bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified Nodal Stage of esophageal cancer based on the evaluation of the hazard rate of the negative and positive lymph node
Authors: Zhang Jinling , Li Hongyan , Zhou Liangjian , Yu lianling , Che Fengyuan , Heng xueyuan
Published: July 2020

Objective: The study aimed to propose a modified Nodal stage of esophageal cancer (EC) on basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously. Method: Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.Results: The numberPLN on prognosis was 1.064, while numberNLN was 0.962. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.08; N2 stage: more than 0.08, but no more than 0.63; N3 stage: more than 0.63. Cross-validation method within the cohort identified the predictive accuracy of this modified N stage, and ROC curve analysis demonstrated the relative superiority of the modified N stage over that of the AJCC N stage.Conclusion: The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage relative accurately than the traditional N stage.
WITHDRAWN: An Integrated Process of Methanol Coagulation and Side Stream Membrane Bioreactor for Treatment of Rice Gruel Wastewater
Authors: Nazia Shaik , Mishra Karishma , Jegatheesan Veeriah , Bhargava Suresh K , Sundergopal Sridhar
Published: July 2020

The demand for water supply is expected to be raised significantly in forthcoming decades. Production of reusable water from industrial and domestic wastewater is a feasible, cost effective and significant positive benefit to the environment. In the present study, the domestic rice gruel wastewater (RGW) was treated with aqueous methanol coagulation integrated aerobic membrane bioreactor (AMBR). Initially, the RGW which is at room temperature was treated with spiral wound hydrophilized - ultrafiltration (HF – UF) 5 kDa membrane module to determine the removal efficiency. Furthermore, the RGW was pre-treated with various coagulants such as methanol, ethanol and HCl. The obtained pre-treated RGW was subjected to the HF – UF 5 kDa side stream AMBR for production of reusable water. The experiments were conducted to determine the turbidity, conductivity, total dissolved solids (TDS) and chemical oxygen demand (COD) were found to be 96 %, 91 %, 91 % and 94.6 %. The overall process was feasible, compact, environmental free, cost effective, eco-friendly.
Facts and Reflections on Initial Public Health Emergency Response to SARS and COVID-19 Pandemics in Mainland China: A Retrospective Comparative Study
Authors: Zhu Huanhuan , Wang Qian , Zhang Tiantian , Liu Xin , Dai Ruiming , Wu Ping , Bai Ge , Wang Ying , Zhou Ping , Luo Li
Published: July 2020

Background: Since December 2019, 2019-nCoV has emerged in Wuhan, China, the fast pace of transmission is wreaking global public health crisis. Country’s reaction speed is critical for the control of public health emergency (PHE), especially in the early stage of an outbreak. Compared with SARS pandemic, whether has the efficiency of initial public health emergency response to COVID-19 in mainland China been improved? And whether is there still existing vulnerabilities in current PHE system? Studies on this topic are relatively few. We tried to find the answers, evidences and alternatives. Methods: We conducted a retrospective comparative study. The speed of hospital reporting, pathogen identification and government decision-making between SARS and COVID-19 were compared by selecting 5 critical events from initial public health emergency response timeline. Besides, combining with the two pandemics' progress curves, we discussed the characteristics of their peak time.Results:(1) SARS completed the entire initial public health emergency response in 127 days, and COVID-19 completed in 44 days. Response speed has been shorted nearly by 3 times. (2) Both the first SARS and COVID-19 cases were reported in 19 days. It doesn't appear that hospital reporting speed becomes faster. (3) The accumulated time completing pathogen identification were 118 days for SARS and 31 days for COVID-19. The speed has been improved by more than 3 times. (4) 9 days after the completion of pathogen identification, national government made emergency policies for SARS while the interval between pathogen identification and national government's decision-making for COVID-19 was 13 days. (5) The peak time of SARS came about 80 days later than that of COVID-19. But both the two pandemics' peak occurred about 20 days after the national government's decision-making, and then the curves went down dramatically.Conclusions: The speed of initial public health emergency response to pandemic has been improved due to faster identification. However, some deficiencies and challenges in early alert and authorities' decision-making still remain. Therefore, Chinese government should put more stress on improving hospital's sensitivity to new emerging infectious diseases and timeliness of government's decision-making.
Nerve Growth Factor is Closely Related to Glucose Metabolism, Insulin Sensitivity and Insulin Secretion in the Second Trimester: A Case-Control Study in Chinese
Authors: Tang Mengyang , Luo Mingjuan , Lu Wenqian , Zhang Rong , Liang Wei , Gu Jianfen , Yu Xuemei , Zhang Xueli , Hu Cheng
Published: July 2020

Objective: Inflammation-related factors have been shown to play a significant role throughout pregnancy. In this study, we aimed to explore the relationships between selected inflammatory cytokines and gestational diabetes (GDM) in Chinese pregnant women.Design and Methods: This was a 1:1 matched case-control study that included 200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester. Serum levels of nerve growth factor (NGF), Interleukin-6 (IL-6), leptin, Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) were measured by enzyme immunoassay. The associations of these inflammatory factors with metabolic parameters were analysed.Results: In the second trimester, GDM patients had higher NGF levels and lower IL-8 levels than did normal controls (P<0.001 and P=0.015, respectively). However, in the third trimester, only lower leptin levels were observed in the GDM group (P=0.031). Additionally, in the second trimester, NGF levels were not only positively associated with fasting, 1-h and 2-h glucose levels and the area under curve of glucose (AUCG), but also positively related to insulin sensitivity and secretion, as suggested by fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment index of β-cell secretion (HOMA-β) (all P<0.05). Moreover, IL-6 and leptin levels were positively correlated with HOMA-IR and HOMA-β, and TNF-α levels were positively related to HOMA-IR (all P<0.05). Except for the relationships between NGF and HOMA-β and TNF-α and HOMA-IR, the other correlations still existed even after adjusting for confounding factors (all P< 0.05). Conclusion: In addition to the positive associations of IL-6 and leptin with insulin resistance and secretion, NGF was higher in the GDM patients and strongly linked to glucose metabolism, insulin resistance and pancreatic β cell function in Chinese pregnant women in the second trimester.
Mature and immature β-cells both contribute to islet function and insulin release
Authors: Nasteska Daniela , Fine Nicholas , Ashford Fiona , Cuozzo Federica , Viloria Katrina , Smith Gabrielle , Dahir Aisha , Dawson Peter , Lai Yu-Chiang , Bastidas-Ponce Aimée , Bakhti Mostafa , Rutter Guy , Fiancette Remi , Nano Rita , Piemonti Lorenzo , Lickert Heiko , Zhou Qiao , Akerman Ildem , Hodson David
Published: July 2020

Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that differences in β-cell maturity, defined using PDX1 and MAFA expression, are required for proper islet operation. Functional mapping of rodent and human islets containing proportionally more mature β-cells revealed defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of mature β-cells led to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, the islet signalling network was found to contribute to differences in maturity across β-cells. During metabolic stress, islet function could be restored by redressing the balance between immature and mature β-cells. Thus, preserving a balance between immature and mature β-cells might be important for islet engineering efforts and more broadly the treatment of type 1 and type 2 diabetes.
Generating Real-World Evidence from Unstructured Clinical Notes to Examine Clinical Utility of Genetic Tests: Use Case in BRCAness
Authors: ZHAO Yiqing , Weroha Saravut J , Goode Ellen , Liu Hongfang , Wang Chen
Published: July 2020

Background: Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information.Methods: We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated on a Foundation-tested women cancer cohort (N=196). Upon retrieval of patients’ genetic information using NLP system, we assessed completeness of genetic data captured in unstructured clinical notes according a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy. Results: We identified seven topics in clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance (VUS). Our rule-based system achieved a precision of 0.87, recall of 0.93 and F-measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F-measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F-measure of 0.82 for seven-topic classification. We found in result-containing sentences, capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies.Conclusions: In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes. Data quality issue such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate real-world utility of genetic information to initiate prescription of targeted therapy.
Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers
Authors: Fernandez-Perez Eduardo Javier , Muñoz Braulio , Bascuñan Denisse Andrea , Peters Christian , Riffo-Lepe Nicolas Osiel , Espinoza María Paz , Morgan Peter James , Filippi Caroline , Bourboulou Romain , Sengupta Urmi , Kayed Rakez , Epsztein Jerome , Aguayo Luis
Published: July 2020

Background: Intracellular amyloid-beta oligomers (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer’s disease (AD). However, to date, no mechanism linking them has been reported. Methods: Here, the effects of human AD brain-derived (h-iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential (AP) firing were investigated in hippocampal neurons in vitro , ex vivo and in vivo. Results: Starting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-related fluorescence changes indicated that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current-clamp recordings suggested that iAβo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. Conclusion: These results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offer an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.
Acute Pulmonary Embolism in Coronavirus Disease 2019
Authors: Guo Yanan , Sun Wenwu , Liu Yanli , Lv Yanling , Zhao Su , Chen Liangkai , Liu Zhengqing , Yu Li
Published: July 2020

Background Pulmonary embolism is a severe condition prone to misdiagnosis given its nonspecific signs and symptoms. Previous studies on the pneumonia outbreak caused by coronavirus disease 2019 (COVID-19) showed a number of patients with elevated d-dimer, whether those patients combined with pulmonary embolism got our attention. Methods Data on clinical manifestations, laboratory and radiological findings, treatment, and disease progression of 19 patients with laboratory-confirmed COVID-19 pneumonia,who completed computed tomographic pulmonary angiography (CTPA) during hospitalization in the Central Hospital of Wuhan from January 2 to March 26, 2020, were reviewed. Results Of the 19 suspected pulmonary embolism and subjected to CTPA patients, six were diagnosed with pulmonary embolism. The Wells’ score of the six patients with pulmonary embolism was 0–1, which suggested a low risk of pulmonary embolism. The median level of d-dimers collected at the day before or on the day of CTPA completion in the patients with pulmonary embolism was 18.36 (interquartile range [IQR]: 6.69–61.46) µg/mL, which was much higher than that in the patients without pulmonary embolism (median 9.47 [IQR: 4.22–28.02] µg/mL). Of the 6 patients diagnosed with pulmonary embolism, all patients received anticoagulant therapy, 5 of which survived and were discharged and 1 died. Conclusion A potential causal relationship exists between COVID-19 infection and pulmonary embolism, but whether this phenomenon is common remains uncertain. The clinical manifestations of COVID-19 patients who developed pulmonary embolism are similar to those of patients with increased d-dimer alone, prompting a significant challenge on differential diagnoses.
Improving knowledge, attitude, and practices of complementary feeding using practical intervention training for parents living in stunting villages in Central Lombok, Indonesia: A community-based study
Authors: Tengkawan Jeslyn , Septisari Ayu Anandhika , Ihyauddin Zulfikar , Karuniawaty Titi Pambudi , Nurbaiti Lina , Dewi Nurhandini Eka , Sekartini Rini
Published: July 2020

BackgroundStunting is one of the major child public health concerns in Indonesia. West Nusa Tenggara (WNT) province, specifically, is still struggling to reduce its stunting prevalence as it is still higher than the average national prevalence, accounted for 31.4% in 2018. Ensuring knowledge, attitude, and practices (KAP) of complementary feeding among parents is relevant to succeeding in the implementation of stunting reduction programs. This study aimed to assess the effectiveness of interventions in the form of seminar and workshop on preparing complementary feeding in stunting villages in Central Lombok, Indonesia.MethodsThis is a quasi-experimental community-based study, held in three stunting villages of Central Lombok, WNT, from June until August 2019. Three villages were chosen randomly from ten stunting-villages in Central Lombok District and divided into three groups, i.e., control group, seminar group and seminar and workshop group. We assessed KAP before and after intervention with a four-week interval.ResultsA total of 205 participants were enrolled in this study, consisting of 67, 70, and 68 participants for the control group, the first intervention group, and the second intervention group, respectively. Most participants had poor knowledge (75.1%) of complementary feeding in the baseline assessment. We found an insignificant change in knowledge, but notable alterations in attitudes and practices after intervention. Seminar intervention could increase practice, while complete intervention (seminar and workshop) could increase both practices and attitudes significantly (p = 0.015 dan p = 0.014). We found that complete intervention was more effective in increasing attitudes compared to the control group (p = 0.039). In contrast, practices in both seminar and complete intervention was increased effectively than controls (p = 0.006 vs. p = 0.008), and no differences between seminar and complete intervention group (p = 0.943).ConclusionsComplementary feeding KAP among parents in stunting villages in Central Lombok was inadequate. Our study showed that the combination of seminar and workshop increased parents’ attitudes and practices, while the seminar only increased parents’ practices. We suggest further prospective study to assess how long the effectivity of such interventions could impact and last; and obtain any cultural concerns.Trial registration: 376/UN18.8/ETIK/2018
Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker
Authors: Bielska Agnieszka , Bauer Witold , Szalkowska Anna , Sidorkiewicz Iwona , Skwarska Anna , Raczkowska Justyna , Ostrowski Damian , Gugala Kamil , Dobrzycki Slawomir , Niemira Magdalena , Kretowski Adam
Published: July 2020

Background

The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlights an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived miRNAs may serve as potential biomarkers for early IHD diagnosis and help to identify diabetic individuals with a predisposition to undergo IHD.
Methods

We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter Technology Platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs.
Results

Our data showed that 9 miRNAs (miR-1224-5p, miR-1303, miR-3147, miR-4455, miR-498, miR-548b-3p, miR-548d-3p, miR-615-3p, miR-651-5p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. In patients with upregulated miRNA, functional enrichment analysis of target genes by IPA indicated networks and canonical pathways involved in the pathology of the cardiovascular system. All tested miRNAs showed high diagnostic value (AUC > 0.8).
Conclusions

Taken together, our findings suggest that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.
Comparative Cost Analysis of Cervical Cancer Screening Programme Based on Molecular Detection of Hpv In Spain
Authors: Ibáñez Raquel , Mareque María , Granados Rosario , Andía Daniel , García-Rojo Marcial , Quílez Jose C , Oyagüez Itziar
Published: July 2020

Background
HPV cervical cancer screening (CCS) must use validated HPV tests based on the molecular detection of either viral mRNA (Aptima HPV Assay – AHPV) or DNA. AHPV has demonstrated the same cross-sectional and longitudinal sensitivity for the detection of HSIL/CIN2 + lesions but with greater specificity than HPV-DNA tests. The study aimed to estimate the total costs of a CCS with a primary HPV test based on the detection of mRNA compared to DNA in women aged 35–65 years for the National Health System.
Methods
A decision-tree-based model to estimate the cost of the CCS until the first colposcopy was designed based on Spanish CCS guidelines. The total cost (€,2019) for CCS with AHPV or DNA tests (HC2 and Cobas) was calculated, including HPV test, liquid-based cytology (LBC) and colposcopy, for a population of 7,263,529 women aged 35–65 years (assuming 70% coverage). Clinical inputs derived from a literature review were validated by a multidisciplinary expert panel. Data from head-to-head studies between different HPV tests were selected. The HPV prevalence used in women aged 35–64 was 7.5% for AHPV, 11.5% for HC2 and 12.4% for Cobas.
Results
The use of AHPV avoided 151,699 (-47%) and 151,165 (-47%) colposcopies and 290,541 (-35%) and 355,913 (-40%) LBC vs HC2 and Cobas, respectively; and allows saving €-39,839,711 vs HC2 and €-41,866,613 vs Cobas.
Conclusions
Assuming that 70% of women from 35–65 years attend the CCS programme, the cost of screening up to the first colposcopy using AHPV would provide cost savings of up to €41.9 million vs DNA tests in Spain.
Pediatric Tuina for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Preschool Children: Study Protocol for a Pilot Randomized Controlled Trial
Authors: Chen Shu Cheng , Yu Juan , Suen Lorna Kwai-Ping , Sun Yan , Pang Ya Zheng , Wang Dong Dong , Zhao Wen Xia , Yeung Jerry Wing Fai
Published: July 2020

Background: Medication and behavior therapy are the conventional treatments for attention deficit hyperactivity disorder (ADHD), but they have limitations for preschool children. Evidence suggests that pediatric tuina might have beneficial effects on this condition. Therefore, we aim to preliminarily assess the effects and feasibility of parent-administered pediatric tuina for ADHD symptoms in preschoolers.Methods: It is a single-center, two-arm, parallel, open-label, pilot randomized controlled trial. Sixty children with pre-specified ADHD symptoms (hyperactivity, anxiety, and sleep disturbance) together with one of their parents will be recruited and randomized into two groups at a 1: 1 ratio. Parents in the parent-administered tuina group (intervention group, n=30) will attend an online training program to learn pediatric tuina skills for ADHD symptoms and conduct this treatment on their children at home. Parents in the parent-child interaction group (comparison group, n=30) will attend an online training about progressive muscle relaxation exercise and do this exercise with their children at home. Additional teaching materials will be provided to the participants in both groups. Both interventions should be carried out every other day during a 2-month treatment period, with each time around 20 minutes. Assessment will be performed at baseline, week4, and week 8. The primary outcome measure is the Swanson, Nolan and Pelham Parent Scale; the secondary outcomes include Preschool Anxiety Scale, Children's Sleep Habits Questionnaire, and Parental Stress Scale. A process evaluation embedded within the outcome evaluation will be performed. Differences in the scale scores and test parameters between groups will be examined using a linear mixed-effects model. Qualitative data will be analyzed using thematic content analysis, facilitated by QSR NVivo.Discussion: This study will provide evidence on the acceptability and feasibility of pediatric tuina for ADHD in preschool children. The process evaluation will help to better understand the facilitators and barriers of the intervention functioning.Trial registration: The study was registered at ClinicalTrials.gov (Identifier: NCT04237259) on 14 February 2020. Protocol version: 2, date June 23, 2020
Factors Contributing to Psychological Distress in the Working Population, With A Special Reference to Gender Difference - A Population-Based Study
Authors: Viertiö Satu , Kiviruusu Olli , Piirtola Maarit , Kaprio Jaakko , Korhonen Tellervo , Marttunen Mauri , Suvisaari Jaana
Published: July 2020

BackgroundPsychological distress refers to non-specific symptoms of stress, anxiety and depression, and it is more common in women. Our aim was to investigate factors contributing to psychological distress in the working population, with a special reference to gender differences. Methods We used questionnaire data from the nationally representative Finnish Regional Health and Well-being Study (ATH) collected in the years 2012–2016 (target population participants aged 20 +, n=96 668, response rate 53%), restricting the current analysis to those persons who were working full-time and under 65 of age (n=34 468). Psychological distress was assessed using the Mental Health Inventory-5 (MHI-5) (cut-off value <=52). We studied the following factors potentially associated with psychological distress: sociodemographic factors, living alone, having children under 18 years of age, lifestyle-related factors, social support, helping others outside of the home and work-related factors. We used logistic regression analysis to examine association between having work-family conflict with the likelihood for psychological distress. We first performed the models separately for men and women. Then interaction by gender was tested in the combined data for those independent variables where gender differences appeared probable in the analyses conducted separately for men and women.Results Women reported more psychological distress than men (11.0% vs. 8.8%, respectively, p<0.0001). Loneliness, job dissatisfaction and family-work conflict were associated with the largest risk of psychological distress. Having children, active participation, being able to successfully combine work and family roles, and social support were found to be protective factors. A significant interaction with gender was found in only two variables: ignoring family due to being absorbed in one’s work was associated with distress in women (OR 1.30 (95% CI 1.00–1.70), and mental strain of work in men (OR 2.71 (95% CI 1.66–4.41).Conclusions Satisfying work, family life and being able to successfully combine the two are important sources of psychological well-being for both genders in the working population.
Removal of a Missing Intrauterine Contraceptive Device After Location Through an Ultrasound: A Case Report Within a Rural Setting and Review of Literature
Authors: Argaw Mesele Damte , Abawollo Hailemariam Segni , Desta Binyam Fekadu , Tsegaye Zergu Taffesse , Belete Dejene Mengistu , Abebe Melkamu Getu
Published: July 2020

Background: In the last decade, (2000- 2019), the modern contraceptive prevalence among married women of reproductive age (14-49 years), has increased by only 2.1%. The slow progress was due to limited access to services and myths surrounding methods held by both users and providers. This case report was identified, diagnosed and managed by a midwife working in rural health center in low resource setting. However, literature is scare on the management of missing Intra-Uterine Contraceptive Device (IUCD) thread removal services of confirmed diagnosis using Vscan or limited ultrasound services in rural health centers. The aim of reporting this case report was developed to enhance easy access to intra-uterine contraceptive method removals, which may address myths associated with difficulties of undergoing the services in rural set-up.A 26 year-old married woman, Gravida 1 and Para 1, attended Mekoy Health Center for IUCD removal service after seven years of protection and internally referred to limited obstetric ultrasound service room due to non- visualization of IUCD thread with Vaginal Speculum examination. An ultrasonography scan however, showed a centrally located copper-T 380A IUCD in the endometrial cavity. As a result, after dilatation of the cervix, a successful removal of the Copper-T 308A was conducted. The client received followed up care for two hours post-procedure and was then discharged.Conclusions: This case highlights the importance of availing diagnostic and removal services in rural set ups to mitigate myths in the community. The availability of limited obstetric ultrasound scanning services can improve the diagnoses and management of conditions in clients. The reported case shows that although, the basic infrastructure was limited, ultrasound scanning and Long Acting Reversible Contraception (LARC) trained midwives can ensure the provision of safe IUCD removal services in rural areas.
Secreted Frizzled-Related Protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway
Authors: Sun Minghui , Wang Weijun , Min Lingtian , Chen Cheng , Li Qing , Weng Wenjie
Published: July 2020

Background
Secreted frizzled–related protein 5 (SFRP5) is an endogenous inhibitor of Wnt5a (wingless-type family member 5a), which has been implicated in anti-inflammatory response. In this study, we aimed to investigate whether SFRP5 could protect chondrocytes against LPS-induced inflammation and apoptosis.
Methods
ATDC5 cells that overexpressed with SFRP5 or not were challenged with LPS to observe the effects of SFRP5 overexpression on LPS-triggered inflammation and apoptosis as well as Wnt5a/JNK activation. Wnt5a was elevated in ATDC5 cells in the presence of SFRP5 overexpression, to determine whether Wnt5a/JNK signaling was involved in the actions of SFRP5.
Results
The mRNA and protein levels of SFRP5 was significantly reduced by LPS in a concentration-dependent manner. Overexpression of SFRP5 in ATDC5 cells inhibited LPS-induced inflammation and apoptosis, as evidenced by decreased production of TNF-α, IL-1β, IL-6 and ROS, together with a reduced ratio of TUNEL-positive cells, a lower expression of Bax and cleaved caspase 3, but a higher expression of Bcl-2. Meanwhile, SFRP5 overexpression also repress Wnt5a and phosphorylated JNK expression. However, the overexpression of Wnt5a considerably weakened the inhibitory effect of SFRP5 on LPS-triggered inflammation and apoptosis. Besides, the level of Wnt5a and JNK phosphorylation, which was inhibited by SFRP5 overexpression, was also partially recovered by Wnt5a overexpression.
Conclusion
SFRP5 could alleviate LPS-induced ATDC5 cells inflammation and apoptosis, this actions may rely on repressing Wnt5a/JNK activation.
Readiness to try extended-released buprenorphine and related factors of interest: comparison between incarcerated and non-incarcerated subjects with opioid use disorder.
Authors: CHAPPUY Mathieu , MEROUEH Fadi , TROJAK Benoit , BACHELLIER Jérôme , BENDIMERAD Patrick , KOSIM Margaux , HJELMSTROM Peter , NUBUKPO Philippe , BROUSSE Georges , ROLLAND Benjamin
Published: July 2020

Background: Extended-release buprenorphine (XR-BUP) are new pharmaceutical products that offer a one-week-, one-month- or six-months-long buprenorphine treatment for subjects with opioid use disorder (OUD). OUD is frequent in incarcerated populations, and XR-BUP has been suggested to be an interesting treatment option in prison. However, some opioid users have deemed that XR-BUP could constitute a threat to the individual freedom of occasionally using drugs, and was also at risk to be coercively used in some situations. It was thus needed to explore whether incarcerated people with OUD were ready to try XR-BUP formulations, and which reasons could warrant their possible interest or apprehension.Methods: This is a secondary analysis of a survey performed between 12/02/2018 and 05/31/2019 among 366 patients with OUD. Participants were recruited in 68 addiction French settings, among which six were prison medical centers. Bivariable and multivariable comparisons between incarcerated and non-incarcerated interviewees with respect to their readiness to try XR-BUP and the reasons of interest in this new option. Odds ratios and their 95% confidence intervals (aORs; 95%CI) were adjusted for gender, age category, level of education, and type of opioid agonist treatment.Results: The data of 317 participants were included in the analyses. While 108 (48.9%) of the 221 non-incarcerated interviewees declared being ready to try XR-BUP, they were 63.5% (61 out of 96) among those incarcerated (p =0.016). Adjusted comparisons found that incarcerated were significantly less attracted by the potential of XR-BUP to reduce withdrawal symptoms (aOR= 0.54; 95%CI= 0.29 – 0.99), and to reduce misuse of buprenorphine (aOR= 0.56; 95%CI= 0.34 – 0.94), but more attracted by receiving a constantly efficacious treatment for a week or month (aOR= 2.91; 95%CI= 1.21 – 6.98), and have a more discreet treatment (aOR= 1.76; 95%CI= 1.01 – 3.10).Conclusions: Relative to non-incarcerated subjects with OUD, those in prison were readier to try XR-BUP and they seemed more attracted by practicability and discretion features.
A Comparison of Diagnostic Performance of Signal Intensity and Volume Related MRI Multiparameters for Assessing Different Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy
Authors: Tan Zhengwu , Zhang Lan , Cheng Lan , Xie Lingling , Lin Zhenyu , Han Ping , Li Xin
Published: July 2020

Background: “Wait-and-see”, has been proposed as a possible method of treatment in patients with locally advanced rectal cancer (LARC) after chemoradiotherapy (CRT), MR is important to predict the pathological tumor regression grade(TRG) to preoperative CRT. This study aims to evaluate the diagnostic value of signal intensity (SI) and volume (V) change rate in magnetic resonance imaging (MR) and determine which ones perform best as a potential biomarker for predicting pathological TRG to preoperative CRT in patients with LARC.Methods: A retrospective analysis of 82 patients with LARC, for whom clinical and imaging data were retrieved from our institute was conducted between Oct 2017and Oct 2019. Patients underwent pre- and post-CRT T2-weighted (T2W), diffusion-weighted (DW)/apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted (ceT1W). V, difference of volume between pre-CRT and post-CRT tumor (△V), V of tumor reduction rate (%△V), as well as SI of tumor (SIt), SI of muscle (SIm), relative SI ratio of tumor/muscle (SIR), changed difference SIR between pre- and post-CRT SIR (△SIR), SIR of tumor changed rate (%△SIR) on T2W, ADC and ceT1W were measured. All of LARC after CRT were confirmed pathologically and classifed into histologic TRG: TRG 0 (complete response), TRG 1 (moderate response), TRG 2 (minimal response), TRG 3 (poor response). Descriptive statistics and areas under the receiver operating characteristic curves (ROC) were generated to compare performance of %△V and %△SIR on T2W, DW, ceT1W for distinguishing between different pathological TRG.Result: Of the 82 patients, TRG 0 (16), TRG 1 (15), TRG 2 (35), TRG 3 (16).Except for ADC-%△SIR, the remaining %△V and %△SIR on T1W, ADC/DWI, ceT1W showed statistics significance between four groups. There was not distinguishable between TRG 1 and TRG 2, TRG 2 and TRG 3 by %△V and/ or %△SIR, the remaining different TRG all were identified by %△V and/ or %△SIR on T2W, ADC/DWI, ceT1W. Compared with other individual %△V or %△SIR, the combination of DW-%△V and T2W-%△SIR (DW-%△V * T2W-%△SIR) yielded higher AUCs to predict TRG 0 from TRG 2 (AUCs: 0.954, sensitivity: 93.75%, specificity: 97.14%) and TRG 3 (AUCs: 1.000, sensitivity: 100%, specificity: 100%), although AUC of all had not significant differences between TRG groups. there was statistically significant differences in post-CRT T restage and ypT stage between fours groups, respectively, but the agreement between post-CRT T restage and ypT is low ( kappa=0.191).Conclusions: V and/or SIR change rate on T2W, DW, ceT1W with high diagnostic performance could be useful in differentiating complete response from non-complete response; SIR change rate could be useful for distinguishing between moderate response and poor response.
Phase I Trial to Evaluate the Tolerance, Pharmacokinetics and Efficacy of the Broad-Spectrum ErbB Family Inhibitor Larotinib Mesylate in Patients with Advanced Solid Tumors
Authors: Liu Jingrui , Li Xiaojiao , Zhu Xiaoxue , Chen Hong , Ding Yanhua
Published: July 2020

Background: The presented phase I, first-in-human study evaluated the tolerance, pharmacokinetics, and preliminary efficacy of larotinib mesylate in patients with advanced solid tumors.Methods: Cancer patients were assigned to receive larotinib mesylate at 50–400 mg dose levels until disease progression or intolerance. Dose-limiting toxicities were assessed during Cycles 0 and 1. Pharmacokinetic evaluations were performed after the first dose and at steady-state. Results: Twenty-five patients with solid tumors were enrolled in the dose-escalation study. No DLTs were observed. Acne-like rash (68.0%), diarrhea (48.0%), paronychia (48.0%), and anemia (48.0%) were the most reported treatment-related adverse events. No clear linear pharmacokinetic characteristic could be drawn, and obvious accumulation was observed. Two patients with non-small cell lung cancer experienced a partial response, and 15 patients had stable disease after treatment. Conclusion: Continuous oral administration of larotinib mesylate at 50–400 mg daily demonstrated a favorable safety profile, and anti-tumor activity was observed in patients with advanced solid tumors.Trial registration: registration no.ChiCTR-OPC-15007153, registered 28 September 2015 at http://www.chictr.org.cn
[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results
Authors: Yadav Madhav Prasad , Ballal Sanjana , Meckel Marian , Roesch Frank , Bal Chandrashekhar
Published: July 2020

Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers.Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8–14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global assessment pain score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0.Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10–14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy.Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.
Unraveling the Role of microRNA and isomiRNA Networks in Multiple Primary Melanoma Pathogenesis
Authors: Dika Emi , Broseghini Elisabetta , Porcellini Elisa , Lambertini Martina , Riefolo Mattia , Durante Giorgio , Loher Phillipe , Roncarati Roberta , Bassi Cristian , Misciali Cosimo , Negrini Massimo , Rigoutsos Isidore , Londin Eric , Patrizi Annalisa , Ferracin Manuela
Published: July 2020

Background Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime about 8% of patients with CM will develop multiple primary melanomas (MPM). Patients affected by MPM could have a genetically determined susceptibility, though germline mutations in hereditary melanoma genes are rarely detected. Methods To better characterize the biology of this subset of melanomas, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a smallRNA sequencing approach and bioinformatic detection of miRNA isoforms. The differential expression of specific miRNAs/isomiRs was obtained using quantitative PCR.Results From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial-mesenchymal transition (EMT). Moreover, the first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p and 146a-5p, were further validated in a larger cohort of single and multiple melanoma samples (N=47). Overall, the Pathway Enrichment Analysis revealed a more differentiated and less invasive status of MPMs. Analyzing our smallRNA seq data, we detected a panel of melanoma-specific miRNA isoforms (isomiRs), which were validated in The Cancer Genome Atlas SKCM cohort. Specifically, we identified hsa-miR-125a-5p|0|-2 isoform as 10-fold over-represented in melanoma and differentially expressed in MPMs. IsomiR-specific target analysis revealed that the miRNA shortening confers a novel pattern of target gene regulations, including genes implicated in melanocyte differentiation and cell adhesion. Conclusions Overall we provided a comprehensive characterization of the miRNA/isomiRNA regulatory network of multiple primary melanomas, highlighting mechanisms of tumor development and correlating miRNA expression with MPM clinical characteristics.
Evaluation Of Clinical Features And Treatment Of Zygomatic Bone Fractures: A 10-Year Retrospective Study
Authors: Iulia Juncar Raluca , Tent Paul Andrei , Mihai Juncar , Anton Arghir Ioan , Oana Arghir Cristina , Mircea Rivis
Published: July 2020

Background
The pattern of zygomatic bone fractures varies in the literature, their features being frequently masked by the presence of associated soft tissue lesions, which make clinical diagnosis and therapeutic indications difficult. The aim of this study was to evaluate the clinical features of zygomatic bone fractures and their interrelation with concomitant overlying soft tissue lesions, in order to improve the diagnosis and the establishment of the correct treatment. We also aimed to assess the type of treatment methods applied depending on the fracture pattern of the zygomatic bone, as well as their effectiveness depending on the incidence rate of postoperative complications.
Methods
A 10-year retrospective evaluation of midface fractures was performed in patients diagnosed and treated in a tertiary Clinic of Oral and Maxillofacial Surgery.
Results
The study included 242 patients with zygomatic bone fractures. The majority of the fractures were displaced n = 179 (73.90%), closed n = 179 (73.90%) and complete n = 219 (90.50%). Hematoma was the most frequent associated soft tissue lesion n = 102 (42.15%) regardless of the fracture pattern (p = 1.000). The incidence of lacerations and excoriations was statistically higher in the case of complete (laceration p = 0.0028/ excoriation p = 0.037), displaced and comminuted zygomatic fractures (laceration p = 0.015/ excoriation p = 0.001). The most frequent type of treatment applied was Gillies reduction (61.98%), followed by ORIF (30.99%). The most frequent postoperative complication was malunion secondary to Gillies treatment (p = 002).
Conclusions
Patients presenting lacerations and excoriations on clinical soft tissue examination will most frequently have an underlying complete, displaced or comminuted zygomatic fracture. The most effective treatment method in the case of displaced, open or comminuted fractures was ORIF, while in the case of non-displaced and closed fractures, conservative treatment was the most effective.
What Influences Modern Contraceptive Utilisation Among Single Mothers in Nigeria? Evidence from Pooled Cross-Sectional Surveys
Authors: Ilesanmi Benjamin Bukky , Solanke Lukman Bola , Musa Musa Balarabe
Published: July 2020

Background: Existing studies in Nigeria and elsewhere have examined the associated factors of modern contraceptive utilisation among different segments of women such as adolescents, never married and women of advanced reproductive age. However, the associated factors of modern contraceptive utilisation among single mothers have been rarely explored. Though, some studies have examined the health and socio-economic conditions of single mothers but the associated factors of modern contraceptive uptake among them were largely ignored. This study therefore examines factors influencing modern contraceptive utilisation among single mothers in Nigeria. Methods: Data were extracted from four consecutive Nigeria Demographic and Health Surveys (NDHSs) implemented between 2003 and 2018. A weighted sample size of 7,215 single mothers was analysed. The outcome variable was current modern contraceptive utilisation. The explanatory variables are sets of selected socio-economic and demographic characteristics such as education, household wealth quintile, place of residence, age, parity and fertility desire. Data analysis was carried out using Stata version 14. Two multivariable logistic regression models were fitted in the study. Results: Findings reveal 11.7% current utilisation of modern contraceptives among single mothers. Improvements in educational attainment and household wealth quintile increases the odds of modern contraceptive use, Muslim single mothers had lower odds of modern contraceptive use (AOR=0.527, p<0.05; 95% CI: 0.366-0.759) and employed single mothers had higher odds of modern contraceptive use (AOR=1.449, p<0.05; 95% CI: 1.123-1.867). Findings further reveal that single mothers who had moderate exposure to the mass media (AOR=1.455, p<0.05; 95% CI: 1.049-1.807), single mothers who had high exposure to the mass media (AOR=1.442, p<0.05; 95% CI: 0.690-1.394) and younger single mothers (AOR=1.377, p<0.05; 95% CI: 1.049-1.807) had higher likelihood of modern contraceptive use. Conclusion: Modern contraceptive utilisation is low among single mothers in Nigeria. A number of socio-demographic characteristics of single mothers exert significant influence on modern contraceptive use. The contraceptive need of women involved in single motherhood may be different from the needs of other groups of women. The development of a special strategy targeting single mothers is thus imperative in the country.