shanjana , Rahman Negar , Rui Bin , Kumar Gaurav , Awasthi Vibhudutta , Breshears Melanie , Kosanke Stanley 
Published: June 2020

Abstract
Background
A surfactant protein-A-derived peptide, which we call SPA4 peptide (amino acids: GDFRYSDGTPVNYTNWYRGE), alleviates lung infection and inflammation. This study investigated the effects of intratracheally administered SPA4 peptide on systemic, lung, and health parameters in an outbred mouse strain, and in an intratracheal lipopolysaccharide (LPS) challenge model.

Methods
The outbred CD-1 mice were intratracheally administered with incremental doses of SPA4 peptide (0.625–10 μg/g body weight) once every 24 h, for 3 days. Mice left untreated and those treated with vehicle were included as controls. Mice were euthanized after 24 h of last administration of SPA4 peptide. In order to assess the biological activity of SPA4 peptide, C57BL6 mice were intratracheally challenged with 5 μg LPS/g body weight and treated with 50 μg SPA4 peptide via intratracheal route 1 h post LPS-challenge. Mice were euthanized after 4 h of LPS challenge. Signs of sickness and body weights were regularly monitored. At the time of necropsy, blood and major organs were harvested. Blood gas and electrolytes, serum biochemical profiles and SPA4 peptide-specific immunoglobulin G (IgG) antibody levels, and common lung injury markers (levels of total protein, albumin, and lactate, lactate dehydrogenase activity, and lung wet/dry weight ratios) were determined. Lung, liver, spleen, kidney, heart, and intestine were examined histologically. Differences in measured parameters were analyzed among study groups by analysis of variance test.

Results
The results demonstrated no signs of sickness or changes in body weight over 3 days of treatment with various doses of SPA4 peptide. It did not induce any major toxicity or IgG antibody response to SPA4 peptide. The SPA4 peptide treatment also did not affect blood gas, electrolytes, or serum biochemistry. There was no evidence of injury to the tissues and organs. However, the SPA4 peptide suppressed the LPS-induced lung inflammation.

Conclusions
These findings provide an initial toxicity profile of SPA4 peptide. Intratracheal administration of escalating doses of SPA4 peptide does not induce any significant toxicity at tissue and organ levels. However, treatment with a dose of 50 μg SPA4 peptide, comparable to 2.5 μg/g body weight, alleviates LPS-induced lung inflammation.
Efficient CRISPR/Cas9 genome editing in a salmonid fish cell line using a lentivirus delivery system
Authors: Gratacap Remi L. , Regan Tim , Dehler Carola E. , Martin Samuel A. M. , Boudinot Pierre , Collet Bertrand , Houston Ross D. 
Published: June 2020

Abstract
Background
Genome editing is transforming bioscience research, but its application to non-model organisms, such as farmed animal species, requires optimisation. Salmonids are the most important aquaculture species by value, and improving genetic resistance to infectious disease is a major goal. However, use of genome editing to evaluate putative disease resistance genes in cell lines, and the use of genome-wide CRISPR screens is currently limited by a lack of available tools and techniques.

Results
In the current study, we developed an optimised protocol using lentivirus transduction for efficient integration of constructs into the genome of a Chinook salmon (Oncorhynchus tshwaytcha) cell line (CHSE-214). As proof-of-principle, two target genes were edited with high efficiency in an EGFP-Cas9 stable CHSE cell line; specifically, the exogenous, integrated EGFP and the endogenous RIG-I locus. Finally, the effective use of antibiotic selection to enrich the successfully edited targeted population was demonstrated.

Conclusions
The optimised lentiviral-mediated CRISPR method reported here increases possibilities for efficient genome editing in salmonid cells, in particular for future applications of genome-wide CRISPR screens for disease resistance.
ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer
Authors: Cheung Chantal Hoi Yin , Hsu Chia-Lang , Lin Tsai-Yu , Chen Wei-Ting , Wang Yi-Ching , Huang Hsuan-Cheng , Juan Hsueh-Fen 
Published: June 2020

Abstract
Background
ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown.

Methods
To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with mass spectrometry-based proteomics using A549 lung cancer cells, and analyzed the differentially expressed proteins of phosphoproteomic and proteomic profiles to determine ZNF322A-modulated pathways.

Results
ZNF322A highlighted a previously unidentified insulin signaling, heat stress, and signal attenuation at the post-translational level. Consistently, protein-phosphoprotein-kinase interaction network analysis revealed phosphorylation of IRS1 and HSP27 were altered upon ZNF322A-silenced lung cancer cells. Thus, we further investigated the molecular regulation of ZNF322A, and found the inhibitory transcriptional regulation of ZNF322A on PIM3, which was able to phosphorylate IRS1 at serine1101 in order to manipulate glucose uptake via the PI3K/AKT/mTOR signaling pathway. Moreover, ZNF322A also affects the unfolded protein response by phosphorylation of HSP27S82 and eIF2aS51, and triggers autophagosome formation in lung cancer cells.

Conclusions
These findings not only give new information about the molecular regulation of the cellular proteins through ZNF322A at the post-translational level, but also provides a resource for the study of lung cancer therapy.
Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses
Authors: Chan Louisa L. Y. , Nicholls John M. , Peiris J. S. Malik , Lau Yu Lung , Chan Michael C. W. , Chan Renee W. Y. 
Published: June 2020

Abstract
Background
Neutrophil is of the most abundant number in human immune system. During acute influenza virus infection, neutrophils are already active in the early phase of inflammation - a time in which clinical biopsy or autopsy material is not readily available. However, the role of neutrophil in virus infection is not well understood. Here, we studied the role of neutrophil in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease.

Methods
Neutrophils were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro. The ability of the naïve neutrophils to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of neutrophils upon influenza virus infection were evaluated.

Results
Our results demonstrated that influenza virus infected alveolar epithelium allowed neutrophil transmigration. Significantly more neutrophils migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Neutrophils were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected neutrophils. H5N1 induced higher cytokine and chemokine gene transcription than H1N1 infected neutrophils, including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was only observed in H1N1 infected neutrophils at 6 hpi while no NET formation was observed upon H5N1 infection.

Conclusion
Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection and might contribute to the severity of H5N1 disease.
The emerging roles of circular RNAs in ovarian cancer
Authors: Yang Xuejing , Mei Jie , Wang Huiyu , Gu Dingyi , Ding Junli , Liu Chaoying 
Published: June 2020

AbstractCircular RNA (circRNA) is a novel class of regulatory noncoding RNA (ncRNA) molecules with a unique covalently closed loop structure. Next-generation sequencing shows that thousands of circRNAs are widely and stably expressed in multiple eukaryotes. As novel regulatory ncRNAs, circRNAs possess several specific molecular functions, including regulating gene transcription and translation, acting as miRNA sponges, and interacting with functional proteins. Ovarian cancer (OvCa) is one of the most aggressive malignant diseases affecting the lives of thousands of women worldwide, and the majority of OvCa cases are diagnosed at advanced stages. Accumulating evidence has revealed the significant roles of circRNAs in the occurrence and progression of OvCa, indicating the function of circRNAs as promising biomarkers and their therapeutic relevance in this disease. This review aims to summarize the mechanisms by which circRNAs mediate OvCa progression as well as their diagnostic and prognostic values in OvCa.