bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness index and weighted correlation network analysis
Authors: Guo Rui , Chu Aining , Gong Yuehua
Published: October 2020

Background: Cancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer. Methods: RNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). WGCNA was used to clustered differentially expressed genes with similar expression profiles to form modules. Furtherly, based on the mRNA expression-based stemness index (mRNAsi), significant modules and key genes were identified. Next, the expression of key genes was further verified by the Oncomine database. Results: MRNAsi scores of GC were significantly higher than that of normal tissue. Additionally, mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the blue module of IGC and the brown module of DGC were both the most significantly associated with mRNAsi. We screened out 16 and 43 key genes for IGC and DGC and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in the Oncomine database and the fate of cells. Conclusions: In this study, 16 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were both associated with cell cycle, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC.
Does the gap between health workers’ expectations and the realities of implementing a Performance-Based Financing project in Mali create frustration?
Authors: ZITTI Tony , FILLOL Amandine , LOHMANN Julia , COULIBALY Abdourahmane , RIDDE Valéry
Published: October 2020

Background: Low- and middle-income countries (LMICs) have seen a shift in the health financing architecture in recent years, particularly in Africa. Performance-Based Financing (PBF) is one of these recent initiatives. Motivating health workers is one of the mechanisms through which PBF is assumed to improve the quality of care. Our study therefore offers a unique opportunity to identifiesy and understand how health workers’ expectations related to their experiences of the first cycle of payment of PBF subsidies, and how it this affected their motivation and sentiments towards the intervention.Our study offers the opportunity to identify and understand, from the first days of implementation of PBF in Mali, how the expectations of health workers related to implementation realities of the first cycle of PBF subsidy payment, and how correspondences and discrepancies affected health worker motivation.Methods: We adopted a qualitative approach using multiple explanatory and contrasting case studies with nested levels of analysis. For our study, we chose three district hospitalsDHs (DH 1, 2 and 3) in three health districts (district 1, 2 and 3) among the ten in the Koulikoro region. Our cases correspond to the three DHs. We followed the principle of data source triangulation. The different data sources used are: the 53 semi-directive interviews conducted with health workers, following the principle of saturation;, field notes, a;and documents relating to the distribution grids of subsidies for each DH.We conducted 53 semi-structured interviews with health workers in three of ten district hospitals in the Koulikoro region Data was analyzed in a mixed deductive and inductive manner.Results: The results show that the PBF subsidies initially led to health workers feeling more motivated to perform their tasks overall. Beyond financial motivation, this was primarily due to PBF allowing them to work better. However, respondents perceived a discrepancy between the efforts made and the subsidies received. The fact that their expectations were not met led to a sense of frustration and disappointment. This, in turn, decreased motivation. Similarly, the way in which the subsidies were distributed and the lack of transparency in the distribution process led to feelings of unfairness among the vast majority of respondents. The results show that frustrations can build up in the early days of the intervention.Conclusion: The PBF implementation in Mali left health workers with initial frustrations. The short overall implementation period did not allow actors to adjust their initial expectations and motivational responses, neither positive and negative. This result underlines how short-term interventions might not just only lack impact, but also instill negative sentiments likely to carry on into the future.
A cross-sectional survey assessing the preparedness of the long-term care sector to respond to the COVID-19 pandemic in Ontario, Canada
Authors: Siu Henry Yu-Hin , Kristof Lorand , Elston Dawn , Hafid Abe , Mather Fred
Published: October 2020

Background: The COVID-19 pandemic is a significant public health emergency that impacts all sectors of healthcare. The negative health outcomes for the COVID-19 infection have been most severe in the frail elderly dwelling in Canadian long-term care (LTC) homes.Methods: An online cross-sectional survey of Ontario LTC Clinicians working in LTC homes in Ontario Canada was conducted to provide the LTC clinician perspective on the preparedness and engagement of the LTC sector during the COVID-19 pandemic. The survey questionnaire was developed in collaboration with the Ontario Long-Term Care Clinicians organization (OLTCC) and was distributed between March 30, 2020 to May 25, 2020. All registered members of the OLTCC and Nurse-led LTC Outreach Teams were invited to participate. The primary outcomes were: 1) the descriptive report of the screening measures implemented, communication and information received, and the preparation of the respondent’s LTC home to a potential COVID-19 outbreak; and 2) the level of agreement, as reported using a five-point Likert scale), to COVID-19 preparedness statements for the respondent’s LTC home was also assessed.Results: The overall response rate was 54% (160/294). LTC homes implemented a wide range of important interventions (e.g. instituting established respiratory isolation protocols, active screening of new LTC admissions, increasing education on infection control processes, encouraging sick staff to take time off, etc). Ample communications pertinent to the pandemic were received from provincial LTC organizations, the government and public health officials. However, the feasibility of implementing public health recommendations, as well as the engagement of the LTC sector in pandemic planning were identified as areas of concern. Medical director status was associated with an increased knowledge of local implementation of interventions to mitigate COVID-19, as well as endorsing increased access to reliable COVID-19 information and resources to manage a potential COVID-19 outbreak in their LTC home.Conclusions: This study highlights the communication to and implementation of recommendations in the Ontario LTC sector, despite some concerns regarding feasibility. Importantly, LTC clinician respondents clearly indicated that better engagement with LTC leaders is needed to plan a coordinated pandemic response.
The Perceived determinants and recommendations by mothers and healthcare professionals on the Loss-To-Follow-Up in Option B+ program and child mortality in the Amhara Region, Ethiopia.
Authors: Kassaw Mesfin Wudu , Matula Samuel T. , Mamo Ayele , Kassie Ayelign , Abate Biruk
Published: October 2020

Background: The third United Nations Sustainable Development Goal includes a commitment to end AIDS-related death by 2030. In line with the Goal, Option B+ programs hold a great promise for eliminating vertical transmission of HIV. Option B+ was introduced in 2013 in Ethiopia. The Global Plan identified Ethiopia as one of 22 high priority countries requiring improvement in the prevention of mother to child HIV transmission services. Despite HIV treatment being free in Ethiopia, only 59% of children are on treatment. The discrepancies in high uptake of Option B+ and low numbers of children in Ethiopia can be attributed to Loss-to-follow-up, which is estimated from 16% to 80%. While LFTU is expected in the region, no-to-minimal evidence exists on the magnitude and its determinants, which hampers the development of interventions and strategies to reduce LFTU.Purpose: To explore the perception of mothers and healthcare providers on determinants of and recommendations to reduce LTFU and HIV exposed infants’ mortality. Methods: An explorative, descriptive qualitative study conducted in five zones in Amhara region. The sample consisted of mothers enrolled in the option B+ programs at the five referral hospitals PMTCT departments, nurses and midwives working in those departments, and HIV officers in the zonal departments. Data were collected in 2019 using in-depth interviews. Data were analyzed using content analysis and deduced to themes. Results: Overall, nine themes were identified from the interviews. Five themes represented the determinants of LTFU and mortality while four themes addressed the recommendations to reduce LFTU among mothers and their children and infant mortality. The determinants themes centered on apathy, stigma and discrimination, poor access to services, healthcare providers behavior and attitudes, and social determinants of health. While recommendations themes suggested that improving access, capitalizing on psychosocial support, education and awareness, and empowerment. Conclusions: Social and structural issues are major contributors to low retention of mothers and death of children due to HIV. A multi-stakeholder approach, including structural changes, are required to support women and their children to ensure that individuals, communities and country enjoy the full benefits of option B+ and lead to an HIV free generation.
Use of Routinely Collected Health Data in Randomised Clinical Trials: Comparison of Trial-Specific Death Data in The BOSS Trial with NHS Digital Data
Authors: Love Sharon , Kilanowski Anna , Yorke-Edwards Victoria , Old Oliver , Barr Hugh , Stokes Clive , Kendall Catherine , Sydes Matthew R
Published: October 2020

Background: A promising approach to reduce the increasing costs of clinical trials is the use of routinely-collected health data as participant data. However, the quality of this data could limit it’s usability as trial participant data. Methods: The BOSS trial is an RCT comparing regular endoscopies versus endoscopies at need in patients with Barrett’s oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely-collected health data source NHS Digital. We investigated completeness, agreement, timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data source alone were investigated using Kaplan-Meier graphs. To assess utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared.Results: NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. Conclusion: NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT.Trial registration: ISRCTN54190466 (BOSS)
Characteristics of the completed chloroplast genome sequence of Xanthium spinosum: Comparative analyses, identification of mutational hotspots and phylogenetic implications
Authors: Raman Gurusamy , Park KyuTae , Kim Joo Hwan , Park SeonJoo
Published: October 2020

Background: The invasive species Xanthium spinosum has been used as a traditional Chinese medicine for many years. Unfortunately, no extensive molecular studies of this plant have been conducted.Results: Here, the complete chloroplast (cp) genome sequence of X. spinosum was assembled and analyzed. The cp genome of X. spinosum was 152,422 base pairs (bp) in length, with a quadripartite circular structure. The cp genome contained 115 unique genes, including 80 PCGs, 31 tRNA genes, and 4 rRNA genes. Comparative analyses revealed that X. spinosum contains a large number of repeats (999 repeats) and 701 SSRs in its cp genome. Fourteen divergences (Pi > 0.03) were found in the intergenic spacer regions. Phylogenetic analyses revealed that Parthenium is a sister clade to both Xanthium and Ambrosia and an early-diverging lineage of subtribe Ambrosiinae, although this finding was supported with a very weak bootstrap value.Conclusion: The identified hotspot regions could be used as molecular markers for resolving phylogenetic relationships and species identification in the genus Xanthium.
Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes 
Authors: Allison Hollie , Holdsworth Gill , McNamara Laoise M
Published: October 2020

Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exhibit exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression.Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. ConclusionsThis study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.
Distinct non-ischemic myocardial late gadolinium enhancement lesions in patients with type 2 diabetes
Authors: Bojer Annemie Stege , Sørensen Martin Heyn , Vejlstrup Niels , Goetze Jens P. , Gæde Peter , Madsen Per Lav
Published: October 2020

Background: Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM. Methods: 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T1-mapping and LGE. Results: 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150±34 vs. 133±33 g, P=0.02), average E/e’(9.9 IQR8.7-12.6 vs. 8.8 IQR7.4-10.7, P=0.04), left atrial maximal volume (102 IQR84.6-115.2 vs. 91 IQR75.2-100.0 mL, P=0.049), NT-proBNP (8.9 IQR5.9-19.7 vs. 5.9 IQR5.9-10.1 µmol/L, P=0.02) and high-sensitive troponin (15.6 IQR13.0-26.1 vs. 13.0 IQR13.0-14.6 ng/L, P=0.007) and a higher prevalence of retinopathy (48 vs. 25 %, p=0.009) and autonomic neuropathy (52 vs. 30.5%, P=0.005).Conclusion A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Clinical trial registration: www.clinicaltrials.gov. Unique identifier: NCT02684331.
The Effects of Nano-Curcumin as A Nutritional Strategy on Clinical and Inflammatory Factors in Children with Cystic Fibrosis: A Protocol Study and Review Article
Authors: Kianifar Hamid Reza , Talebi Saeedeh , Safarian Mahammad , Sayedi Seyed Javad , Jaafari Mahmod Reza , Shaye Zahra Abbasi , Ranjbar Golnaz
Published: October 2020

Background: Cystic fibrosis(CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of Nano-curcumin on clinical and inflammatory markers in children with CF.Methods: This prospective, double blind control trial will be conducted at Akbar Children's Hospital in Mashhad, Iran. children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 milligrams considering the body surface of the patients will be administrated for three months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after three mounts.Discussion: Due to the multifarious effects of curcumin on CF disease, it can be used as a nutritional strategy in the treatment of cystic fibrosis.Trial registration: Iranian Registry of Clinical Trials, IRCT20200705048018N1, Registered on 2020-07-10, https://en.irct.ir/search/result?query=IRCT20200705048018N1
Ocular Syphilis with Optic Disc Neovascularization Treated with Bevacizumab Evaluated by OCT Angiography and Electroretinography
Authors: Miura Gen , Baba Takayuki , Takeishi Marie , Tatsumi Tomoaki , Yokouchi Hirotaka , Yamamoto Shuichi
Published: October 2020

We present our findings in an atypical case of ocular syphilis with optic disc neovascularization that was treated with intravitreal bevacizumab and followed by multimodal imaging and electroretinography. A 29-year-old man presented with a chief complaint of night blindness of one-year duration. Our initial examination showed that an optic disc neovascularization was present, and the optical coherence tomographic (OCT) images showed a reduction in the length of the ellipsoid zone of both eyes. Fluorescein angiography showed leakage from the optic disc neovascular tissue, and the presence of nonperfused areas in the peripheral retina. Blood test was strongly positive for syphilis. He was administered oral amoxicillin and prednisolone. He was also treated with an intravitreal injection of bevacizumab which led to a rapid suppression of the neovascularization. However, panretinal photocoagulation had to be performed because OCT angiography and fluorescein angiography detected residual neovascularization. Although these treatments suppressed the activity of the ocular syphilis, electrophysiological improvements were not seen even one year after the initial treatment. OCT angiography and electroretinogram are useful techniques for monitoring the effectiveness of the treatments.
Comparison of qSOFA score, SOFA score, and SIRS criteria for the prediction of infection and mortality among surgical intermediate and intensive care patients
Authors: Koch Christian , Edinger Fabian , Fischer Tobias , Brenck Florian , Hecker Andreas , Katzer Christian , Markmann Melanie , Sander Michael , Schneck Emmanuel
Published: October 2020

Background It is crucial to rapidly identify sepsis so that adequate treatment may be initiated. Accordingly, the Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) score are used to evaluate intensive care unit (ICU) and non-ICU patients, respectively. As demand for ICU beds rises, the intermediate care unit (IMCU) carries greater importance as a bridge between the ICU and the regular ward. This study aimed to examine the ability of SOFA and qSOFA scores to predict suspected infection and mortality in IMCU patients.Methods Retrospective data analysis included 13,780 surgical patients treated at the IMCU, ICU, or both between 01/01/2012 and 09/30/2018. Patients were screened for suspected infection (i.e., the commencement of broad-spectrum antibiotics) and then evaluated for the SOFA score, qSOFA score, and the 1992 defined systemic inflammatory response syndrome (SIRS) criteria.Results Suspected infection was detected in 1,306 (18.3%) of IMCU, 1,365 (35.5%) of ICU, and 1,734 (62.0%) of IMCU/ICU encounters. Overall, 458 (3.3%) patients died (IMCU: 45 [0.6%]; ICU: 250 [6.5%]; IMCU/ICU: 163 [5.8%]). All investigated scores failed to predict suspected infection independently of the analyzed subgroup. Regarding mortality prediction, the qSOFA score performed sufficiently within the IMCU cohort (AUCROC SIRS: 0.72 [0.71-0.72]; SOFA: 0.52 [0.51-0.53]; qSOFA: 0.82 [0.79-0.84]), while the SOFA score was predictive in patients of the IMCU/ICU cohort (AUCROC SIRS 0.54 [0.53-0.54]; SOFA 0.73 [0.70-0.77]; qSOFA 0.59 [0.58-0.59]).Conclusions None of the assessed scores was sufficiently able to predict suspected infection in surgical ICU or IMCU patients. While the qSOFA score is appropriate for mortality prediction in IMCU patients, SOFA score prediction quality is increased in critically ill patients.
Potential Mechanism of Guizhi Decoction in Hypertension Treatment Based on Network Pharmacology and Dahl Salt-Sensitive Rat Model
Authors: Chen Ji-ye , Zhang Yong-jian , Wang Yong-cheng , Zhou Guo-feng , Yang Jin-long , Ma Du-fang , Li Zhao-yu , Li Xiao
Published: October 2020

Introduction: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore its therapeutic effects and potential mechanisms in the treatment of hypertension using network pharmacology and experimental validation.Methods: The active ingredients and corresponding targets were collected from Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from multiple databases, and multiple networks were constructed to identify key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD on hypertension. Results: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension- related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets to perform experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2(MMP-2), and MMP9. Pathway enrichment results indicated that 56 overlapping targets mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD showed tight binding ability with the key targets. Experimental results demonstrated that compared with the group fed a high-salt diet in this study, the GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL6, CCL2, IL1β, MMP2 and MMP9 in rats.Conclusions: The potential mechanism of the therapeutic effect of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.
Evaluation of non-small cell lung cancer treatment strategies in a region of China with low-risk for COVID-19
Authors: Yu Minhao , Cheng Yalin
Published: October 2020

Purpose This study analyzed the morbidity and mortality associated with non-small cell lung cancer (NSCLC) and evaluated treatment strategies for it in a low-risk area of COVID-19 in China. Materials and methods: We selected patients admitted to Sichuan Science City Hospital from September 2019 to February 2020 and divided them into experimental and control groups. The treatment strategy was evaluated by patients’ prognosis. Results: 9,010 patients were hospitalized. The total morbidity was 0.699%, of which 0.504% was observed in the control group and 0.991% in the experimental group (P=0.024). The total mortality was 0.999/103, of which 0.630/103 was observed in the control group and 1.413/103 in the experimental group (P=0.322). Therapy discontinuation and cancer progression in the experimental group were significantly higher than the control group (P＜0.001, P=0.007). The treatment methods and prognosis were not significantly different for early-stage patients between the two groups. Late-stage patients in the experimental group experienced significantly lower percentages of non-surgical treatments (P＜0.001), higher percentages of discontinued therapies (P＜0.001), lower percentages for prognosis of wellness (P＜0.001), and higher percentages of cancer progression (P＜0.001) than the control group. Conclusion: NSCLC exhibited significantly higher morbidities during the COVID-19 pandemic. The mortality in the experimental group was slightly higher than the control group, while the difference in cancer progression was significant. It is feasible to perform surgery for early-stage NSCLC patients, and treatment should not be suspended for late-stage patients in regions with low-risk for COVID-19 infection.
Boson-peak-like anomaly caused by transverse phonon softening in strain glass
Authors: Ren Shuai , Zong Hongxiang , Tao Xuefei , Sun Yonghao , Sun Bao An , Xue Dezhen , Ding Xiangdong , Wang Wei Hua
Published: October 2020

Strain glass is considered as a new glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, which exhibits many novel functionalities, yet its nature remains unclear. In this study, we reported a new dynamic relaxation behavior in strain glass that was thought to be only present in structural glasses. An abnormal hump was observed in strain glass around 10 K upon normalizing the specific heat (Cp) by cubed temperature, quite similar to the boson peak in metallic glass. The simulation studies showed that this boson-peak-like anomaly in Cp corresponds to excess low-frequency vibrational modes that stem from the transverse acoustic (TA) phonon softening of the non-transforming regions surrounding the nanodomains. The phonon softening takes place in the TA branches not associated with the martensitic transformation displacements. This work may provide a useful perspective for understanding the nature of glassy states and associated vibrational properties.
Profiling and analysis of chemical compounds using pointwise mutual information
Authors: Svozil Daniel , Čmelo Ivan , Voršilák Milan
Published: October 2020

Pointwise mutual information (PMI) is a measure of association used in information theory. In this paper, PMI is used to characterize several publicly available databases (DrugBank, ChEMBL, PubChem and ZINC) in terms of association strength between compound structural features resulting in database PMI interrelation profiles. As structural features, substructure fragments obtained by coding individual compounds as MACCS, PubChemKey and ECFP fingerprints are used. The analysis of publicly available databases reveals, in accord with other studies, unusual properties of DrugBank compounds which further confirms the validity of PMI profiling approach. Z-standardized relative feature tightness (ZRFT), a PMI-derived measure that quantifies how well the given compound’s feature combinations fit these in a particular compound set, is applied for the analysis of compound synthetic accessibility (SA), as well as for the classification of compounds as easy (ES) and hard (HS) to synthesize. ZRFT value distributions are compared with these of SYBA and SAScore. The analysis of ZRFT values of structurally complex compounds in the SAVI database reveals oligopeptide structures that are mispredicted by SAScore as HS, while correctly predicted by ZRFT and SYBA as ES. Compared to SAScore, SYBA and random forest, ZRFT predictions are less accurate, though by a narrow margin (AccZRFT = 94.5%, AccSYBA = 98.8%, AccSAScore = 99.0%, AccRF = 97.3%). However, ZRFT ability to distinguish between ES and HS compounds is surprisingly high considering that while SYBA, SAScore and random forest are dedicated SA models, ZRFT is a generic measurement that merely quantifies the strength of interrelations between structural feature pairs. The results presented in the current work indicate that structural feature co-occurrence, quantified by PMI or ZRFT, contains a significant amount of information relevant to physico-chemical properties of organic compounds.
Global changes in oceanic mesoscale currents over the satellite altimetry record
Authors: Martinez-Moreno Josue , Hogg Andrew , England Matthew , Constantinou Navid C. , Kiss Andrew E. , Morrison Adele
Published: October 2020

Oceanic eddies play a profound role in mixing tracers such as heat, carbon, and nutrients, thereby regulating regional and global climate. Yet, it remains unclear how global oceanic eddy kinetic energy has evolved over the past few decades. Furthermore, coupled climate model predictions generally fail to resolve oceanic mesoscale dynamics, which could limit their accuracy in simulating future climate change. Here we show a global statistically significant increase of the eddy activity using two independent observational datasets of mesoscale variability, one directly measuring currents and the other from sea surface temperature. Regions characterized by different dynamical processes show distinct evolution in the eddy field. For example, eddy-rich regions such as boundary current extensions and the Antarctic Circumpolar Current show a significant increase of 2% and 5% per decade in eddy activity, respectively. In contrast, most of the regions of observed decrease are found in the tropical oceans. Because eddies play a fundamental role in the ocean transport of heat, momentum, and carbon, our results have far-reaching implications for ocean circulation and climate, and the modelling platforms we use to study future climate change.
Engineering Escherichia Coli for the Utilization of Ethylene Glycol
Authors: Pandit Aditya Vikram , Harrison Emma , Mahadevan Radhakrishnan
Published: October 2020

Background: A considerable challenge in the development of bioprocesses for producing chemicals and fuels has been the high cost of feedstocks relative to oil prices, making it difficult for these processes to compete with their conventional petrochemical counterparts. Hence, in the absence of high oil prices in the near future, there has been a shift in the industry to produce higher value compounds such as fragrances for cosmetics. Yet, there is still a need to address climate change and develop biotechnological approaches for producing large market, lower value chemicals and fuels.Results: In this work, we study ethylene glycol (EG), a novel feedstock that we believe has promise to address this challenge. We engineer Escherichia coli (E. coli) to consume EG and as a case study for chemical production, examine glycolate production. The best fermentation performance led to the production of 10.4 g/L of glycolate after 112 hours of production time in a fed-batch bioreactor. Our results clearly suggest that oxygen concentration is an important factor in the assimilation and use of EG as a substrate. We also find that the uptake rates for EG are sufficient to satisfy commercial benchmarks for productivity and yield. Finally, our use of metabolic modeling sheds light on the intracellular distribution through central metabolism implicating flux to 2-phosphoglycerate as the primary route for EG assimilation.Conclusion: Overall, our work suggests that EG could provide a renewable starting material for commercial biosynthesis of fuels and chemicals that may achieve economic parity with petrochemical feedstocks while sequestering carbon dioxide.
Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy
Authors: Liu Xiaolong , Ma Zhen , Yu Yang , Paul Maswikiti Ewetse , Ma YanLin , Bai YuPing , Li XueMei , Gu BaoHong , Qi WenBo , Chen Hao
Published: October 2020

Background, Chemotherapy resistance based on the use of fluorouracil and cisplatin is one of the most encountered clinical problems resulting from post operation and gives rise to poor prognosis in patients diagnosed with gastric cancer (GC). Methods , this study aims to combine autophagy-related genes (ATGs) to provide an investigation of the susceptibility of victims with gastric malignancy to postoperative chemotherapy. Based on the TCGA database, gene expression data for GC patients undergoing and are using chemotherapy were integrated and analyzed. Prognostic genes were screened based on univariate and various analysis regression models. Subjects were divided into those with high and low-risk groups. This was analyzed by the utilization of the median risk score approach. The product limit estimator method had to be used to evaluate the OS and DFS. The accuracy of the prediction was resolved by the subject curve analysis. In addition, the carrying out of proper analysis was done in our work for some detailed assessments. The differential expression of ATGs is mainly related to chemotherapy resistance. Results, a total of 9 ATGs of chemotherapy administration outcomes in these suffers were screened. Based on GEO and TCGA databases, the model accurately predicted DFS and OS after chemotherapy administration. Conclusions, this study established prognostic markers based on 9 genes, which can predict ATGs related to chemotherapy susceptibility of GC patients, and provide better individualized treatment regimens for clinical practice.
Rare Metastases in Colorectum of Infiltrating Ductal Breast Cancer: A Rare Case Report and Review
Authors: Zhang Zhijun , Li Tao , Li Yuemin , Li Dongxu , Zhang Kai
Published: October 2020

Background: Breast ductal carcinoma hardly metastasizes to colorectum and the effect of surgery is controversial. We treated one case of patients with breast ductal carcinoma metastasizes to colorectum with surgery and discussed current management experience of breast cancer metastasizing to colorectum by reviewing the literature. Case Presentation: A 37-year-old woman underwent a modified radical mastectomy three years ago for right breast cancer and developed left breast cancer with right breast cancer suspiciously metastasizing to colorectum, left ovary along with oviduct, pancreas, and left acetabulum according to positron emission tomography-computed tomography. Then she had chosen to give up further therapy but was admitted to our department complaining of shapeless feces and mucus pus and blood in stool for 2 years with the process of aggravating symptoms for recent 2 months. Colonoscopy revealed the existence of colorectal carcinoma. She received laparoscopic combined abdominal perineal resection and bilateral ovarian salpingectomy. Postoperative pathology as well as immunohistochemistry supported the origin of primary breast infiltrating ductal cancer. She remained tamoxifen therapy and was alive until she was lost to follow-up.Conclusions: Clinicians must pay attention to any gastro-intestinal symptoms of patients with a medical history of breast cancer since the incipient symptoms of breast cancer metastasis to colorectum are insidious. Definite diagnosis may be difficult even by endoscopy. Surgery should be considered as a therapeutic option and definite diagnostic means combined with immunohistochemistry.
Prognostic role of PHYH for Overall Survival (OS) in clear cell Renal Cell Carcinoma (ccRCC)
Authors: Qiu Zhengqi , Zezhi Guo , Lei Jiang , He Qiu , Jinyao Pan , Ying Ao
Published: October 2020

This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analysed by Univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene-gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e-19). Kaplan-Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e-05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p=0.025), high stage (StageIII & IV, p=5.604e-05), High level of stage_T (T3-4, p=4.373e-05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p<0.05). Nomogram including Clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway and Renin angiotensin system were differentially enriched in PHYH high expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p<0.05). We suspect that Elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism and RAS might be the key pathways regulated by PHYH in CCRC.
Impact of a visual indicator on the noise level in an emergency medical dispatch center - a pilot study
Authors: Outrey Justin , Pretalli Jean-Baptiste , Pujol Sophie , Brembilla Alice , Desmettre Thibaut , Lambert Christophe , Labourey Jean-Marc , Mauny Frédéric , Khoury Abdo
Published: October 2020

Background A maximum of 52 to 55 dB(A) is recommended in order to prevent adverse events in call centres. We aimed at assessing the noise level and the impact of a visual noise indicator on the ambient noise level in a French Regional Emergency Medical Dispatch Centre (EMDC). Methods We conducted an observational study in the EMDC of the SAMU25 (University Hospital of Besancon). We measured the noise level using a SoundEarII® noise indicator (Dräger Medical SAS, France). The measurement took place in two phases on three consecutive days from 00:00 to 11:59 PM. At baseline, phase 1, the device recorded the average ambient noise for each minute without visual indication. Secondly, phase 2 included a sensor mounted with a light that would turn on if noise ever exceeded 65 and 75 dB(A). Results The sound level was greater than 52 dB(A) in 97.2% and 66.8% of the time in phases 1 and 2 respectively; this level was greater than 55 dB(A) in 84.9% and 43.9% of the time in phases 1 and 2 respectively.Conclusions The noise levels were higher than recommended and sometimes close to legal limits, requiring preventive measures. The noise indicator had a positive effect on the ambient noise level. This work will allow the implementation of effective prevention solutions and, based on future assessments, could improve operators’ well-being and better care for patient.
Characterization of Confirmed and Suspected COVID-19 Pneumonia Patients in a Retrospective Cohort Study in Wuhan
Authors: Xi Maomao , Cui Dan , Liu Qiaomei , Li Lili , Yin Yilin , Dong Fang , Xiong Di , Wu Yuwei , Guo Hongrong , Bao Min , Li Zhanghua , Luo Man , Wu Juan , Xie Weiguo , Wu Qingming , Peng Anlin , Wu Jinhu , Tan Yiqing , Sun Jianbin , Luo Pengcheng , Huang Zan , Huang Xiaodong
Published: October 2020

Background: A methodical comparison of confirmed and suspected COVID-19 patients has not been previously reported. Therefore, we thoroughly analyzed the demographic and clinical characteristics between these groups to identify mortality risk factors.Methods: A retrospective cohort of 1,276 hospitalized COVID-19 pneumonia patients at Tongren Hospital (Wuhan, China; January 27 to March 3, 2020) was studied. Cox regression analyses were performed to evaluate multiple mortality risk factors. Results: Both cohorts of confirmed (n=797) and suspected (n=479) patients exhibited typical demographic, clinical, and radiological characteristics. Treatment methods were consistent and both groups shared similarities in many demographic and clinical characteristics: age (≥65, 45.9% vs 41.8%, P=0.378) and lung disease (12.5% vs 14.6%, P=0.293). However, confirmed patients exhibited more severe disease manifestations than those in suspected patients: a higher incidence of fever (65.4% vs 58.0%, P<0.01), lower lymphocyte count (1.12×109/L vs 1.22×109/L, P=0.022), higher C-reactive protein (CRP) (11.60 mg/L vs 7.61mg/L, P=0.021), and more severe radiographic manifestations (lung infection incidence, 3.8% vs 3.0%, P=0.014; ground-glass opacity lesion incidence, 2.3% vs 2.0%, P=0.033). The dynamic profiles of lymphocytes, monocytes, D-dimer, and CRP, clearly delineated confirmed patients from suspected patients exhibiting critical illness. Cox regression analysis demonstrated that lung disease (adjusted hazard ratio 8.972, 95% CI: 3.782-21.283), cardiovascular disease (3.083, 1.347-7.059), neutrophil count (1.189, 1.081-1.307), age (1.068, 1.027-1.110), and ground-glass opacity lesions (1.039, 95% 1.013-1.065), were the main risk factors for mortality in confirmed patients; lung disease (14.725, 2.187-99.147), age (1.076, 1.004-1.153), and CRP level (1.012, 95% CI 1.004-1.020) were the primary factors in suspected patients.Conclusions: Suspected patients with serious illness should seek medical attention to reduce mortality. Multiple factors must be assessed to determine the mortality risk and the appropriate treatment.
Butyrophilin-like 9 regulates immune infiltration and serves as a prognostic marker in lung adenocarcinoma
Authors: Ma Weishuang , Liang Jiaming , Zhang Siyuan , Ningdong Hu , Chen Zisheng , Tian Dongbo
Published: October 2020

Background: Butyrophilin (BTN) and butyrophilin-like (BTLN) belong to immunoglobulin superfamily, and also pertain the B7 co-stimulatory molecules family, which has multiple roles in immune modulation. Whether the BTNL9 expression in lung adenocarcinoma (LUAD) correlates with outcome has not been evaluated.Materials and methods: Oncomine and GEPIA were used to analyze the BTNL9, while its mRNA expression in LUAD and corresponding adjacent tissues was investigated using TIMER. The clinical prognosis of BTNL9 was assessed in the GEPIA, Kaplan-Meier plotter, and OncoLnc. Besides, the correlation between BTNL9 and tumor-infiltrating immune cells (TILs) was analyzed using TIMER and GEPIA. The correlation between BTNL9 expression and drug response was analyzed using CARE.Results: BNL9 expression was significantly low in LUAD. Low BTNL9 expression was associated with poor OS, and its expression was found to be regulated by both epigenetic regulation and post-transcriptional modification. BTNL9 expression was significant positively correlated with ImmuneScore and ESTIMATEScore. Moreover, BTNL9 expression was positively correlated with infiltrating levels of B cells, CD4+T, and macrophages, but Kaplan-Meier analysis showed that BTNL9 expression in B cells and DCs was significantly associated with OS. Furthermore, BTNL9 expression has significant positive CARE scores. Conclusions: Low BTNL9 expression can prevent the infiltration of naïve B cells and DCs in the tumor microenvironment and worsen the outcome in LUAD patients. Besides, these findings also suggest the potential role of BTNL9 as a prognostic biomarker and a new immuno-target.
Risk of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients with solid tumors who received systemic chemotherapy: two retrospective studies
Authors: Kuroda Junko , Kusumoto Shigeru , Kimata Tsukasa , Kataoka Tomomi , Hibi Satoshi , Nakane Shigeki , Choshi Masakazu , Tashiro Yuusuke , Takemoto Masashi , Tanaka Yasuhito , Komatsu Hirokazu , Kawada Kenji , Muro Kei , Kimura Kazunori
Published: October 2020

Background: There is little evidence regarding the risk of hepatitis B virus (HBV) reactivation in solid tumor patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs) who received systemic chemotherapy. Methods: We conducted two retrospective studies; a single-center retrospective study to measure the incidence of HBV reactivation in 1,376 HBsAg-negative patients with solid tumors who received systemic chemotherapy, and a multicenter retrospective study to clarify the clinical features of HBV reactivation in HBsAg-negative patients with solid tumors who received systemic chemotherapy at 5 institutions. HBV reactivation was defined as reappearance of HBsAg or detection of HBV DNA levels of 1.3 log IU/mL or more in both studies.Results: With a median follow-up time of 607 days, HBV reactivation was confirmed in 2 of 218 patients with resolved HBV infection in the single-center study. Of the 12 patients with HBV reactivation who were diagnosed at a median HBV DNA of 1.3 log IU/mL in the multicenter study, no HBV-related hepatitis was observed. The median time from the first chemotherapy to confirmed HBV reactivation was 141 days. Of the 11 patients in whom both anti-HBc and anti-HBs were measured, all were seropositive for anti-HBc, and 7 were seronegative for anti-HBs at baseline.Conclusions: The risk of HBV reactivation was estimated to be 0.9% in HBsAg-negative patients with solid tumors who received systemic chemotherapy. Seronegativity for anti-HBs at baseline may be an important risk factor for HBV reactivation in these patients.