bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of EUS-guided FNB using a Franseen needle for tissue acquisition and microsatellite instability evaluation in unresectable pancreatic lesions
Authors: Sugimoto Mitsuru , Irie Hiroki , Takagi Tadayuki , Suzuki Rei , Konno Naoki , Asama Hiroyuki , Sato Yuki , Nakamura Jun , Takasumi Mika , Hashimoto Minami , Kato Tsunetaka , Kobashi Ryoichiro , Kobayashi Yasuyuki , Hashimoto Yuko , Hikichi Takuto , Ohira Hiromasa
Published: August 2020

Background: The efficacy of immune checkpoint blockade in the treatment of microsatellite instability (MSI)-high tumors was recently reported. Therefore, the acquisition of histological specimens is desired in cases of unresectable solid pancreatic lesions (UR SPLs). This study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for UR SPL tissue acquisition and MSI evaluation.Methods: A total of 195 SPL patients who underwent EUS-guided fine-needle aspiration (EUS-FNA) or EUS-FNB (EUS-FNAB) between January 2017 and March 2020 were enrolled in this study. Among them, 89 SPL patients (FNB: 28 patients, FNA: 61) underwent EUS-FNAB using a 22-G needle (UR SPLs: 58 patients, FNB: 22, FNA: 36) (UR SPLs after starting MSI evaluation: 23, FNB: 9, FNA: 14).Results: The puncture number was significantly lower in FNB than in FNA (median (range): 3 (2-5) vs 4 (1-8), P < 0.01, UR SPLs: 3 (2-5) vs 4 (1-8), P = 0.036). Histological specimen acquisition was more common in FNB than in FNA (92.9% (26/28) vs 68.9% (42/61), P = 0.015, UR SPLs: 100% (22/22) vs 72.2% (26/36), P < 0.01). The histological specimen required for MSI evaluation was acquired more often in FNB than in FNA (88.9% (8/9) vs 35.7% (5/14), P = 0.03).Conclusions: EUS-FNB using a Franseen needle could be efficient for histological specimen acquisition and sampling the required amount of specimen for MSI evaluation in UR SPL patients.
Evolutionary Pattern of Macaca Fascicularis in Southeast Asia Inferred Using Y-chromosomal Gene
Authors: Rovie-Ryan Jeffrine J , Khan Faisal Ali Anwarali , Abdullah Mohd Tajuddin
Published: August 2020

Background: We analyzed a combined segment (2,032-bp) of the sex-determining region and the testis-specific protein of the Y-chromosome (Y-DNA) gene to clarify the gene flow and phylogenetic relationships of the long-tailed macaques (Macaca fascicularis) in Southeast Asia. Phylogenetic relationships were constructed using the maximum likelihood, Bayesian inference, and the median-joining network from a total of 164 adult male M. fascicularis from 62 localities in Malaysia, including sequences from the other regions from previous studies. Results: Based on Y-DNA, we confirm the presence of two lineages of M. fascicularis: the Indochinese and Sundaic lineages. The Indochinese lineage is represented by M. fascicularis located northwards of the Surat Thani-Krabi depression region and is contaminated by the Macaca mulatta Y-DNA. The Sundaic lineage is free from such hybridization event, thus defined as the pure carrier of the M. fascicularis Y-DNA. We further revealed that the Sundaic lineage differentiated into two forms: the insular and the continental forms. The insular form, which represents the ancestral form of M. fascicularis, consists of two haplotypes: a single homogenous haplotype occupying the island of Borneo, Philippines, and southern Sumatra; and the Javan haplotype. The more diverse continental form consists of 17 haplotypes in which a dominant haplotype was shared by individuals from southern Thai Peninsular (south of Surat Thani-Krabi depression), Peninsular Malaysia, and Sumatra. Uniquely, Sumatra contains both the continental and insular Y-DNA which can be explained by a secondary contact hypothesis. Conclusions: Overall, the findings in this study are important: 1) to help authority particularly in Malaysia on the population management activities including translocation and culling of conflict M. fascicularis, 2) to identify the unknown origin of captive M. fascicularis used in biomedical research, and; 3) the separation between the continental and insular forms warrants for the treatment as separate management units.
Circular RNA circMYL1 inhibit proliferation and promote differentiation of myoblasts by sponging miR-2400
Authors: Elnour Ibrahim E. , Wang Xiaogang , Zhansaya Toremurat , Zhanerke Akhatayeva , Khan Rajwali , Cheng Jie , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Chen Hong
Published: August 2020

Background
Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) involved in regulating skeletal muscle development by sponging microRNAs (miRNAs). This study aimed to define the circMYL1 molecular mechanisms in the regulation of bovine myogenesis and to disclose its regulatory mechanism through miR-2400 interaction.
Methods
The potential role of circMYL1 was identified in the proliferation of bovine myoblast through mRNA and protein expression of proliferation marker genes (PCNA, CyclinD1, and CDK2), cell counting kit-8 (CCK8) assay, flow cytometry analysis, and EdU assay. Analysis of the expression of differentiation marker genes (MyoD, MyoG, and MYH2) and immunofluorescence of Myosin heavy chain (MyHC) was used to assess cell differentiation.
Results
The proliferation analysis revealed that circMYL1 inhibited the proliferation of bovine primary myoblast. Furthermore, the differentiation analysis demonstrated that circMYL1 promoted the differentiation of bovine primary myoblast. The luciferase screening and RNA immunoprecipitation (RIP) assays found that circMYL1 could have interaction with miR-2400. Additionally, we demonstrated that miR-2400 promoted proliferation and inhibited differentiation of bovine primary myoblast, while circMYL1 may eliminate the effects of miR-2400, as showed by rescue experiments.
Conclusions
Our results revealed that a novel circular RNA of circMYL1 could inhibit proliferation and promote differentiation of myoblast by sponging miR-2400.
Experimental realization of phase-controlled dynamics with hybrid digital-analog approach
Authors: Tao Ziyu , Zhang Libo , Li Xiaole , Niu Jingjing , Luo Kai , Yi Kangyuan , Zhou Yuxuan , Jia Hao , Liu Song , Yan Tongxing , Chen Yuanzhen , Yu Da-Peng
Published: August 2020

Quantum simulation can be implemented in pure digital or analog ways, each with their pros and cons. By taking advantage of the universality of a digital route and the eﬃciency of analog simulation, hybrid digital-analog approaches can enrich the possibilities for quantum simulation. We use a unique hybrid approach to experimentally perform a quantum simulation of phase-controlled dynamics resulting from a closed-contour interaction (CCI) within certain multi-level systems in superconducting quantum circuits. Due to symmetry constraints, such systems cannot host an inherent CCI. Nevertheless, by assembling analog modules corresponding to their natural evolutions and specially designed digital modules constructed from standard quantum logic gates, we can bypass such constraints and realize an eﬀective CCI in these systems. Based on this realization, we demonstrate a variety of related and interesting phenomena, including phase-controlled chiral dynamics, separation of chiral enantiomers, and a new mechanism to generate entangled states based on CCI.
Definitive-intent uniform megavoltage fractioned radiotherapy protocol for presumed canine intracranial gliomas: retrospective analysis of survival and prognostic factors in 38 cases (2013-2019).
Authors: DEBREUQUE MAUD , DE FORNEL Pauline , DAVID INGRID , DELISLE FRANCOISE , DUCERVEAU MARIE-NOELLE , DEVAUCHELLE PATRICK , THIBAUD JEAN-LAURENT
Published: August 2020

Background: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumors. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumor imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners. Results: The MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2±7.4% and 49.0±9.8%. Initial clinical signs were related to survival, as well as tumor characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed. Conclusions: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumor control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI descriptions (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
Encoding Motivation Prediction Errors in the Human Dopaminergic Reward System
Authors: Ni Yinmei , Wang Sidong , Su Jie , Li Jian , Wan Xiaohong
Published: August 2020

The dopaminergic reward system encoding the reward PE signals is vital for reinforcement learning (RL). Although this reward PE hypothesis has been extensively validated, it remains considerable debates on the alternative account of motivation. In the current study, we diverted the participants’ motivation from the conditioned stimulus (CS)-associated valences to the CS-elicited actions in a variant Pavlovian conditioning task under appetitive and aversive conditions. We found that the regions in the dopaminergic reward system did not encode such bidirectional reward PE signals, but the PE magnitudes, namely, the motivation PE signals. These neural signals without indicating the directions of learning could not be directly used for model-free RL, but probably for model-based control. Specifically, the ventral striatum during the feedback phase might encode the need of adjusting the learning policy, while the putative substantia nigra pars compacta (SNc) in the midbrain and the putamen during the prediction phase might sustain the intended actions. Meanwhile, the primary motor cortex encoded the salience PE signals for model-free RL. Therefore, our findings demonstrate that the human dopaminergic reward system could encode the motivation PE signals to substantialize model-based control, rather than model-free learning, suggesting that its involvement in RL should be motivation-dependent.
Can We Use Targeted Next-Generation Sequencing an Alternative Method to the Conventional Tests in Haematological Malignancies?
Authors: Atli Emine Ikbal , Gurkan Hakan , Atli Engin , Kirkizlar Hakki Onur , Yalcintepe Sinem , Demir Selma , Demirci Ufuk , Eker Damla , Mail Cisem , Kalkan Rasime , Demir Ahmet Muzaffer
Published: August 2020

Introduction: Advanced diagnostic methods give a huge advantage for identification of the abnormalities in myeloid malignancies. Researchers tried to show the potential importance of genetic tests both before the onset of the disease and during the remission. Large testing panels prevents false negative results in myeloid malignancies. But the important question is how can be merged with conventional cytogenetic and molecular cytogenetic techniques together with NGS technologies. Methods: In this paper, we draw an algorithm for evaluation of the malignancies. In order to evaluation of genetic abnormities we performed cytogenetics, molecular cytogenetics and NGS testing panels in hematologic malignancies. In this study, we analyzed 132 patients which are referred to Medical Genetics Laboratory within different type of hematologic malignancies. We highlighted possible algorithm for cytogenetically normal cases.Results: We analyzed cytogenetically normal patients by using NGS 141 gene panel and we detected two or more pathogenic variations in 20 out of 132 patients.Conclusions: Despite of long turnaround time conventional techniques is still golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot easily be identified by conventional techniques that conditions advanced technologies are recommended.
Whole-genome microsynteny-based phylogeny of angiosperms
Authors: Zhao Tao , Xue Jiayu , Zwaenepoel Arthur , Kao Shu-min , Li Zhen , Schranz M. , de Peer Yves Van
Published: August 2020

Plant genomes are generally very complex and dynamic structures, and vary greatly in size, organization, and architecture. This is mainly due to the often-excessive numbers of transposable and repetitive elements, as well as to the fact that many plants are ancient or recent polyploids. Such (recurrent) whole-genome duplications are usually followed by genomic rearrangements, gene transpositions and gene loss, making local gene order-based phylogenetic inference particularly challenging. Nevertheless, microsynteny, i.e. the conservation of local gene content and order, has been recognized as a valuable and alternative phylogenetic character to sequence-based characters (nucleotides or amino acids) for the inference of phylogenetic trees, but to date its application for reconstructing larger phylogenies has been, for several reasons, limited. Here, by combining synteny network analysis, matrix representation, and maximum likelihood, we have reconstructed a microsynteny-based phylogenetic tree for more than 120 available high-quality plant genomes, representing more than 50 different plant families and 30 plant orders within the angiosperms. Comparisons with sequence alignment-based trees and current phylogenetic classifications show that we reconstruct very accurate and robust phylogenies, albeit with sometimes important alternative sister-group relationships. For instance, our synteny-based tree positioned Vitales as early-diverging eudicots, Saxifragales belongs to superasterids, and magnoliids as sister to monocots. We discuss how synteny-based phylogeny can be complementary to traditional methods and could provide additional insights into some long-standing controversial phylogenetic relationships.
A Sixteen-years Delay in Sun-related Terrestrial Warming
Authors: Nieuwenhuizen A.C.T. , Jager C. de , Nieuwenhuijzen H.
Published: August 2020

In an earlier paper De Jager et al. (2018) studied the relation between the intensity variations of the variable equatorial and polar solar magnetic energy sources and that of the average terrestrial northern hemisphere ground temperature. It was found that during the period 1610 to about 1920 the variation in the smoothed terrestrial temperature and those of the solar magnetic radiation are well correlated but that after that an additional temperature increase became prominent, to reach around the year 2000 a value of about one degree above the sun-dependent forecast. In the present paper an additional aspect of the above material is described, and we find that, apart from the above mentioned features, there is a delayed component of the sun-related heating with a time lag of about 16 years. The resulting relation between the variable flux of the solar magnetic energy and the average - smoothed – northern hemisphere ground temperature is presented in our final diagram, Fig. 13. Our results confirm earlier findings by other authors that ascribe such a time lag to glacier warming and cooling.
Mild Hyponatremia is Associated with Low Skeletal Muscle Mass, Physical Function Impairment, and Depressive Mood in the Elderly
Authors: Fujisawa Chisato , Umegaki Hiroyuki , Sugimoto Taiki , Samizo Satoshi , Huang Chi Hsien , Fujisawa Haruki , Sugimura Yoshihisa , Kuzuya Masafumi , Toba Kenji , Sakurai Takashi
Published: August 2020

Background: Mild hyponatremia (serum sodium 130-135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly. Methods: We enrolled 75 participants with mild hyponatremia and 2872 with normonatremia (serum sodium, 136-145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan’s National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined. Results: One-way analysis of covariance showed that the participants with mild hyponatremia had significantly lower SMI, GS, WS, OLS time, and score on the 15-item Geriatric Depression Scale compared with those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with weaker GS (odds ratio [OR]: 2.3, p = 0.048), slower WS (OR: 7.6, p = 0.01) and shorter OLS time (OR: 2.1, p = 0.03) as well as with severe depressive mood (OR: 2.6, p = 0.001) but not with sarcopenia (OR: 1.9, p = 0.09) or SMI (OR: 1.7, p= 0.1). Conclusions: Our results suggest mild hyponatremia in the elderly was associated with impairment of physical function, especially including WS and OLS, and depressive mood.
Early warning score using electronically-held data for patients discharged from intensive care units
Authors: Pimentel Marco , Johnson Alistair , Darbyshire Julie , Tarassenko Lionel , Clifton David , Walden Andrew , Rechner Ian , Young Duncan , Watkinson Peter
Published: August 2020

Rationale. Intensive care units (ICUs) admit the most severely ill patients. Once these patients are discharged from the ICU to a step-down ward, they continue to have their vital signs monitored by nursing staff, with early warning score (EWS) systems being used to identify those at risk of deterioration. Objectives. We report the development and validation of an enhanced continuous scoring system for predicting adverse events, which combines vital signs measured routinely on acute care wards (as used by most EWSs) with a risk score of a future adverse event calculated on discharge from ICU.Methods. A modified Delphi process identified common, and candidate variables frequently collected and stored in electronic records as the basis for a ‘static’ score of the patient’s condition immediately after discharge from the ICU. L1-regularised logistic regression was used to estimate the in-hospital risk of future adverse event. We then constructed a model of physiological normality using vital-sign data from the day of hospital discharge, which is combined with the static score and used continuously to quantify and update the patient’s risk of deterioration throughout their hospital stay. Data from two NHS Foundation Trusts (UK) were used to develop and (externally) validate the model.Measurements and Main Results. A total of 12,394 vital-sign measurements were acquired from 273 patients after ICU discharge for the development set, and 4,831 from 136 patients in the validation cohort. Outcome validation of our model yielded an area under the receiver operating characteristic curve (AUROC) of 0.724 for predicting ICU re-admission or in-hospital death within 24h. It showed an improved performance with respect to other competitive risk scoring systems, including the National EWS (NEWS, 0.653). Conclusion. We showed that a scoring system incorporating data from a patient’s stay in ICU has better performance than commonly-used EWS systems based on vital signs alone.
Risk Factors for Transfusion-Related Acute Lung Injury in Critical Patients Admitted in Intensive Care Unit: A Systematic Review and Meta-Analysis
Authors: Hu Lunyang , Wang Baoli , Jiang Yong , Zhu Banghui , Wang Chen , Yu Qing , Hou Wenjia , Xia Zhaofan , Wu Guosheng , Sun Yu
Published: August 2020

Background: Until now, transfusion-related acute lung injury (TRALI) has been considered to be the leading cause of blood transfusion-related diseases and death. And there is no clinically effective treatment plan for TRALI. The aim of this study was to systematically summarize the literature on risk factors for TRALI in critical patients. Methods: Electronic searches (up to March 2020) were performed in the Cochrane Library, Web of Knowledge, Embase, and PubMed databases. We included studies reporting on the risk factors of TRALI for critical patients and extracted the risk factors. Finally, third studies met the inclusion criteria. Results: We summarized and analyzed the potential risk factors of TRALI for critical patients in 13 existing studies. The host-related factors were age (odds ratio (OR) [95% confidence interval] = 1.16 [1.08-1.24]), sex (OR = 1.26 [1.16-1.38]), tobacco use status (OR = 3.82 [1.91-7.65]), chronic alcohol abuse (OR = 3.82 [2.97-26.83]), fluid balance (OR = 1.24 [1.08-1.42]), shock before transfusion (OR = 4.41 [2.38-8.20]), and ASA score of the recipients (OR = 2.72 [1.43-5.16]). The transfusion-related factors were the number of transfusions (OR = 1.40 [1.14-1.72]) and fresh frozen plasma (FFP) units (OR = 1.21 [1.01-1.46]). The device-related factor was mechanical ventilation (OR = 4.13 [2.20-7.76]). Conclusions: The risk factors for TRALI in this study included age, sex, tobacco use, chronic alcohol abuse, fluid balance, shock before transfusion, ASA score, number of transfusions, FFP units and mechanical ventilation. Our study suggests that host-related risk factors play a more important role in the occurrence and development of TRALI than blood transfusion-related risk factors.
Oral toxicity to high level sodium fluoride causes impairment of autophagy
Authors: Oka Shunichi , Li Xiaoyan , Zhang Fengzhu , Taguchi Chieko , Tewari Nitesh , Kim Il-Shin , Zhong Liangjun , Arikawa Kazumune , Liu Yi , Bhawal Ujjal K.
Published: August 2020

Background: Gingival recession and concomitant alveolar bone resorption are hallmarks of periodontal diseases and excessive fluoride intake has some deleterious effects on teeth, bone and soft tissues. Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Methods: HCEM2 cementoblast cells in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Real-time quantitative RT-PCR and Western blotting were performed to characterize the mRNA and protein expression levels of markers for autophagy, apoptosis, and oxidative stress. C57BL/6 mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels of autophagy, apoptosis, and oxidative stress markers.Results: Cementoblasts exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin1 and LC3-II, elicited excessive apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Consistently, the in vivo results verified the findings of the in vitro study and treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. These results correlated with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in 5 mM NaF-induced cell death. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin1 expression was abrogated by 5 mM NaF.Conclusion: Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.
Guidelines Translation for Distress Management in Cancer Patients Based on CAN-IMPLEMENT: Adaptation Part
Authors: Fu Liang , Yang Yang , Hu Yan , Lu Zhenqi , Zhang Xiaoju , Huang Mingzhu , Li Yuanyuan , Zhu Fuzhong , Wang Yang , Huang Zhe
Published: August 2020

Background
Almost all cancer patients experience some level of distress, which has significantly reduced their quality of life. Nowadays evidence-based practice in various fields of health care is increasing, and it has played an important role. This study aimed to clarify the theme of guideline adaptation, integrate relevant clinical practice guidelines on distress management in cancer patients, and develop the Cancer-related Distress Management Guidelines.
Methods
A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) was used as the research framework, which include three phases. Here the Adaptation Part (Phase 1) was reported: adaptation of relevant clinical practice guidelines on the distress management in cancer patients to form the Cancer-related Distress Management Guidelines.
Results
The physical symptom distress score (0.61 ± 0.58) was almost equal to the psychological symptom distress score (0.61 ± 0.70) among cancer patients in Shanghai. A work plan for the adaptation of Cancer-related Distress Management Guidelines was developed. Two clinical practice guidelines related to distress management in cancer patents were included after searching, screening, assessment and selection. The domain scores of the draft the Cancer-related Distress Management Guidelines on Appraisal of Guidelines for Research and Evaluation II (AGREE II) were 80.00% (scope and purpose), 82.78% (stakeholder involvement), 87.50% (rigour of development), 73.89% (clarity and presentation), 73.75% (applicability), 87.50% (editorial independence) respectively. The scores of most recommendations on feasibility, appropriateness, meaningfulness and effectiveness were 90.0% or higher. The final guidelines included 13 recommendations.
Conclusions
The psychological symptoms and physical symptoms were both worthy of attention in cancer patients. The quality of the draft the Cancer-related Distress Management Guidelines was well-accepted based on two included guidelines. Most recommendations received positive and constructive feedback on feasibility, appropriateness, meaningfulness and effectiveness. The final guidelines was formed based on the revision of the first draft guidelines.
Clinical scoring for the failure of non-invasive ventilation in acute respiratory failure patients in the Emergency Department.
Authors: liengswangwong Wijittra , Yuksen Chaiyaporn Mahidol , Thepkong Tipanun , Nakasint Pornita , Jenpanitpong Chetsadakon
Published: August 2020

Background Non-invasive mechanical ventilation (NIV) has become an alternative to an invasive artificial airway for the management of acute respiratory failure (ARF). NIV failure causes delayed intubation, which eventually has been associated with increased morbidity and mortality. This study aimed to develop the clinical scoring system of NIV failure in ARF patients. Methods This study was a diagnostic, retrospectively cross-sectional, and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between February 2017 and December 2017. We included all of the acute respiratory failure patients aged >18 years and received non-invasive ventilation (NIV). Clinical factors associated with NIV failure were recorded. The predictive model and prediction score for NIV failure were developed by multivariable logistic regression analysis. Result A total of 329 acute respiratory failure patients have received NIV success (N = 237) and failure (N = 92). This study showed that NIV failure was associated with heart rate > 110 bpm, systolic BP < 110 mmHg, SpO2 < 90%, arterial pH < 7.30 and serum lactate. The clinical scores were classified into three groups: low, moderate, and high. Conclusion We suggested that the novel clinical scoring of the NIV failure in this study may use as a good predictor for NIV failure in the emergency room.
HSPA4 knockdown retarded progression and development of colorectal cancer
Authors: Zhang Mingliang , Dai Weigang , Li Zhanyu , Tang Liang , Chen Jianhui , Chen Chuangqi
Published: August 2020

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.
Multivariate Analysis of Early Surgical Management Factors Affecting Posttraumatic Penoscrotal Avulsion Injury: A Level I Trauma Center Study
Authors: KIM MIN JI , Lee Dong Hwan , Park Dong HA , Lee Il Jae
Published: August 2020

Background To conduct an accurate evaluation of patients presenting with posttraumatic penoscrotal injuries, and to formulate a treatment algorithm based on this assessment. Methods We conducted a retrospective chart review study. Patients with penoscrotal defects admitted to our level Ⅰ trauma center from 2017 to 2019 were evaluated. The Braden scale score was used for wound evaluation and the Korean patient classification system (KPCS) was used for assessment of severity. Univariate and multivariate analyses were performed for potential risk factors associated with early surgical management. Results In total, there were 58 male patients, and the average Braden scale score was 12.08 ± 2.54, with the scrotum (36.20%), and the penile shaft (32.76%) being popular sites for injuries. The wounds requiring surgical treatment were 20.68% (n=12), with local flaps (33.33%) being most commonly used. The significant predictors of advanced wounds which required surgical treatment were old age (p=0.026, Odds Ratio [OR] 8.238), orthopedic combined injuries (p=0.044, OR 1.088), intubation (p=0.018, OR 9.625), restrain (p=0.036, OR 0.157) and blood transfusion (p<0.001, OR 2.462).Conclusion In multiple trauma patients, penoscrotal defects caused by high-speed trauma are an important matter of concern. Specifically, patients with combined skeletal injuries or requiring respiratory care were prone to advanced wounds. We proposed a five-category algorithm to manage such patients, which included severity of the patient’s condition, respiration, hemodynamic status, comorbidity, and immobilization. Additionally, inter-departmental cooperation and active intervention by plastic surgeons is needed for the comprehensive treatment of such injuries. Trial registration This study was performed in line with the principles of the Declaration of Helsinki. The study and all its protocols were approved by the institutional review board of Ajou Medical Center (approval no. AJIRB-MED-MDB-17-254). The need for informed consent was waived by the institutional review board of our hospital due to the retrospective design of the study.
Global transcriptional regulation by cell-free sup of S. Typhimurium peptide transporter mutant leads to inhibition of intraspecies biofilm initiation
Authors: Chandra Kasturi , Muralidhara Prerana , Kamanna Sathisha , Tatu Utpal , Chakravortty Dipshikha
Published: August 2020

Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause ¼th of the diarrhoeal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although the biofilm removal or dispersal have been studied widely, the inhibition of initiation Salmonella biofilm has not been studied much. This study was conducted to determine the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation inducible proline peptide transporter mutant (ΔyjiY) strain. Our study shows that Salmonella ΔyjiY culture supernatant inhibits biofilm initiation by regulating biofilm associated transcriptional network. This work demonstrates that highly abundant proteases like ecotin, HslV and GrpE cleave the protein aggregates, whereas global transcription regulators H-NS, FlgM regulate expression of SPIs and flagellar genes. Relatively low abundance of flavoredoxin, glutaredoxin, thiol peroxidase etc. leads to accumulation of ROS within the biofilm, and subsequent toxicity. This work further suggests that targeting these oxidative stress relieving proteins might be a good druggable choice to reduce Salmonella biofilm.
Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies
Authors: Bacha Mohsinul Mulk , Nadeem Humaira , Rehman Shafiq Ur , Sarwar Sadia , Imran Aqeel , Zaib Sumera , Arif Muazzam , Iqbal Jamshed
Published: August 2020

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.
LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop
Authors: Zhu Li , Zhang Yan-Jun , Wang Bin , Yang Li , Zheng Yi-Qiong , Sun Lin-De , Tian Lin , Chen Tao , Wang Jian Dong
Published: August 2020

Background: Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood.Methods: TCGA data was utilized to screen out lncRNAs dysregulated in breast cancer. The expression level of genes were analyzed and measured by RT-qPCR. The effects of PCDHB17P in breast cancer were determined in vitro and in vivo. Bioinformatics analysis was applied to predict the target between genes in breast cancer and verified via luciferase reporter assays, RNA Immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP).Results: LncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decree ased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer.Conclusions: Our research demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.
Bioinformatics Analysis of the Regulatory lncRNA-miRNA-mRNA Network in Patients with Neuropathic Pain
Authors: Zhang Huai-Gen , Liu Li , Song Zhi-Ping , Zhang Da-Ying
Published: August 2020

Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Methods: Here, we explore the key molecules involved in the development of NP condition via identification of lncRNA-miRNA-mRNA expression pattern of patients with NP. We identified differentially expressed miRNAs, lncRNA and mRNA through a comprehensive analysis strategy. Subsequently, we used bioinformatics approach to perform pathway enrichment analysis on DEGs and protein-protein interaction analysis. Combined with the three datasets, the lncRNA-miRNA-mRNA network was constructed. It will then be used as targets for drug prediction. Results: The results showed that a total of 8,251 DEGs (4,193 upregulated and 4,058 downregulated) were identified from the three microarray datasets, 959 DEmiRs (455 upregulated and 504 downregulated), 2,848 DElncs (1,324 upregulated and 1,524 downregulated). GO analysis showed that DEGs are mainly enriched in blood circulation, regulation of membrane potential and regulation of ion transmembrane transport. KEGG results showed that DEGs are enriched in neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and MAPK signaling pathway. When the correlation is set to above 0.8, a total of 31 lncRNAs, 36 miRNAs and 24 mRNAs were screened in the lncRNA-miRNA-mRNAs network. The results of drug prediction indicated the targeted drugs mainly include INDOMETHACIN, GLUTAMIC ACID and PIRACETAM. Conclusion: The lncRNA-miRNA-mRNA network has been carried out a comprehensive biological information analysis and predicted the potential therapeutic application of drugs in patients with NP. The corresponding data has a certain reference for studying the pathological mechanism of NP.
RIP3 mediates TCN-induced necroptosis through activating mitochondrial metabolism and ROS production in apoptosis-resistant cancer cells
Authors: Zhao Xu , Quan Jing , Tan Yue , Liu Ying , Liao Chaoliang , Li Zhenzhen , Liao Weihua , Liu Jikai , Cao Ya , Luo Xiangjian
Published: August 2020

Background: Resisting cell death is one of the hallmarks of cancer. Necroptosis is a form of non-caspase dependent necrotic cell death mediated by receptor-interacting protein kinase-1/3 (RIP1/3), which represents another mode of programmed cell death besides apoptosis. Growing evidence supports that RIP3 has emerged as a critical regulator of necroptosis and can be activated by several stimuli to trigger necroptotic cell death in a RIP1-independent manner. RIP3 also acts as an energy metabolism regulator associated with switching cell death from apoptosis to necroptosis. Natural products provide a unique source for the discovery of innovative leading compounds and drugs, which exhibits promising anticancer activities through inducing cell death and enhancing chemotherapeutic sensitivity. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes and shows potent anti-tumor bioactivity. However, the underlying mechanism is not fully understood.Methods: Cell permeability assay and transmission electron microscopy were applied to identify the death pattern induced by TCN in apoptotic-resistant cancer cells. We used Seahorse extracellular flux analyzer to examine the cellular oxygen consumption rate (OCR) and flow cytometry to detect mitochondrial reactive oxygen species (ROS) content. Xenograft animal experiment was performed to assess the effect of TCN synergized with cisplatin to enhance chemotherapeutic sensitivity of tumor cells. Results: Our current findings revealed that RIP3 mediated TCN-induced necroptosis through activating mitochondria energy metabolism and ROS production in apoptotic-resistant cancer cells. RIP3 might be involved in sensitizing tumor cells to chemotherapy induced by TCN. Conclusions: Activating RIP3 to induce necroptosis through reprogramming mitochondrial energy metabolism and ROS production contributes to the anti-tumor activity of TCN. Moreover, TCN could be exploited for therapeutic gain through up-regulating RIP3 to sensitize cancer chemotherapy.
Coupling of the atmosphere and sediment melts across the Archean-Proterozoic transition
Authors: Liebmann Janne , Spencer Christopher , Kirkland Christopher , Bucholz Claire , Xia Xiao-Ping , Martin Laure , Kitchen Nami , Shumlyanskyy Leonid
Published: August 2020

The Archean-Proterozoic transition marks a time of fundamental geologic, biologic, and atmospheric changes to the Earth system, including oxygenation of the atmosphere (termed the Great Oxygenation Event; GOE), and the emergence of continents above sea-level. The impacts of the GOE on Earth’s surface environment are imprinted on the geologic record, including the attenuation of mass-independent fractionation of sulfur isotopes (S-MIF). Temporally overlapping geologic and geochemical observations (e.g. a change in oxygen isotope ratio of sediment melts) imply the widespread subaerial emergence of continents was coeval with atmospheric oxygenation. Here we present triple sulfur isotope ratios in pyrite and oxygen isotope ratios in garnet and zircon in a global suite of Archean and Proterozoic sediment-derived granitoids. These crustal melts record an increase in average 18O/16O isotope ratio and a disappearance of S-MIF in the Paleoproterozoic. The coupled behaviour of sulfur and oxygen isotope signatures imply a potential causal link between the emergence of continents and atmospheric oxygenation at ~2.3 Ga.
LncRNA KCNK15-AS1 inhibits pancreatic cancer progression by promoting the expression of its binding protein ACTR3B
Authors: Wu Pengfei , Yuan Hao , Ding Xiangya , Chen Qun , Ge Wanli , Meng Lingdong , Huang Xumin , Shen Peng , Lu Yichao , Lu Zipeng , Jiang kuirong
Published: August 2020

Background

LncRNAs are reported to play an essential role in multiple tumors, including pancreatic cancer. LncRNAs could impact tumor growth via RNA-binding proteins, working as a coactivators of transcription factors or impacting their gene expression via posttranscriptional regulation. Our study aimed to elucidate the function and mechanism of lncRNA KCNK15-AS1 and its binding protein ACTR3B in PC progression. Our previous data indicated that KCNK15-AS1 is downregulated in PC tissues and cell lines compared to normal controls.
Methods

In this study, we overexpressed KCNK15-AS1 and ACTR3B in both BxPC-3 and Mia-PaCa-2 cells to detect the cellular phenotype in vitro and in vivo. RNA pulldown assays, mass spectrometry assays and RNA-binding protein immunoprecipitation assays were used to verify KCNK15-AS1 RNA binding protein ACTR3B. Luciferase reporter assay and ubiquitination assay were proceeded to detect the mechanism KCNK15-AS1 upregulated ACTR3B expression.
Results

Our results showed that overexpression of KCNK15-AS1 significantly inhibited the proliferation, colony formation and migration of PC cells. ACTR3B was screened by RNA pulldown and mass spectrometry assays. RNA-binding protein immunoprecipitation assays confirmed that KCNK15-AS1 physically bound to ACTR3B. Furthermore, mechanistic analyses demonstrated that KCNK15-AS1 promoted ACTR3B expression by inhibiting ACTR3B ubiquitin-mediated degradation and enhancing its promoter activity. Additionally, ACTR3B presented low expression in PC tissues and cell lines, and PC cell growth was significantly repressed when ACTR3B was overexpressed. Moreover, knockdown of ACTR3B in KCNK15-AS1-overexpressing cells reversed the effects of KCNK15-AS1 on PC cell growth via the cyclin D1/CDK4 axis.
Conclusion

Briefly, our study indicated that the lncRNA KCNK15-AS1/ACTR3B/cyclin D1/CDK4 axis may inhibit PC progression, which provides a potential therapeutic target for PC.
Evaluation the energy production potential of aggressively invasive Prosopis juliflora Sw (Fabacea): an emerging threat in the Bundala Ramsar Wetland
Authors: Bandara W.A.R.T.W. , Ranasinghe Oshadi Ruwanthika , Vlosky Richard
Published: August 2020

Prosopis juliflora is an invasive plant species rapidly expanding in the Asian and African continents. Invasion of P. juliflora in Bundala Ramsar Wetland (BRW) in Sri Lanka has created a number of biodiversity and conservation issues. This study was conducted to assess the possibility to utilize this invasive plant as a fuel source for local industries. The moisture content, wood density, ash content, volatile matter, fixed carbon content, biomass/ash ration and calorific value of P. juliflora were measured and compared with Leucaena leucocephala, which is a widely used fuelwood source in Sri Lanka and elsewhere. P. juliflora , performed better than L. leucocephala for most of these parameters. Ash content was comparatively higher in P. juliflora than that of L. leucocephala ; however, biomass to ash ratio of P. juliflora was significantly lower (at 0.05 level of significance) than that of L. leucocephala, suggesting its suitability as a fuelwood source. Further, the fuel value index of P. juliflora (3,276) was slightly lower than that of L. leucocephala (3,336), a non-significant difference. P. juliflora and L. leucocephala reached Fiber Saturation Point values within drying periods of 24 and 27 days, respectively. According to our estimates of energy properties, 1 Kg of P. juliflora could be used to substitute 0.5 L of diesel and furnace oil as well as 5 kWh (5 units) of electricity. As such, we recommend harvesting P. juliflora from BRW as a potential fuelwood energy source for local industries.