bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Need for Affect and Cognition Culture-Dependent? Implications for Global Public health Campaigns: A Cross-Sectional Study
Authors: Zhang Min , Zhu Bei , Yuan Chunlan , Chao Chao , Wang Jiaofeng , Ruan Qingwei , Bao Zhijun , Chen Jie , Arceneaux Kevin (Vin) , Wielen Ryan Vander , Siegle Greg Jeremy
Published: October 2020

Background: Cultural differences in affective and cognitive intrinsic motivations could introduce challenges to global public health campaigns, which use cognitive or affective goals to evoke desired attitudes and proactive health-promoting actions. This study aimed to demonstrate cross-cultural differences in affective and cognitive intrinsic motivations, and discuss the potential value of this information in public health promotion.Methods: A cross-sectional survey, using cross-culturally validated need for affect (NFA) and need for cognition (NFC) scales, was carried out among 1166 Chinese participants and compared to published data from 980 American participants. Additionally, we assessed a highly prevalent symbolic geriatric health condition, hearing loss, in 500 community-dwelling seniors. MANOVA test and Hedge’s g statistic were employed to compare the NFA and NFC levels between individuals from different countries and between seniors with and without hearing loss. The relation of early healthcare seeking intention to NFA and NFC was also explored.Results: The primary Chinese sample demonstrated decreased NFA and NFC in contrast to their American peers. This difference was preserved in the senior sample. Moreover, seniors with hearing loss had even lower NFA and NFC than those without hearing loss. Intention for early healthcare seeking was low but was associated with intrinsic motivation.Conclusions: There was a general lack of affective and cognitive intrinsic motivation in Chinese individuals, particularly in seniors with hearing loss, compared with their American peers. These differences, point to a potential challenge in framing effective messages for some cultures in the geriatric public health domain. Ideally, recognizing and understanding this challenge will inspire consideration of novel persuasive strategies for these audiences.
Hodgkin Lymphoma Management; A 20-year Retrospective Study
Authors: Ghazizadeh Farid , Noroozi Mehran , Hejazi Sasan , Sedokani Amin
Published: October 2020

Object: Hodgkin lymphoma (HL) is one of the pediatric and adult cancers, with a cure rate of over 90% and high long-term survival rates by treatment with chemotherapy alone or combined with radiotherapy (RT). However, survivors of pediatric HL are at high risk of secondary cancers and cardiovascular disease due to treatment. Considering the complications of RT, we aimed to evaluate the consequences and outcomes of the treatment with and without RT in a retrospective study in the pediatric oncology department of Urmia medical sciences university.Method: We carried a cross-sectional retrospective study by referring and review of records for all patients admitted in Motahari hospital with HL diagnosis from 1995 to 2016. The incomplete records and taking chemotherapy out of protocol were our exclusion criteria. The staging of disease was classified by the Ann Arbor staging system.Results: 35 patients enrolled in our study that 54.3% were female and 45.7% were male patients. The mean age of patients was 10.08±6.38 years. 10 (28.6%) cases classified in stage 1, 13 (37.1%) case in stage 2, 9 (25.7%) cases in stage 3, and 3 (8.6%) cases in stage 4. 30 patients (85.7%) were treated by chemotherapy and 5 (14.3%) patients with chemotherapy and radiation combination. In our study, the overall survival was 97.1% of patients who treated with chemotherapy alone and one patient died due to drug side effects. That is comparable with the result of other studies that treated patients with chemotherapy and radiotherapy.Conclusion: According to our findings chemotherapy without radiotherapy as initial treatment in Hodgkin lymphoma would have similar results of concomitant radiotherapy and chemotherapy, so with consideration of cost and harms of radiation therapy, we suggest a limitation of radiation therapy to patients with resistant disease that do not respond to chemotherapy solo-protocols.
Impulsivity Mediates the Association Between Parenting Styles and Self-harm in Chinese Adolescents
Authors: Ran Hailiang , Fang Die , Donald Ahouanse Roland , Wang Rui , Che Yusan , He Xingting , Wang Tianlan , Xu Xiufeng , Lu Jin , Xiao Yuanyuan
Published: October 2020

Background: Parenting styles were positively associated with self-harm (SH) in adolescents. Nevertheless, little is known concerning the mechanism behind this association. This study primarily aims to evaluate the potential mediation of impulsivity in the association between parenting styles and SH in Chinese adolescents. Methods: A population-based sample of 3146 adolescents in southwest China were surveyed by using self-administered questionnaires. Logistic regression analyses were used to measure the association between parenting styles and SH. Path model further examined mediation of impulsivity in this association. Results: The prevalence of SH was 47.0% (95% CI: 36.3%-58.0%). Impulsivity and mother’s over-protection were significantly associated with SH. Impulsivity showed a salient mediation, accounting for 23.4% of the total association. Parenting styles of father and mother showed disparate roles in the hypothesized path model. Conclusions: Our major findings suggested that, for Chinese adolescents with harsher maternal parenting style, impulsivity-centered intervention measures might be effective in reducing parenting style related SH.
Intervertebral foramen injection of plerixafor attenuates CCD-induced low back pain in rats through down-regulation of Nav1.8 and Nav1.9
Authors: Yang Fei , Wu Huang-Hui , Chen Lu , Chen Guo-Zhong , Wu Xiao-Zhi
Published: October 2020

BackgroundLow back pain, an extremely common chronic pain, is now the number one cause of disability globally. On the chronic compression of the dorsal root ganglion (CCD) model, a typical low back pain model, previous study has discovered that C-X-C chemokine receptor type 4 (CXCR4) involved in mediating low back pain. However, the underlying molecular mechanisms and whether it has the potential to serve as an applicable target for clinical treatment of low back pain remains unclear. MethodsCCD-induced low back pain model was established by inserting stainless steel L-shape rod into the intervertebral foramen at L5 level. Multiple pain behaviors including mechanical hyperalgesia and allodynia, thermal hyperalgesia and cold allodynia were evaluated. The role of CXCR4 in CCD-induced pain was assessed by intraganglionar CXCR4 siRNA injection and intervertebral foramen injection of plerixafor, a selective CXCR4 antagonist. The expression change of CXCR4, Nav1.8 and Nav1.9 was examined by immunofluorescent staining.ResultsWe showed that the CXCR4 were dramatically up-regulated in the compressed dorsal root ganglion (DRG) neurons in CCD model, and intraganglionar CXCR4 siRNA injection significantly reduced CCD-induced multiple pain behaviors, including mechanical hyperalgesia and allodynia, thermal hyperalgesia and cold allodynia. The expression of Nav1.8 and Nav1.9 in the compressed DRG were also enhanced after CCD, and which were remarkably reversed by intervertebral foramen injection of plerixafor at the compression level. Moreover, intervertebral foramen injection at the compression level of plerixafor and ropivacaine as well as A-803467, a Nav1.8 selective blocker, were all able to reverse CCD-induced multiple pain behaviors. However, the analgesic duration of plerixafor maintained at least for 24 h which was much longer than that of A-803467 and ropivacaine. Finally, we found intervertebral foramen injection of plerixafor at the adjacent non-compression level has no effect on CCD-induced pain and intervertebral foramen injection of plerixafor in normal rats did not affect their basal pain sensitivity.ConclusionsOur study provides evidence that CXCR4-Nav1.8/Nav1.9 axis in compressed DRG contributed to CCD-induced low back pain and intervertebral foramen injection of plerixafor was a potential and applicable therapeutic strategy for the treatment of low back pain.
IgM Mesangial Deposition Predicts Relapses of Adult-Onset Minimal Change Disease
Authors: Yang Cheng-Wen , Chen Fan-Yu , Chang Fu-Pang , Ho Yang , Yang An-Hang , Tarng Der-Cherng , Yang Chih-Yu
Published: October 2020

Background: Immunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence regarding the impact of IgM mesangial deposition on the treatment responses or outcomes in adult-onset MCD is lacking.Methods: In this retrospective cohort study, 37 adult patients with MCD received kidney biopsy from January 2010 to May 2020. According to IgM mesangial deposition by immunofluorescence microscopy, the patients were divided into two groups (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for two years between the two groups.Results: Regarding the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission, there was no statistically significant difference between the two groups. Compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group within the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116-0.784, p = 0.010).Conclusions: Our findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, prolonged and combined immunosuppressive therapy with close follow-up may be considered in MCD adults with IgM mesangial deposition.
Genetic Susceptibility to Multiple Sclerosis: Interactions between Conserved Extended Haplotypes of the MHC and other Susceptibility Regions
Authors: Goodin Douglas S , Khankhanian Pouya , Gourraud Pierre-Antoine , Vince Nicolas
Published: October 2020

BACKGROUNDTo study the accumulation of MS-risk resulting from different combinations of MS-associated conserved-extended-haplotypes (CEHs) of the MHC and three non-MHC “risk-haplotypes” nearby genes EOMES, ZFP36L1, and CLEC16A. Many haplotypes are MS-associated despite having population-frequencies exceeding the percentage of genetically-susceptible individuals. The basis of this frequency-disparity requires explanation. MEHTODSWTCCC SNP-data was phased at the MHC and three non-MHC susceptibility-regions. CEHs at the MHC were classified into five haplotype-groups: (HLA-DRB1*15:01~DQB1*06:02~a1)-containing (H+); extended-risk (ER); all-protective (AP); neutral (0); and the single-CEH (c1). MS-associations for different “risk-combinations” at the MHC and other non-MHC “risk-loci” and the appropriateness of additive and multiplicative risk-accumulation models were assessed.RESULTSDifferent combinations of “risk-haplotypes” produce a final MS-risk closer to additive rather than multiplicative risk-models but neither model was consistent. Thus, (H+)-haplotypes had greater impact when combined with (0)-haplotypes than with (H+)-haplotypes, whereas, (H+)-haplotypes had greater impact when combined with a (c1)-haplotypes than with (0)-haplotypes. Similarly, risk-genotypes (0,H+), (c1,H+), (H+,H+) and (0,c1) were additive with risks from non-MHC risk-loci, whereas risk-genotypes (ER,H+) and (AP,c1) were unaffected.CONCLUSIONSGenetic-susceptibility to MS is essential for MS to develop but actually developing MS depends heavily upon both an individual’s particular combination of “risk-haplotypes” and how these loci interact.
Incidence and risk factors of micronutrient deficiency in patients with IBD and intestinal Behçet’s disease: Folate, Vitamin B12, 25-OH-vitamin D, and Ferritin
Authors: Park Yong Eun , Park Soo Jung , Park Jae Jun , Cheon Jae Hee , Kim TaeIl , Kim Won Ho
Published: October 2020

Background
Patients with inflammatory bowel disease (IBD) and intestinal Behçet’s disease (BD) are vulnerable to micronutrient deficiencies due to diarrhea-related gastrointestinal loss and poor dietary intake caused by disease-related anorexia. However, few studies have investigated the incidence and risk factors for micronutrient deficiency.
Methods
We retrospectively analyzed 205 patients with IBD who underwent micronutrient examination, including folate, vitamin B12, 25-OH-vitamin D, and/or ferritin level quantification, with follow-up blood tests conducted 6 months later.
Results
Eighty patients (39.0%), who were deficient in any of the four micronutrients, were classified as the deficiency group, and the remaining 125 (61.0%) were classified as the non-deficient group. Compared to those in the non-deficiency group, patients in the deficiency group were much younger, had more Crohn's disease (CD) patients, more patients with a history of bowel operation, and significantly less 5-amino salicylic acid usage. Multivariate analysis revealed that CD and bowel operation were significant independent factors associated with micronutrient deficiency.
Conclusions
The incidence of micronutrient deficiency was high (39.0%). Factors including CD, bowel operation, and younger ages were found to be associated with higher risks of deficiency. Therefore, patients with IBD, especially young patients with CD who have undergone bowel resection surgery, need more attention paid to micronutrition.
Development and Validation of a Hypoxia-Related Gene Pairs Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
Authors: Ding Zhao , Li Hefeng , Yu Deshun
Published: October 2020

Objective Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.Methods Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.Results A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, and T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, and T cells CD8, etc. were significantly higher in the low-risk group.Conclusion In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.
Application of Modified Michaelis – Menten Equations for Determination of Enzyme Inducing and Inhibiting Drugs
Authors: Saganuwan Saganuwan Alhaji
Published: October 2020

Pharmacokinetics is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (e.g. ethyl alcohol,) first order kinetics (e.g. piroxicam) and mixed order kinetics (e.g. ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased Km and Vmax. Hence literatures were searched with a view to translating in vitro-in vivo enzyme kinetics to pharmacokinetic/pharmacodynamic parameters for determination of enzyme inducing and inhibiting drugs inorder to achieve optimal clinical efficacy and safety. Findings have shown that theophylline, voriconazole, phenytoin, thiopental, fluorouracil, thyamine and thymidine are enzyme inducers whereas mibefradil , metronidazole isoniazid and puromicin are enzyme inhibitors. They are metabolized and eliminated according to Michaelis-menten principle. The order could be mixed but may change to zero or first order depending on drug concentrations and frequency of drug administration. Hence, pharmacokinetic-pharmacodynamic translation can be optimally achieved by incorporating newly derived Michaelis-Menten equations into pharmacokinetic parameters for clinical efficacy and safety of therapeutics.
Analysis of the Effect of Duloxetine in the Treatment of Early Pain After Total Knee Arthroplasty
Authors: Wang Tao , He Sen
Published: October 2020

OBJECTIVE: Total knee arthroplasty is one of the most effective treatments for advanced degeneration of the knee. Knee replacement surgery has achieved excellent clinical results, not only solving the patients' pain, but also solving the social problems. The objective of this study was to examine the effect of duloxetine, a selective serotonin norepinephrine reuptake inhibitor, on the treatment of early pain in patients after TKA.METHODS: The study is a randomized controlled trial. Sixty patients who underwent TKA from January 2020 to June 2020 were selected for inclusion in the study, and equally assigned to a celecoxib group and a duloxetine group. There were 22 males and 38 females; the average age was 60.3±5.1 (56-74) years. The celecoxib group was given celecoxib 200mg/bid. The duloxetine group received duloxetine 30mg/bid. Analgesic medication was applied from the first postoperative day in the two groups for 4 weeks. The effectiveness of analgesia was assessed by the postoperative VAS walking pain score, HAMD-17 (Hamilton Depression Scale) score and the WOMAC pain score (Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC). The proportion of adverse events in the two groups was also compared to further evaluate the analgesic effect and safety. RESULTS: There was no significant difference in VAS score between groups on postoperative day three but duloxetine was superior to the celecoxib group at postoperative weeks one, two and four (p < 0.05). The HAMD-17 scores in both groups decreased at week four compared to preoperative values (p < 0.05), but the duloxetine group's HAMD-17 score was superior to the celecoxib group four weeks postoperatively (P < 0.05). The WOMAC pain scores of the duloxetine group were superior to the celecoxib group (P < 0.05) at postoperative weeks one, two and four. There was no significant difference in the incidence of adverse events.CONCLUSION: Duloxetine has a good effect on postoperative analgesia after TKA and can relieve patients' depression and anxiety, and promote rapid recovery. Thus, we can infer that duloxetine can be used to treat early postoperative pain after knee arthroplasty.
WITHDRAWN: Treatment Outcomes of Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy
Authors: Yeh Shyh-An , Hwang Tzer-Zen , Wang Chih-Chun , Yang Chuen-Chien , Lien Ching-Feng , Wang Chien-Chung , Hsu Tun-Yen , Hsu Ruey-Feng , Shih Yu-Chen , Huang Yaw-Chang , Hsieh Meng-Che , Gau Jhy-Shyan , Chang Liyun , Lee Tsair-Fwu
Published: October 2020

Background: Nasopharyngeal cancer shows good response to intensity-modulated radiotherapy. However, there is no clear evidence for the benefits of routine application of image-guided radiotherapy. The purpose of this study was to perform a retrospective investigation of the treatment outcomes, treatment-related complications and prognostic factors for nasopharyngeal cancer treated with intensity-modulated radiotherapy and image-guided radiotherapy techniques.Methods: Retrospective analysis was carried out on 326 consecutive nasopharyngeal cancer patients treated between 2004 and 2015. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded.Results: The 5-year overall survival and disease-free survival rates of these patients were 77.9% and 70.5% respectively. Age, AJCC stage, retropharyngeal lymphadenopathy, treatment interruption, and Body Mass Index were independent prognostic factors for overall survival. Age, AJCC stage, retropharyngeal lymphadenopathy, image-guided radiotherapy, and Body Mass Index were independent prognostic factors for disease-free survival.Conclusion: Intensity-modulated radiotherapy significantly improves the treatment outcomes of nasopharyngeal cancer. With the aid of image-guided radiotherapy, the advantage of intensity-modulated radiotherapy might be further amplified.
Tumor Specific Hypoxia-Activated Expression of Cardiac Peptides Using an Engineered Subtype of Escherichia Coli Suppresses Tumor Growth, Angiogenesis and Metastasis in Mouse Model of Breast Cancer
Authors: Darvishi Behrad , Samadi Mitra , Majidzadeh-A Keivan , Salehi Malihe , Jalili Neda , Noorinejad Zeinab , Mosayebzadeh Marjan , Mohammadnejad Ahad , Sharifkhatibi Azadeh , Moradi-kalbolandi Shima , farahmand leila
Published: October 2020

BackgroundApplication of genetically modified non-pathogenic bacteria expressing specific anti-tumor proteins under certain conditions specific to tumors is an effective approach for selective targeting of tumors. We developed here, for the first time, a novel spatiotemporal cancer targeted therapy applying engineered E. coli bacteria with capability of expressing cardiac peptides under hypoxic conditions of tumor. MethodE. coli BW25133 was transformed with construction of co-expressing cardiac hormones and GFP. Bacteria bearing constructs were then IV administered in mice bearing tumors and then tumor localization, as well as tumor proliferation, invasion and angiogenesis biomarkers (Ki-67, VEGFR, CD31and MMP9), changes in cytokine profile, suppression of tumor growth and survival were analyzed. ResultsIV Administered bacteria bearing constructs could specifically localize at tumor site and express cardiac peptides under hypoxic conditions. Administration of bacteria significantly enhanced survival rate, suppressed tumor progression and lowered expression levels of MMP-9, VEGFR2, CD31 and Ki67 as potent markers for angiogenesis, tumor proliferation and metastasis. Furthermore, applied bacteria resulted in significant reduction in the expression of IL-1β, IL-6, GC-SF, IL-12 and TNF-α proinflammatory cytokines, whereas increasing IL-10, IL-17A and INF-γ cytokines. ConclusionOverall, administration of E. coli bearing cardiac hormone expression construct could effectively suppress tumor growth, angiogenesis, invasion and metastasis while enhancing survival rate in mice model of breast cancer.
Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-assisted Decision-support Models 
Authors: Liu Hailang , Tang Kun , Peng Ejun , Wang Liang , Xia Ding , Chen Zhiqiang
Published: October 2020

Background: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions.Methods: We retrospectively collected data from prostate cancer (PCa) patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF) and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots were used to investigate the extent of over- or underestimation of predicted probabilities relative to the observed probabilities in models. Results: In total, 530 PCa patients were included, with 371 patients in the training dataset and 159 patients in the testing dataset. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730 and 0.695, respectively, followed by SVM (AUC 0.740, 95% confidence interval [CI]: 0.690–0.790), LR (AUC 0.725, 95% CI: 0.674–0.776) and RF (AUC 0.666, 95% CI: 0.618–0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC 0.735, 95% CI: 0.656–0.813), followed by SVM (AUC 0.723, 95% CI: 0.644–0.802), LR (AUC 0.697, 95% CI: 0.615–0.778) and RF (AUC 0.607, 95% CI: 0.531–0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. Conclusion: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.
Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group
Authors: Provencio Mariano , Terrasa Josefa , Garrido Pilar , Campelo Rosario García , Aparisi Francisco , Diz Pilar , Aguiar David , García-Giron Carlos , Hidalgo Julia , Aguado Carlos , González Jorge Jose García , Esteban Emilio , Gómez-Aldavarí Lorenzo , Moran Teresa , Juan Oscar , Chara Luís Enrique , Marti Juan Luis , Castro Rafael López , Ortega Ana Laura , Moreno Elia Martínez , Coves Juan , Peña Ana M. Sánchez , Bosch-Barrera Joaquim , Gastaldo Amparo Sánchez , Núñez Natalia Fernández , Barco Edel del , Cobo Manuel , Isla Dolores , Majem Margarita , Navarro Fátima , Calvo Virginia
Published: October 2020

Background: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain.Methods: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. 155 patients were enrolled (August 2016-December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources.Results: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. 155 patients were evaluable for response, 1.3% complete response, 40.7% partial response, 31% stable disease and 11.6% progressive disease. Objective response rate was 42%. Median progression-free survival was 9.4 months. 49% reported an adverse event, the majority of which (78%) were grade 1 or 2. The resource cost study indicates early use is warranted. Conclusion: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events.Clinical trial registration number: NCT03790397
The Identification of the Anthracycline Aclarubicin as an Effective Cytotoxic Agent for Pancreatic Cancer
Authors: Brouwer Thomas , Zanden Sabina Y van der , Eendenburg Jaap DH van , Bonsing Bert A , de Miranda Noel FCC , Neefjes Jacques J , Vahrmeijer Alexander L
Published: October 2020

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, mainly due to its delayed diagnosis and lack of effective therapeutic options. Therefore, it is imperative to find novel treatment options for PDAC. Here, we tested a series of conventional chemotherapeutics together with anthracycline compounds as single agents or in combination, determining their effectivity against established commercial and patient-derived, low passage PDAC cell lines.MethodsProliferation and colony formation assays were performed to determine the anti-cancer activity of anthracyclines; aclarubicin and doxorubicin, on commercial and patient-derived, low passage PDAC cell lines. In addition, the effect of standard of care drugs gemcitabine and individual components of FOLFIRINOX were also investigated. The assays involved short-term exposure to the drugs in order to mimic pharmacokinetics in a patient.ResultsAclarubicin showed superior anti-tumor activity compared to other anthracyclines and standard of care drugs (gemcitabine and individual components of FOLFIRINOX) in a patient-derived, low passage PDAC cell line. Importantly, the combination of gemcitabine and aclarubicin showed a synergistic effect at a dose range where the single agents by themselves were ineffective. Subsequent testing in commercial cell lines showed similar cytotoxic effects of aclarubicin in two out of three cell lines. Gemcitabine and doxorubicin had variable responses between the cell lines, but their effect never exceeded that of aclarubicin.ConclusionsAclarubicin is cytotoxic for commercial and patient-derived low-passage PDAC cell lines, at doses lower than peak serum concentrations for patient treatment. Our findings support a (re-)consideration of aclarubicin as a backbone of new combination regimens for pancreatic cancer patients.
Comprehensive Analysis of the Expression and Prognosis for IRXs in Non-small Cell Lung Cancer
Authors: Wang Qiongzi , Qiu Xueshan
Published: October 2020

Iroquoishomeobox transcription factor family （IRXs）have been increasingly reported to play roles in suppressing or promoting a variety of cancers, however, little is known about their expression and prognostic value in terms of human lung cancer. In this study, Oncomine, GEPIA, Kaplan-Meier plotter, and cBioPortal databases were used to analyze the different expression patterns and prognostic values of six IRXs in NSCLC and examine their related functions and pathways using GO enrichment. Compared with normal lung cancer tissues, the expression of IRX1 and IRX2 in NSCLC tissues was significantly lower and was positively correlated with the 10-year survival rate of patients. Higher expression of IRX4 was related to terminal tumors, and suggested a poor prognosis. It was also found that IRXs may play a tumor-suppressive role in the localization of cytoplasm in NSCLC, while localization in the nucleus suggests a more malignant behavior. Together these results suggest that IRX1 and IRX2 may be prognostic indicators of LUAD, and that IRX4 could be a potential target for LUAD treatment.
Non-lithifying microbial ecosystem dissolves peritidal lime sand
Authors: Present Theodore , Gomes Maya , Trower Elizabeth , Stein Nathan , Lingappa Usha , Naviaux John , Thorpe Michael , Cantine Marjorie , Fischer Woodward , Knoll Andrew , Grotzinger John
Published: October 2020

Microbialites accrete where environmental conditions and microbial metabolisms promote lithification, commonly through carbonate cementation. On Little Ambergris Cay, Turks and Caicos Islands, microbial mats occur widely in peritidal environments above ooid sand, but they do not become lithified or preserved. Sediment cores and porewater geochemistry indicate that aerobic respiration and sulfide oxidation inhibit lithification, dissolving calcium carbonate sand despite widespread aragonite precipitation from platform surface waters. In tidally pumped environments, primary productivity and respiration can negate the effects of taphonomically-favorable seawater chemistry on carbonate mineral saturation and microbialite development.
Challenges Experienced by Midwives Working in Rural Communities of the Bongo District in the Upper East Region of Ghana. A Qualitative Study
Authors: Adatara Peter , Amooba Philemon Adoliwine , Afaya Agani , Salia Solomon Mohammed , Avane Mabel Apaanye , Kuug Anthony , Maalman Raymond Saa-Eru , Atakro Confidence Alorse , Attachie Irene Torshie , Atachie Constancia
Published: October 2020

IntoductionGlobally, a total of 295 000 women lost their lives due pregnancy and childbirth in 2017, with sub-Saharan Africa and South Asia accounting for approximately 86% of all maternal deaths. Currently the Maternal Mortality Ratio (MMR) in Ghana is uncceptably high with about 308 deaths/100,000 live births in 2017 and most of these maternal deaths occur less in urban areas than in rural areas. As midwives play a vital role in maternity care and in the reduction of MMR, this study therefore sought to explore and describe challenges experienced by midwives working in rural communities in the Bongo District of the Upper East region of Ghana.MethodsA qualitative descriptive exploratory design was used to gain better insight into midwives’ experiences of working and providing women-centred midwifery care in rural areas of Ghana. A total of 30 midwives providing midwifery care in rural areas of the Upper East region of Ghana for at least three years were purposefully selected for this study. Data were collected using individual semi-structured interviews and analysed through qualitative content analysis. ResultsFive main themes emerged from the data analysis. These thematic areas included inadequate infrastructure (lack of bed and physical space), lack of logistics, shortage of midwifery staff, lack of motivation, and limited in-service training opportunities.ConclusionThe study concludes that although the rural midwives perform a multidisciplinary function in providing midwifery care in rural northern Ghana, they experience a myriad of challenges in providing midwifery care. There is the need for the Ghana Health Service and other stakeholders to motivate midwives working in rural areas through policy interventions such as rural incentive allowances, supportive supervision and in-service training opportunities for midwives in order to encourage them to accept posting to rural areas of Ghana to improve maternal and child health care.
Human Interferon Inducible Transmembrane Protein 3 (IFITM3) Inhibits Influenza Virus A Replication and Inflammation by Interacting with ABHD16A
Authors: Chen Liang , Limei Zhu , Jun Chen
Published: October 2020

Background: Studies have shown that human interferon inducible transmembrane proteins (hIFITMs) family proteins have broad-spectrum antiviral capabilities. Preliminary studies in our laboratory have preliminarily proved that hIFITMs have the effect of inhibiting influenza viruses. In order to further study its mechanism and role in the occurrence and development of influenza A, relevant studies have relevant studies have been carried out.Methods: Fluorescence quantitative polymerase chain reaction (PCR) detection, yeast two-hybrid test and optical confocal microscopy were used to investigate the effect of hIFITM3 on influenza virus A (IVA) replication, the interaction with human abhydrolase domain containing 16A (hABHD16A) and the expression of inflammation-related factors.Results: In HEK293 cells, overexpression of hIFITM3 protein significantly inhibited the replication of IVA at 24h, 48h, and 72h; yeast two-hybrid experiment proved that hIFITM3 interacts with hABHD16A; laser confocal microscopy observations showed that hIFITM3 and hABHD16A co-localized in cell membrane area; the expression level of inflammation-related factors in cells overexpressing hIFITM3 or hABHD16A was detected by fluorescence quantitative PCR, and the results showed that the mRNA levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-a and for cyclooxygenase 2 (COX2) were significantly increased. But when hIFITM3/hABHD16A was co-expressed, the mRNA expression levels of these cytokines were significantly reduced except COX2. When influenza virus infected cells co-expressing hIFITM3/hABHD16A, the expression level of inflammatory factors decreased compared with the control group, indicating that hIFITM3 can play an important role in regulating inflammation balance.Conclusions: This study confirmed that hIFITM3 has an effect of inhibiting IVA replication. Furthermore, it was found that hIFITM3 interacts with hABHD16A, following which it can better inhibit the replication of influenza virus and the inflammatory response caused by the disease process.
Characterization of Genes Associated with TGA7 During the Floral Transition
Authors: Xu Xiaorui , Xu Jingya , Yuan Chen , Hu Yikai , Liu Qinggang , Chen Qianqian , Zhang Pengcheng , Shi Nongnong , Qin Cheng
Published: October 2020

BackgroundThe TGA family has ten members and plays vital roles in plant defence and development in Arabidopsis. However, involvement of TGAs in control of flowering time remains largely unknown and requires further investigation. ResultsTo study the role of TGA7 during the floral transition, we first tested phenotypes of tga7 mutant, which displayed delay-flowering phenotype under both long-day and short-day conditions. We then performed flowering genetic pathways analysis and found that both autonomous and thermosensory pathways may affect TGA7 expression. Furthermore, to reveal differential gene expression profiles between wild-type (WT) and tga7, cDNA libraries were generated for WT and tga7 mutant seedlings at 9 DAG (days after germination). For each library, deep-sequencing produced approximately 6.67 Gb of high-quality sequences with the majority (84.55%) of mRNAs between 500 and 3000 nucleotides in length. Three hundred and twenty-five differentially expressed genes (DEGs) were identified between WT and tga7 mutant seedlings. Among them, four genes are associated with flowering time control. Differential expression of the four flowering-related DEGs was further validated by qRT-PCR.ConclusionsTransciptomic sequencing coupled with flowering genetic pathways analysis provides a framework for further studying the role of TGA7 in promoting flowering.
Ethnic Conflict as a Risk Amplifier for Resurgent P. Vivax Malaria in Temperate Zones: A Case Study from the Caucasus Region.
Authors: Hirschfeld Katherine , de Beurs Kirsten , Brayfield Brad , Melkonyan Ani
Published: October 2020

Background: One of the most protracted post-Soviet conflicts of the 1990s was a territorial dispute between Armenia and Azerbaijan over the contested Karabakh region. Years of ethnic violence led to the displacement of nearly a million refugees, as well as a public health crisis that included epidemics of malaria, diphtheria and other preventable diseases. Malaria is not usually considered a health risk in temperate climates, but seasonal epidemics were widespread throughout the Caucasus in the early decades of the twentieth century. Methods: This paper combines qualitative historical research with geospatial analysis to explore how endemic malaria was controlled during the Soviet era, and how ethnic conflict reconfigured local ecologies to facilitate the re-emergence of P. vivax after the Soviet collapse in the 1990s. Results: This research reveals that ethnic conflicts have specific qualities that increase risks of infectious and vector borne disease outbreaks, even in places that have successfully achieved a modern health and mortality profile. The risk amplifiers of ethnic conflicts include 1) the creation of contested spaces controlled by separatists that are outside of any national public health surveillance system; 2) mass population movements and refugee outflows due to ethnic violence; and 3) changes in land use that expand potential mosquito breeding sites throughout the conflict zone. Conclusions: Ongoing hostilities between Armenia and Azerbaijan, combined with the repopulation of key vector species (specifically An. sacharovi) lead us to conclude that contemporary populations in the Caucasus remain vulnerable to resurgent outbreaks of ethno-nationalist violence as well as the return of seasonal malaria, even after decades of successful control.
Qualitative Assessment of Patients’ Perspectives and Needs from Community Pharmacists in Substance Use Disorder Management
Authors: Fatani Sarah , Bakke Daniel , D’Eon Marcel , El-Aneed Anas
Published: October 2020

Background: Substance use disorder (SUD) is a major health concern affecting Canadians and their health care system. SUD treatment plans addressing patients’ needs and choices have demonstrated improved treatment outcomes. It is essential for health care providers, including community pharmacists, to understand patients' needs and prioritize them. Therefore, this study explores the perspective of patients living with SUD regarding community pharmacist services and the delivery of care in a community pharmacy setting located in the small urban center of, Saskatoon, Saskatchewan, Canada.Methods: A qualitative methodology was used for this research inquiry. Four focus groups were conducted in Saskatoon, with a total of 20 individuals who had experienced substance use and accessed community pharmacy services. The discussion of the four focus groups was transcribed verbatim and analyzed independently by two researchers. Agreement on the emergent themes was reached through discussion between the two researchers. Results: Data analysis resulted in four themes that described participants' perspectives about community pharmacists. The four emergent themes are: 1) experience of people living with SUD in a community pharmacy, 2) services provided by community pharmacists, 3) the methadone maintenance program, and 4) needs from community pharmacists. Conclusion: There is significant potential for the patient-pharmacist relationship to address the varying needs of patients living with SUD and improve their overall health care experience. Patients who use substances are receptive to pharmacists' services beyond dispensary; however, respectful communication, provision of drug-related information, and counseling are among the primary demands. Future research should focus on studying the impact of meeting the needs of patients on their treatment outcomes.
A Nomogram to Predict Postoperative Complications in Elderly with Total Hip Replacement
Authors: Tan Xiujuan , Ge Fengmin , Mo Guixi , Li Zhiyi , Gu Xiaoxia , Zhang Liangqing
Published: October 2020

Background: By analyzing the risk factors of postoperative complications in elderly patients with hip replacement, We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients.Methods: A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients. A nomogram was developed by R software and validated to predict the risk of postoperative complications.Results: Multivariate logistic regression analysis revealed that age (OR=1.05, 95%CI: 1.00-1.09) , renal failure(OR=0.90, 95% CI: 0.83～0.97) , Type2 diabetes (OR=1.05, 95% CI: 1.00～1.09) , ALB (OR=0.91, 95% CI: 0.83～0.99) were independent risk factors of postoperative complication in elderly patients with hip replacement (P＜0.05) . For validation of the nomogram, ROC curve revealed that the model predicting postoperative complication in elderly patients with hip replacement was the area under the curve of 0.8254(95% CI: 0.78～0.87) , the slope of the calibration plot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (x2 = 10.16, P=0.4264), calibration in R Emax=0.176, Eavg=0.027, which all demonstrated that the model was of good accuracy. Conclusion: The nomogram predicting postoperative complications in patients with total hip replacement constructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination and accuracy, which was of clinical significance.
Integrated CNV-seq, Karyotyping and SNP-array Analyses for Effective Prenatal Diagnosis of Chromosomal Mosaicism
Authors: Ma Na , Xi Hui , Chen Jing , Peng Ying , Jia Zhengjun , Yang Shuting , Hu Jiancheng , Pang Jialun , Zhang Yalan , Hu Rong , Wang Hua , Liu Jing
Published: October 2020

Background: Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) provide advantage in detecting low-level mosaicism compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods: A total of 72 mosaicism cases identified by karyotyping or CMA were recruited in this study, and 67 samples (40 sex chromosome aneuploidy, 22 autosomal aneuploidy and 5 submicroscopic CNVs) were eventually analyzed by CNV-seq. Results: CNV-seq not only identified all 43 chromsomal aneuploidies or submicroscopic CNVs detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. Besides, the level of mosaicism defined by CNV-seq range from 6% to 92%. Conclusion: In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform we used. This study provides strong evidence for applying CNV-seq as an alternative prenatal diagnostic test.
Novel Association Between Asthma and Osteoarthritis: A Nationwide Health and Nutrition Examination Survey
Authors: Koo Hyeon-Kyoung , Song Pamela , Lee Joo-Hyun
Published: October 2020

Backgrounds: Asthma and osteoarthritis (OA) are medical conditions that disable physical activity and deteriorate patients’ quality of life. Despite the high prevalence, there are limited studies focusing on the comorbid condition and association between asthma and OA. The aim of study was to assess the prevalence and identify the clinical considerations for this special population.Methods: Adult patients aged over 40 years who completed questionnaire assessments and spirometry were enrolled from Korean National Health and Nutrition Examination Survey. Asthma and OA were defined on the history of doctor-diagnosed disease. Radiographic severities of OA were measured using the Kellgren/Lawrence grading system. Chronic obstructive pulmonary disease (COPD) as a comparative respiratory disease was diagnosed on the basis of spirometric results.Results: A total of 9344 subjects were enrolled, and the prevalence of asthma and COPD were 4.6%±0.3% and 12.0%±0.5%, respectively. The prevalence of OA in the asthma group was 31.9%±2.8%, which was significantly higher than those in the COPD (17.8%±1.5%) or control (16.2%±0.6%) groups. OA was more prevalent in asthma patients after adjusting for age, sex, body mass index, and smoking status (OR, 1.65; 95% CI, 1.27-2.13). After further adjustment of this model for prescription of OA medication, OA was still independently associated with asthma (OR, 1.56; 95% CI, 1.10-2.20). In contrast, the relationship of OA medication with asthma was not significant (P=0.64). This relationship was evident in subjects with asthma without airflow limitation measured by spirometry (OR, 1.97; 95% CI, 1.32-2.93). Moreover, radiographic severity of knee OA correlated with asthma (OR, 1.10; 95% CI, 1.0-1.21). Conclusions: OA shows a high prevalence in patients with asthma, with the prevalence being higher than that in COPD patients or controls. The comorbid characteristics of these two conditions need to be considered in clinical practice.