ARTICLE | doi:10.20944/preprints201804.0192.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: abnormal ECG; ECG processing, feature extraction; heart beat classification, abnormality detection
Online: 16 April 2018 (06:28:25 CEST)
Automated Electrocardiogram (ECG) processing is an important technique which helps in identifying abnormalities in the heart before any formal diagnosis. This research presents a real-time and lightweight R-assisted feature extraction algorithm and a heartbeat classification scheme which achieves highly accurate abnormality detection. In the proposed algorithm, we extract fifteen features from each heartbeat taken from raw Lead-II ECG signals. The features carry medically valuable information such as locations, amplitude and energy of ECG waves (P, Q, R, S, T waves) which are then used for detection of any abnormality that might be present in the heartbeat using various classification algorithms. We have used four popular databases from Physionet and extracted ten thousand ECG signals from each for training the models and benchmarking results. Four classification models i.e. Naïve Bays, k-Nearest Neighbor, Neural Network, Decision Tree were used for abnormality detection validating the efficiency of the system.
REVIEW | doi:10.20944/preprints201704.0059.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Keywords: vitamin D deficiency; diabetic retinopathy; meta-analysis.
Online: 11 April 2017 (06:16:22 CEST)
Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.
REVIEW | doi:10.20944/preprints202009.0709.v1
Subject: Life Sciences, Biochemistry Keywords: Escherichia coli; Clostridium perfringens; broiler; antibiotic-free; production; chicken
Online: 29 September 2020 (12:46:00 CEST)
United States is the largest producer and the second largest exporter of broiler meat in the world. In the U.S, broiler production is largely converting to antibiotic-free programs which has caused an increase in morbidity and mortality within broiler farms. Escherichia coli and Clostridium perfringens are two important pathogenic bacteria readily found in the broiler environment and result in annual billion-dollar losses from colibacillosis, gangrenous dermatitis, and necrotic enteritis. Broiler industry is in search of non-antibiotic alternatives including novel vaccines, prebiotics, probiotics, and housing management strategies to mitigate production losses due to these diseases. This review provides an overview of the broiler industry and antibiotic free production, current challenges, and emerging research on antibiotic alternatives to reduce pathogenic microbial presence and improve bird health.
REVIEW | doi:10.20944/preprints202005.0235.v1
Subject: Life Sciences, Other Keywords: strap muscle invasion; prognosis; differentiated thyroid carcinoma; meta-analysis; review
Online: 14 May 2020 (11:35:41 CEST)
Gross strap muscle invasion (gSMI) in patients with differentiated thyroid cancer (DTC) was defined as high-risk recurrent group in the 2015 American Thyroid Association guidelines. However, controversy persists because several studies suggested gSMI had little effect on disease outcome. Herein, a systematic review and meta-analysis was conducted to investigate impact of gSMI on outcome of DTC. Methods: A systematic search of electronic databases (PubMed, EMBASE, Cochrane Library, and MEDLINE) for studies published until February 2020 was performed. Case-control studies and randomized controlled trials that studied the impact of gSMI on outcome of DTC were included. Results: Six studies (all retrospective studies) involving 13639 patients met final inclusion criteria. Compared with no extrathyroidal extension (ETE), patients with gSMI were associated with increased risk of recurrence (P=0.0004,OR, 1.46; 95% CI: 1.18 to 1.80) and lymph node metastasis (LNM) (P<0.00001,OR 4.19;95% CI. 2.53 to 6.96). For mortality (P=0.34,OR 1.47;95% CI:0.67 to 3.25), ten-year disease-specific survival (P=0.80, OR 0.91;95% CI:0.44 to 1.88) and distant metastasis (DM) (P=0.21, OR 2.94;95% CI. 0.54 to 15.93), there was no significant difference between gSMI and no ETE group. In contrast with maximal ETE, patients with gSMI were associated with decreased risk of recurrence (P<0.0001,OR, 0.58; 95% CI: 0.44 to 0.76) , mortality (P=0.0003,OR 0.20;95% CI:0.08 to 0.48), LNM (P=0.0003,OR 0.64;95% CI. 0.50 to 0.81) and DM (P=0.0009,OR 0.28;95% CI. 0.13 to 0.59). Conclusions: DTC patients with gSMI had a higher risk of recurrence and LNM than those without ETE. However, in contrast with maximal ETE, a much better prognosis was observed in DTC patients with only gSMI. The findings of our meta-analysis provide supportive evidence for the validity of the T category changes in the 8th edition American Joint Committee on Cancer system. The actual impact of gSMI should be re-evaluated and revised in the recurrent risk stratification system in the future.
ARTICLE | doi:10.20944/preprints201903.0012.v1
Subject: Life Sciences, Virology Keywords: SHIV; Macrobrachium rosenbergii; Macrobrachium nipponense; Procambarus clarkii; white head; Histopathology; Susceptible species; Viral load
Online: 1 March 2019 (12:49:53 CET)
Macrobrachium rosenbergii is a valuable freshwater prawn in Asian aquaculture. In recent years, a new symptom that was generally called as ‘white head’ caused high mortality in M. rosenbergii farms in China. Samples of M. rosenbergii, M. nipponense, Procambarus clarkii, M. superbum, Penaeus vannamei, and Cladocera from a farm suffering from ‘white head’ in Jiangsu Province were collected and analyzed in this study. Pathogen detection showed that all samples were positive for Shrimp hemocyte iridescent virus (SHIV). Histopathological examination revealed dark eosinophilic inclusions and pyknosis in hematopoietic tissue, hepatopancreas and gills of M. rosenbergii and M. nipponense. Blue signals of in situ DIG-labeled LAMP (ISDL) appeared in hematopoietic tissue, hemocytes, hepatopancreatic sinus, and antennal gland. TEM of ultrathin sections showed a large number of SHIV particles with a mean diameter about 157.9 nm. The virogenic stromata and budding virions were observed in hematopoietic cells. Quantitative detection by TaqMan probe based real-time PCR of different tissues in natural infected M. rosenbergii showed that hematopoietic tissue contained the highest SHIV load with a relative abundance of (25.4±16.9)%. Hepatopancreas and muscle contained the lowest SHIV load with a relative abundance at (2.44±1.24)% and (2.44±2.16)%, respectively. Above results verified that SHIV is the pathogen causing ‘white head’ in M. rosenbergii, and M. nipponense and Pr. clarkii are also the susceptible species of SHIV.
ARTICLE | doi:10.20944/preprints201709.0157.v1
Subject: Chemistry, Organic Chemistry Keywords: rare earth metal complexes; 1,3-bis(oxazolinymethylidene)isoindoline ligand; polymerization; isoprene; cis-1,4-selectivity
Online: 29 September 2017 (14:50:39 CEST)
A series of novel chiral nonmetallocene pincer-type rare earth metal dialkyl complexes bearing the chiral monoanionic tridentate C2-symmetric 1,3-bis(oxazolinymethylidene)isoindoline (BOXMI) ligand (BOXMI)Ln(CH2SiMe3)2 1-3 (1, Ln = Sc, yield = 57%; 2, Ln = Lu, yield = 55%; 3, Ln = Y, yield = 62%) have been prepared in moderate yields via the acid-base reaction between the BOXMI ligand and rare earth metal tri(trimethylsilylmethyl) complexes. The X-ray diffractions show that both of the complexes 1 and 2 contain one Boxmi ligand and two trimethylsilylmethyl ligands, adopting a distorted-trigonal-bipyramidal configuration. In the presence of cocatalyst such as borate and AlR3, these complexes 1-3 exhibit high activities up to 6.8 × 104 (g of polymer)/(molLn h) and high cis-1,4-selectivities up to 97%) in the polymerization of isoprene in toluene, yielding the cis-1,4-polyisoprenes with high molecular weights (Mn up to 710000 g/mol) and bimodal molecular weight distributions (Mw/Mn = 2.0-4.5).
ARTICLE | doi:10.20944/preprints202208.0171.v2
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: combination; antimicrobial resistance; selection index; collateral sensitivity; mutant prevention concentration; minimal inhibitory concentration; fractional inhibitory concentration index; stress factor
Online: 13 September 2022 (07:53:32 CEST)
Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. In our previous work, it had been concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here three aspects were further explored. First, the power function (y=axb, a > 0) correlation between the SI (y) of one agent and the ratio value (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a1 × MIC1 = a2 × MIC2 and b1 + b2 = -1 were discovered from both equations of y=a1xb1 and y=a2xb2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations show greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These results together of above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.
ARTICLE | doi:10.20944/preprints202203.0076.v1
Online: 4 March 2022 (09:10:15 CET)
The COVID-19 pandemic has now become very severe as never before due to the overwhelming spread of Omicron. We found that Omicron outbreak can be effectively prevented by inactivated vaccines, which averted an outbreak of more than 1.6 million people in Hangzhou, China. The 36 mutations in the target spike protein of Omicron neutralizing antibody enable it to evade the immune protection afforded by vaccines. This is because that mRNA and adenovirus-vector vaccines are designed to recognize the spike (S) glycoprotein of the SARS-CoV-2 wild-type (WT) strain. However, Inactivated vaccines contain the whole viral antigens and remain stable in their recognition of newly emerging variants of SARS-CoV-2. Our study confirmed the advantage of inactivated vaccines in the face of highly mutated Omicron variant and provided a basis for the development of effective vaccines to prevent future long-term transmission, mutation and recurrence of SARS-CoV-2.
ARTICLE | doi:10.20944/preprints202206.0010.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; ARDS; Cytokine Storm; Spike S1 protein; SARS-CoV-2, Long COVID; ACE2; A549 cells; Caco-2 cells
Online: 1 June 2022 (09:49:27 CEST)
The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.
CASE REPORT | doi:10.20944/preprints202103.0601.v1
Subject: Medicine & Pharmacology, Allergology Keywords: MLL-SEPT6; TRAF3; FGFR3; Acute Myelogenous Leukemia; Child.
Online: 24 March 2021 (16:20:43 CET)
The MLL gene is a site of frequent rearrangement in acute leukemia with multiple fusion partners, but MLL-SEPT6 rearrangement is rare in clinical leukemia practice, and only 13 cases have been reported. We describe the case of an acute myelogenous leukemia child with MLL-SEPT6 rearrangement whose age of onset and accompanying gene mutations differs from previous reports. Considering the poor prognosis of leukemia children with MLL-SEPT6 rearrangement and the unsatisfactory results of existing treatments, the study of this case may provide new theories for diagnosis and treatment of MLL-SEPT6-associated childhood acute leukemia.
ARTICLE | doi:10.20944/preprints202104.0311.v1
Subject: Materials Science, Biomaterials Keywords: Chitosan; Silver nanoparticles; Graphene oxide; Nanocomposites; Antibacterial property; Drug delivery
Online: 12 April 2021 (13:59:44 CEST)
In this work, we designed and fabricated a multifunctional nanocomposite system which consists of chitosan, raspberry-like silver nanoparticles and graphene oxide. Room temperature atmospheric pressure microplasma (RT-APM) process provides a rapid, facile, and environment-friendly method for introducing silver nanoparticles into the composite system. By loading different drugs onto the polymer matrix and/or graphene oxide, our composite can achieve a pH controlled dual drug release with release profile specific to the drugs used. In addition to its strong antibacterial ability against E. coli and S. aureus, our composite also demonstrates excellent photothermal conversion effect under irradiation of near infrared lasers. These unique functionalities point to it’s the potential of nanocomposite system in multiple applications areas such as multimodal therapeutics in healthcare, water treatment, and anti-microbial, etc.
CASE REPORT | doi:10.20944/preprints202005.0079.v1
Online: 5 May 2020 (12:14:41 CEST)
Herein, we reported a case of complete excision of the jejunum for the treatment of esophageal cancer. A 62-year-old male was admitted with complaints of “difficulty in eating for one month and chest pain for 10 days". For complete gastrectomy and colonic polyposis, we chose the jejunum. We completely excised the jejunum and its vessels, anastomosed to the esophageal tumor resection, with no significant complications. This case showed that complete excision of the jejunum with bowel and vessels is an alternative surgical method for the treatment of esophageal cancer with free bowel shortage and no torsion of blood vessels.
ARTICLE | doi:10.20944/preprints202004.0441.v1
Online: 24 April 2020 (12:06:33 CEST)
Background: The Corona Virus Disease 2019 (COVID-19) is spreading globally now. However, the clinical presentation that predict prognosis of the patients are still largely unknow. Methods: We enrolled 393 patients infected with COVID-19 and 30 patients with common pulmonary bulla and reviewed their clinical features to evaluate the potential prognostic value of pulmonary vesicles, especially in the patients with severe symptoms. One COVID-19 patient with vesicles was treated by bullectomy for last resort, and its characteristics of the patient’s perioperative laboratory tests was analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. Results: Patients infected with COVID-19 showed more dependence on ventilator, occurrence of super resistant bacteria, and prone to vesicle formation than common bulla (p<0.05). Disease severity is associated with age, sex, and usage of ventilator, ECMO and antibiotics, super resistance bacteria and vesicle formation (p<0.05). The average mortality rate of COVID-19 patients was 4.10% (25.4% in severe patients, 0.00% in mild patients). Interestingly, the mortality rate further increased in severe patients with pulmonary vesicles than those without pulmonary vesicles (35.7% vs 22.4%, p=0.0442). One COVID-19 patient with vesicles underwent bullectomy and had a poor prognosis, who showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. Conclusions: Patients infected with COVID-19 are more prone to form pulmonary vesicles showed on chest CT scans, as an important poor prognosis factor, especially in the severe patients.
Subject: Biology, Anatomy & Morphology Keywords: Arabidopsis; HY2; salt stress; seed germination; proteome; DRPs
Online: 16 July 2021 (13:04:26 CEST)
Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). And Arabidopsis Long Hy-pocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in plant stress response signal network remains unknown. Here, we described the func-tion of the HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2 which positively mediated the expression of downstream stress-related genes of RD29A, RD29B and DREB2A. Further quantitative proteomics showed the patterns of 7,391 proteins under salt stress. HY2 was then found to specifically regulate 215 differentially regulated proteins (DRPs) which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic & metabolic, hormone response (SA, JA, ABA, ethylene), reactive oxygen spe-cies (ROS) metabolic, photosynthesis and detoxification pathway to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifi-cally-regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to re-sist salt stress.
ARTICLE | doi:10.20944/preprints202005.0077.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: centromere protein F (CENPF); Estrogen Receptor beta; Lung Adenocarcinoma (LUAD); WGCNA package; non-small cell lung cancer (NSCLC)
Online: 5 May 2020 (12:08:59 CEST)
The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.
ARTICLE | doi:10.20944/preprints201701.0033.v1
Subject: Life Sciences, Virology Keywords: H7N9 avian influenza; pseudovirus; neutralization assay; relative luminescence units (RLU)
Online: 6 January 2017 (10:21:52 CET)
In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.