bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-expandable metallic stenting as a bridge to elective surgery versus emergency surgery for acute malignant right-sided colorectal obstruction
Authors: Li Bing , Cai Shi-Lun , Lv Zhen-Tao , Zhou Ping-Hong , Yao Li-Qing , Shi Qiang , Qi Zhi-Peng , Sun Di , Yalikong Ayimukedisi , Xu En-Pan , Xu Jian-Min , Zhong Yunshi
Published: July 2020

Background
Data are limited regarding the advantages of a self-expandable metal stent (SEMS) as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC), as most studies concentrated on this technique used in left-sided colon. This study aimed to evaluate the outcomes of patients (including stage IV cases) with acute MORC treated by initial SEMS placement vs emergency surgery (ES).
Methods
Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups.
Results
In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. 29.0% (27/93) of the patients with stage II and III disease experienced disease progression, when the distant metastasis rates for the SEMS and ES groups were 21.4% (6/28) and 18.5% (12/65), respectively (P = 0.740) and local site relapse presented in 2 (7.1%) patients of the SEMS group and in 7 (10.8%) patients of the ES group (P = 0.719). After colectomy for synchronous liver metastases, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs combined resection was 3.258 (95% CI 0.858–12.370; P = 0.041).
Conclusion
Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.
Severe physical inactivity in chronic obstructive pulmonary disease: changes in systemic inflammation after pulmonary rehabilitation – a pilot study
Authors: Thyregod Mimi , Løkke Anders , Skou Søren T. , Larsen Jacob , Bodtger Uffe
Published: July 2020

Background The purpose was to investigate whether severe physical inactivity (SPI) is associated with altered levels of common inflammatory markers as compared to higher Physical activity levels (PALs), and whether pulmonary rehabilitation would reduce the levels of systemic inflammation in SPI in patients with COPD. Methods This prospective, cohort study was conducted in four rehabilitation centers in Region Zealand, Denmark. We included patients with COPD referred for 7-12 weeks of pulmonary rehabilitation (2-hours of exercise therapy and education twice weekly). We measured b-eosinophils, p-fibrinogen, p-CRP, s-IL-6, s-CD 163, nasal lavage-IL-8, and daily physical activity, using a validated activity monitor, SenseWear®, at baseline and after rehabilitation. SPI was defined as PAL <1.4.Results In total, 31 of 57 patients were SPI at baseline, and seven (23%) of these patients improved to non-SPI after pulmonary rehabilitation. We observed no significant differences in the primary endpoint i.e. change in systemic inflammation between patients who remained SPI at both time pints vs. patients who improved PAL from SPI at baseline to non-SPI at follow-up. At baseline, SPI was associated with significantly higher p-fibrinogen levels (p=0.04) than non-SPI, but no other differences were observed between SPI and non-SPI Conclusion In a cohort of patients with COPD attending pulmonary rehabilitation, we could not demonstrate any differences or changes in systemic inflammation or PAL following rehabilitation between patients with SPI and non-SPI. This might be a true negative finding or due to a high pro-inflammatory drive in all patients regardless of SPI status or study limitations such as suboptimal levels of rehabilitation intensity and SPI cut-off level. The study was registered at ClinicalTrials.gov (NCT01700296), https://register.clinicaltrials.gov. Registered in November 2012.
Genomic signatures in pediatric advanced stage Burkitt lymphoma/leukemia in a Chinese population detected by next generation sequencing
Authors: Lei Xiaoying , Yin Nange , Guo Yuxia , Song Ling , Zhu Jin , Xiao Jianwen
Published: July 2020

Background: Burkitt lymphoma/leukemia (BL/BAL) is the most common lymphoma in children, and the sporadic subtype is dominant in Chinese populations. MYC gene translocations are essential for sporadic BL/BAL (sBL/BAL), but other gene mutations also play important roles in the development of sBL/BAL. Methods: The clinical data of ten Chinese children with sBL/BAL were collected, and next generation sequencing of their tumor tissues was conducted. Cases of BL and diffuse large B cell lymphoma (DLBCL) were also collected from a database, and bioinformatics analysis was conducted.Results: Nine boys and one girl were enrolled in the study, including six BL patients (stage III) and four BAL patients (stage IV). The average age at diagnosis was 100.10±13.39m; overexpression of CD20 was detectable, and MYC rearrangements were confirmed. The patients received combination treatment of chemotherapy and rituximab. All patients achieved complete remission and survived. Germline causal gene mutations were detected in four (40%) patients by whole-exome sequencing (WES); ID3, BRCA2, ARID1A and SMARCA4 mutations, in addition to MYC mutations, were the most common somatic mutations. The gene functions in etiology were different between the BL and DLBCL datasets. The identified mutated genes were enriched and connected by GO or KEGG pathways, and it seemed that the PI3K-Akt signaling pathway or the EGFR-TKI resistance pathway played important roles in the etiology of sBL/BAL. Conclusion: sBL/BAL is a highly aggressive but curable lymphoma; its etiology and pathology require additional research. The molecular hallmark of sBL/BAL is MYC translocation, whereas additional chromosomal abnormalities and gene mutations also occur and play roles in the progression of the disease. The PI3K-Akt signaling pathway seems to play important roles in the development of sBL/BAL, and sBL/BAL may be inhibited by this signaling pathway. The EGFR-TKI resistance pathway was also analyzed in sBL/BAL patients, revealing that EGFR-TKI treatment is invalid in this disease. Further research is needed for hypothesis development and possible mechanism discovery.
Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model
Authors: Takagi Tomoharu , Kabata Tamon , Hayashi Katsuhiro , Fang Xiang , Kajino Yoshitomo , Inoue Daisuke , Ohmori Takaaki , Ueno Takuro , Yoshitani Junya , Ueoka Ken , Yamamuro Yuki , Tsuchiya Hiroyuki
Published: July 2020

Background: Adipose-derived stem cells (ADSCs) represent an abundant source of multipotent adult stem cells easily isolated from subcutaneous adipose tissue. With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Methods: Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Results: Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Conclusions: Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes by secretion of trophic factors.
Investigation of outpatient’s satisfaction of elderly patients with chronic pain:a survey
Authors: An Guanghui , Fang Bin , Zhang Panpan , Huang Xiaojing
Published: July 2020

BackgroundThere are more and more elderly patients with chronic pain, and there is a certain particularity in this group. The rapid development of the Internet and smart devices has brought a series of convenience measures for the outpatient in our hospital. But the impact of these new methods on the experience of elderly patients with chronic pain is not known yet.MethodsIn this study, the outpatient satisfaction questionnaire with six questions was used to investigate the problems in elderly chronic pain outpatient consultation. ResultsIn the survey of 100 patients, the overall satisfaction of the visiting experience was 63.5%, the satisfaction of locating the clinic was only 35%,the satisfaction of getting the examination report was 47%, the satisfaction of outpatient visit time choice was 60%, the satisfaction of the consultation process was 69%，the satisfaction of nursing service was 80%,and the satisfaction of the consultation service was 90%. ConclusionThe experience of medical service of elderly outpatients with chronic pain is poor in the background of modern and intelligentialized medical practice. To improve the experiences of these patients, it is necessary that the hospital provide additional supports to assist those patients during the outpatient service.
Understanding forgotten exposures towards achieving Sustainable Development Goal 3: the case of herbal medicine use in Tanzania
Authors: Kessy Anna Tengia , Msalale George Chombe
Published: July 2020

Background: In most sub-Sahara African countries, herbal medicines are widely used during pregnancy and labour for various motives despite their unclear pharmacology and potential toxicity. Considering the United Nations Sustainable Development Goal (SDG) 3, exposure to herbs during pregnancy should be restricted in order to safeguard the health of mothers and newborns. This study aimed to assess the proportion of mothers using herbal medicines during pregnancy and delivery and to determine factors associated with the practice.Methods: This cross-sectional quantitative study gathered information from 340 mothers who delivered a live baby in the preceding two years. Using a two-stage-sampling technique, we selected and interviewed mothers attending reproductive, maternal and child health clinics in Tabora, in central Tanzania. We compared proportions using chi-square test and performed a Poisson regression analysis to determine independent correlates of herbal use.Results: Over 60% of mothers in Tabora used herbal medicines during pregnancy and delivery. Major reasons for use were shortening of labour duration, 81 (38.9%) and reducing labour pain, 58 (27.9%). Independent factors of herbal use were distance to the nearest health facility, adjusted prevalence ratio (aPR = 1.12, 95%CI = 1.00,1.25), perception of herbs as safe, (aPR = 1.16, 95%CI = 1.05,1.29) and health care providers’ stance on the use of herbs, (aPR = 1.14, 95%CI = 1.04,1.25).Conclusions: Use of herbal medicines during pregnancy and delivery in Tanzania is high. This calls for comprehensive investigations on the effects of herbs used during pregnancy and delivery as a step towards understanding contributions of forgotten exposures en route for achieving SDG 3. Additionally, health care providers ought to include health education messages during antenatal visits on the undesirable effects of using herbs.
An energy charge sensor for balancing RNA polymerase recycling and hibernation
Authors: Wahl Markus , Pei Hao-Hong , Hilal Tarek , Chen Zhuo , Huang Yong-Heng , Gao Yuan , Said Nelly , Loll Bernhard , Rappsilber Juri , Belogurov Georgiy , Artsimovitch Irina
Published: July 2020

Cellular RNA polymerases can become trapped on DNA or RNA, threatening genome stability and limiting free enzyme pools, or enter dormancy. How RNA polymerase recycling into active states is achieved and balanced with quiescence remains elusive. We structurally analyzed Bacillus subtilis RNA polymerase bound to the NTPase HelD. HelD has two long arms: a Gre cleavage factor-like coiled-coil inserts deep into the RNA polymerase secondary channel, dismantling the active site and displacing RNA; a unique helical protrusion inserts into the main channel, prying β and β’ subunits apart and dislodging DNA, aided by the δ subunit. HelD release depends on ATP, and a dimeric structure resembling hibernating RNA polymerase I suggests that HelD can induce dormancy at low energy levels. Our results reveal an ingenious mechanism by which active RNA polymerase pools are adjusted in response to the nutritional state.
Dynamic Memristor-based Reservoir Computing for High-Efficiency Spatiotemporal Signal Processing
Authors: Zhong Yanan , Tang Jianshi , Li Xinyi , Gao Bin , Qian He , Wu Huaqiang
Published: July 2020

Reservoir computing (RC) is a highly efficient network for processing spatiotemporal signals due to its low training cost compared to standard recurrent neural networks. The design of different reservoir states plays a very important role in the hardware implementation of RC system. Recent studies have used the device-to-device variation to generate different reservoir states; however, this method is not well controllable and reproducible. To solve this problem, we report a dynamic memristor-based RC system. By applying a controllable mask process, we reveal that even a single dynamic memristor can generate rich reservoir states and realize the complete reservoir function. We further build a parallel RC system that can efficiently handle spatiotemporal tasks including spoken-digit and handwritten-digit recognitions, in which high classification accuracies of 99.6% and 97.6% have been achieved, respectively. The performance of dynamic memristor-based RC system is almost equivalent to the software-based one. Besides, our RC system does not require additional read operations, which can make full use of the device nonlinearity and further improve the system efficiency. Our work could pave the road towards high-efficiency memristor-based RC systems to handle more complex spatiotemporal tasks in the future.
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.
Combining External Medical Knowledge for improving Obstetric Intelligent Diagnosis
Authors: Zhang Kunli , Cai Linkun , Song Yu , Liu Tao , Zhao Yueshu
Published: July 2020

Background: Data-driven medical health information processing has become a new development trend in obstetrics. Electronic medical records (EMRs) are the basis of evidence-based medicine and important information source for intelligent diagnosis. To obtain diagnostic results, doctors combine clinical experience and medical knowledge in their diagnosis process. External medical knowledge provides strong support for diagnosis. Therefore, how to make full use of EMRs and medical knowledge in intelligent diagnosis is worth studying.Methods: As an EMR usually contains multiple types of diagnostic results, the intelligent diagnosis can be treated as a multi-label classification task. We propose a novel neural network model called Knowledge-aware Hierarchical Diagnosis Model (KHDM) in which Chinese obstetric EMRs and external medical knowledge can be synchronously and effectively used for intelligent diagnostics. In the KHDM, EMRs and external knowledge documents are integrated by the attention mechanism contained in the hierarchical deep learning framework. In this way, we enrich the language model with curated knowledge documents, combining the advantages of both to make a knowledge-aware diagnosis.Results: We evaluate our model on a real-world Chinese obstetric EMR dataset show that KHDM achieves an accuracy of 0.8929, which exceeds that of the most advanced classification benchmark methods.Conclusion: In this paper, an improved model combining medical knowledge and an attention mechanism is proposed, which is based on the problem of the diversity of diagnostic results in Chinese EMRs. KHDM can effectively integrate domain knowledge to greatly improve the accuracy of diagnosis, and we also verify the model's interpretability advantage.
Efficient Protection of Probiotics for Delivery to the gastric tract by Cellulose Sulphate Encapsulation
Authors: Gunzburg Walter Henry , Aung Myo Myint , Toa Pauline , Ng Shirelle , Read Eliot , Tan Wee Jin , Brandtner Eva Maria , Dangerfield John , Salmons Brian
Published: July 2020

Gut microbiota in humans and animals play an important role in health, aiding in digestion, regulation of the immune system and protection against pathogens. Changes or imbalances in the gut microbiota (dysbiosis) have been linked to a variety of local and systemic diseases, and there is growing evidence that restoring the balance of the microbiota can restore health. This can be achieved by oral delivery of members of the microbiome (including probiotics) or by fecal microbiome transplantation. In order to provide their health promoting effects, microbiota must survive (i) transport and storage (i.e. shelf life) and (ii) transit through the highly acid conditions in the stomach and bile salts in the small intestine. We have developed a cell encapsulation technology based on the natural polymer, cellulose sulphate (CS) that protects members of the microbiota from stomach acid and bile.
Barriers in Implementing the Dying Patient Law: The Israeli Experience - A Qualitative Study
Authors: Zigdon Avi , Nissanholtz-Gannot Rachel
Published: July 2020

Background Coping with end-of-life issues is a major challenge for governments and health systems. Despite progress in legislation, many barriers exist to its full implementation. This study is aimed at identifying these end-of-life barriers in relation to Israel.Methods Qualitative in-depth interviews using professionals and decision makers in the health-care and related systems (n=37) were carried out, along with two focus groups based on brainstorming techniques consisting of nurses (n=10) and social workers (n=10). Data was managed and analyzed using Naralyzer software.Results Qualitative analysis showed identification of six primary barriers: 1) law, procedures, and forms; 2) clinical aspects; 3) human aspects; 4) knowledge and skills of medical teams; 5) communication; and 6) resource allocation. These were further divided into 44 sub area barriers.Conclusions This study highlights the role of the family doctor in end-of-life by training physicians in decision-making workshops and increasing their knowledge in the field of palliative medicine. Effectively channeling resources, knowledge, and support for medical teams, by accounting for the structure and response of the units for home treatment will improve patient's access to information on and support for end-of-life laws, as well as reduce legislative barriers in other countries that face the same issues.
Health-Care Organization For The Management and Surveillance of SARS-CoV-2 Infection in Children During Pandemic in Italy
Authors: Nunziata Francesco , Bruzzese Eugenia , Poeta Marco , Pierri Luca , Catzola Andrea , Ciccarelli Gian Paolo , Vassallo Edoardo , Montella Emma , Vecchio Andrea Lo , Guarino Alfredo
Published: July 2020

Background: In comparison with adults, severe acute respiratory syndrome (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods: We designed a hub-and-spoke system involving a Hub Centre to provide relevant healthcare information, based on the use of telemedicine and stringent admission criteria. Result: Between March and April 2020, the Hub Centre managed a total of 119 children (62 males, 52%; median age, 5.5 years; interquartile range [IQR], 2; 10) with suspected or confirmed COVID-19. Of the 119 children, 90 were managed in cooperation with family paediatricians and 29 with hospital-based physicians. In total, 8 (6.7%) children were hospitalised, with a median length of hospital stay of 10 days (IQR, 8.5 days; range, 4–22 days). Conclusion: case-by-case management allows a global evaluation in which the clinical condition is one determinant in medical decision-making along with the use of isolation to prevent the spread of COVID-19 among family members and cohabitants, and biocontainment measures. Large centres could coordinate paediatric COVID-19 cases through telemedicine, taking advantage of the generally milder presentation in children but also considering their dependence on adults and risk of infection spreading.
Differences in Objectively Measured Daily Physical Activity Patterns Related to Depressive Symptoms in Community Dwelling Women - mPED Trial
Authors: Figueroa Caroline , Vittinghof Eric , Aguilera Adrian , Fukuoka Yoshimi
Published: July 2020

Background:Physical activity(PA) has been identified as an effective depression treatment.However, knowledge on how variation in day-to-day PA relates to depression is lacking. Purpose:The purposes of this cross-sectional analysis were to 1) compare overall objectively measured baseline daily steps and duration of moderate to vigorous PA (MVPA) and 2) examine differences in steps and MVPA on days of the week between women with high and low depressive symptoms, enrolled in the mobile phone based physical activity education (mPED) trial.Methods:The Center for Epidemiological Studies Depression Scale was used to categorize low and high depressive symptom groups.We used linear mixed-effects models to examine the associations between steps and MVPA and depression-status both overall and by day of the week,adjusting for selected demographic variables and their interactions with day of the week.Results:275 women were included in the final analysis, of which 217 had low and 58 had high depressive symptoms. We found that day of the week modified the associations of depression with both daily steps and MVPA. Women with high depressive symptoms were characterized by reduced activity at the end of the week (Friday: 832 fewer steps, 95% CI:116 to 1548, p=0.023; 8.9 lower MVPA, 95% CI:2.2 to 15.5, p=0.009), whereas women with low depression showed an increase in physical activity.Conclusions:Day of the week might be an important target for personalization of physical activity interventions. Future work should evaluate potential causes of alterations in daily activity patterns in depression.Trial RegistrationClinicalTrials.gov#:NCTO1280812registered January 21, 2011
Intestinal Protozoan Infections Shape Fecal Bacterial Microbiota in Children from Guinea-Bissau.
Authors: Huth Sebastian von , Thingholm Louise B. , Kofoed Poul-Erik , Bang Corinna , Rühlemann Malte C. , Franke Andre , Holmskov Uffe
Published: July 2020

Background: Intestinal parasitic infections, caused by helminths and protozoa, are globally distributed and major causes of worldwide morbidity. The gut microbiota may modulate parasite virulence and host response upon infection. The complex interplay between parasites and the gut microbiota is poorly understood, partly due to sampling difficulties in remote areas with high parasite prevalence and burden. Results: In a large study of children in Bissau, Guinea-Bissau, we found high prevalence of intestinal parasites, including hookworms, Entamoeba spp. and Giardia lamblia. By high-quality sequencing of the 16S rRNA gene of fecal samples stored on filter paper from a total of 1,204 children, we demonstrate that the bacterial microbiota is more or less unaltered by helminth infections, whereas it is shaped by the presence of both pathogenic and non-pathogenic protozoa, including Entamoeba spp. and Giardia lamblia. Within-sample (alpha) diversity remains largely unaffected, whereas overall community composition (beta diversity) is significantly affected by infection with both nonpathogenic Entamoeba coli (R2=0.0131, P= 0.0001) and Endolimax nana (R2=0.00902, P= 0.0001), and by pathogenic Entamoeba histolytica (R2=0.0164, P= 0.0001) and Giardia lamblia (R2=0.00676, P= 0.0001). Heavy infection load with multiple parasite species induces more pronounced shifts in microbiota community than mild ones. A total of 31 bacterial genera across all four major gut bacterial phyla associates with protozoan infection, including increased abundance of Prevotella, Campylobacter and two Clostridium clades (IV and WIVb), and decreased abundance of Collinsella (associated with irritable bowel syndrome), Lactobacillus, Ruminococcus, Veillonella and one Clostridium clade (XVIII). Further, we demonstrate that filter papers are usable for storage of samples at room temperature in large-scale studies where immediate freezing is not possible with minor alterations of microbiota composition. Conclusion: In the present largest-to-date study, we demonstrate that the fecal bacterial microbiota is shaped by intestinal parasitic infection, with most pronounced associations for protozoan species. Our results provide insights into the interplay between the microbiota and intestinal parasites, which are useful to understand infection outcome and design further studies aimed at optimizing treatment strategies.
A Research of the Predictive Values of E2F Factors in Colorectal Cancer
Authors: Zhang Jiang , Yang Xiudeng , Zhang Zhixue , Xiang Lili
Published: July 2020

Background: E2F family of transcription factors are related to cell cycle and apoptosis with activate or repress function on human cancer. Their critical role in colorectal cancer (CRC), including colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), were widely investigated with contradictory and ambiguous results. Methods: In this study, we explored the expressions of these eight E2F genes and their predictive values on the overall survive (OS) and disease-free survival (DFS) in CRC patients by means of bioinformatic databases, such as ONCOMINE, GEPIA, DAVIA and cBioPortal.Results: We found that the transcriptional levels of E2F1/2/3/5/7/8 were significantly higher in CRC patients than that in normal samples, while the E2F4/6 showed no significantly difference from GEPIA database. The transcriptional levels of all eight E2F factors showed no correlation with four tumor stages, except for the E2F3 is significantly varied in COAD patients. Survival analysis based on GEPIA database indicated that lower E2F3 and E2F4 mRNA expressions were significantly associated with the OS of the COAD patients.Conclusions: This study manifested that the E2F1/2/3/5/7/8 are potential biomarkers of CRC patients, and E2F3 could be used as the predictive factor of tumor stage in COAD patients. E2F3 and E2F4 might be the prognostic markers for COAD patients.
Initial Diastolic Dysfunction is a Powerful Predictor of 5-year Mortality in Peripheral Arterial Disease Patients undergoing Percutaneous Transluminal Angioplasty
Authors: Kim Kyung-Hee , Rha Seung Woon , Choi Byoung Geol , Byun Jae-Kyung , Kim Woohyeun , Choi Cheol Ung , Seo Hong-Seog
Published: July 2020

Background

Peripheral arterial disease (PAD) and heart failure share common risks and are associated with increased morbidity and mortality. However, it is unknown whether cardiac function can be an independent predictor of long-term mortality in patients with PAD.
Methods

In total, 902 patients who underwent percutaneous transluminal angioplasty for PAD were enrolled. The patients were categorized into three groups according to the left ventricular ejection fraction (LVEF): reduced EF (< 40%, n = 62); mid-range EF (40–49%, n = 76); and preserved EF (≥ 50%, n = 764). Echocardiographic (EF, ratio of mitral inflow velocity to annular velocity E/eʹ ≥ 15, and others) and clinical parameters were tested using stepwise logistic regression analysis to determine independent predictors of 5-year mortality.
Results

A higher proportion of patients with reduced EF had ischemic heart disease than those with preserved EF (77.4% vs. 56.8%, p < 0.001). Up to 5 years, patients with reduced EF and mid-range EF showed a higher incidence of total death than those with normal EF. However, there was no difference in the incidence of myocardial infarction, stroke, and revascularization among the three groups. After multivariable adjustment, the ratio of E/eʹ ≥ 15 was the only strong predictor of total mortality (hazard ratio, 6.14; 95% confidence interval, 3.7–10.1;p < 0.01).
Conclusion

Patients with PAD and reduced EF undergoing PTA had a higher incidence of total death during the 5-year follow-up. Initial tissue Doppler E/eʹ ≥ 15, a non-invasive estimate of left atrial filling pressure, was the only independent predictor of long-term mortality.
MAGAN: Mask Attention Generative Adversarial Network for Liver Tumor CT Image Synthesis
Authors: Liu Yang , Meng Lu , Zhong Jianping
Published: July 2020

Background: For deep learning, the size of the dataset greatly affects the final training effect. However, in the field of computer-aided diagnosis, medical image datasets are often limited and even scarce.Methods: We aim to synthesize medical images and enlarge the size of the medical image dataset. In the present study, we synthesized the liver CT images with a tumor based on the mask attention generative adversarial network (MAGAN). We masked the pixels of the liver tumor in the image as the attention map. And both the original image and attention map were loaded into the generator network to obtain the synthesized images. Then the original images, the attention map, and the synthesized images were all loaded into the discriminator network to determine if the synthesized images were real or fake. Finally, we can use the generator network to synthesize liver CT images with a tumor.Results: The experiments showed that our method outperformed the other state-of-the-art methods, and can achieve a mean peak signal-to-noise ratio (PSNR) as 64.72dB.Conclusions: All these results indicated that our method can synthesize liver CT images with tumor, and build large medical image dataset, which may facilitate the progress of medical image analysis and computer-aided diagnosis.
Differential Diagnosis of Multiple Primary and Intra-lung Metastasis of Lung Cancer by Multiple Gene Detection
Authors: Liuyang Xu , Jin Chen , Yupeng Zeng , Pan Ji , Shuaishuai Zhuo , Xiao Li , Zhang Zhihong
Published: July 2020

Objective

To study the differential diagnosis of MPLC and IM by detecting the different lesions of the same patient. To explore the differences in prognosis between MPLC and IM, and to explore the factors affecting the prognosis of multi-focal lung cancer.
Methods

Fifty patients with multi-focal lung cancer were screened, and the relevant clinical information was noted; the patients were diagnosed by ACCP standard. Mutations of the lesions were detected by ARMS-PCR, and the detected genes included EGFR, ALK, ROS1, MET, KRAS, RET, HER-2, BRAF, NRAS and PIK3CA. The results of genetic testing were compared with those of ACCP standard diagnosis.
Results

We analyzed a total of 101 tumors from 50 patients. Classification based on gene testing contradicted the clinicopathologic diagnosis in 10 (20%) of the comparisons, identifying independent primaries in 6 cases diagnosed as metastasis and metastases in 4 cases diagnosed as independent primaries. Another 7(14%) tumor pairings were assigned an “equivocal” result based on gene testing. The results of gene testing of the remaining 33(66%) tumor pairings were consistent with the clinicopathologic diagnosis. The mutant heat map indicated that IM patients have a higher rate of mutation consistency than MPLC patients.
Conclusion

Multi-gene detection of multi-focal lung cancer has a certain auxiliary effect on the differential diagnosis of MPLC and IM, which can complement the clinical standards, but also has some limitations.
Determinants of breakfast consumption among adolescent girls: Application of the Health Promotion Model using Structural Equation Modeling
Authors: Imani-Nasab Mohammad-Hassan , ardalan Arash , Cheraghi Nasim , Piri Zahra Asadi , Ebrahimzadeh Farzad , bastami fatemeh
Published: July 2020

Background: Breakfast is an important sign of healthy nutrition for normal growth and development. Breakfast is considered as the most important meal of the day which is ignored by many adolescents. The purpose of this study was to predict breakfast behavior based on Pender Health Promotion Model(HPM) constructs using structural equation model(SEM).Methods: A descriptive-analytical study was performed on 450 high school female students in west of Iran in 2019. Sampling was done through a multi-stage method.The questionnaire contained two parts. The first part of which was about demographic and behavior of breakfast consumption; and the second part was a questionnaire based on Health Promotion Model. Data were analyzed by means of SPSS and AMOS both version of 20 software and using Chi-square test as well as regression correlation model.Results: The constructs of behavioral perceptions, commitment to action plan and behavioral effects explained 47% of the variance of breakfast intake behavior. In the structural equation model, the value of the chi-square statistic test came up to 429.2429 which was divided by resulted degree of freedom (1785), 2.405 and 5%, respectively (P<0.001). Fit indexes were either acceptable or good.Conclusion: The HPM is a suitable theory for predicting the commitment to action plan and behavior of breakfast consumption in Iran.The structural equation model was evaluated as a comprehensive model through both direct and indirect approaches to predict the relationship between breakfast consumption and the predictive factors. This model showed a multi-factorial nature of the predictive factors.
Changes in Lipid Composition associated with Electronic Cigarette Use
Authors: Middlekauff Holly , Williams Kevin , Su Baolong , Haptonstall Kacey , Araujo Jesus , Wu Xiaohui , Kim Jason , Sallam Tamer
Published: July 2020

Background- Electronic cigarette use is on the rise despite a number of reports linking electronic cigarettes with adverse health outcomes. Recent studies have suggested that alterations in lipid signaling may be one mechanism by which electronic cigarettes contribute to lung pulmonary function. Vitamin E acetate, for example, is synthetic form of Vitamin E transported via lipids, found to be associated with electronic cigarette associated lung injury. Lipids are absolutely critical for normal lung physiology and perturbations in a number of lipid pathways have been associated with respiratory illness. Is it conceivable that electronic cigarette use even in seemingly healthy cohorts are associated with alterations in lipid pathways? Methods- To investigate quantitative alterations in the plasma lipidome associated with electronic cigarette use in healthy we obtained plasma samples from 119 male and female participants with who were either: 1) chronic tobacco cigarette (TC) smokers (>12 months of self-reported TC use), 2) chronic Electronic cigarette (EC) users (>12 months of self-reported EC use), or 3) non-users. We measured quantitative lipid species across different lipid sub-classes from plasma samples using the Sciex Lipidyzer. Results- We found that male and female tobacco and electronic cigarette users had distinct lipidome signatures across a number of lipid species although the vast majority of lipids were unchanged when compared to non-users. Intriguingly, we found that female but not male electronic cigarette users had lower levels of plasmalogens, critical glycerophospholipids secreted by alveoli and required for normal surfactant function. Conclusions- In summary, our study does not reveal striking global changes in the lipidome associated with electronic cigarette use but we observed sex-specific changes in phospholipids known to be critical for lung function.
Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis
Authors: Wan Xiaoyu , Tian Xinbei , Du Jun , Lu Ying , Xiao Yongtao
Published: July 2020

Background: The limited understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies.The aim of this study was to investigate the role of long non-coding RNA H19 (lncRNA H19) in the progression of IPF. Methods: Bleomycin was used to induce pulmonary fibrosis in mice. The mRNAs and proteins expression in lung tissues with bleomycin-induced pulmonary fibrosis was determined by quantitative real-time polymerase chain reaction and western blot. H19 deficiency (H19-/-) were generated by CRISPR/Cas9 and were used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo.Results: The expression of H19 was up-regulated in fibrotic lungs patients with IPF and mouse lungs obtained from bleomycin-treated mice. H19 deficiency reduced bleomycin-induced pulmonary inflammation and inhibited the activation of Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGFβ-Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. H19 depletion attenuated the lung regeneration and reduced expression of activated Egfr. Conclusions: Our data suggest that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.
The efficacy of combination therapies including antiviral drugs, methylprednisolone and daily proning in 20 patients with COVID-19 requiring invasive mechanical ventilation—Case series in a single critical care center in Osaka, Japan
Authors: Shimazu Haruka , Yoshiya Kazuhisa , Tamagaki Keisuke , Okamoto Yasutaka , Nakano Hitoshi , Okubata Hiroto , Miyano Yumiko , Matsunami Shuhei , Maruyama Shuhei , Kanayama Shuji , Iwamura Hiromu , Wada Daiki , Yoshihara Tomoyuki , Saito Fukuki , Nakamori Yasushi , Kuwagata Yasuyuki
Published: July 2020

Background: Since December 2019, the COVID-19 infection has drastically spread across China and the world, including Japan. Few reports so far have clarified the prognosis and treatment of critically ill patients managed with invasive mechanical ventilation. This study aimed to present the clinical courses of 20 critically ill patients with invasive mechanical ventilation, which may be valuable for determining future therapies and intensive care of critically ill patients with COVID-19.Methods: In this observational, single-center, cohort study, we included 20 critically ill patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to our hospital ICU and required invasive mechanical ventilation. The patients’ general characteristics, laboratory data, treatments, and outcomes were assessed between survivors and non-survivors.Results: Among these 20 patients, 14 patients survived and 6 patients died. The lowest lymphocyte count (93 vs 279/μL, p<0.01) and the lowest platelet count (12 vs 152×103/μL, p<0.01) were significantly lower, and the highest KL-6 value (1584 vs 546 U/mL, p=0.02) was significantly higher, in the non-survivor group versus the survivor group during the patients’ ICU stay. In addition to antiviral treatments and daily proning of the patients, methylprednisolone was administered to all patients to control cytokine storm syndrome following the virus infection. Six patients died from complications such as fungal infection, but no patients died of respiratory failure. As a result, none of the patients required ECMO.Conclusion: This report described the prognosis of COVID-19 patients required invasive mechanical ventilation in a single Japanese critical care center. Multidisciplinary treatments using a single protocol, including antiviral therapies, anti-inflammatory therapies, and respiratory physiotherapies, were effective for critically ill COVID-19 patients who required invasive mechanical ventilation.
GLUT5 (SLC2A5) enables fructose-mediated proliferation independent of ketohexokinase
Authors: Liang Roger Jie , Taylor Samuel , Nahiyaan Navid , Song Junho , Murphy Charles J , Dantas Ezequiel , Cheng Shuyuan , Hsu Ting-Wei , Ramsamooj Shakti , Grover Rahul , Hwang Seo-Kyoung , Ngo Bryan , Cantley Lewis C , Rhee Kyu Y , Goncalves Marcus DaSilva
Published: July 2020

Background: Fructose is an abundant source of carbon and energy for cells to use for metabolism, but only certain cell types use fructose to proliferate. Tumor cells that can metabolize fructose have a fitness advantage over their neighboring cells, but the proteins that mediate fructose metabolism in this context are unknown. Here, we investigated the determinants of fructose-mediated cell proliferation.Methods: We quantified the ability of 14 cell lines to proliferate in fructose-containing media (i.e. the fructolytic ability) using live cell imaging and crystal violet assays. The expression and abundance of proteins related to fructose metabolism were assessed using RT-qPCR and western blot, respectively, for each cell line. Using a positive selection approach, we “trained” the non-fructolytic PC3 cell line to utilize fructose for proliferation. RNA-seq was then performed to identify key transcriptional changes associated with fructolytic ability. We overexpressed and deleted proteins associated with fructose metabolism, and performed metabolic profiling using the Seahorse Bioanalyzer and LC/MS-based metabolomics.Results: We found that neither the tissue of origin nor expression level of any single gene related to fructose catabolism determine a cell’s fructolytic ability. Cells cultured chronically in fructose can develop fructolytic ability if SLC2A5, encoding the fructose transporter, GLUT5, gets upregulated. Overexpression of GLUT5 in non-fructolytic cells enables growth in fructose-containing media across cells of different origins. GLUT5 permitted fructose to flux through glycolysis using hexokinase (HK) and not ketohexokinase (KHK).Conclusions: We show that GLUT5 is a robust and generalizable driver of fructose-dependent cell proliferation. This indicates that fructose uptake is a limiting factor for fructose-mediated cell proliferation. We further demonstrate that cancer cell proliferation with fructose is independent of KHK.
Significance of Druggable Targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on Curatively Resected Esophageal Squamous Cell Carcinoma
Authors: Lee Hong Kyu , Kwon Mi Jung , Ra Yong Joon , Lee Hee Sung , Kim Hyoung Soo , Nam Eun Sook , Cho Seong Jin , Park Hye-Rim , Min Soo Kee , Seo Jinwon , Choe Ji-Young , Min Kyueng-Whan , Kang So Young
Published: July 2020

Background: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. Methods: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. Results: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9%, 12.5%, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P>0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P<0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P=0.023, P=0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P=0.006, P=0.002). Conclusions: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.