bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting Constraints of Fourth-Generation Quarks and Leptons
Authors: Verma Aayush
Published: September 2020

Standard Model is well-performing under the three-generation, but in the wake of more physics, fourth-generation leptons and quarks are introduced. In this paper, We will be reviewing various constraints surrounding quarks and leptons of 4th Generation and tried to show the importance of quarks to understand the baryogenesis. We talked about, reviewed existing parameters and set the updated lower limits of t’ and b’ by analysis. And predicted an updated version of lower mass bounds quarks and leptons. It is also reviewed that fourth generation leptons are primarily not possible because of disintegration of Higgs Boson and an interpretation has been setup. And in final, we talked about the Unified Standard Model.
Fostering Accessible Online Education Using Galaxy as an e-learning Platform
Authors: Serrano-Solano Beatriz , Erxleben Anika , Gallardo-Alba Cristóbal , Rasche Helena , Hiltemann Saskia , Föll Melanie , Fahrner Matthias , Dunning Mark J. , Schulz Marcel , Scholtz Beáta , Clements Dave , Nekrutenko Anton , Batut Bérénice , Grüning Björn
Published: September 2020

The COVID-19 pandemic is shifting the teaching paradigms to an online setting all over the world. The Galaxy framework caters to computational biologists a set of features to facilitate the online learning process and make it accessible to everyone. Besides the high-quality training materials, Galaxy provides easy access to data and the possibility to share the progress and achievements, both student to student and student to instructor. By combining the different features offered by the Galaxy framework and by choosing the adequate communication channels, effective training activities can be designed inclusively, regardless of the students' environments.
Stability Analysis of Delayed Tumor-Antigen-Activated Immune Response in combined BCG and IL-2 Immunotherapy of Bladder Cancer
Authors: Bunimovich-Mendrazitsky Svetlana , Shaikhet Leonid
Published: September 2020

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).
Neuronal Lipoprotein Lipase Deficiency Alters Neuronal Function and Hepatic Metabolism
Authors: Bruce Kimberley D. , Wang Hong , Dobrinskikh Evgenia , Rudenko Ivan , Gao Hong , Libby Andrew , Gorkhali Sachi , Yu Tian , Zsombok Andrea , Eckel Robert
Published: September 2020

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here we show that despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox [LPL KD]) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to WT controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of the free vs. bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in, or over-expressing, LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.
A Meta-analysis of Comorbidities in COVID-19: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection?
Authors: Ramachandran Srinivasan , Singh Manoj Kumar , Mobeen Ahmed , Chandra Amit , Joshi Sweta
Published: September 2020

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.
Polymethyl Methacrylate Cement Fill as a Definitive Treatment for Massive Bone Defect After Infected Internal Fixation in Bicondylar Tibial Fracture
Authors: Reito Aleksi , Ylitalo Antti
Published: September 2020

Case:

A 62-year-old woman sustained a bicondylar proximal tibial fracture. She had a deep infection after open reduction and internal fixation resulting in massive metaphyseal bone loss. Because only subchondral bone was left, the cavity was filled with cement after pins were used to support the proximal tibia. Then, a hinged knee-spanning external fixator (EF) was applied. After the removal of the EF, the patient was almost pain free and tolerated full weight-bearing, and no further surgeries were needed.

Conclusion:

The cemented wires technique proved to be a good short-term and possibly a reasonable long-term treatment approach for infected nonunion with massive bone loss still maintaining lower leg alignment.
Atypical Subtrochanteric Femur Fracture and Hip Osteoarthritis Treated with a Revision Monoblock Stem and Strut Allograft
Authors: Heckmann Nathanael D. , Yang JaeWon , DeBenedetti Anne , Della Valle Craig J.
Published: September 2020

Case:

A 73-year-old woman was diagnosed with a nondisplaced incomplete atypical bisphosphonate-related subtrochanteric femur fracture and ipsilateral hip osteoarthritis. She was treated with a total hip arthroplasty using a monoblock revision stem and a strut allograft to provide adjunctive mechanical and biological support. At the final follow-up, the patient had no pain, the stem was well fixed, and the allograft strut had incorporated; however, a persistent fracture line was noted.

Conclusion:

When an atypical femur fracture coexists with hip osteoarthritis, total hip arthroplasty may be a reasonable treatment option to address the fracture and concomitant hip osteoarthritis with a single surgical intervention. However, consideration should be given to using a stem with distal fixation and augmenting the construct with a strut allograft.
An updated explanation of ancestral karyotype changes and reconstruction of evolutionary trajectories to form Camelina sativa chromosomes
Authors: Zhang Zhikang , Meng Fanbo , Sun Pengchuan , Yuan Jiaqing , Ge Ke , Liu Chao , Wang Weijie , Wang Xiyin
Published: September 2020

Background: Belonging to lineage Ⅰ of Brassicaceae, Camelina sativa is formed by two hybridizations of three species (three sub-genomes). The three sub-genomes were diverged from a common ancestor, likely derived from lineage Ⅰ (Ancestral Crucifer karyotype, ACK). The karyotype evolutionary trajectories of the C. sativa chromosomes are currently unknown. Here, we managed to adopt a telomere-centric theory proposed previously to explain the karyotype evolution in C. sativa. Results: By characterizing the homology between A. lyrata and C. sativa chromosomes, we inferred ancestral diploid karyotype of C. sativa (ADK), including 7 ancestral chromosomes, and reconstructed the evolutionary trajectories leading to the formation of extant C. sativa genome. The process involved 2 chromosome fusions. We found that sub-genomes Cs-G1 and Cs-G2 may share a closer common ancestor than Cs-G3. Together with other lines of evidence from Arabidopsis, we propose that the Brassicaceae plants, even the eudicots, follow a chromosome fusion mechanism favoring end-end joining of different chromosomes, rather than a mechanism favoring the formation circular chromosomes and nested chromosome fusion preferred by the monocots. Conclusions: The present work will contribute to understanding the formation of C. sativa chromosomes, providing insight into Brassicaceae karyotype evolution.
Genome wide analysis reveals genetic divergence between Goldsinny wrasse populations
Authors: Jansson Eeva , Besnier Francois , Malde Ketil , André Carl , Dahle Geir , Glover Kevin A.
Published: September 2020

Background: Marine fish populations are often characterized by high levels of gene flow and correspondingly low genetic divergence. This presents a challenge to define management units. Goldsinny wrasse (Ctenolabrus rupestris) is a heavily exploited species due to its importance as a cleaner-fish in commercial salmonid aquaculture. However, at the present, the population genetic structure of this species is still largely unresolved. Here, full-genome sequencing was used to produce the first genomic reference for this species, to study population-genomic divergence among four geographically distinct populations, and, to identify informative SNP markers for future studies. Results: After construction of a de novo assembly, the genome was estimated to be highly polymorphic and of ~600Mbp in size. 33 235 SNPs were thereafter selected to assess genomic diversity and differentiation among four populations collected from Scandinavia, Scotland, and Spain. Global FST among these populations was 0.015–0.092. Approximately 4% of the investigated loci were identified as putative global outliers, and ~1% within Scandinavia. SNPs showing large divergence (FST>0.15) were picked as candidate diagnostic markers for population assignment. 173 of the most diagnostic SNPs between the two Scandinavian populations were validated by genotyping 47 individuals from each end of the species’ Scandinavian distribution range. 69 of these SNPs were significantly (p<0.05) differentiated (mean FST_173_loci=0.065, FST_69_loci=0.140). Using these validated SNPs, individuals were assigned with high probability (≥ 94%) to their populations of origin.Conclusions: Goldsinny wrasse displays a highly polymorphic genome, and substantial population genomic structure. Diversifying selection likely affects population structuring globally and within Scandinavia. The diagnostic loci identified now provide a promising and cost-efficient tool to investigate goldsinny wrasse populations further.
Once the child is delivered, he is no more your baby,” Exclusive Breastfeeding experiences of first-time mothers in Kassena-Nankana Municipality, Ghana - a qualitative study
Authors: Adda Louisa , Opoku-Mensah Kwabena , Dako-Gyeke Phyllis
Published: September 2020

Background Exclusive Breastfeeding (EBF) for the first six months of life is globally accepted as the preferred method for infant feeding. In Ghana, an estimated 84% of children < 2 months old are exclusively breastfed. But by age 4 to 5 months, only 49% continue to receive EBF. This situation continues to deteriorate. Thus, the need to explore perceptions, practices as well as factors that influence EBF in Ghana. Methods Using a qualitative design, four focus group discussions were conducted among first-time mothers and eight in-depth interviews with health workers and traditional birth attendants. The study was conducted in four communities in the Kassena-Nankana municipality of Ghana. Discussions and interviews were recorded and later transcribed verbatim to English language. The transcribed data was then coded with the aid of analysis computer software (Nvivo version 10.0) and later analyzed for the generation of themes. Results Exclusive breastfeeding is practiced among first-time mothers due to its perceived benefits; which include nutritional advantage, ability to enhance growth whilst boosting immunity and its economic value. However misconceptions as well as, certain cultural practices (e.g. giving herbal concoctions, breastmilk purification rites), and relational influences, may threaten a mother’s intention to exclusively breastfeed. Relational influences are mainly from mother in-laws, traditional birth attendants, grandmothers, herbalists and other older adults in the community. Conclusions Although first time mothers attempt EBF, external influences make it practically challenging. The availability and utilization of information on EBF was found to positively influence perceptions towards EBF, leading to change in attitude towards the act. Thus, the practice of community-based health services may be strengthened to provide support for first-time mothers as well as continuous education to the mother in laws, female elders and community leaders who influence decision making on breastfeeding of infants
Liver fibrosis assessments using FibroScan, Virtual-Touch tissue quantification, the FIB-4 index, and Mac-2 binding protein glycosylation isomer levels compared with pathological findings of liver resection specimens in patients with hepatitis C infection
Authors: Ueda Naoyuki , Kawaoka Tomokazu , Imamura Michio , Aikata Hiroshi , Nakahara Takashi , Murakami Eisuke , Tsuge Masataka , Hiramatsu Akira , HAYES C.NELSON , Yokozaki Michiya , Chayama Kazuaki
Published: September 2020

BackgroundEvaluation of fibrosis stage is important to monitor progression of liver disease and risk of hepatocellular carcinoma (HCC). While liver biopsy is the gold standard, the method is invasive and faces several limitations. The aim of this study was to determine correlations among METAVIR scores and FibroScan, Virtual-Touch tissue quantification (VTQ), fibrosis index based on four factors (FIB-4 index), and Mac-2 binding protein glycosylation isomer (M2BPGi) level , and for examine differences in the reliability of non-invasive methods to evaluate fibrosis.MethodsWe used liver resection specimens from patients with hepatitis C virus (HCV), correlations were assessed between METAVIR scores and non-invasive method. Receiver operating characteristic (ROC) curves were generated to determine the sensitivity, specificity, and cut off values of the methods.ResultsAll Patients group: In F0-2 vs F3-4, the areas under the ROC curve (AUC) (0.85) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p=0.002) and that (0.67) of M2BPGi (p=0.001). The AUC (0.83) of VTQ was significantly higher than that (0.67) of FIB-4 index (p=0.01) and that (0.67) of M2BPGi (p=0.002). In F0-3 vs F4, the AUC (0.86) of VTQ was significantly higher than that (0.65) of FIB-4 index (p=0.04). The AUC (0.89) of FibroScan was significantly higher than that (0.65) of FIB-4 index (p=0.002) and that (0.76) of M2BPGi (p=0.02).Non-SVR group: In F0-2 vs F3-4, the AUC (0.85) of FibroScan was significantly higher than that (0.84) of FIB-4 index (p=0.02) and that (0.73) of M2BPGi (p=0.003). The AUC (0.84) of VTQ was significantly higher than that (0.74) of FIB-4 index (p=0.04). In F0-3 vs F4, the AUC (0.91) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p=0.003) and that (0.78) of M2BPGi (p=0.02). The AUC (0.88) of VTQ was significantly higher than that of FIB-4 index (0.67) and that of M2BPGi (0.78) (p=0.04).ConclusionsFibroScan and VTQ best reflected the results of hepatic fibrosis diagnosis using liver resection specimens among the four examination methods evaluated.
DeepGRN: Prediction of transcription factor binding site across cell-types using attention-based deep neural networks 
Authors: Chen Chen , Hou Jie , Shi Xiaowen , Yang Hua , Birchler James A. , Cheng Jianlin
Published: September 2020

BackgroundDue to the complexity of the biological systems, the prediction of the potential DNA binding sites for transcription factors remains a difficult problem in computational biology. Genomic DNA sequences and experimental results from parallel sequencing provide available information about the affinity and accessibility of genome and are commonly used features in binding sites prediction. The attention mechanism in deep learning has shown its capability to learn long-range dependencies from sequential data, such as sentences and voices. Until now, no study has applied this approach in binding site inference from massively parallel sequencing data. The successful applications of attention mechanism in similar input contexts motivate us to build and test new methods that can accurately determine the binding sites of transcription factors.ResultsIn this study, we propose a novel tool (named DeepGRN) for transcription factors binding site prediction based on the combination of two components: single attention module and pairwise attention module. The performance of our methods is evaluated on the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge datasets. The results show that DeepGRN achieves higher unified scores in 6 of 13 targets than any of the top four methods in the DREAM challenge. We also demonstrate that the attention weights learned by the model are correlated with potential informative inputs, such as DNase-Seq coverage and motifs, which provide possible explanations for the predictive improvements in DeepGRN.ConclusionsDeepGRN can automatically and effectively predict transcription factor binding sites from DNA sequences and DNase-Seq coverage. Furthermore, the visualization techniques we developed for the attention modules help to interpret how critical patterns from different types of input features are recognized by our model.
Flagella by numbers: comparative genomic analysis of the supernumerary flagellar systems among the Enterobacterales
Authors: De Maayer Pieter , Pillay Talia , Coutinho Teresa A
Published: September 2020

Background: Flagellar motility is an efficient means of movement that allows bacteria to successfully colonize and compete with other microorganisms within their respective environments. The production and functioning of flagella is highly energy intensive and therefore flagellar motility is a tightly regulated process. Despite this, some bacteria have been observed to possess multiple flagellar systems which allow distinct forms of motility. Results: Comparative genomic analyses showed that, in addition to the previously identified primary peritrichous (flag-1) and secondary, lateral (flag-2) flagellar loci, three novel types of flagellar loci, varying in both gene content and gene order, are encoded on the genomes of members of the order Enterobacterales. The flag-3 and flag-4 loci encode predicted peritrichous flagellar systems while the flag-5 locus encodes a polar flagellum. In total, 798/4,028 (~20%) of the studied taxa incorporate dual flagellar systems, while nineteen taxa incorporate three distinct flagellar loci. Phylogenetic analyses indicate the complex evolutionary histories of the flagellar systems among the Enterobacterales. Conclusions: Supernumerary flagellar loci are relatively common features across a broad taxonomic spectrum in the order Enterobacterales. Here, we report the occurrence of five (flag-1 to flag-5) flagellar loci on the genomes of enterobacterial taxa, as well as the occurrence of three flagellar systems in select members of the Enterobacterales. Considering the energetic burden of maintaining and operating multiple flagellar systems, they are likely to play a role in the ecological success of members of this family and we postulate on their potential biological functions.
Pharmacokinetic herb-drug interactions between Aidi injection and Doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma
Authors: Lu Yuan , Pan Jie , Zhu Xiaoqing , Zhang Shuai , Chunhua Liu , Sun Jia , Li Yueting , Chen Siying , Huang Jing , Cao Chuang , Wang Yonglin , Li Yongjun , Liu Ting
Published: September 2020

Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
Barriers and Facilitators to Colorectal Cancer Diagnosis in New Zealand: A Qualitative Study
Authors: Blackmore Tania , Norman Kimberley , Kidd Jacquie , Cassim Shemana , Chepulis Lynne , Keenan Rawiri , Firth Melissa , Jackson Christopher , Stokes Tim , Weller David , Emery Jon , Lawrenson Ross
Published: September 2020

Background: New Zealand (NZ) has high rates of colorectal cancer but low rates of early diagnosis. Due to a lack of understanding of the pre-diagnostic experience from the patient’s perspective, it is necessary to investigate potential patient and health system factors that contribute to longer diagnostic intervals. Previous qualitative studies have discussed delays using The Model of Pathways to Treatment, but this has not been explored in the NZ context. This study aimed to understand the patient experience and perception of their general practitioner (GP) through the diagnostic process in the Waikato region of NZ. In particular, we sought to investigate potential barriers and facilitators that contribute to longer diagnostic intervals.Methods: Ethical approval for this study was granted by the New Zealand Health and Disability Ethics Committee. Twenty-eight participants, diagnosed with colorectal cancer, were interviewed about their experience. Semi-structured interviews were audio recorded, transcribed verbatim and analysed thematically using The Model of Pathways to Treatment framework (intervals: appraisal, help-seeking, diagnostic).Results: Participant appraisal of symptoms was a barrier to prompt diagnosis, particularly if symptoms were normalised, intermittent, or isolated in occurrence. Successful self-management techniques also resulted in delayed help-seeking. However if symptoms worsened, disruption to work and daily routines were important facilitators to seeking a GP consultation. Participants positively appraised GPs if they showed good technical competence and were proactive in investigating symptoms. Negative GP appraisals were associated with a lack of physical examinations and misdiagnosis, and left participants feeling dehumanised during the diagnostic process. However high levels of GP interpersonal competence could override poor technical competence, resulting in an overall positive experience, even if the cancer was diagnosed at an advanced stage. Māori participants often appraised symptoms inclusive of their sociocultural environment and considered the impact of their symptoms in relation to family.Conclusions: The findings of this study highlight the importance of tailored colorectal cancer symptom communication in health campaigns, and indicate the significance of the interpersonal competence aspect of GP-patient interactions. These findings suggest that interpersonal competence be overtly displayed in all GP interactions to ensure a higher likelihood of a positive experience for the patient.
Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway
Authors: Li Jian , Ye Danli , Shen Peng , Liu Xiaorong , Zhou Peirong , Zhu Guifang , Xu Yangwei , Fu Yun , Li Xuanqi , Sun Jingbo , Xu Jia , Zhang Qingling
Published: September 2020

Background: The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms’ tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated. Methods: WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses.Results: The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression.Conclusions: The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.
Recovery of moderate COVID-19 disease in a liver transplant recipient on continued immunosuppression
Authors: Mathiasen Victor Dahl , Karlsen Stine , Ott Peter , Jensen-Fangel Søren , Leth Steffen
Published: September 2020

The authors have requested that this preprint be withdrawn due to author disagreement.
The impact of diabetes mellitus on acute kidney injury after coronary artery bypass grafting
Authors: Wang Rui , Zhang Hang , Zhu Yifan , Chen Wen , Chen Xin
Published: September 2020

Background: Diabetes mellitus(DM) is an indicator affects postoperative mortality and morbidity after coronary artery bypass grafting (CABG). Acute kidney injury (AKI) is one of the frequent postoperative complications after CABG. This multi-centre register study designed to investigate the impact of DM on postoperative AKI in primary isolated CABG patients. Methods: We included all patients (n =4325) from Jiangsu Province CABG register who underwent primary isolated CABG from September 2017 to August 2019. The patients were divided into 3 groups: No-DM group(n=3067), DM-oral group (DM with oral hypoglycemic agents, n=706) and DM-insulin group (DM with insulin treatment, n=552). The development and severity of AKI were based on Acute Kidney Injury Network (AKIN) criteria. Results: There were totally 338, 108 and 145 patients developed AKI in No-DM, DM-oral and DM-insulin group respectively. Comparing with No-DM group , DM-oral group had a higher rate of AKI(χ2=10.071, p=0.002), DM-insulin group had a higher rate(χ2=94.042, p＜0.001) and severity of AKI(χ2=10.649, p=0.005). The adjusted odds ratio for AKI was 1.26 (95% CI 1.03-1.57) in DM-oral group and 3.92 (95% CI 3.27-5.16) in DM-insulin group, in comparison with No-DM group. Conclusions: Independent of baseline renal function or cardiac function, DM was associated with an increased risk of AKI after CABG, especially in patients with insulin treatment, who also had a higher severity of AKI.
Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial
Authors: Yuan Tao , Liu Shixuan , Dong Yingyue , Fu Yong , Tang Yan , Zhao Wei-Gang
Published: September 2020

Background: We aimed to evaluate the effects of short-term therapy with dapagliflozin on serum uric acid (SUA) and urinary uric acid (UUA) levels in patients with type 2 diabetes.Methods: In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited into the control group. Data of anthropometric measurements, SUA, 24-hour UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-hour oral glucose tolerance test (OGTT) were collected in both treatment and control groups; all examinations were repeated after treatment. The area under the curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, while insulin resistance and islet β-cell function were reflected by indexes calculated according to the data obtained from the OGTT.Results: The weight and serum lipid parameters showed no differences before and after treatment with dapagliflozin for one week. We found SUA levels decreased from 347.75 ± 7.75 μmol/L before treatment to 273.25 ± 43.18 μmol/L after treatment, with a statistically significant difference (P=0.001) and was accompanied by a significant increase in FEUA from 0.009 to 0.029 (P=0.035); there was a linear correlation between SUA and FEUA levels. Glucose control, insulin sensitivity and islet β-cell function were improved to a certain extent. We also found a positive correlation between the decrease in glucose levels and the improvement in islet β-cell function.Conclusions: The SUA-lowering effect of dapagliflozin could be driven by increasing UA excretion within one week of treatment, and a certain degree of improvement in glucose levels and islet β-cell function were observed.
Steroid metabolites for diagnosing and predicting clinicopathological features in cortisol-producing adrenocortical carcinoma.
Authors: Suzuki Sawako , Minamidate Tomoki , Shiga Akina , Ruike Yutarou , Ishiwata Kazuki , Naito Kumiko , Ishida Akiko , Deguchi Hanna , Fujimoto Masanori , Koide Hisashi , Tatsuno Ichiro , Ikeda Jun-ichiro , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro
Published: September 2020

Background: Approximately 60% of adrenocortical carcinomas (ACC) are functional, and Cushing’s syndrome is the most frequent diagnosis that has been revealed to have a particularly poor prognosis. Since 30% of ACC present steroid hormone-producing disorganization, measurement of steroid metabolites in suspected ACC is recommended. Previous reports demonstrated that steroid hormone precursors or their urine metabolites, which can be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC-MS) respectively, are useful for distinguishing ACC from cortisol-producing adenomas (CPA); however, despite high precision, LC-MS/MS and GC-MS require a highly trained team, are expensive and have limited capacity. Methods: Here, we examined 12 serum steroid metabolites using an immunoassay, which is a more rapid and less costly method than LC-MS/MS, in cortisol-producing ACC and CPA. Further, the correlation of each steroid metabolite to the classification stage and pathological status in ACC was analyzed. Results: Reflecting disorganized steroidogenesis, the immunoassay revealed that all basal levels of steroid precursors were significantly increased in cortisol-producing ACC compared to CPA; in particular, 17-hydroxypregnenolone (glucocorticoid and androgen precursor ) and 11-deoxycorticosterone (mineralocorticoid precursor) showed a large area under the ROC curve with high sensitivity and specificity when setting the cut-off at 1.78 ng/ml and 0.4 mg/ml, respectively. Additionally, a combination of androstenedione and DHEAS also showed high specificity with high accuracy. In cortisol-producing ACC, 11-deoxycortisol (glucocorticoid precursor) showed significant positive correlations with predictive prognostic factors used in ENSAT classification, while testosterone showed significant positive correlations to the Ki67-index in both men and women.Conclusion: Less expensive and more widely available RIA and ECLIA may also biochemically distinguish ACC from CPA and may predict the clinicopathological features of ACC.
Lateral lymph node dissection reduces local recurrence of locally advanced lower rectal cancer in the absence of preoperative neoadjuvant chemoradiotherapy: A systematic review and meta-analysis
Authors: Gao Xiang , Wang Cun , Yu Yong-Yang , Yang Lie , Zhou Zong-Guang
Published: September 2020

Background: The role of lateral lymph node dissection (LLND) in the treatment of locally advanced lower rectal cancer remains controversial. The present study was conducted to compare total mesorectal excision (TME) with or without LLND among patients with lower rectal cancer in clinical stage II/III.Methods: PubMed, Embase, Ovid, Cochrane Library, Google Scholar, and the ClinicalTrials.gov databases were systematically searched for publications that compared TME with or without LLND among patients with lower rectal cancer in clinical stage II/III. Subgroup analysis was performed based on whether preoperative neoadjuvant chemoradiotherapy (nCRT) was undertaken. The hazard ratios (HR), relative risk (RR), and weighted mean difference (WMD) were pooled.Results: Twelve studies that included 4458 patients were identified in the current meta-analysis. Collected data demonstrated that TME with LLND was associated with significantly longer operation time (WMD 90.73 min, P<0.001), more intraoperative blood loss (WMD 303.20 mL, P<0.001), and postoperative complications (RR=1.35, P=0.02). Urinary dysfunction (RR 1.44, P=0.38), sexual dysfunction (RR 1.41, P=0.17), and postoperative mortality (RR=1.52, P=0.70) were similar between the two groups. No statistically significant differences were observed in OS (HR 0.93, P=0.62), DFS (HR 0.99, P=0.96), total recurrence (RR 0.98, P=0.83), lateral recurrence (RR 0.49, P=0.14) or distant recurrence (RR 0.95, P=0.78) between the two groups regardless the use of nCRT. LLND significantly reduced local recurrence rate of patients who did not receive nCRT (RR 0.71, P=0.004), while the difference was not significant when nCRT was performed (RR 0.70, P=0.36).Conclusions: Our study found out LLND could not significantly improve survival in locally advanced lower rectal cancer but could reduce the local recurrence in the absence of preoperative nCRT. The advantage of controlling local recurrence might be replaced with nCRT.Registration: The protocol for this meta-analysis was registered prospectively with PROSPERO (CRD42020135575) on May 16, 2019.
Birth preparedness and complication readiness among women of reproductive age in Kenya and Tanzania: a community-based cross-sectional survey
Authors: Orwa James , Gatimu Samwel Maina , Mantel Michaela , Luchters Stanley , Mugerwa Micheal A. , Brownie Sharon , Subi Leonard , Mrema Secilia , Nyaga Lucy , Edwards Grace , Mwasha Loveluck , Isangula Kahabi , Selestine Edna , Jadavji Sofia , Pell Rachel , Mbekenga Columba , Temmerman Marleen
Published: September 2020

Introduction: Delayed health-seeking continues to contribute to preventable maternal and neonatal deaths in low resource countries. Some of the strategies to avoid the delay include early preparation for the birth and detection of danger signs. We aimed to assess the level of practice and factors associated with birth preparedness and complication readiness (BPCR) in Kenya and Tanzania.Methods: We conducted community-based multi-stage cross-sectional surveys in Kilifi and Kisii counties in Kenya and Mwanza region in Tanzania and included women who delivered two years preceding the survey (2016–2017). A woman who mentioned at least three out of five BPCR components was considered well-prepared. Bivariate and multivariable proportional odds model were used to determine the factors associated with the BPCR. The STROBE guidelines for cross-sectional studies informed the design and reporting of this study.Results: Only 11.4% (59/519) and 7.6% (31/409) of women were well-prepared for birth and its complications in Kenya and Tanzania, respectively, while 39.7% and 30.6% were unprepared, respectively. Level of education (primary: adjusted odds ratio (aOR): 1.59, 95% CI: 1.14–2.20, secondary: aOR: 2.24, 95% CI: 1.39–3.59), delivery within health facility (aOR: 1.63, 95% CI: 1.15–2.29), good knowledge of danger signs during pregnancy (aOR: 1.28, 95% CI: 0.80–2.04), labour and childbirth (aOR: 1.57, 95% CI: 0.93–2.67), postpartum (aOR: 2.69, 95% CI: 1.24–5.79), and antenatal care were associated with BPCR (aOR: 1.42, 95% CI: 1.13–1.78).Conclusion: Overall, most pregnant women were not prepared for birth and its complications in Kilifi, Kisii and Mwanza region. Improving level of education, creating awareness on danger signs during preconception, pregnancy, childbirth, and postpartum period, and encouraging antenatal care and skilled birth care among women and their male partners/families are recommended strategies to promote BPCR practices and contribute to improved pregnancy outcomes in women and newborns.
Distinct role of 5’UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code.
Authors: Colliva Andrea , Tongiorgi Enrico
Published: September 2020

The neurotrophin Brain-derived neurotrophic factor (BDNF) is encoded by multiple bipartite transcripts. Each BDNF transcript is composed by one out of eleven alternatively spliced exons containing the 5’untranslated region (UTR), and one common exon encompassing the coding sequence (CDS) and the 3’UTR with two variants (short and long). In neurons, BDNF mRNA variants have a distinct subcellular distribution, constituting a “spatial code”, with exon 1, 3, 5, 7 and 8 located in neuronal somata, exon 4 extending into proximal dendrites, and exon 2 and 6 reaching distal dendrites. We previously showed that the CDS encodes constitutive dendritic targeting signals (DTS) and that both the 3’UTR-short and the 3’UTR-long contain activity-dependent DTS. However, the role of individual 5’UTR exons in mRNA sorting remains unclear. Here, we tested the ability of each different BDNF 5'UTRs to affect the subcellular localization of the green fluorescent protein (GFP) reporter mRNA. We found that exon 2 splicing isoforms (2a, 2b, and 2c) induced a constitutive dendritic targeting of the GFP reporter mRNA towards distal dendritic segments. The other isoforms did not affect GFP-mRNA dendritic trafficking. Through a bioinformatic analysis, we identified five unique cis-elements in exon 2a, 2b, and 2c which might contribute to building a DTS. This study provides additional information on the mechanism regulating the cellular sorting of BDNF mRNA variants.
Unraveling the Influence of Non-Fullerene Acceptor Molecular Packing on Phovoltaic Performance of Organic Solar Cells
Authors: Sun Yanming , Ye Linglong , Weng Kangkang , Xu Jinqiu , Du Xiaoyan , Chandrabose Sreelakshmi , Chen Kai , Zhou Jiadong , Han Guangchao , Tan Songting , Xie Zengqi , Yi Yuanping , Li Ning , Liu Feng , Hodgkiss Justin , Brabec Christoph
Published: September 2020

In non-fullerene organic solar cells (OSCs), the long-range structure ordering induced by end group π–π stacking of fused-ring non-fullerene acceptors is considered as the critical factor in realizing efficient charge transport and high power conversion efficiency. Here, we demonstrate that side-chain engineering of non-fullerene acceptors could drive the fused-ring backbone assembly from a π–π stacking mode to an intermixed packing mode, and to a non-stacking mode to refine its solid-state properties. Different from the above-mentioned understanding, we find that close atom contacts in a non-stacking mode can form efficient charge transport pathway through close side atom interactions. The intermixed solid-state packing motif in active layers could enable OSCs with superior efficiency and reduced non-radiative recombination loss compared with devices based on molecules with the classic end-group π–π stacking mode. Our observations provide new insights into the influence of non-fullerene acceptor molecular packing on exciton dissociation, charge transport, and recombination losses, and open a new avenue in material design that endows better photovoltaic performance.
Blocking of Efflux Transporters in Rats Improves Translational Validation of Brain Radioligands
Authors: Shalgunov Vladimir , Xiong Mengfei , L'Estrade Elina T , Raval Nakul R , Andersen Ida Vang , Edgar Fraser G , Speth Nikolaj Raahauge , Bærentzen Simone Larsen , Hansen Hanne Demant , Donovan Lene Lundgaard , Nasser Arafat , Peitersen Siv Thorlund , Kjær Andreas , Knudsen Gitte Moos , Syvänen Stina , Palner Mikael , Herth Matthias Manfred
Published: September 2020

Background: Positron Emission Tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation of PET tracers is often conducted in rodents due to the accessibility of disease models as well as economic considerations. Compared to larger species, rodents display a higher expression and/or activity of efflux transporters such as the P-glycoprotein (P-gp). Low brain uptake could, therefore, be species-specific and uptake in rodents not be predictive for that in humans. We hypothesized that a better prediction from rodent data could be achieved when a tracer is evaluated under P-gp inhibition. Consequently, we compared the performance of eight neuroreceptor tracers in rats with and without P-gp inhibition including a specific binding blockade. This data set was then used to predict the binding of these eight tracers in pigs.Methods: PET tracers targeting serotonin 5-HT2A receptors ([18F]MH.MZ, [18F]Altanserin, [11C]Cimbi-36, [11C]Pimavanserin), serotonin 5-HT7 receptors ([11C]Cimbi-701, [11C]Cimbi-717 and [11C]BA-10) and dopamine D2/3 receptors ([18F]Fallypride) were used in the study. The brain uptake and target-specific binding of these PET radiotracers were evaluated in rats with and without inhibition of P-gp. Rat data were subsequently compared to the results obtained in pigs.Results: Without P-gp inhibition, the amount of target-specific binding in the rat brain was sufficient to justify further translation for three out of eight evaluated tracers. With P-gp inhibition, five out of eight tracers justifyied further translation. The performance in pigs could correctly be predicted for six out of eight tracers when rat data obtained under P-gp inhibition were used, compared to four out of eight tracers without P-gp inhibition.Conclusions: P-gp strongly affects the uptake of PET tracers in rodents, but false prediction outcomes can be reduced by evaluating a tracer under P-gp inhibition.
Are Healthcare Professionals Sufficiently Aware of Dental Ethics? Fields Research in Southeast Turkey
Authors: Bakir Elif Pinar , Bakir Seyhmus , Sonkaya Ezgi , Ünal Samican Ünal
Published: September 2020

Background: The aim of this study was to evaluate the awareness of healthcare personnel in the Dentistry Faculty of Dicle University about “the legal responsibilities of dental practitioners” and “patient rights”. Methods: The study included 150 volunteers who were healthcare workers in the Faculty of Dentistry , Dicle University between June and July 2019. The subjects were randomly selected from five different Professional groups and data were collecte dusing a single data collection form. All items on the form were grade dusing a 5-point Likert –type response. In the statistical analyses, Pearson’ s Chi-square, Yates Chi-square and the Fisher Exact tests were used. Results:The questionnaire responses showed that 61.3% of the study participants had received training on patient rights and 56.7% had information about the legal responsibilities of dentists. The rate of dentists who had received training was below average and 38.9% of the dentists reported not having any information about their own legal responsibilities. A positive response was given to the items on the questionnaire by 58% and a negative responseby 33%. The responses to some items were seen to have been affected by variables such as age, gender and professional group.Conclusion: Although some confusion was experienced by the healthcare personel about patient rights and the legal responsibilities of dentists, the levels of awareness were evaluated as satisfactory.