bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of lncRNA-miRNA-mRNA regulatory network and correlation between prognostic biomarker PDGFRB and immune infiltrates in stomach adenocarcinoma
Authors: Yang Guang , Wu Ying , Zheng yi Ru , Jin shun Zai , Yan Bin
Published: February 2022

Purpose: Gastric cancer is a highly malignant and heterogeneous tumour with a poor prognosis and a high recurrence rate. Overexpressed PDGFRB has a correlation with poor survival outcomes in several malignancies. The objective of our study was to evaluate the prognostic value of PDGFRB and identify a lncRNA-miRNA-mRNA ceRNA network involved in stomach adenocarcinoma.Methods: RNA-sequencing data, miRNA-sequencing data and corresponding patient clinical information were collected from the TCGA database. All statistical analysis was performed through the edgeR package. ENCORI database was applied to screen out miRNAs and lncRNAs interacting with the target gene. A lncRNA-miRNA-mRNA ceRNA network was constructed through Cytoscape. For DEmiRNAs, DElncRNAs and mRNA，the differences between the overall survival of high-expression and low-expression group were evaluated by R language. TIMER 2.0 and GEPIA database were used to evaluate the value of PDGFRB in immune cell infiltration and immunotherapy. Results: Compared with normal tissue samples, PDGFRB was significantly upregulated in stomach adenocarcinoma. The upregulated expression of PDGFRB was significantly related to histologic grade, topography and clinical stage. LncRNA CASC15 and has-miR-30e-5p were identified to have correlations with PDGFRB. Patients with an elevated PDGFRB, lncRNA CASC15 and a decreased has-miR-30e-5p had a poor prognosis, in which elevated PDGFRB was an independent poor prognostic factor. In addition, the positive associations among PDGFRB, tumor infiltrating immune cells and immunotherapy were also observed. Conclusions: An increased PDGFRB may serve as a promising and potential independent prognostic biomarker of a poor survival and therapeutic targets in stomach adenocarcinoma.
Effect of Residual Alkali Level in Softwood Kraft Cooking
Authors: Brännvall Elisabet , Norberg Lars , Karlström Katarina
Published: February 2022

In washing of softwood pulp, pH is reduced to such low levels that re-precipitation of dissolved lignin may result. It was hypothesized that the lower the residual alkali after cooking, the higher the risk of lignin re-precipitation, which in turn would affect the subsequent oxygen delignification stage negatively. To test the hypothesis, kraft cooks were performed to different residual alkali levels, ranging from 5 to 15 g/l and the delignified chips were subjected to different washing strategies and then oxygen delignified. However, the results show that even at low residual alkali, lignin stays in solution and only minor amounts of lignin re-precipitate during washing. The amount was irrespective of the residual alkali level in the cook and amounted to 1-2 kappa number units. No effect of residual alkali level was observed on the performance of the oxygen delignification stage. The residual alkali level affected the lignin concentration in the lumen after cooking. At the low residual alkali level, the lignin concentration in the lumen liquor was equal to the free liquor and as the residual alkali level increased, the lignin concentration in the lumen increased, while the lignin concentration in the free black liquor remained on the same level at all residual alkali levels.
Improving hypertension awareness and management in Vietnam through a community-based model
Authors: McGuire Helen , Van Truong Bui , Tu Hien Le Thi , Thanh Huyen Nguyen , Murray Marge , Shellaby Jason , Aerts Ann , George Roshini , Hodges Mary
Published: February 2022

Hypertension prevalence in Vietnam is high, but few people are aware of their disease status. Detection, diagnosis, and treatment are limited, so new approaches are needed to improve awareness and manage the condition, especially at the primary health care level. The Communities for Healthy Hearts programme operated in four districts of Ho Chi Minh City, with the aim of increasing awareness and ensuring linkage to care. Interventions focused on extending services beyond health facilities to convenient community locations; training cadres of community volunteers to screen, refer, and follow up with clients; training health workers in facilities to diagnose, educate, and manage patients referred from the community; and supporting the process with digital case tracking. Community-based blood pressure screenings took place in client homes, commune health stations, and non-traditional sites such as coffee shops, dentists’ offices, marketplaces, neighbourhood watch/security posts, and tailor shops. In total, 121,273 adults aged 40 and older were screened. Of these, 25.1% had elevated blood pressure or a previous hypertension diagnosis and were referred to health facilities. Of those referred, 56.2% were confirmed to have hypertension, and of those confirmed, 75.2% were treated. Of those treated, 51.0% achieved blood pressure control, a favourable outcome over past programmes.
The role of routine laboratory tests after unilateral total knee arthroplasty
Authors: Li An an , Zhang Yu , zhang Hao , xiao Shi-ning , long xin-hua , Wang Shi-jiang , zhou yang
Published: February 2022

BackgroundRecent studies suggest that routine laboratory tests are not required within 1 day after partial knee arthroplasty. This study aimed to evaluate the utility of routine postoperative laboratory tests after initial unilateral total knee arthroplasty(TKA) in an Asian population and to identify risk factors associated with abnormal test results.MethodsThe clinical data of patients who underwent original unilateral TKA from 2015 to 2020 were retrospectively analyzed. Patient characteristics and laboratory test values were recorded. Multivariate binary logistic regression analysis was also performed to identify risk factors associated with 3 abnormal laboratory values.ResultsA total of 713 patients were included in this study and underwent relevant laboratory tests within 3 days of TKA surgery. However, only a small proportion of patients with anemia (8.1 %), hypoalbuminemia (9.9 %), and abnormal serum potassium levels (3.4 %) required clinical intervention after surgery. Binary logistic regression analysis revealed that independent risk factors for postoperative blood transfusion in TKA patients included preoperative hemoglobin level, estimated blood loss, and age. Related risk factors for postoperative albumin supplementation were preoperative albumin level, intraoperative blood loss and operation time. In addition, lower body mass index (BMI) and preoperative hypokalemia were found to be potential risk factors for postoperative potassium supplementation.ConclusionSince more than 90% of abnormal postoperative laboratory tests do not require clinical intervention, the authors believe that it is of little significance for patients with primary unilateral TKA to receive routine laboratory tests after surgery. However, in patients with established risk factors, postoperative laboratory testing is still necessary.
A study of libration points and analysis of their stability behavior in-ring body problem under albedo effect
Authors: Kumar Manoj , Kushvah Badam Singh
Published: February 2022

Our intention in this article is to analyze the fundamental analysis of the zones and their existing libration points under the solar radiation pressure and albedo effects. We can feel about albedos at any Nature’s property wherever the Sun rays exist. As we know that important phase of the dynamical system of any celestial body is its stability and the factors which change its behavior of motion. This research article presents an explicit analysis of the albedo effect for ring body problems for a specific value of v = 6, which explains the behavior of existing zone’s stability, shifting of their libration points with monotonicity and the characteristic roots of δ confirms the behavior of stability condition for existing zones as well as their existing libration points in a synodic frame of references. We observed that in this problem from an experimental point of view, a little change in v, changes the complete behavior of the problem and leaves a nice platform of the proof. In this problem, β plays a significant role, which affects firstly the whole dynamics of peripheral primaries, the mass parameters β = 0 and β ≠ 0 generally confirm that this synodic system wears, an absence of a center of mass and the presence of the center of mass, respectively. We have observed in this article is the libration point L0, which exists in the center and has peripheral primary P0, remains unchanged throughout applying the albedo effect. The stability analysis confirms the location of the libration points, whether it is stable, unstable, etc., but here we have seen the more interesting things i.e., most of the locations of the libration points except exceptionals are found unstable. This article also shows the momentum of the position of all the libration points with their existing zone as well as peripheral primaries, by the effect of the radiation pressure and albedo. It is also analyzed here that this complete problem works in a certain short and very sensitive range set (−1.75, 1.75) because this problem is filled with trigonometric periodic functions. In this problem, we have considered only the real roots of the axis x, y, whereas imaginary roots are not considered. For stability analysis, we have taken both real and complex roots of δ. Results of this article for v = 6 may help us to analyze an imaginary behavior of our solar system’s planets in a blank paper, provided by certain rules and regulations by equations of motion because real behavior may be far away from us. By the present study, it is found that the whole behavior of the system for various v whenever change, which can be extended later in another way.
Obsession to fairness and Topical Steroid induced acne: A situation analysis of patients presenting in dermatology clinic at a private hospital in Karachi
Authors: Ghouse Afza Naureen , Ashraf Erum , Khan Zara , Siddiqui Sitwat
Published: February 2022

The authors have requested that this preprint be removed from Research Square.
Cancer immunohistogram prediction of the efficacy of immune checkpoint inhibitors in urological cancer patients: A preliminary study
Authors: Kijima Toshiki , Kubo Terufumi , Nishihara Daisaku , Nukui Akinori , Hirohashi Yoshihiko , Torigoe Toshihiko , Kamai Takao
Published: February 2022

We developed an immunohistogram representing an individual cancer-immunity cycle based on immunohistochemical analyses. We evaluated its predictive ability for immune checkpoint inhibitors (ICI) efficacy in 11 patients with urothelial carcinoma and 7 patients with renal cell carcinoma who underwent surgery and received ICIs for disease recurrence. Immunohistochemical analyses for CD8, TIA-1, HLA class I, HLA-DR, and PD-L1 were performed and scored 0–3. T-cell infiltration pattern was classified into desert, excluded, partially inflamed, and inflamed. Tumors with an inflamed or partially inflamed pattern and positive scores (score ≥ 1) for all five immune markers were classified as “immune-hot” and others were classified as “immune-cold”. Association between the immunohistogram and ICI treatment efficacy was evaluated with objective response rates, disease control rate (DCR), progression-free survival (PFS), and cancer-specific survival (CSS). Eight (44%) and 10 (56%) of patients had immune-hot and immune-cold tumors, respectively. Immune-hot tumors showed higher DCR (100% vs. 40%, p < 0.01), longer PFS (median unreached for hot, 1.3 months for cold, p < 0.01), and longer CSS (median unreached for hot, 3.3 months for cold, p = 0.04) than immune-cold tumors. The immunohistogram could be clinically useful as an accessible biomarker for precision cancer immunotherapy in urological cancer.
Expanding the Scope of Emergency IPV Sheltering: Moral Entrepreneurs and the Co-Sheltering of Companion Animals
Authors: Lindsay Sarah May
Published: February 2022

Purpose: Companion animals are rarely co-sheltered in intimate partner violence (IPV) shelters in Canada, despite their common consideration as family, and an awareness of the “the Link” between human and nonhuman abuse. This article reports on the few IPV facilities in Ontario who do house their clients’ companion animals and seeks to identify how co-sheltering is emerging as part of the evolution of IPV sheltering. Methods: This study is part of a larger research project, which utilizes semi-structured interviews with Ontario IPV shelter workers and volunteers to assess how companion animals fit in these facilities. Guided by the principles of action research, these conversations were textually analyzed for themes and sentiments regarding co-sheltering. This paper reports on co-shelter facilities and practices present in the larger sample. Results:We find that co-sheltering is a grassroots action undertaken by moral entrepreneurs who engage in covert and overt actions to expand the circle of care in these spaces. These actions are also found to be in response to the ongoing social problem of gendered violence; these moral entrepreneurs follow in the footsteps of those who began to organize in the 1970s from a feminist standpoint, addressing a gap in shelter and safety for women affected by this social problem. Conclusions: We find that the provision of co-sheltering in IPV facilities appears to depend solely on the action of shelter workers “on-the-ground”, who identify an urgent need to expand the scope of care in their shelter to include clients’ companion animals. More research is needed to learn about IPV co-shelters elsewhere in the country, and to study the impact of this inclusive housing option on the lives of clients, workers, and companion animals.
Potential Risks of Agricultural Intensification in Tropical Catchments: the Case of Lake Naivasha
Authors: Onyango Joel , Kitaka Nzula , Bruggen J. J.A. Van , Irvine Kenneth , Simaika John
Published: February 2022

The use of both fertilizers and pesticides in the Lake Naivasha Catchment, is associated with agricultural intensification and has resulted in enrichment of aquatic ecosystems with nutrients, coupled with exposure of aquatic biota to pesticide residues affecting aquatic ecosystem structure and function. This study explored the changes in land use and related it with the concentrations of nutrients and selected pesticides, to show the potential of combined (nutrients and pesticides) risks associated with agricultural intensification in Lake Naivasha catchment, a tropical catchment in Kenya. The results indicate that between 1989 and 2019 there was an increase of cropland by 623 km2, a reduction of forest cover by 200 km2, increase of grasslands by 534 km2, a reduction in bare soils by 100 km2, and an increase of 540 km2 of built area. The land cover changes were correlated with increased concentrations of nutrients and pesticides in surface waters across sampling sites monitored in 2015. The results further indicated that while the concentrations of nitrogen and phosphorus indicated a potential stoichiometric nitrogen limitation, increase in forest cover resulted in decreased nutrient concentrations in the river water. Concentrations of DDT and technical HCH active ingredients indicated significant relationships between land use changes and intensification. Areas with extensive farming systems were associated with higher concentrations of TP and ∑DDT compared with areas of high intensification, which may reflect high connectivity between intensive agricultural systems and river ecosystems. When combined nutrients and pesticides were considered, most of the lower reaches of the rivers draining to L. Naivasha were of poor water quality status as defined by Kenyan water quality regulations. The changes in land cover and agricultural intensification in the Naivasha catchment needs management and policy frameworks that manage the combined contamination from nutrients and pesticide residues. Enhanced investment in institutional and policy reforms, and an integrated review of water quality standards and monitoring indicators that combine biological, physical, and chemical monitoring, is necessary for future management of the catchment.
The association of growth differentiation factor-15 levels and osteoporosis in patients with thalassemia
Authors: Teawtrakul Nattiya , Chansai Siriyakorn , Yamsri Supawadee , Chansung Kanchana , wanitpongpun Chinadol , Lanamtieng Theerin , Phiphitaporn Pisa , Fucharoen Supan , Pongchaiyakul Chatlert
Published: February 2022

Introduction: Ineffective erythropoiesis is a significant risk factor for osteoporosis in individuals with thalassemia. Growth differentiation factor-15 (GDF15), a biomarker of ineffective erythropoiesis, has previously been found to be elevated in thalassemia patients. The purpose of this study was to examine the association between GDF15 levels and osteoporosis in patients with thalassemia. Methods: A cross-sectional study was conducted in 130 adult patients with thalassemia at Srinagarind Hospital, Thailand. Bone mineral density (BMD) at the lumbar spine was evaluated by dual-energy X-ray absorptiometry (DXA), and with a Z-score of less than -2.0 SD was defined as osteoporosis. GDF-15 was measured using the enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to examine the associated factors with the development of osteoporosis. Receiver operator characteristic (ROC) curve analysis was used to estimate the threshold of GDF15 in predicting osteoporosis.Results: Osteoporosis was detected in 55.4% (72/130) of the patients. Advanced age and high GDF15 levels were positively associated with osteoporosis, while an increased hemoglobin level was negatively associated with osteoporosis in patients with thalassemia. In this study, the GDF15 level’s ROC demonstrated a good performance in predicting osteoporosis (AUC=0.77). Using a cut-off point of GDF15 ≥ 20,000 pg/mL, the sensitivity and specificity were 90.2% and 60.3%.Conclusions: The prevalence of osteoporosis is high among adult thalassemia patients. Age and high GDF15 levels were significantly associated with osteoporosis in this study. A higher hemoglobin level is associated with a lower risk of osteoporosis. The findings of this study suggest that GDF15 could be used as a predictive biomarker for osteoporosis in patients with thalassemia. Adequate red blood cell transfusions and suppression of GDF15 function may be beneficial in preventing or delaying osteoporosis progression.
Altered Temporal-Parietal Morphological Similarity Networks in Non-Small Cell Lung Cancer Patients Following Chemotherapy: An MRI Preliminary Study
Authors: Chen Gong , Wu Chuan , Liu Yuan , Fang Zengyi , Luo Liping , Lai Xin , Wang Weidong , Dong Li
Published: February 2022

Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases, and chemotherapy-related brain changes (known as “chemobrain”) in NSCLC patients were found in previous studies. However, the effects of platinum-based chemotherapy on the brain structural networks are still unclear. Structural magnetic resonance imaging (sMRI) data were collected from 32 NSCLC patients following platinum-based chemotherapy, 36 NSCLC patients without chemotherapy, and 39 healthy controls. Clinical physiological indicators of NSCLC patients were collected. Then, morphological similarity networks were constructed using individual MRI data, and topological properties were calculated using the graph theory method. Differences between the three groups were investigated using one-way ANOVA and two-sample t-test, and relations between the topological properties and clinical physiological indicators were calculated. We found that degree (F(2,104) = 18.367, p < 0.001) and nodal efficiency (F(2,104) = 12.546, p < 0.001) in temporal-parietal networks were significantly reduced in NSCLC patients following platinum-based chemotherapy compared to healthy controls/patients without chemotherapy. These changes (p < 0.05) were positively correlated with clinical measures, including thrombocytes, granulocytes and hemoglobin, and were negatively correlated with measures of triglycerides and cholesterol levels. Network properties including clustering coefficient (F(2,104) = 41.435, p < 0.001), number of K-edges (F(2,104) = 40.304, p < 0.001), density of K-edges (F(2,104) = 40.304, p < 0.001), global efficiency (F(2,104) = 42.585, p < 0.001) and small-world (F(2,104) = 37.132, p < 0.001) were also significantly reduced. These results indicate that platinum-based chemotherapy might cause cerebrovascular damage and clinical indicators’ changes, which then cause the properties of morphological similarity networks’ changes in the temporal and parietal lobes. This study may help us better understand the “chemobrain” in NSCLC patients.
Long Noncoding RNA PVT1 Predicts Poor Prognosis and Promotes the Progression of Colorectal Cancer Through the MiR-24-3p/NRP1 Axis in Zebrafish Xenografts
Authors: Yin Hailin , Gu Shanye , Li Guiqin , Yu Hanxu , Zhang Xishan , Zuo Yangsong
Published: February 2022

BackgroundLong noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models.MethodsThe expression level of PVT1 in CRC tissues was analyzed in TCGA and GEO database. The prognosis of PVT1 in CRC was assessed by analyzing the correlation between the expression level of PVT1 and overall survival in CRC patients by Kaplan-Meier survival analysis. The CCK-8 and colony formation assays were performed to study the proliferation of CRC cells, and transwell assays was used to assess the migration of CRC cells in vitro. The targeting relationships among PVT1, miR-24-3p and Neuropilin 1 (NRP1) was predicted by StarBase, and examined by dual-luciferase reporter assays. The expression levels of PVT1, miR-24-3p and NRP1 were quantified by quantitative real time PCR and/or western blotting. The zebrafish CRC xenograft models were used to study the function of PVT1, miR-24-3p and NRP1 in vivo.ResultsBioinformatics analysis showed that PVT1 was upregulated in CRC tissues and highly associated with poor prognosis. Knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells in vitro. In zebrafish xenografts, silencing of PVT1 also suppressed the growth and metastasis of CRC cells. miR-24-3p, binding with PVT1, negatively regulated the progression of CRC cells. Inhibition of miR-24-3p counteracted the effects of PVT1 knockdown. In addition, miR-24-3p could regulate CRC progression by targeting NRP1 directly. Moreover, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of PVT1 knockdown on CRC progression in vitro and in vivo.ConclusionsOur study reveals that PVT1 promoted the proliferation and metastasis of CRC via regulating miR-24-3p/NRP1 axis, and it could be a prognosis biomarker of CRC. This study provides a potential therapeutic target for CRC patients.
A Retrospective Cohort Study of the Effect of Rapid Versus Delayed-result Procalcitonin Testing on Antibiotic Use at a Community Hospital
Authors: Anderson Elizabeth , White Brittany , Goodwin Emily , Alkhateeb Fadi , White Cyle
Published: February 2022

Background: Procalcitonin is a serum biomarker used to distinguish bacterial infection from viral or noninfectious syndromes. Primary literature shows mixed data on use of procalcitonin for de-escalation of antimicrobials. Delays in test results of send-out procalcitonin assays may result in prolonged antimicrobial durations. It is unknown whether availability of in-house assays may shorten time to antibiotic de-escalation. Aim: This retrospective, cohort study compared antibiotic durations of treatment between groups with a rapid-result versus a delayed send-out, procalcitonin test modality.This study was exempt from Ethics Committee Approval, as determined by the Institutional Review Board at the study site.Methods: Adult hospitalized patients were included if they had at least one procalcitonin test performed during the study period. The primary outcome compared mean duration of antimicrobial therapy between groups receiving a rapid-result procalcitonin test and a delayed-result test. Secondary outcomes included incidence of Clostridiodes difficile infection, mention of procalcitonin testing in the electronic medical record in reference to antimicrobial therapy decision making, and presence of comorbidities which affect procalcitonin levels independent of infection.Results: A total of 350 lab results were analyzed. The duration of antimicrobial treatment between groups was not statistically different with the median duration of treatment in the send-out group being 2.95 days compared to 3.35 in the in-house group, p=0.856. Patient comorbidities with potential to lead to a noninfectious elevation or falsely high level of procalcitonin were common. Conclusion: Use of a rapid-result procalcitonin assay does not reduce hospital antimicrobial therapy duration as compared with send-out testing.
Validation of the Sleep Disturbance Scale for Children (SDSC) in Infants and Toddlers from Mainland China
Authors: Chen Xianrui , Lin Xiaoxia , Xu Ping , Chen Yanhui , Chen Shan , Yao Yonghua
Published: February 2022

A Chinese version of the sleep disturbance scale for children (SDSC) has been validated for 5 to 16-year olds. However, the assessment tool of sleep disturbance in infants and young children from mainland China is relatively rare and limited, and clinicians cannot objectively, accurately, and comprehensively screen for early detection and intervene to treat them. Background:To evaluate the reliability and validity of SDSC among infants (aged 6 months to 36 months) in mainland China, and to provide a reference for expanding the application of the SDSC for the Chinese infants (SDSC-I). Methods: From April to November 2021, parents of infants from Fuzhou, Quanzhou, Longyan, Sanming and Nanping in Fujian Province completed the SDSC which is specifically for infants and toddlers. The reliability and validity of the scales were estimated by item analysis, standard Cronbach's alpha coefficient, exploratory factor analysis (EFA), confirmatory factorial analyses (CFA) and other measurement characteristics. Results: 432 out of 469 samples were valid. Through item selections and exploratory factory analysis, the SDSC-I concluded 6 dimensions (Disorders of Initiating Sleep, Disorders of Maintaining Sleep, Sleep Hyperhidrosis, Sleep Breathing Disorders, Parasomnias, and Non-Restorative Sleep and Excessive Somnolence) including 23 items. Cronbach's α coefficient of the scale was 0.863, for the 6 dimensions were within 0.576–0.835. The values of parameters for content validity of the scale were: IR = 0.87, I-CVI > 0.78, Kappa value > 0.74, S-CVI/UA = 0.87, S-CVI/Ave = 0.98. Principal component analysis revealed that, the KMO value was 0.84, the factor loading of items ranged from 0.328–0.849, with 6 factors of eigenvalue > 1, which could explain 58.274% of the total variance. The results of the confirmatory factor analysis showed: χ2/DF was 3.556, RMSEA was 0.077, CFI was 0.809, and SRMR was 0.070. Conclusions: The SDSC-I has been proved to be reliable and valid, and it can assess the sleep problems of infants in a comprehensive and detailed manner. Therefore, the scale is useful for early screening and adetection of sleep disorders by clinicians, and is worthy of popularization and application.
SSR markers in revealing extent of genetic diversity and phylogenetic relationships among chickpea core collection accessions for Western Himalayas
Authors: Mir Reyazul Rouf , Mir ASMA Hamid , BHAT MOHD ASHRAF , Fayaz Humaira , Wani Aijaz A , Dar Sher A , Maqbool Showkat , Yasin Mohammad , Mir Javid Iqbal , Khan Mohd Anwar , Sofi Parvaze A , El-Sappah Ahmed H , Thudi Mahendar , Varshney Rajeev K
Published: February 2022

Background: The exploration of genetic diversity is the key source of germplasm conservation strategies and the potential to widen its genetic base. The globally growing demand for chickpea suggests superior/climate-resilient varieties, which in turn necessitatesthe germplasm characterization to unravel underlying genetic variation. Methodology and Results: A chickpea core collection comprising of diverse 192 accessions which include cultivated Cicer arietinum, and wild C. reticulatum, C. echinospermum, and C. microphyllum specieswere investigated to analyze their genetic diversity and relationship, by assaying 33 unlinked simple sequence repeat (SSR) markers. The results amplifieda total of 323 alleles, ranging from 2 to 8withan average of4.25 alleles per locus. Expected heterozygosity (He) differed from 0.46 to 0.86 with an average of 0.68. Polymorphic information content (PIC) ranged from 0.73 to 0.98 with an average of 0.89. Analysis of molecular variance (AMOVA) showed that most of the variation was among individuals (87%). Cluster analysis resulted in the formation of four distinct clusters. Cluster I represented all cultivated and clusters II, III, and IV comprised a heterogeneous group of cultivated and wild chickpea accessions. Conclusion: We report considerable diversity and greater resolving power of SSR markers for assessingvariability and interrelationship among the chickpea accessions. The chickpea core is expected to be an efficient resource for breeders for broadening its genetic base and provides useful insight for selective breeding of desirable traits and in the identification of target genes for genomics-assisted breeding. Keywords: Chickpea, Core collection, Genetic diversity, Microsatellites, Cluster analysis.
Correlation Analysis of Metabolic Characteristics and the Risk of Metabolic-Associated Fatty Liver Disease–Related Hepatocellular Carcinoma
Authors: Xie Xuancheng , Yang Jinhui , Zheng Mengyao , Guo Weibo , Zhou Ying , Xiang Zhao , Li Yuting
Published: February 2022

Metabolic-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease worldwide and the main cause of hepatocellular carcinoma (HCC). To explore the risk factors of MAFLD-HCC, we evaluated the independent and combined effects of metabolic characteristics on the risk of MAFLD-HCC. We retrospectively analyzed 135 MAFLD-HCC patients who were treated at the Second Affiliated Hospital of Kunming Medical University from January 2015 to December 2020 and 137 MAFLD patients as the control group. Independent and joint effects of metabolic traits on the risk of HCC were evaluated. Each metabolic feature was significantly correlated with the increased risk of MAFLD-HCC (p < 0.05); obesity had the strongest correlation (adjusted odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.66–5.70). In patients with superimposed features, HCC risk was higher with more metabolic features (p < 0.05). Patients with concurrent obesity, prediabetes, and hypertension had the highest risk of HCC (adjusted OR = 5.7, 95% CI = 1.47–21.78). The correlation between metabolic characteristics and risk of MAFLD-HCC in patients without cirrhosis was basically consistent with the overall analysis. Metabolic characteristics increase the risk of MAFLD-HCC, and the risk is positively correlated with the number of metabolic characteristics. Obesity has the strongest correlation with HCC.
Transcriptional Waves Induced by ATP and LPS in Primary Microglial Culture Reveal Multiple Inflammatory States
Authors: Linial Michal , Zohar Keren , Lezmi Elyad , Reichert Fanny , Eliyahu Tsiona , Rotshenker Shlomo , Weinstock Marta
Published: February 2022

The primary role of microglia is to respond effectively to various disturbances to maintain brain homeostasis. In this study, we stimulated murine neonatal microglial cells with benzoyl ATP (bzATP) and lipopolysaccharide (LPS) and monitored their ability to secrete pro-inflammatory cytokines together with the changes in the transcriptome of the culture. Activation by bzATP, an agonist of purinergic receptors, induces a short-lived wave of transcriptional changes. However, a long-lasting transcriptional profile affecting thousands of genes occurs already at 3 hours after activation with a combination of bzATP and LPS. The transcriptomic profile is dominated by induced cytokines (e.g., IL1-a and IL1-b) and chemokines, in addition to upregulation of cytokine membrane receptors and their direct regulators. We identified the TNF and NF-kB signaling pathways as the principal hubs for many differentially expressed genes. Many of the reported inflammatory-related genes were upregulated by orders of magnitude. We conclude that the kinetics of microglial activation and specific combinations of stimuli yield coordinated and robust transcriptional waves. We propose that the primary microglia culture could be beneficial for studying brain inflammation associated with aging, injury, and neurodegenerative diseases.
RRP9 Promotes Gemcitabine Resistance in Pancreatic Cancer Via Activating AKT Signaling Pathway
Authors: Zhang Zhiqi , Yu Haitao , Yao Wenyan , Zhu Na , Miao Ran , Liu Zhiquan , Song Xuwei , Xue Chunhua , Cai Cheng , Cheng Ming , Zhang Xiaoping , Lin Ke , Qi Dachuan
Published: February 2022

BackgroundPancreatic cancer (PC) is a highly lethal malignancy regarding digestive system, which is the fourth leading factor of cancer-related mortalities in the globe. Prognosis is poor due to diagnosis at advanced disease stage, low rates of surgical resection, and resistance to traditional radiotherapy and chemotherapy. In order to develop novel therapeutic strategies, further elucidation of the molecular mechanisms underlying PC chemoresistance is required. Ribosomal RNA biogenesis has been implicated in tumorigenesis. Small nucleolar RNAs (snoRNAs) is responsible for post-transcriptional modifications of ribosomal RNAs during biogenesis, which have been identified as potential markers of various cancers. Here, we investigate the U3 snoRNA-associated protein RRP9/U3-55K along with its role in the development of PC and gemcitabine resistance.MethodsqRT-PCR, western blot and immunohistochemical staining assays were employed to detect RRP9 expression in human PC tissue samples and cell lines. RRP9-overexpression and siRNA-RRP9 plasmids were constructed to test the effects of RRP9 overexpression and knockdown on cell viability investigated by MTT assay, colony formation, and apoptosis measured by FACS and western blot assays. Immunoprecipitation, immunofluorescence staining and luciferase assays were utilized to demonstrate a relationship between RRP9 and IGF2BP1. A subcutaneous xenograft tumor model was elucidated in BALB/c nude mice to examine the RRP9 role in PC in vivo.ResultsSignificantly elevated RRP9 expression was observed in PC tissues than normal tissues, which was negatively correlated with patient prognosis. We found that RRP9 promoted gemcitabine resistance in PC in vivo and in vitro. Mechanistically, RRP9 activated AKT signaling pathway through interacting with DNA binding region of IGF2BP1 in PC cells, thereby promoting PC progression, and inducing gemcitabine resistance through a reduction in DNA damage and inhibition of apoptosis. Treatment with a combination of the AKT inhibitor MK-2206 and gemcitabine significantly inhibited tumor proliferation induced by overexpression of RRP9 in vitro and in vivo.ConclusionsOur data reveal that RRP9 has a critical function to induce gemcitabine chemoresistance in PC through the IGF2BP1/AKT signaling pathway activation, which might be a candidate to sensitize PC cells to gemcitabine.
HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma
Authors: Khattak Muhammad A , Oey Oliver , Gandhi Aesha , Reid Anna L , Abed Afaf , Calapre Leslie , Morici Michael , Chopra Abha , Meniawy Tarek , Millward Michael , Ziman Melanie , Gray Elin S
Published: February 2022

Background:Predictive biomarkers of response to immune checkpoint inhibitors (ICI) are currently being evaluated in many studies. We evaluated whether germline Human Leukocyte Antigen (HLA) status can influence the response to immunotherapy.Materials and Methods:Advanced melanoma patients undergoing treatment with pembrolizumab were recruited between August 2014 to January 2020. 121 patients were recruited, with a median follow up of 40.1 months. We dichotomised the cohort based on homozygosity in one or more HLA-I alleles (n=29) and those with maximal heterozygosity (n=84).Results:Our analysis did not show any association between HLA-I homozygosity and PFS (HR 1.06, 95% CI: 0.60-1.87, p = 0.83) or OS (HR 0.98, 95% CI: 0.51-1.191, p = 0.97). Similarly, we did not find any impact of HLA-II homozygosity (46 homozygous and 67 heterozygous) on PFS (HR 1.08, 95% CI: 0.66-1.79, p = 0.741) or OS (HR 1.52, 95% CI: 0.80-2.85, p = 0.19). Notably, the HLA-B27 supertype was associated with reduced PFS (HR 2.19, 95% CI: 1.19-4.02, p=0.02), and OS (HR:2.20, 95% CI:1.85-4.47, p=0.0075). Multivariate analyses confirmed that the HLA-B27 genotype is an independent predictor of shorter PFS and OS. The HLA-B27 association with reduced OS was validated in an independent cohort of 114 cases from the MSK-IMPACT cohort (HR 3.17, 95% CI: 1.01-10.01, p=0.01).Conclusions:Patients with HLA-B27 supertype have worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.
Hymenobacter erythromyxa sp. nov., and Hymenobacter radioresistens sp. nov., Gamma and UV radiation resistant bacteria isolated from a Gamma ray irradiated soil
Authors: Park Yuna , Maeng Soohyun , Oh Hye Jin , Bang Minji , Jeon Ji Young , Lim Chi Hong , Lim Sangyong , Jung Hee Young , Kim Myung Kyum , Sriniva Sathiyaraj
Published: February 2022

Two Gram-negative, gamma and UV tolerant bacterial strains, DG25AT and DG25BT, were isolated from soil samples exposed to 3kGy gamma radiation collected in Seoul, Korea. The cells grown on R2A agar at 25 °C were pink to red in colour. The phylogenetic analysis based on 16S rRNA gene sequence revealed that the strains belong to the genus Hymenobacter. The closest degrees of 16S rRNA gene sequence similarities to these strains, DG25AT and DG25BT, were found with Hymenobacter tibetensis NRRL B-51271T (96.5% and 96.6%, respectively). The multilocus sequence analysis (MLSA) tree based on the 14 housekeeping genes suggested that these two strains are distinct from other Hymenobacter species and represent novel candidates. The G+C contents of genomic DNA of DG25AT and DG25BT are 57.2 and 56.8 mol%, respectively. Chemotaxonomic data revealed that the strains contain iso-C15:0, anteiso-C15:0, C16:1 ω5c, summed feature3 (C16:1 ω7c/ C16:1 ω6c), and summed feature4 (anteiso B-C17:1 / iso I- C17:1) as the major fatty acids, and major polar lipid for both strains was phosphatidylethanolamine (PE). In addition, the strains showed resistance to gamma and UV radiation. Based on these data, each of strains DG25AT and DG25BT should be classified as a novel species, for which the names Hymenobacter erythromyxa sp. nov. (DG25AT =KCTC 32451T= JCM 19445T) and Hymenobacter radioresistens sp. nov., are proposed (DG25BT = KCTC 32452T = JCM 19444T).
Computer–controlled Intraligamentary local anaesthesia in extraction of mandibular primary molars: randomised controlled clinical trial
Authors: Helmy Rodaina H. , Zeitoun Sarah I. , El–Habashy Laila M.
Published: February 2022

Background: Local anesthesia (LA) poses a threat in children more than the treatment process itself, so pediatric dentists are always demanding less painful techniques. Computer-controlled Intraligamentary anaesthesia (CC–ILA) is designed to reduce injection pain and side effects of conventional techniques.Aim: To assess pain experience using Computer-controlled Intraligamentary anaesthesia (CC–ILA) during injection and its effectiveness in controlling pain during extraction of mandibular primary molars in pediatric patients.Design: Randomized controlled clinical trial, parallel groups.Methods: Fifty healthy cooperative children, aged 5–7 years with mandibular primary molars indicated for extraction. They were randomly allocated to two groups according to Local-anaesthetic technique: test group received CC–ILA and control group received Inferior alveolar nerve block (IANB). Pain was measured during injection and extraction: physiologically using Heart rate (HR), subjectively using Face-Pain-Scale (FPS), and objectively using Sound-Eye-Motor scale (SEM). Patients were recalled after 24 hours to record lip-biting events. Data was collected and analysed.Results: A total of 50 children (29 females and 21 males) with mean age 6.10 ± 0.76 participated in the study. There were significantly lower scores in the heart rate in the CC–ILA group during injection (p=0.04), but no significant difference was recorded between the two groups during extraction (p=0.17). The SEM and FPS showed significant lower scores in the CC–ILA group during injection (p<0.0001, p<0.0001) and extraction (p<0.0001, p=0.01) respectively. No children in CC–ILA group reported lip-biting after 24-hours compared to 32% in IANB (p<0.0001).Conclusion: CC–ILA provides significantly less painful injections than conventional techniques and has proved to be as effective as IANB during extraction of mandibular primary molars. An important advantage of this technique was the complete absence of any lip/cheek biting events. Trial Registration: The study was prospectively registered in ClinicalTrials.gov with the identifier: NCT04739735 on 26th of January 2021, https://clinicaltrials.gov/ct2/show/NCT04739735.
Coping Strategies and their Association with Diabetes Emotional Distress, Depression and Diabetes Self-Care among People living with Diabetes in Zambia
Authors: Hapunda Given
Published: February 2022

Background
Utilising coping strategies to reduce and manage the intensity of negative and distressing emotions caused by diabetes is essential. However, little is known about the use of coping strategies among people living with diabetes in Sub-Saharan African countries like Zambia. This study investigates coping strategies used by people with diabetes in Zambia and how these are associated with diabetes-specific emotional distress, depression and diabetes self-care.
Methods
Cross-sectional data from 157 people with diabetes were collected. Coping styles were measured using the Brief COPE, distress using the Problem Areas in Diabetes, depression using the Major Depression Inventory and self-care using the Diabetes Self-Care scale.
Results
Data showed that adaptive coping strategies were the most frequently used coping strategies among Zambian individuals with diabetes. Maladaptive coping strategies were related to increased diabetes distress and depression. Emotional support was related to better diabetes self-care, while self-blame was related to poor diabetes self-care.
Conclusion
There is a need to help individuals with diabetes identify adaptive strategies that work best for them in order to improve their quality of life.
Effect of parenting intervention through “Care for Child Development guideline” on early child development and behaviors: A randomized controlled trial
Authors: Bemanalizadeh Maryam , Badihian Negin , Khoshhali Mehri , Badihian Shervin , Hosseini Neda , Purpirali Marziye , Abadian Mansoore , Yaghini Omid , Daniali Seyedeh Shahrbanoo , Kelishadi Roya
Published: February 2022

BackgroundSeveral studies showed that parenting intervention programs play a core component in early child development. Considering the limited healthcare resources in developing countries, a group design intervention might be cost-effective.Methods This randomized controlled trial was conducted from February 2020 to February 2021 at an outpatient public Pediatrics clinic in Isfahan, Iran. We included 210 pregnant women aged 18-45 years in their third trimester and followed their children for 18 months. The intervention group underwent 5 educational group sessions, each lasting for almost 45 minutes. The main outcomes were the children's development and behaviors based on Bayley Scales of Infant and Toddler Development-III (BSCID-III) at 12 months and Children Behavior Checklist (CBCL) at 18-month of age.ResultsOverall, data of 181 children were included in the current study, including 80 in the intervention group and 101 controls. The adjusted median differences were significantly lower in the intervention group than in controls for attention problems (-3.38; SE=1.59; P=0.035), anxiety problems (-2.28; SE=1.03; P=0.007) and pervasive developmental problems (-5; SE= 1.16; P<0.001) based on CBCL results. However, the difference of proportions was not significant in none of the BSCID-III domains in the intervention and control groups. ConclusionIn this study, parenting interventions through CCD group sessions were significantly effective on several child’s behavior domains, but not on children’s development. Although CCD is known to improve children’s development and behaviors, the feasible method of its delivery to a large population, especially in developing countries, remains to be determined.Trial RegistrationIRCT20190128042533N2, Date of registration: 16/01/2020, www.irct.ir
Dissipation Dynamic And Processing Factor Of Myclobutanil In Tomato
Authors: Qi Yanli , Cao Junli , Li Jindong , Li Chunyong , Ren Pengcheng , Qin Shu
Published: February 2022

The effect of different processing factors on myclobutanil levels during canned tomato paste production was investigated. A validated residue analysis method was developed to identify myclobutanil by using QuEChERS extractionand UPLC-MS/MS analysis. To eliminate the matrix effect, a matrix-matched standard calibration curve was applied for accurate quantification. Myclobutanil miscible oil was sprayed under field conditions, and then tomato fruits were collected. The disspation of myclobutanil in tomato fruits followed a first-order dynamic equation with a half-life of 2.88 days. The result was similar to that in previous reports. The half-lives of myclobutanil in plants were short. The results of processing experiment indicated that the processing factors were all less than 1, showing that the processing procedure significantly decreased the residual level of myclobutanil canned tomato paste in comparison with the raw agricultural commodity. Washing, peeling, and homogenization played a critical role in reducing pesticide residues.