bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study
Authors: Komori Akira , Abe Toshikazu , Yamakawa Kazuma , Ogura Hiroshi , Kushimoto Shigeki , Saitoh Daizoh , Fujishima Seitaro , Otomo Yasuhiro , Kotani Joji , Sakamoto Yuichiro , Sasaki Junichi , Shiino Yasukazu , Takeyama Naoshi , Tarui Takehiko , Tsuruta Ryosuke , Nakada Taka-aki , Hifumi Toru , Iriyama Hiroki , Naito Toshio , Gando Satoshi
Published: July 2020

Background
Frailty is associated with morbidity and mortality in patients in intensive care units (ICUs). However, the characteristics of frail patients with suspected infection, including sepsis, remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs.
Methods
This is a secondary analysis of a multicenter cohort study conducted by 22 ICUs in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes between three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score 1–3), vulnerable (score 4), and frail (score 5–9). We conducted subgroup analysis of patients with sepsis defined based on Sepsis-3 criteria. We also produced Kaplan–Meier survival curves for 90-day survival.
Results
We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median rating of 3 (3–5) on the CFS were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 were (31.4%) frail. The median age of the patients was 72 years (IQR 60 − 81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (4–10), 8 (5–11), and 7 (5–10), respectively (p = 0.59). The patients' median body temperatures were as follows: fit 37.5 (36.5–38.5)℃; vulnerable 37.5 (36.4–38.6)℃; and frail 37.0 (36.3–38.1)℃ (p < 0.01). C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (4.6–24.5), 12.1 (3.9–24.9), 10.5 (3.0–21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ according to frailty (p = 0.19). Kaplan–Meier survival curves showed little difference in the mortality rate during the acute phase. However, more vulnerable and frail patients died after the acute phase than fit patients; this difference was not statistically significant (p = 0.25). Compared with fit or vulnerable patients, fewer frail patients were discharged.
Conclusion
Frail and vulnerable patients with suspected infection, including sepsis, tend to have poor disease outcomes after the acute phase of infection.
Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy
Authors: Wu Jianjun , Cai Peian , Lu Zhenhui , Zhang Zhi , He Xixi , Zhu Bikang , Zheng Li , Zhao Jinmin
Published: July 2020

Background: The differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology.Methods: To identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early-stages, the gene expression profiles with temporal series were downloaded to reveal the distinct fates when BMSCs adopt a committed lineage. For both OS and AD lineages, the profiles of day 2–4 were compared with day 0 to screen the differentially expressed genes (DEGs), respectively. Next, the functional enrichment analysis was utilized to find out the biological function, and Protein-Protein Interaction network to predict the central genes. Finally, experiments were performed to verify our finding.Results: FoxO signaling pathway with central genes like FoxO3, IL6 and CAT, is the crucial mechanism of OS, while Rap1 signaling pathway of VEGFA and FGF2 enrichment is more significant for AD. Besides, PI3K-Akt signaling pathway might serves as the latent mechanism about the initiation of differentiation of BMSCs into multiple lineages.Conclusion: Above hub genes and early-responder signaling pathways control osteogenic and adipogenic fates of BMSCs, which maybe mechanistic models clarifying the changes of bone metabolism in the clinical progress of osteoporosis. The findings provide a crucial reference for the prevention and therapy of osteoporosis.
Longwall Top Coal Caving Design for Thick Coal Seam in Very Poor Strength Surrounding Strata
Authors: Jangara Hossein , Ozturk C. Atilla
Published: July 2020

Alpu lignite field is an important coal deposit with nearly 2 billion tons of coal resources located in the middle of Turkey. The mine deposit consists of three main seams. The thickness of two of them vary from 4 m to 30 m. The surrounding rock mass is very poor in terms of strength. The high clay content and weak rock mass make mechanized mining difficult. In this research, applicability of the longwall top coal caving method was investigated. The very weak strength behavior of the coal and the surrounding strata increases the importance of research in the mine site in terms of ground control. The aim is to design the mechanized longwall mine based on ground control principles. First of all, classification of the roof, coal, inter-burden, and floor strata were classified based on geotechnical aspects. Then, cavability index, shield, and floor bearing capacity were investigated. Different methods were applied to understand the limitations of a mechanized system that is very critical due to the very low strength strata. According to the main results, roof strata was classified as immediately caving while mining height was calculated as 5 m to 6 m. Finally, the relations among geotechnical characterizations of roof and floor strata, cutting and caving heights, and required shield capacity were presented based on analytical and numerical applications. The proposed approach can be used as a ground control method for the applicability as well as the limitations of mechanized longwall mining design in weak strata conditions.
Maternal Obesity Influences Birth Weight more than Gestational Diabetes
Authors: Alfadhli Eman M
Published: July 2020

BACKGROUNDMaternal obesity and gestational diabetes (GDM) are commonly encountered during pregnancy. Both conditions are independently associated with unfavorable pregnancy consequences. The objective of this study was to compare the effects of obesity and GDM on birth weight, macrosomia, and other adverse pregnancy outcomes.METHODSThis was a prospective study involving 531 women with a singleton pregnancy attending the Maternity and Children’s Hospital, Medina, Saudi Arabia. Participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks. The International Association of Diabetes and Pregnancy Study Groups criteria were used for GDM diagnosis. BMI was assessed at the first antenatal visit, and obesity was defined as a BMI ≥30.0 kg/m2. Women were divided into 4 groups: non-GDM nonobese (reference group), GDM nonobese, obese non-GDM, and obese GDM. Clinical characteristics and adverse pregnancy outcomes were compared. RESULTSThe mean age and BMI of the participants were 30.5 years and 29.3 kg/m2, respectively. GDM was diagnosed in 50.2% of the participants, and obesity was diagnosed in 47.8% of the participants. Obese women with GDM were the oldest and heaviest among all women. The mean birth weight increased in order among the four groups; it was highest in the infants in the obese GDM group, followed by those in the obese non-GDM, GDM nonobese and reference groups. Obesity and GDM alone or in combination were associated with higher rates of macrosomia and cesarean deliveries than the reference group. Neonatal intensive care unit (NICU) admission was higher in infants in the GDM nonobese and obese GDM groups. The rate of low Apgar score was significantly higher in infants in the obese GDM group than in infants in the reference group.CONCLUSIONSMaternal obesity seems to influence birth weight more than GDM, while GDM is associated with a greater risk of admission to the NICU. The combination of both conditions is associated with the greatest risk of adverse pregnancy outcomes.
Identification of a six-gene signature predicting overall survival for Oxaliplatin and 5-Fluorouracil resistant Colon cancer and potential drug-repurposing
Authors: Yang Feng , Cai Shaoyi , Su Riya , Ling Li , Tao Liang , Wang Qin
Published: July 2020

Background

Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC) is a major medical problem. Therefore, detailed mechanisms and predictive markers are urgently needed. The aim of this study was to identify key pathways, a robust prognostic gene signature and potential drug-repurposing.
Methods

In order to confirm the predictive markers and detailed molecular mechanisms of L-OHP and 5-Fu chemoresistant CRC, we performed weighted correlation network analysis (WGCNA), an unsupervised analysis method, to identify the chemoresistant CRC significantly related genes. Then, the gene prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Subsequently, the time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve were performed to assess the prognostic capacity of the model. Simultaneously, pathway enrichment was done to identify the key pathways involved in chemoresistant CRC. Moreover, we explored how the hub genes interacted with key pathways and transcription factors. Then, we found the potential drug target by the subcellular location fo hub genes. Finally, we identified the potential drug-repurposing by virtual screening for chemoresistant CRC according to ZINC 15 database.
Results

We identified the key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): Ribosome KEGG pathway. Moreover, six hub-genes prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Additionally, the detailed interactions among the pathway and hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) were examined by protein-protein interaction (PPI) network and shortest-pathway analysis. Furthermore, ANO1 was considered the potential drug target based on the subcellular location and ZINC000018043251 was verified the potential drug by virtual screening.
Conclusions

Our study identified a novel six-gene resistant signature for CRC prognosis prediction and the molecular details of these interactions between hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) and Ribosome key pathways. Furthermore, ZINC000018043251 was verified the potential drug for ANO1 by virtual screening, which might help to improve the outcome of CRC patients.
The Investigation of Genetic and Clinical Features in Patients with Hereditary Spastic Paraplegia in Central-Southern China
Authors: Wang Chen , Zhang Yun-Jian , Xu Ci-Hao , Li De , Liu Zhi-Jun , Wu Yan
Published: July 2020

Objective Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. We describe the genetic and clinical features of a cohort of five HSP families from central-southern China. Methods Using targeted exome-sequencing technology, we investigated the genetic and clinical features in five HSP families. We review the clinical histories of these patients as well as the molecular and functional characterization of the associated gene variants. We also performed functional analyse of an intron variant of SPAST in vitro.Results We identified a known SPAST mutation (p.Pro435Leu) in a family with autosomal dominant HSP (AD-HSP) and four novel variants in three HSP families and a sporadic case. These identified four novel variants include a SPG11 nonsense variant (p.Val1979Ter), two B4GALNT1 variants (p.Ser475Phe and c.1002+2T>G), and a splicing site variant in SPAST (c.1245+5G>A). Minigene analysis of the SPAST splicing variant（c.1245+5G>A）revealed that the mutation resulted in mRNAs with a loss of exon 9. The SPG4 family carrying SPAST c.1245+5G>A exhibited obviously genetic anticipation, with a decreased age at onset and increased severity in successive generations. The proband with p.Val1979Ter variant in SPG11 showed characteristic clinical feature of early-onset, severe spasticity, and corpus callosum atrophy which were highly suggestive of the diagnosis of SPG11-associated HSP. Conclusions Our findings strongly support variable phenotype of B4GALNT1-related SPG26 and also expand the clinical and mutation spectrum of HSP caused by mutations in SPG4, SPG11, and B4GALNT1. These results will help to improve the efficiency of early diagnosis in patients clinically suspected of HSP.
Chiropractic student perspectives on the use of virtual radiography simulation: An observational study reporting on chiropractic students’ perception on the use of virtual radiography as a clinical learning tool
Authors: Shanahan Madeleine , Molyneux Tom , Vindigni Dein
Published: July 2020

Background

Virtual radiography provides students with an opportunity to practise their clinical skills in patient positioning and evaluating radiographic images. The purpose of this pilot study was to introduce Projection VR™, a software radiography simulation program, into a student chiropractic program and evaluate its potential application as a teaching and learning tool.
Methods

Undergraduate chiropractic students, enrolled in a radiographic course (unit within the chiropractic program), were invited to attend a scheduled laboratory where they were introduced to, and undertook purposefully designed activities using the radiography simulation. At the end of this activity, students were asked to complete an online survey to describe their perceptions of the educational value of the software program. Descriptive and inferential statistics were used to evaluate outcomes.
Results

Responses were received from 44 out of the 47 students who attended the scheduled laboratory (response rate 92%). Overall students were positive about this simulation identifying that it was easy to use (95%) and that they could control the equipment as needed (95%). The main reported benefits included students being enabled to repeat tasks until they were satisfied with the results (98%) and being able to quickly assess images and determine if changes needed to be made (98%). Participants reported improvement in their understanding of the effect of exposure factors on patient radiation dose (93%) as well as their technical image evaluation (84%) and problem-solving skills (80%).
Conclusions

The results of this study suggest that virtual radiography is a valuable complementary resource in providing chiropractic students with radiographic knowledge and skills.
Cisplatin-Resistant Gastric Cancer Cells Promote the Chemoresistance of Cisplatin-Sensitive Cells via Exosomal RPS3 Mediated PI3K-Akt-cofilin-1 Signaling Axis
Authors: Sun Mengyao , Xu Bo , Wu Qiuxue , Cai Si , Chen Wenlian , Li Dong , Zhang Hui , Tang Qingfeng
Published: July 2020

Background: Cisplatin is an important agent in first-line chemotherapy against gastric cancer (GC). However, consequential drug resistance limits its effectiveness for the treatment of GC. Exosomes which are loaded with proteins, lipids and RNAs, have been proven to transfer malignant phenotype. This study aims to explore the role and mechanism of exosomal RPS3 protein in transmitting a chemoresistance phenotype from cisplatin resistant to cisplatin sensitive gastric cancer cells.Methods: A cisplatin resistant gastric cancer cell line SGC7901R was established by continuously grafting SGC7901S cells into cisplatin-containing culture medium. Exosomes from SGC7901R and SGC7901S were obtained and confirmed through ultracentrifuge and Nano Analyzer. By LC-MS/MS analysis methods, we detected the differentially expressed proteins in SGC7901R cells exosomes and SGC7901S cells exosomes. Western blotting was used to verify the differential expression of exosomal RPS3 between cisplatin resistant and parental cell lines. Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of exosomal RPS3 protein in GC.Results: SGC7901R cell derived exosomes were readily taken up by cisplatin sensitive SGC7901S cells, thus triggering off a phenotype of chemoresistance in the receptor cells. Subsequently, it was demonstrated that exosomal RPS3 was essential for inducing chemoresistance of receptor cells as shown by the acquisition of this phenotype in SGC7901S cells with enforced expression of RPS3. Further mechanism study demonstrated that cisplatin‑resistant gastric cancer cells-derived exosomal RPS3 enhanced the chemoresistance of cisplatin‑sensitive gastric cancer cells through the PI3K-Akt-cofilin-1 signaling pathway.Conclusion: Cisplatin resistant gastric cancer cells communicate with sensitive cells through the intercellular delivery of exosomal RPS3 and activation of the PI3K-Akt-cofilin-1 signaling pathway. Targeting exosomal RPS3 protein in cisplatin resistant gastric cancer cells may thus be a promising strategy to overcome cisplatin resistance in gastric cancer.
Sex-Dependent Differences in the Secretome of Human Endothelial Cells
Authors: Cattaneo Maria Grazia , Banfi Cristina , Brioschi Maura , Lattuada Donatella , Vicentini Lucia M.
Published: July 2020

Background: Cellular sex has been rarely considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and ‘omics approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.Methods: We performed proteomic and gene ontology (GO) analyses of secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and western blot techniques, and efferocytosis through the ability of the macrophage cell line RAW-264.7 to engulf apoptotic ECs. Protein expression and silencing efficacy were assessed by RT-qPCR. Results: Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison to female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 proved that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis was independent of PTX3 expression. Conclusions: Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.
ECG Heartbeat Classification Based on Signal-to-Image Transformation Using Convolutional Neural Networks
Authors: Degirmenci Murside , Ozdemir Mehmet Akif , Izci Elif , Akan Aydin
Published: July 2020

Background: Electrocardiogram (ECG) is a method of recording the electrical activity of the heart and provides a diagnostic mean for heart-related diseases. An arrhythmia is any irregularity of heartbeat that causes an abnormality in one’s heart rhythm. Early detection of arrhythmia has great importance to prevent many diseases. Manual analysis of ECG signal is not sufficient for quickly identifying arrhythmias that may cause sudden deaths. Hence, many studies have been presented to developed computer-aided diagnosis (CAD) systems to automatically identify arrhythmias.Methods: This paper proposes a novel deep learning approach to identify arrhythmias in ECG signals. The signals are obtained from MIT-BIH arrhythmia database and are categorized according to five arrhythmia types. The proposed approach identifies arrhythmia classes by using Convolutional Neural Network (CNN) architecture trained by two-dimensional (2D) ECG beat images. CNN architecture is selected due to high image recognition performance. ECG signals are segmented into heartbeats, then each heartbeat is transformed into a 2D grayscale image. The heartbeat images are used as input for the CNN. Results: The proposed CNN model is compared to other common CNN architectures such as LeNet and ResNet-50 to evaluate the performance of our study. Overall, the proposed study achieved 99.7% test accuracy in the classification of five different ECG arrhythmias.Conclusions: Testing results demonstrate that CNN trained by ECG image representations provide outstanding classification performance of arrhythmic ECG signals and outperforms similar network architectures. Hence, the proposed approach provides a robust method for the classification of ECG arrhythmias.
Self-awareness of HbA1c and its association with glycemic control among patients with type 2 diabetes: A multicenter study
Authors: Almutairi Joud Shabeeb , Almigbal Turky H , Alraheem Hiba Y , Mujammami Muhammad H , AlMogbel Turki A , Alshahrani Abdullah M , Zahrani Abdullah M Al , Batais Mohammed A
Published: July 2020

Background
Diabetes-related complications can be prevented by maintaining good glycemic control. Despite huge efforts to obtain acceptable glycemic control among diabetics, this has not yet been achieved. Thus, there is a need to discover all factors that might affect glycemic control. Here, our main aim was to assess the association between self-awareness of Hemoglobin A1c (HbA1c) among Saudi patients with type 2 diabetes and glycemic control, thereby identifying those factors that might affect the glycemic control.
Methods
The data for this study was collected using questionnaires through interviews among 600 patients with type 2 diabetes. The study was conducted in outpatient diabetes clinics in tertiary hospitals in Riyadh, Qassim and Jeddah, Saudi Arabia. The data collection was done during the period from March and April 2018. The subject’s self-awareness about the HbA1c test was assessed based on the combined score of four questions. The latest HbA1c result before the time of data collection was obtained from medical records. Frequencies and percentages were calculated for all categorical variables used in the analysis. Means and standard deviations were calculated for continuous variables. A p-value of less than 0.05 was considered statistically significant for all analyses.
Results
The mean age of the respondents was 54.7 years, and the mean duration of diabetes was 11.9 years. The prevalence of HbA1c self-awareness was approximately 40%. Overall, 63.9% accurately reported their Hemoglobin A1C Self-Knowledge (HbA1csk). The prevalence of good glycemic control (defined as HbA1c less than 7.0%) was 21.0%. Five of the participants’ characteristics were associated with better glycemic control: good HbA1c self-awareness (OR = 3.25, 95%CI: 1.15–9.24), duration of diabetes (negatively associated with glycemic control) (OR = 0.91, 95%CI: 0.87–0.95), discussed HbA1c target with the health care provider (OR = 2.42, 95%CI: 1.22–4.79), monthly income between 10,001 and 15,000 SR (OR = 2.28, 95%CI: 1.13–4.60), and number of follow up visit (OR = 0.77, 95%CI: 0.63–0.94).
Conclusions
We conclude that there is a positive association between HbA1c self-awareness and glycemic control. Glycemic control was good among those who were educated about the meaning of the test, their levels, and their target goal. Awareness among health care providers regarding the role of the patient’s education about their condition might help in providing the patient with optimal care. Further studies with different experimental designs are needed to study this association, which will contribute to the development of a structured educational program.
Cerebral fat embolization with paroxysmal sympathetic hyperactivity syndrome and septic shock at high altitude: A case report and literature review
Authors: Li Min , Zhu Gang , Guo Hao , Ge Shun Nan , Gao Guo Dong , Qu Yan
Published: July 2020

BackgroundCerebral fat embolism (CFE) syndrome at high altitude was rare complicated with paroxysmal sympathetic hyperactivity (PSH) syndrome and septic shock. It is a challenge to differential diagnosis and treatment at high altitude. Case presentationThis case presents a CFE with PSH and septic shock of a 23-year-old man occurred at high altitude of 3800 meters above sea level, transferred by airplane successfully and cured in the department of neurosurgery, Xi`an Tangdu Hospital.Conclusions It is key that CFE with PSH can be rapid diagnosed and treatment bundles of septic shock should be initiated as soon as possible. Early neurological rehabilitation played an important role for good outcome.
Trends and Predictors of Sexually Transmitted Infections Among Sexually Active Ugandan Female Youths: Evidence from Three Demographic and Health Surveys, 2006-2016
Authors: Masanja Veronicah , Wafula Solomon Tsebeni , Ssekamatte Tonny , Isunju John Bosco , Mugambe Richard K , Hal Guido Van
Published: July 2020

Background: Female adolescents and young women have the highest risk of curable sexually transmitted infections (STIs) globally. Data on the prevalence of STIs among young women in Uganda are limited. In this study, we investigated the time trends and determinants of STIs among adolescent girls and young women (15-24 years) in Uganda. Methods: We estimated the percentage of women 15-24 years from three recent consecutive Uganda Demographic and Health Surveys (2006, 2011, and 2016), who reported acquiring an STI within 12 months of the studies and examined the changes over time. A pooled multivariable logistic regression was used to examine predictors of actors associated with reporting an STI were assessed using.Results: The pooled STI prevalence was 26.0%. About 22.0% of youths reported an STI in 2006. This increased to 36.3% in 2011, before declining to 23.1% in 2016. Youths aged 20-24 years reported a higher STI prevalence (27.3%) compared to young participants (23.6%). Prevalence of STIs was significantly higher among female youths with multiple total lifetime partners (adjusted odds ratio (aOR 1.6, 95% CI 1.4-1.6). Similarly, women who were sexually active in the last 4 weeks prior to the interview (aOR 1.3, 95% CI 1.1-1.6), and women affiliated to Islam (aOR 1.3, 95% CI 1.1-1.6) or other religions (aOR 1.8, 95% CI 1.1-2.9) were more likely to report an STI. Living in Northern Uganda was found protective against STIs (aOR 0.5, 95% CI 0.3-0.7).Conclusion: The prevalence of STIs was high among female youths, 15-24 years. There is a need to adopt a holistic approach to the diagnosis and management of STIs among youths, as well as the integration of STI services in daily health care systems to increase their access to sexual and reproductive health services.
Transcatheter arterial infusion combined with radioactive particles in the treatment of advanced body/tail pancreatic cancer: a retrospective cohort study
Authors: Han Shilong , Cao Chuanwu , Yuan Yifeng , Chen Jun , Yin Linan , Xu Huirong , Liu Jingzhou , Wang Wujie , Li Yuliang , Wang Lizhou , Zhou Shi , Li Fenqiang , Wang Wenhui , Ji Jiansong , Long Haideng , Yin Shiwu , Li Jue , Han Jianjun , Liu Ruibao , Li Maoquan , Zhang Xiaoping
Published: July 2020

Background
Patients with advanced body/tail pancreatic cancer have poor quality of life and low overall survival rate. In recent years, interventional diagnosis and treatment of advanced pancreatic cancer have become increasingly widespread. This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail cancer pancreatic by assessing the short-term and overall survival rates.
Methods
We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable and no other confirmed malignant tumors, patients were assigned into three groups according to their treatment. Analyses with regard to the clinical responses, the 6, 12, and 18-month survival rates and overall survival rates were performed.
Results
The median survival time was 6 months in the control group, 10 months in the TAI group and 13 months in the TAI combined group. The Kaplan–Meier estimates of the OS among the three groups, indicating that there is significant difference among three groups (P༜0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P༜0.002).
Conclusions
In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.
Evaluation of the Reporting of Safety and Immune-Related Adverse Events in Clinical Trials of FDA-Approved Immune Checkpoint Inhibitors in Oncology
Authors: Karimian Zahra , Mavoungou Sandra , Salem Joe-Elie , Tubach Florence , Dechartres Agnes
Published: July 2020

Background – While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs. Methods – MEDLINE was searched via PubMed to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared reporting and evaluated concordance in reported safety data between both sources. Results – Of 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8% and 8.8% of published trials respectively, compared to 11.8% and 5.9% of registry results. Evaluating the concordance of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had concordant data between both sources.Conclusions – The reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.
Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study
Authors: Mahmood Reem , Shaw Danielle , Descamps Tine , Zhou Cong , Morgan Robert D. , Mullamitha Saifee , Saunders Mark , Mescallado Nerissa , Backen Alison , Morris Karen , Little Ross A. , Cheung Susan , Watson Yvonne , O’Connor James P. B. , Jackson Alan , Parker Geoff J. M. , Dive Caroline , Jayson Gordon C.
Published: July 2020

Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to firstly define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.Methods: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).Results: 20 patients were recruited to the study. Results showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. Across all patients, the MRI perfusion parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p=0.025).Conclusions: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecular targeted therapies such as anti-angiogenic agents.
The Sigma 2 Receptor Promotes and the Sigma 1 Receptor Inhibits Mu-Opioid Receptor-Mediated Antinociception
Authors: Sánchez-Blázquez Pilar , Cortés-Montero Elsa , Rodríguez-Muñoz María , Merlos Manuel , Garzón-Niño Javier
Published: July 2020

The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR) and is also implicated in the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout mice. σ2R-/- animals developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the σ1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and β-endorphin increased in σ1R-/- mice and diminished in σ2R-/- mice. The analgesic effect of morphine was increased in σ2R-/- mice by treatment with S1RA. However, σ2R-/- mice and wild-type mice exhibited comparable antinociceptive responses to the delta receptor agonist [D-Pen2,5]-encephalin (DPDPE), the cannabinoid type 1 receptor agonist WIN55212-2 and the alfa2-adrenergic receptor agonist clonidine. These findings suggest that σ2R and σ1R have selective regulatory effects on MOR-mediated analgesia, with σ2R promoting MOR-mediated analgesia and σ1R inhibiting it. Our study may help identify new pharmacological targets for diminishing pain perception and improving opioid detoxification therapies.
Metabolic profiles of whole serum and serum-derived exosomes are different in head and neck cancer patients treated by radiotherapy
Authors: Wojakowska Anna , Zebrowska Aneta , Skowronek Agata , Rutkowski Tomasz , Polański Krzysztof , Widlak Piotr , Pietrowska Monika , Marczak Lukasz
Published: July 2020

Background
Serum metabolome reflects a general patient's body response to both disease state (e.g., cancer) and implemented treatment (e.g., radiotherapy, RT). Though serum-derived exosomes are an emerging type of liquid biopsy, a metabolite content of these vesicles remains under-researched yet. In this pilot study, we aimed to compare metabolite profiles of the whole serum and serum-derived exosomes in the context of differences between cancer patients and healthy controls as well as patients’ response to RT.
Methods
Serum samples were collected from 10 healthy volunteers and 10 patients with head and neck cancer, in the latter group samples were taken before and after the end of RT. Exosomes were isolated from serum by the size-exclusion chromatography. Metabolites were purified from the complete serum and exosomes using a methanol extraction and analyzed by the gas chromatography-mass spectrometry (GC-MS).
Results
An untargeted GC-MS-based approach allowed the detection of 182 and 46 metabolites in serum and exosomes, respectively (33 compounds were present in both types of specimens). The unsupervised analyses revealed that metabolite profiles of the whole serum but not serum-derived exosomes enabled the separation of all 3 groups of samples. There were 27 compounds whose serum levels were markedly different (large effect size) between control and cancer samples and 12 compounds whose serum levels were markedly different between cancer pre-RT and post-RT samples. On the other hand, only 4 metabolites present in exosomes showed markedly different levels between cancer and control samples. Noteworthy, metabolites that differentiated cancer and control samples, either serum or exosomes, were associated with energy metabolism pathways. Serum metabolites affected by RT were associated with pathways involved in the metabolism of amino acids, sugars, lipids, and nucleotides.
Conclusions
Metabolite profile of serum-derived exosomes is less complex than that of the complete serum. However, cancer-specific features of energy metabolism could be detected in both types of specimens. On the other hand, in contrast to RT-induced changes observed in serum metabolome, this pilot study did not reveal a specific radiation-related pattern of exosome metabolites.
Knowledge, perception and implementation of personal protective measures by citizens during the COVID-19 outbreak in Northern Cyprus: a cross-sectional survey
Authors: Yilmaz Azze Buket , Guler Emrah , Baddal Buket
Published: July 2020

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated over 8 000 000 cases of the coronavirus disease 2019 (COVID-19) worldwide and has led to the implementation of strict measures in all countries. The aim of this study was to investigate the knowledge, attitude and implementation status of personal protective measures (PPMs) by ordinary citizens in Northern Cyprus and their access to personal protective equipment (PPE) during the COVID-19 outbreak.Subject and Methods: This was a cross-sectional study based on internet-based survey. A total of 406 participants were recruited between May 1 and 4, 2020 via authors’ networks to complete a questionnaire. Participants were asked to indicate how often they implemented the five PPMs recommended by the World Health Organization (WHO), their daily frequency of hand hygiene events, their COVID-19 knowledge as well as the availability of PPE in their hometown.Results: The prevalence of the five PPMs ranged from 65.0% to 95.6%, with the highest being hand hygiene and the lowest being avoiding touching the eyes, nose, and mouth. Hand hygiene events were recorded to be more than 10 per day in 47.3% of the participants. Gloves (86.2%), surgical masks (52.2%), and cloth face masks (47.3%) were the most commonly used PPE in public areas. The majority of the responders were aware of the incubation time (90.4%) and indirect route of viral transmission (89.7%), whereas knowledge of droplet (72.2%) and aerosol transmission (43.6%) were lower. Knowledge was gained mainly through social media and TV.Conclusion: Overall, citizens implemented protective measures effectively and were strictly coherent to government-induced curfew and self-isolation measurements with a high public awareness.
Various Far-Field Hydrological Responses During 2015 Gorkha Earthquake at Two Distant Wells
Authors: Huang Xudong , Zhang Yu
Published: July 2020

Aquifer hydraulic parameter can change during earthquakes. Continuous monitoring of the response of water level to seismic waves or solid Earth tides provides an opportunity to document how earthquakes influence hydrological properties. Here we use data of two groundwater wells, Dian-22 (D22) and Lijiang (LJ) well, in southeast Tibet Plateau in response to the 2015 Mw 7.8 Gorkha earthquake to illustrate hydrological implications. The coherences of water level and seismic wave before and after the far-field earthquake show systematic variations, which may confirm the coseismic dynamic shaking influence at high frequencies (f > 8 cpd). The tidal response of water levels in these wells shows abrupt coseismic increases of both phase shift and amplitude ratio after the earthquake, which may be interpreted as an increase in the horizontal permeability of a confined aquifer in D22 well, and an occurrence in the vertical permeability of a switched semiconfined aquifer with larger epicentral distance and but high seismic ground motion. Using the continuous transmissivity monitoring, we show that the possible preseismic initial for ~ 1 day, coseismic response for ~ 3 days and postseismic healing for ~ 10 days during the earthquake. Thus, the dynamic shaking during the Gorkha earthquake may have caused confined aquifers to semiconfined aquifers by reopening of preexisting vertical fractures and later healing at epicentral distances about 1500 km.
KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum
Authors: Alvarez-Fernandez Ana , Bernal María J. , Villajos Isabel Fradejas , Ramírez Alexandra Martín , Yu Noor Azian Md , Suárez Marta Lanza , Hisam Shamilah , Perez-Ayala Ana , Rubio Jose M
Published: July 2020

Background
The emergence and spread of antimalarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known antimalarials. This antimalarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorfisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programs. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum.
Methods
Three SNPs involved in most cases of resistance to the most widespread antimalarial treatments have been analyzed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analyzed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method.
Results
The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analyzed.
Conclusions
The KASP assays developed in our study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.
CD4 T-Cell Immune Stimulation of HER2+ Breast Cancer Cells in Response to Trastuzumab In Vitro
Authors: Song Patrick N. , Mansur Amer , Dugger Kari J. , Davis Tessa R. , Howard Grant , Yankeelov Thomas E. , Sorace Anna G.
Published: July 2020

Introduction: The HER2+ tumor immune microenvironment is composed of macrophages, natural killer cells, and tumor infiltrating lymphocytes, which produce pro-inflammatory cytokines. Determining the effect of T-cells on HER2+ cancer cells during therapy could guide immunogenic therapies that trigger antibody-dependent cellular cytotoxicity. This study utilized longitudinal in vitro time-resolved microscopy imaging to measure T-cell influence on trastuzumab in HER2+ breast cancer.Methods: Fluorescently-labeled breast cancer cells (BT474, SKBR3, MDA-MB-453, and MDA-MB-231) were co-cultured with CD4+ T-cells (Jurkat cell line) and longitudinally imaged to quantify cancer cell viability when treated with trastuzumab (10, 25, 50 and 100 g/mL). The presence and timing of T-cell co-culturing was manipulated to determine immune stimulation of trastuzumab-treated HER2+ breast cancer. HER2 and TNF- expression were evaluated with western blot and ELISA, respectively. Significance was calculated using a two-tailed parametric t-test.Results: The viability of HER2+ cancer cells significantly decreased when exposed to 25 g/mL trastuzumab and T-cells, compared to cancer cells exposed to trastuzumab without T-cells (p = 0.01). The presence of T-cells significantly increased TNF- expression in trastuzumab-treated cancer cells (p = 0.02). Conversely, cancer cells treated with TNF- and trastuzumab had a similar decrease in viability as trastuzumab-treated cancer cells co-cultured with T-cells (p = 0.49).Conclusions: The presence of T-cells significantly increases the efficacy of targeted therapies and suggests trastuzumab may trigger immune mediated cytotoxicity. TNF- expression suggests cytokines may interact with trastuzumab-induced HER2 receptor blockade. Examining molecular mechanisms of breast cancer immune infiltration has the potential to improve response to targeted therapies.
The Physiological and Microbiological Characteristics of Cement Dust Polluted Soil Around Lafarge Cement Industry
Authors: Sowunmi Kehinde , Shoga Suliat , M. Adewumi O. , A. Oriyomi F. , Sowunmi Lukman
Published: July 2020

The authors have requested that this preprint be removed from Research Square.