bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer development in COPD patients: retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea
Authors: Ahn Song Vogue , Lee Eunyoung , Park Bumhee , Jung Jin Hee , Park Ji Eun , Sheen Seung Soo , Park Kwang Joo , Hwang Sung Chul , Park Jae Bum , Park Hae-Sim , Park Joo Hun
Published: April 2020

Background: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. Methods: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N=313,553), former smokers without COPD (N=41,359), smokers without COPD (N=112,627), never-smokers with COPD (N=7,789), former smokers with COPD (N=1,085), and smokers with COPD (N=2,677). Results: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among former smokers, p<0.01). Age, male gender, lower BMI, low exercise level, smoking, and COPD were independent factors associated with the development of lung cancer (p<0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p < 0.01). Conclusion: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.
QTL Mapping of Web Blotch Resistance in Peanut by High-throughput Genome-wide Sequencing
Authors: Liu Hua , Sun Ziqi , Zhang Xinyou , Qin Li , Qi Feiyan , Wang Zhenyu , Du Pei , Xu Jing , Zhang Zhongxin , Han Suoyi , Li Shaojian , Gao Meng , Zhang Lina , Cheng Yujie , Zheng Zheng , Huang Bingyan , Dong Wenzhao
Published: April 2020

Background: Web blotch is one of the most important foliar diseases worldwide in peanut (Arachis hypogaea L.). The identification of quantitative trait loci (QTLs) for peanut web blotch resistance represents the basis for gene mining and the application of molecular breeding technologies.Results: In this study, a peanut recombinant inbred line (RIL) population was used to map QTLs for web blotch resistance based on high-throughput genome-wide sequencing. Frequency distributions of disease grade and disease index in five environments indicated wide phenotypic variations in response to web blotch among RILs. A high-density genetic map was constructed, containing 3,634 bin markers distributed on 20 peanut linkage groups (LGs) with an average genetic distance of 0.5 cM. In total, eight QTLs were detected for peanut web blotch resistance in at least two environments, explaining from 2.8% to 15.1% of phenotypic variance. Two major QTLs qWBRA04 and qWBRA14 were detected in all five environments and were linked to 40 candidate genes encoding nucleotide-binding site leucine-rich repeat (NBS-LRR) or other proteins related to disease resistances. Conclusions: The results of this study provide a basis for breeding peanut cultivars with web blotch resistance.
A single mutation in ACTR8 gene results in lineage-specific expression in primates
Authors: Choe Se-Hee , Park Sang-je , Cho Hyeon-Mu , Park Hye-Ri , Lee Ja-Rang , Kim Young-Hyun , Huh Jae-Won
Published: April 2020

Background: Alternative splicing (AS) generate various transcripts from a single gene and thus plays a significant role in transcriptomic diversity and proteomic complexity. Alu elements are primate-specific transposable elements (TEs) and can provide a donor or acceptor site for AS. In a study on TE-mediated AS, we recently identified a novel AluSz6-exonized ACTR8 transcript of a crab-eating monkey (Macaca fascicularis). In the present study, we sought to analyse the molecular mechanism of AluSz6-derived exonization in ACTR8 gene. Results: We performed RT-PCR and genomic PCR using the tissue RNA and DNA samples from the crab-eating monkey and various other primates, including humans, to study AluSz6-derived exonization in ACTR8 gene and transcript variants expression. AluSz6 integration was estimated to have occurred before the divergence of simians and prosimians. The novel transcript was expressed only in Old world monkeys and apes, and humans. Lineage-specific expression of ACTR8 gene was due to a ‘G’ duplication in the AluSz6 sequences of Old world monkey and ape lineages. Six alternative transcripts (TV1-TV6) generated by various AS mechanisms were newly identified. Based on in-silico analysis, the alternative transcripts were transcribed into new isoforms with C-terminus deletion. Conclusion: ‘G’ duplication together with TE exonization and AS via various mechanisms resulted in a different fate of ACTR8 gene expression during primate evolution.
Durability of Single Tablet Regimen for Patients with HIV infection in Southern Taiwan: data from a real world setting
Authors: Chang Hui-Min , Chou Chen-Hsi , Tsai Hung-Chin
Published: April 2020

Background: A single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real world settings. Our aim was to investigate the durability of different initial STR regimens in patients starting STR in southern Taiwan Method: This was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure (defined as plasma HIV RNAs≧200 copies/mL after 24 weeks). Secondary endpoints were STR discontinuation due to toxicity/intolerance. Survival analysis was done using Kaplan–Meier and Cox regression.Results: Two hundred and twenty-three patients were included: Over a median (IQR) of 86 (60-112) weeks, 25 patients (11%) experienced virological failure; the 1 year probability of virological failure was 11% (8/70) for Efavirenz/Emtricitabine/ Tenofovir Disoproxil Fumarate, 7% (4/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate and 13% (13/99) for Abacavir/Dolutegravir/Lamivudine. Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to Efavirenz/Emtricitabine/ Tenofovir Disoproxil Fumarate, treatment with Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (AHR 8.39, CI 1.98-35.58, p=0.004) and Abacavir/Dolutegravir/Lamivudine (AHR 8.40, CI 2.39-29.54, p=0.001) were more likely to have treatment failure. However, when the risk of treatment failure was compared between two different STRs, treatment with Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate was not found to have higher risk of treatment failure when compared to Efavirenz/Emtricitabine/ Tenofovir Disoproxil Fumarate (log rank test p=0.116). The predictors for treatment failure included age≦30 years old (AHR 3.73, CI 1.25-11.17, p=0.018), switch between different STR (AHR 2.3, CI 1.18-4.50, p=0.001) and free of active syphilis infection (AHR 0.24, CI 0.08-0.73, p=0.012). The risk factor for treatment discontinuation included younger age≦30 years old (AHR 3.82, CI 1.21-12.37, p=0.023), treatment with Efavirenz/Emtricitabine/ Tenofovir Disoproxil Fumarate (AHR 8.65 , CI 2.64-28.39 , p<0.001) and free of active syphilis infection (AHR0.16, CI 0.04-0.62, p=0.006). Conclusion: Younger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection
M2 Macrophagy-derived Exosomal MiRNA-5106 Induces Bone Mesenchymal Stem Cells towards Osteoblastic Fate by Targeting Salt-inducible Kinase 2 and 3
Authors: Xiong Yuan , Chen Lang , Yan Chenchen , Zhou Wu , Yu Tao , Sun Yun , Cao Faqi , Xue Hang , Hu Yiqiang , Chen Dong , Mi Bobin , Liu Guohui
Published: April 2020

Background Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo , and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. Results We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 ( SIK2 and SIK3 ) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo . Conclusions Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.
Shotgun proteomics of peach fruit reveals major metabolic pathways associated to ripening
Authors: Nilo-Poyanco Ricardo , Moraga Carol , Benedetto Gianfranco , Orellana Ariel , Almeida Andréa Miyasaka
Published: April 2020

BackgroundFruit ripening in Prunus persica melting varieties involves several physiological changes that have a direct impact on the fruit organoleptic quality and storage potential. By studying the proteomic differences between the mesocarp of mature and ripe fruit, it would be possible to highlight critical molecular processes involved in the fruit ripening.ResultsTo accomplish this goal, the proteome from mature and ripe fruit was assessed from the variety O’Henry through shotgun proteomics using 1D-gel (PAGE-SDS) as fractionation method followed by LC/MS-MS analysis. Data from the 131,435 spectra could be matched to 2,740 proteins, using the peach genome reference v1. After data pre-treatment, 1,663 proteins could be used for comparison with datasets assessed using transcriptomic approaches and for quantitative protein accumulation analysis. Close to 26% of the genes that code for the proteins assessed displayed higher expression at ripe fruit compared to other fruit developmental stages, based on published transcriptomic data. Differential accumulation analysis between mature and ripe fruit revealed that 15% of the proteins identified were modulated by the ripening process, with glycogen and isocitrate metabolism, and protein localization overrepresented in mature fruit, as well as cell wall modification in ripe fruit. Potential biomarkers for the ripening process, due to their differential accumulation and gene expression pattern, included a pectin methylesterase inhibitor, a gibbellerin 2-beta-dioxygenase, an omega-6 fatty acid desaturase and an ACC oxidase. These genes would be regulated by transcription factors enriched in zinc finger and GAGA-binding transcriptional activator protein domains.ConclusionsShotgun proteomics is an unbiased approach to get deeper into the proteome allowing to detect differences in protein abundance between samples. This technique provided a resolution so that individual gene products could be identified. Many proteins likely involved in cell wall and sugar metabolism, aroma and color, change their abundance during the transition from firm to soft fruit.
Prognostic value of programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma
Authors: Zhang Qun , Li Feng , Cai Peng , Li Hongwei , Yin Hongmei , Zhu Chaomang , Zhang Lei , Li Duojie
Published: April 2020

Background

To investigate the expression of PD-L1(programmed death-ligand 1)in patients with esophageal squamous cell carcinoma (ESCC) and its clinical significance.
Methods

The tissue expression of PD-L1 protein in 139 cases of ESCC and 50 adjacent non-malignant epithelial tissues (> 5 cm from the tumor resection margins) were identified by immunohistochemical staining. Subsequently, the relationship between expression and the observed clinical characteristics was analyzed.
Results

The positive expression rate of PD-L1 protein was increased in tumor tissues compared to that of adjacent noncancerous mucosa tissues (40.3% vs. 22.0%, P < 0.05). The findings also indicated that PD-L1 protein expression had no significant correlation with age, gender, tumor location, differentiation and lymph node (N) status (P > 0.05). The 91 months follow-up Kaplan-Meier survival analysis showed that patients in positively expressed PD-L1 group experienced a lower survival rate compared to their negatively expressed PD-L1 counterparts (32.1% vs. 48.2%, P < 0.05). The COX regression analysis results suggested that PD-L1 represented an independent prognosis factor for ESCC.
Conclusions

The findings indicated that PD-L1 plays an important role in the progression of ESCC and might represent a potential therapeutic and prognostic target for ESCC patients.
The primary total knee arthroplasty: a global analysis
Authors: Gao Jiaxiang , Xing Dan , Dong Shengjie , Lin Jianhao
Published: April 2020

Background

The use of total knee arthroplasty (TKA) in treatment of chronic degenerative pathologies of the knee has boasted of an experience of 50 years. The aim of this bibliometric and visualized study is to comprehensively examine the current status and global trends of TKA research.

Methods

Publications related to TKA research from 2010 to 2019 were retrieved from Web of Science database, and then analyzed through bibliometric methodology. As for the visualized study, the software VOS viewer was utilized for bibliographic coupling, coauthorship, cociation, and co-occurrence analysis, along with further simulation of publication trends in this field.

Results

A total of 8631 publications were eventually included. The number of publications tends to increased annually over the worldwide. The United States was the pioneer which has made tremendous contribution, with the most publications and citations, as well as the highest H-index. The JOURNAL OF ARTHROPLASTY has published most papers, while CLINICAL ORTHOPAEDICS AND RELATED RESEARCH has the highest citation frequency. Hospital for Special Surgery have made the greatest contribution when total publication number and coauthorship were taken together. Studies could be divided into five clusters: “alignment study”, “revision TKA study”, “complication study”, “rehabilitation study”, and “perioperative management study”, which have a trend of balanced development in this field.

Conclusions

There will be an increasing number of publications on TKA research according to the current global trends, and the United States maintained the leadership in this area. Additionally, a trend of balanced development may exist in the field of TKA research, accompanied with inherent changes of hotspots in each cluster.
The effect of omega-3 and vitamin D co-supplementation on glycemic control and lipid profiles in reproductive-aged women with pre-diabetes and hypovitaminosis D: A randomized controlled trial
Authors: Naeeni Masoumeh Rajabi- , Dolatian Mahrokh , Qorbani Mostafa , Vaezi Amir Abbas
Published: April 2020

Background Prediabetes can predispose the individual to type 2 diabetes in the long-term. The present study was conducted to determine the effectiveness of vitamin D and omega-3 co-supplementation on glycemic control and serum lipid profiles in women of reproductive age with prediabetes and hypovitaminosis D. Methods The present factorial, triple-blind, clinical trial was conducted on 168 women of reproductive age with prediabetes and hypovitaminosis D. The participants were assigned to four groups based on block randomization method: the placebo group received omega-3 and vitamin D placebos; the omega-3 group took omega-3 supplements and vitamin D placebos; the vitamin D group received omega-3 placebos and vitamin D supplements and the co-supplementation group. The groups received every two weeks 50,000 IU pearls of vitamin D and twice-daily doses of 1000-mg omega-3 tablets or placebos for eight weeks. Dietary intake, physical activity, anthropometric indices and blood biochemical tests were measured at the beginning and end of the study. Analysis was performed using two-way mixed ANOVA. Results A significant reduction was observed in fasting glucose, insulin, homeostasis model assessment-beta cell function, weight and waist circumference in the co-supplementation group compared to the other three groups (P<0.05). Moreover, high-density lipoprotein-cholesterol levels increased significantly in the co-supplementation group compared to the other three groups (P<0.05). Despite the fact that homeostasis model assessment-insulin resistance, total cholesterol, triglyceride and low-density lipoprotein-cholesterol levels decreased after intervention in the co-supplementation group, there was no significant difference between the groups in these outcomes. Conclusion Vitamin D and omega-3 co-supplementation improved fasting serum glucose, insulin, high-density lipoprotein-cholesterol level, homeostasis model assessment-beta cell function, weight and waist circumference in women of reproductive age with prediabetes and hypovitaminosis D. This co-supplementation can therefore be recommended for glycemic control in these women.
Opinions towards the water-related Payments for Ecosystem Services (PES) schemes: The stakeholders’ point of view
Authors: Paletto Alessandro , Báliková Klára , De Meo Isabella
Published: April 2020

Background: Forests provide a wide range of water-related ecosystem services (WES) vital for human well-being such as groundwater recharge, runoff and water discharge to streams, soil erosion protection, aesthetic landscape and recreational opportunities. Sustainable forest management and afforestation/reforestation practices can maintain and improve the long-term provision of WES. In this context, new market-based mechanisms – Payments for Ecosystem Services (PES) – can promote sustainable forest management by reducing negative externalities. To implement PES schemes for WES, many stakeholders with different knowledge, interests, and needs must be consulted and involved in the design and implementation process.Methods: The aim of this study is to investigate stakeholders’ opinions on the relationships between forests and water resources and the water-related Payments for Ecosystem Services (PES) schemes in Italy. A semi-structured questionnaire was administered by email to 39 stakeholders identified through a stakeholder analysis. The stakeholders were classified in four groups: buyers (15.4% of stakeholders), sellers (15.4%), intermediaries (43.6%), and knowledge providers (25.6%).Results and conclusions: The results show that the three most important WES provided by forests are soil erosion reduction, followed by provision of habitats for different species and surface runoff reduction. The respondents emphasize the importance of regulating and supporting services, while they minimize the importance of cultural services. For the sample of respondents, market-based instruments have an efficiency comparable to regulatory instruments, but a shared value for ecosystem services among stakeholders is required in the implementation of PES schemes. According to respondents' opinions, the public authority should play the role of both buyer and regulator, while the other stakeholders should be consulted (citizens) or actively involved (farmers’ and forest owners’ associations) in the decision-making process related to the PES schemes.
Effect of green tea catechins on uric acid metabolism after alcohol ingestion in Japanese men: a randomized crossover study
Authors: Kawakami Yuka , Yasuda Arisa , Hayashi Motoki , Akiyama Misuzu , Asai Toshihiko , Hosaka Toshio , Arai Hidekazu
Published: April 2020

Background Alcohol consumption is associated with hyperuricemia and gout. Previous studies have indicated a role for green tea catechins in uric acid (UA) metabolism. This study aimed to elucidate the effect of green tea catechins in terms of enhancing urinary excretion of UA and xanthine/hypoxanthine (Xa/HX) after alcohol ingestion.Methods In a randomized crossover study, 10 healthy subjects consumed test meals, including a Japanese distilled spirit (Shōchū) with water (SW) or Shōchū with catechin-rich green tea (SC), each containing 20 g of alcohol. The SC contained 617 mg of total catechin. Serum and urine UA and Xa/HX concentrations were measured. Blood samples were collected after 2.5 h, and urine samples were collected between 0 and 5 h after consuming the test meal.Results Urine UA and Xa/HX excretions were significantly higher in the SC group than in the SW group ( P < 0.05). UA clearance and fractional UA excretion tended to increase more in the SC group than in the SW group. No significant differences in S-UA and S-Xa/Hx concentrations were observed between the SW and SC groups.Conclusions Based on these observations, it was concluded that green tea catechins can enhance the excretion of UA and Xa/HX, even though alcohol is ingested.Trial registration The protocol was approved by the Ethics Committee of the University of Shizuoka and registered with UMIN (University Hospital Medical Information Network in Japan). Trial registration number: UMIN000040076. Registered 7 April 2020 – Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045687
Authorship diversity among systematic reviews in eyes and vision
Authors: Qureshi Riaz , Han Genie , Fapohunda Kolade , Abariga Samuel , Wilson Renee , Li Tianjing
Published: April 2020

Importance : The inclusion of people from diverse backgrounds, and with different lived experiences is critical to ensuring the questions addressed in systematic reviews (SRs). The subsequent conclusions and recommendations made, are relevant and sensitive to the setting.Objective : To assess the gender and geographic diversity of authors among all Cochrane SRs in eyes and vision as compared with a random sample of non-Cochrane SRs of interventions in the field of eyes and vision.Design : The Cochrane Eyes and Vision United States Satellite maintains a database of SRs in the field of eyes and vision. We selected all (n = 313) Cochrane Library intervention SRs and a random sample of 313 non-Cochrane Library intervention SRs for this study. We extracted gender (‘woman,’ ‘man,’ or ‘unknown’) using a previously developed algorithm and location based on country and the World Health Organization region – of the first and corresponding authors using their full names and affiliations.Results : From the 626 reviews included in our sample, we identified 756 unique authors who comprised 887 author positions (i.e., first and/or corresponding authors). We were able to ascertain the gender of 652/756 (86%) authors: 279 women, and 373 men. Among Cochrane reviews, the proportions of women in first and/or corresponding author positions were consistent and approximately equal to men. Among non-Cochrane reviews, the representation of women was markedly lower as corresponding authors than other positions. We identified a location for each author and found most authors of Cochrane reviews were from the United Kingdom (31%) and United States of America (26%), whereas most authors of non-Cochrane reviews were from China (34%).Conclusions and relevance : Cochrane SRs in eyes and vision appear to have equal representation of women and men among the first and corresponding authors. Compared with non-Cochrane SRs in eyes and vision, Cochrane SRs appear to have a greater concentration of authors who are based in European and North American countries, possibly due to the locations of the Cochrane editorial teams. Cochrane Eyes and Vision should continue to recruit authors from around the world in locations that reflect the global burden of eye disease.
Chestnut tannins and their relationship in promoting broiler growth by altering the metabolic phenotype in the cecum.
Authors: Lee Annah , Pont Gabriela Cardoso Dal , Jarvis Stephanie , Farnell Morgan B , Battaglia Michele , Arsenault Ryan J , Kogut Michael H
Published: April 2020

Background As the demand for alternatives to antibiotic growth promoters (AGPs) increases in food animal production, phytobiotic compounds gain in popularity due to their ability to mimic the desirable bioactive properties of AGPs. Chestnut tannins (ChT) are one of many phytobiotic compounds utilized as feed additives, particularly in South America, for broiler chickens due to its favorable antimicrobial and growth promotion capabilities. While studies have observed the microbiological and immunological effects of ChT, there is a lack of studies evaluating the metabolic function of ChT in the host. Therefore, the objective of this study was to characterize the cecal metabolic changes induced by ChT inclusion and how they relate to growth promotion. Results A total of 500 day-of-hatch Cobb 500 chicks were separated into five feed treatment groups: control, 1% ChT, 0.2% ChT, 0.08% ChT, and 0.03% ChT. The cecas from all the chicks in the treatment groups were collected on days 2, 4, 6, 8, and 10 post-hatch. The cytokine mRNA qRT-PCR was determined using TaqMan gene expression assays for IL-1B, IL-6, IL-8, IL-10, and IFN-γ quantification. The cytokine expression showed highly significant increased expressions of IL-6 and IL-10 on days 2 and 6, while the other pro-inflammatory cytokines did not have significantly increased expression. The results from the kinome array demonstrated that the cecas from birds fed with 1% ChT had significant (p < 0.05) metabolic alterations based on the number of peptides when compared to the control group across all days tested. Conclusions Based on the results, the increased expression of IL-6 appeared to be strongly indicative of altered metabolism while the increased expression of IL-10 indicated the regulatory effect against other pro-inflammatory cytokines other than IL-6. The ChTs initiate a metabolic mechanism during the first ten days in the broiler. For the first time, we show that a phytobiotic product initially modulates metabolism rather than immunity while also potentially supporting growth and feed efficiency downstream. In conclusion, an IL6-mediated immunometabolic phenotypic alteration in the ceca of chickens fed ChT may indicate the importance in the gut of enhanced broiler health.
Displacement in root apex and changes in incisor inclination affect alveolar bone remodeling in adult bimaxillary protrusion patients: a retrospective study
Authors: Mao Huimin , Yang Andi , Pan Yue , Li Houxuan , LEI Lang
Published: April 2020

Background: Periodontal health is of great concern for periodontists and orthodontists in the inter-disciplinary management of patients with bimaxillary protrusion. The aim of present study is to investigate changes in the alveolar bone in the maxillary incisor region and to explore its relationship with displacement of root apex as well as changes in the inclination of maxillary incisors during incisor retraction. Methods: Samples in this retrospective study consisted of 38 patients with bimaxillary protrusion. Cone-beam computed tomography (CBCT) images was taken before(T0) and after (T1) treatment. Alveolar bone thickness (ABT), height (ABH) and area (ABA) were utilized to evaluate changes in the alveolar bone, while incisor inclination and apex displacement were used to assess changes in the position of maxillary central and lateral incisors. Correlations between alveolar bone remodeling and apex displacement as well as changes in the inclination were investigated. Results: The labial ABT of central and lateral incisors at the mid-root third was increased. In contrast, the palatal ABT at crestal, mid-root and apical third level were consistently decreased. ABH was not altered on the labial side, while significantly decreased on the palatal side. ABA was not significantly increased on the labial side, but significantly decreased on the palatal side, leading to a significantly reduced total ABA. Orthodontic treatment significantly reduced inclination of upper incisors. Changes in the amount (T1-T0) of ABA was remarkably correlated with apex displacement and changes of inclination (T1-T0); in addition, using the multivariate linear regression analysis, changes of ABA on the palatal side (T1-T0) can be described by following equation: Changes of palatal ABA (T1-T0) = -3.258- 0.139× changes of inclination (T1-T0) + 2.533×apex displacement (T1-T0). Conclusions: Retraction of incisors in bimaxillary protrusion patients may compromise periodontal bone support on the palatal side. An equation that incorporated the displacement of root apex and change in the incisor inclination may enable periodontist-orthodontist interdisciplinary coordination in assessing treatment risks and developing an individualized treatment plan for adult patients with bimaxillary protrusion.
Autologous bone marrow mononuclear cell transplantation therapy improved symptoms in patients with refractory diabetic peripheral neuropathy via the mechanisms of paracrine and immunomodulation
Authors: Wei Wei , Li Li , Deng Lin , Wang Zhong-jing , Dong Jing-jian , Lyu Xiao-Yu , Jia Ting , Wang Li , Wang Hong-xiang , Mao Hong , Zhao Shi
Published: April 2020

Background: We recently reported that transplantation of autologous bone marrow mononuclear cells (BM-MNCs) may be an effective and promising therapy to treat refractory diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the potential mechanisms of BM-MNCs therapy.Methods: This clinical study recruited 60 patients with DPN, 30 T2DM patients without complications, 30 healthy control participants. All clinical parameters, the levels of inflammatory markers and growth factors in three groups were compared. All patients with DPN received one intramuscular injection of BM-MNCs and clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks. Then they were divided into the responder and non-responder groups based on the improvement of nerve conduction velocity. Binary logistic regression was performed to evaluate the corresponding prognostic factors for BM-MNCs treatment.Results: Patients in DPN group had higher level of tumor necrosis factor-α (TNF-α) and lower level of vascular endothelial growth factor (VEGF) than those in control group. DPN group had the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among three groups. The level of nerve growth factor (NGF) in DPN group was slightly lower than that in DM group. Neuropathic symptoms were significantly improved after BM-MNCs injection. Thirty five of 54 patients with DPN (64.8%) reached the primary endpoint, and were regarded as the responders. Compared to non-responders, responders were younger, had a longer history of diabetes, and had higher numbers of mobilized CD34+ cells and BM-MNCs. The levels of TNF-α and sICAM-1 decreased just after BM-MNCs injection in both groups and slowly reverted to baseline levels. The durations of downtrend of TNF-α and sICAM-1 in responder group lasted longer than that in non-responder group. Serum level of VEGF in responder group increased immediately after BM-MNC therapy, and reached the highest point after the injection for 12 weeks. On the other hand, VEGF levels in the non-responder group only increased slightly. The number of applied CD34+ cells (OR=1.567, 95% CI 1.106-2.222, p=0.012) and duration of diabetes (OR=0.760, 95% CI 0.597-0.967, p=0.025) were the independent predictors of responding to BM-MNCs therapy. No adverse event associated with the treatment was observed during follow-up observations.Conclusions: BM-MNCs transplantation is an effective and promising therapeutic strategy to treat refractory DPN. The immune regulation and paracrine function of BM-MNCs may contribute to the improvement of DPN.
ATR and p-ATR are Emerging Prognostic Biomarkers and DNA Damage Response Targets in Ovarian Cancer
Authors: feng wenlong , Dean Dylan C. , Hornicek Francis J. , Wang Jinglu , Jia Yanyan , Shi Huirong , Duan Zhenfeng
Published: April 2020

Background: Although ATR has an established role in DNA damage response in various cancers, its clinical and prognostic significance in ovarian cancer remains largely unknown. The aims of this study are to assess the expression, function and clinical prognostic relationship of ATR, p-ATR in ovarian cancer. Methods: We confirmed ATR and p-ATR expressions by immunohistochemistry in a unique ovarian cancer tissue microarray constructed of paired primary, recurrent and metastatic tumor tissues from 26 individual patients. ATR specific siRNA and ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on ovarian cancer cell proliferation, apoptosis, and DNA damage. ATR expression and the associated proteins of the ATR/Chk1 pathway in ovarian cancer cell lines were evaluated by Western blotting. The clonogenicity was also examined using clonogenic assays. A 3D cell culture model was performed to mimic the in vivo ovarian cancer environment to further validate the effect of ATR inhibition on ovarian cancer cells. Results: We show recurrent ovarian cancer tissues express higher levels of ATR and p-ATR than their patient-matched primary tumor counterparts. Additionally, higher expression of p-ATR correlates with decreased survival in ovarian cancer patients. Treatment of ovarian cancer cells with ATR specific siRNA or ATR inhibitor VE-822 led to significant apoptosis and inhibition of cellular proliferation, with reduced phosphorylation of Chk1 (p-Chk1), Cdc25c (p-Cdc25c), Cdc2 (p-Cdc2), and increased expression of cleaved PARP and γH2AX. Inhibition of ATR also suppressed clonogenicity and spheroid growth of ovarian cancer cells. Conclusion: Our results support the ATR and p-ATR pathway as a prognostic biomarker, and targeting the ATR machinery is an emerging therapeutic approach in the treatment of ovarian cancer.
Pyrotinib sensitizes 5‑fluorouracil‑resistant HER2-positive breast cancer cells to 5‑fluorouracil
Authors: Yi Jianing , Yi Pingyong , Chen Shuai , Li Qian , Wu Runzhang , Du Yang , Zou Lianhong , Fan Peizhi
Published: April 2020

BACKGROUND: Clinical trials have shown that pyrotinib+ capecitabine significantly improved efficacy of patients with human epidermal growth factor receptor 2(HER2) +breast cancer. However, whether pyrotinib sensitizes 5‑Fluorouracil(5‑FU)‑resistant breast cancer cells to 5‑FU is unknown. This study aimed to investigate the effects of pyrotinib on HER2+breast cancer cells with resistance to 5‑FU and provide new clues for the pyrotinib treatment in 5-FU-resistant breast cancer.METHODS: the 5‑FU‑resistant breast cancer cell lines SK-BR-3/FU and MAD-MB-453/FU were established by continuous exposure of the parental cells to 5‑FU.The effects of pyrotinib on these cell lines were examined by growth inhibitory activity assay, reverse transcription‑quantitative polymerase chain reaction, Western blot analysis, high-performance liquid chromatography and animal experiments.RESULTS: Pyrotinib inhibited the proliferation of 5-FU-resistant and parental HER2-positive breast cancer cells and re-sensitized resistant cells to 5-FU by decreasing the expression of thymidylate synthase(TS) and ABC transporter subfamily G member 2(ABCG2). In a xenograft model, combination treatment with 5-FU and pyrotinib showed greater antitumor activity than either agent alone. CONCLUSIONS: Our results offer a preclinical rationale for clinical investigations of combination treatment with pyrotinib and 5-FU for 5-FU-resistant HER2-positive breast cancer.
Influence of modification of dental porcelains with hybrid nanomaterial on surface characteristics, antimicrobial, chemical, and mechanical properties
Authors: Vidal Carla Larissa , Ferreira Izabela , Ferreira Paulo Sergio , Valente Mariana Lima da Costa , Teixeira Ana Beatriz Vilela , Reis Andrea Candido dos
Published: April 2020

Evaluated the effect of incorporation of the nanostructured silver vanadate decorated with silver nanoparticles (β-AgVO3) into dental porcelains on surface characteristics, antimicrobial, chemical, and mechanical properties. The percentages of 2.5% and 5% of β-AgVO3 were incorporated into commercial dental porcelains IPS Inline and Ex-3 Noritake. Surface characteristics were evaluated by SEM/EDS. Antimicrobial activity were investigated against Streptococcus mutans, Streptococcus sobrinus, Aggregatibacter actinomycetemcomitans, and Pseudomonas aeruginosa, by colony counts (CFU/mL), metabolic activity, and multiphoton microscopy. The chemical and mechanical behavior was evaluated by silver (Ag+) and vanadium (V4+/V5+) ions release, microhardness, roughness, and fracture toughness. Statistical tests Kruskal-Wallis and Dunn’s post-hoc were applied for antimicrobial analysis and ions release, and ANOVA and Bonferroni's post-hoc, for mechanical analysis. The nanomaterial interferes in the material’s morphology but does not alter the porcelain’s components. IPS Inline 5% reduced S. mutans and S. sobrinus (p<0.05), and Ex-3 Noritake 5% reduced S. sobrinus (p<0.05). The IPS Inline 2.5% reduced A. actinomycetemcomitans (p<0.05). IPS Inline 5% released more Ag+ (p<0.05), and Ex-3 Noritake 2.5% released more V4+/V5+ (p<0.05). The β-AgVO3 increased the fracture toughness of IPS Inline, the roughness for all groups, and decreased the microhardness of 2.5% group (p<0.05). β-AgVO3 incorporation influenced on morphology but not altered the porcelain’s components, promoted antimicrobial activity against S. mutans, S. sobrinus, and A. actinomycetemcomitans, due to the Ag+ and V4+/V5+ released and influenced the porcelain’s mechanical properties.
Reconstructing and Forecasting the COVID-19 Epidemic in the US Using a 5-Parameter Logistic Growth Model
Authors: Chen Ding-Geng , Chen Xinguang , Chen Jenny Ke
Published: April 2020

Background: Many studies have modeled and predicted the epidemic of COVID-19 in the US using data that starts from the first reported cases. However, because of the shortage of test services to detect the infected, this approach is subject to error due to under-detection in the early period of the epidemic. We attempted a new approach to overcome this limitation and to provide data supporting the public policy decisions against the life-threatening COVID-19 epidemic.Methods: Documented data by CDC were used, including daily new and cumulative cases of confirmed COVID-19 in the US from January 22 to April 6, 2020. A 5-parameter logistic growth model was used to reconstruct the epidemic. Instead of all data in the whole study period, we fitted data in a 2-week window from March 21 to April 4 (approximately one incubation period) during which massive testing services were in position. With parameters obtained from the modeling, we reconstructed and predicted the epidemic and evaluated the under-detection.Results: The data fit the model satisfactorily. The estimated daily growth rate was 16.8% (95% CI: 15.95%, 17.76%) overall, with 4 consecutive days having a doubling growth rate. Based on the modeling result, the tipping point for new cases to decline will be on April 7 th , 2020, with 32,860 new cases. By the end of the epidemic, a total of 792,548 (95% CI: 789,162-795,934) will be infected. Based on the model, a total of 12,029 cases were not detected from the first case from January 22 to April 4.Conclusions: Study findings suggest the usage of a 5-parameter logistic growth model with reliable data that comes from a specified window period, where governmental interventions are appropriately implemented. In addition to informing decision-making, this model adds one tool for use to capture the underlying COVID-19 epidemic caused by a novel pathogen.
Brief psychotherapy administered by non-specialised health workers to address risky substance use in inpatients with multi-drug resistant tuberculosis: A feasibility and acceptability study
Authors: Calligaro Gregory Louis , De Wit Zani , Cirota Jacqui , Orrell Catherine , Myers Bronwyn , Decker.Sebastian@web.de Sebastian Decker , Stein Dan , Sorsdahl Katherine , Dawson Rodney
Published: April 2020

Background : Only 55% of multi-drug resistant tuberculosis (MDR-TB) cases worldwide complete treatment, with problem substance use a risk for default and treatment failure. Nevertheless, there is little research on psychotherapeutic interventions for reducing substance use among MDR-TB patients in general, and on their delivery by non-specialist health workers in particular. Objectives : To explore the feasibility and acceptability of a non-specialist health worker-delivered 4-session brief motivational interviewing and relapse prevention (MI-RP) intervention for problem substance use and to obtain preliminary data on the effects of this intervention on substance use severity, depressive symptoms, psychological distress and functional impairment at 3 months after hospital discharge. Methods : Between December 2015 and October 2016, consenting MDR-TB patients admitted to Brewelskloof Hospital who screened at moderate to severe risk for substance-related problems on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were enrolled, and a baseline questionnaire administered. In the four weeks prior to planned discharge, trained counsellors delivered the MI-RP intervention. The baseline questionnaire was re-administered three-months post-discharge and qualitative interviews were conducted with a randomly selected sample of participants (n=10). Results : Sixty patients were screened: 40 (66%) met inclusion criteria of which 39 (98%) were enrolled. Of the enrolled patients, 26 (67%) completed the counselling sessions and the final assessment. Qualitative interviews revealed participants’ perceptions of the value of the intervention. From baseline to follow-up, patients reported reductions in substance use severity, symptoms of depression, distress and functional impairment. Conclusion : In this feasibility study, participant retention in the study was moderate. We found preliminary evidence supporting the benefits of the intervention for reducing substance use and symptoms of psychological distress, supported by qualitative reports of patient experiences. Randomised studies are needed to demonstrate efficacy of this intervention before considering potential for wider implementation. Trial registration : South African National Clinical Trials Register (DOH-27-0315-5007) on 01/04/2015 (http://www.sanctr.gov.za). Funding: National Institute for Drug Abuse (NIDA), AIDS Clinical Trials Group (ACTG).
Rapid spread of mutant alleles in worldwide COVID-19 strains revealed by genome-wide SNP analysis
Authors: Zhu Zhenglin , Liu Gexin , Meng Kaiwen , Yang Liuqing , Meng Geng
Published: April 2020

The novel coronavirus (COVID-19) has become a pandemic and is threatening human health globally. Here, we report 14 newly evolved COVID-19 single nucleotide polymorphism (SNP) alleles those underwent a rapid increase (12 cases) or decrease (2 cases) in their frequency from between 10% and 50% in the last three months. The 14 SNPs are mostly (13/14) located in the coding region and are mainly (9/14) nonsynonymous substitutions. Out of the 14 SNPs, 12 SNPs showed a complete linkage in SNP pairs and clustered into 4 linkage groups, named LG_1 to LG_4. SNPs located in 514 and 27046 are independent events. Analyses in population genetics show that the increases in the new alleles result from genetic differentiation between Europe and America. We found that the mutants in LG_1 are driven by balancing selection and arose rapidly in Europe but not in America. The mutants in LG_2 and LG_3, also driven by balancing selection, arose rapidly in American but not in European strains. Based on analysis of geographic COVID-19 cases worldwide, we found that the mutants in LG_1 positively correlate the fatality rate of COVID-19 while those in LG_2 and LG_3 negatively correlate with the fatality rate. The correlations are statistically significant, suggesting that the virus strains possessing mutants in LG_1 are more aggressive, while those in LG_2 and LG_3 are in opposite. Further analysis revealed that mutants in LG_1 have been identified more frequently in European strains than in American strains, while mutants in LG_2 and LG_3 have been found more frequently in American strains. This may partially explain the higher fatality rates of COVID-19 infection in Italy, England and France, compared with the United States. These findings should be instructive for epidemiological surveys and disease control of COVID-19 in the future.
Nematicide efficacy at managing Meloidogyne arenaria and non-target effects on free-living nematodes in peanut production
Authors: Grabau Zane J. , Mauldin Mark D. , Habteweld Alemayehu , Carter Ethan T.
Published: April 2020

Meloidogyne arenaria (peanut root-knot nematode (PRKN)) is a major pest of peanut. Nematicide application is an important tool for the management of PRKN. Nematicides with minimal effects on free-living nematodes are desired. Fluopyram nematicide is recently introduced in peanut production and needs to be assessed. The objective of this research is to evaluate fluopyram and the established nematicides 1,3-Dichloropropene (1,3-D) and aldicarb for efficacy at managing PRKN and impacts on free-living nematodes. Nematicides were evaluated in field studies in 2017 and 2018 conducted in commercial peanut fields. All nematicides increased peanut yield in 2017 compared with untreated control, but did not affect soil PRKN abundances or root galling. In 2018, PRKN infestation was too low to accurately assess PRKN management by nematicides. Aldicarb and fluopyram did not affect any free-living nematode trophic group or individual genera. In contrast, 1,3-D decreased total fungivore and fungivore genera Filenchus and Aphelenchus soil abundances, but did not affect bacterivores, omnivore-predators, total herbivores, or any other nematode genera. In summary, 1,3-D, but not aldicarb or fluopyram, had non-target effects on free-living nematodes, particularly fungivores.