bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe traumatic brain injury and hypotension is a frequent and lethal combination in mountain trauma patients – an analysis of the International Alpine Trauma Registry
Authors: Rauch Simon , Marzolo Matilde , Cappello Tomas Dal , Ströhle Mathias , Mair Peter , Pietsch Urs , Brugger Hermann , Strapazzon Giacomo , Group IATR Study
Published: November 2020

Background: Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multi-trauma in remote and mountainous areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension.Methods: Data from the International Alpine Trauma Registry including mountain multi-trauma patients (ISS≥16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP <110 mmHg on hospital arrival.Results: A total of 287 patients were included. Fifty (17%) had TBI and hypotension, 92 (32%) suffered TBI without hypotension and 145 (51%) patients did not have TBI. Patients in group 1 were more severely injured (mean ISS 43.1±17.4 vs 33.3±15.3 vs 26.2±18.1 for group 1 vs 2 vs 3, respectively, p<0.001). Mean SBP on hospital arrival was 83.1±12.9 vs 132.5±19.4 vs 119.4±25.8 mmHg (p<0.001) despite patients in group 1 received more fluids. Patients in group 1 had higher INR, lower haemoglobin and lower base excess (p<0.001). The rate of hypothermia on hospital arrival was different between the groups (p=0.029). Patients in group 1 had the highest mortality (24% vs 10% vs 1%, p<0.001).Conclusion: Multi-trauma in the mountains goes along with severe TBI in almost 50%. One third of patients with TBI is hypotensive on hospital arrival and this is associated with a worse outcome. No single variable or set of variables easily obtainable at scene was able to predict admission hypotension in TBI patients.
Excessive sedation as a risk factor for delirium: a comparison between two cohorts of critically-ill patients with and without COVID-19
Authors: Rasulo Frank A , Calza Stefano , Piva Simone , Marchesi Mattia , Nocivelli Gian Piero , Cattaneo Sergio , Matta Basil , Cunningham Daniel , Filippini Matteo , Terranova Francesco , Beretta Silvia , Latronico Nicola
Published: November 2020

Background: Excessive sedation has been associated with poor outcome in critically-ill patients with acute respiratory Distress Syndrome (ARDS). The on-going pandemic has seen many critically-ill COVID-19 with ARDS, yet the incidence of excessive sedation and its association to delirium in these patients has to date not been assessed. We aimed at comparing the incidence and outcome of excessive sedation and delirium in two cohorts of critically-ill patients. Methods: This was an international, dual center retrospective analysis of prospectively collected data from two cohorts of critically ill patients, with and without COVID-19 disease, pertaining to two different hospital settings. Depth of sedation was monitored through processed EEG and delirium through the Confusion Assessment Method for the ICU(CAM-ICU). The main outcomes were the incidence of excessive sedation and delirium between the two cohorts, and secondary outcomes were length of ICU and hospital stay and mechanical ventilation duration.Results: Fifty-seven non-COVID-19 and 21 COVID-19 patients were included, 38(49%) of whom had ARDS. Twenty-seven(47.3%) non-COVID-19 and 11(52.3%) COVID-19 patients fulfilled the criteria for excessive sedation. Excessively sedated patients were older(p=0.034) and had delirium more frequently(p<0.001). There was a trend in excessive sedation in ARDS patients, while there was no correlation between excessive sedation and COVID-19 diagnosis. COVID-19 with ARDS was related to delirium at the limit of significance. On adjusted analysis excessive sedation was independently related to delirium(p=0.008). Patients with delirium had longer MV duration, ICU-LOS and H-LOS. In the adjusted analysis, delirium was an independent predictor of ICU-LOS(p=0.005) and MV duration(p=0.039). SAPS II was higher in the non-COVID-19 patients when compared to COVID-19 patients. Despite this, COVID-19 patients remained ventilated for a longer period of time, had a longer ICU and H-LOS. Conclusion: Besides age, excessive sedation might represent an important risk factor for delirium in COVID-19 and non-COVID-19 critically ill patients, which may lead to an increased ICU-LOS, H-LOS and MV duration. The use of continuous EEG-based monitoring for quantification of sedation depth, along with frequent delirium assessment in critically-ill COVID-19 patients is warranted along with larger prospective trials aimed at verifying weather the use of EEG-based monitoring leads to improved outcome.
Clinical outcomes of gastroscopy in critically ill patients using high-dose proton pump inhibitor for suspected bleeding
Authors: Kwack Won Gun
Published: November 2020

Background: Gastroscopy is a useful procedure for gastrointestinal (GI) bleeding. No definite clinical guidelines recommend on the choice of gastroscopy implementation in the intensive care unit (ICU) patient with suspected GI bleeding. The objective of this retrospective study was to compare the clinical effectiveness of gastroscopy in critically ill patients using high-dose proton pump inhibitor for suspected bleeding.Methods: ICU patients using a high-does proton pump inhibitor for suspected GI bleeding from January 2015 to February 2020 were retrospectively included. Massive GI bleeding, such as hematemesis and hematochezia, were excluded. After propensity score matching (PSM) between the gastroscopy and no gastroscopy groups, the change in hemoglobin level, requirement of RBC transfusion, length of ICU stay, and ICU mortality were compared. Results: Of the 116 subjects included, 34 patients had gastroscopy during ICU stay. Among the gastroscopy group, 13 (38.2%) patients showed normal findings, and the most frequent abnormal finding was gastric ulcer (n = 9, 26.5%), and 12 patients (35.3%) had a hemostatic procedure. After PSM, the gastroscopy group needed more red blood cell transfusion than the no-gastroscopy group (P = 0.01). There was no significant difference in the change in hemoglobin level (P = 0.10), length of ICU stay (P = 0.64), and ICU mortality (P = 0.55).Conclusion: This retrospective study showed that gastroscopy had no definite clinical benefit in ICU patients using high-dose proton pump inhibitor for suspected GI bleeding.
Is mild hypernatremia an independent predictor of poor clinical outcome in neurocritically ill patients?
Authors: Lee Yun Im , Ahn Joonghyun , Ryu Jeong-Am
Published: November 2020

Background: Hypernatremia is a common complication encountered during the treatment of neurocritically ill patients. However, it is unclear whether clinical outcomes correlate with the severity of hypernatremia in such patients. Therefore, we investigated the impact of hypernatremia on mortality of these patients, depending on the degree of hypernatremia.Methods: Among neurosurgical patients admitted to the intensive care unit (ICU) in a tertiary hospital from January 2013 to December 2019, patients who were hospitalized in the ICU for more than 5 days and whose serum sodium levels were obtained during ICU admission were included. Hypernatremia was defined as the highest serum sodium level exceeding 150 mEq/L observed. We classified the patients into four subgroups according to the severity of hypernatremia and performed propensity score matching analysis.Results: Among 1,146 patients, 353 patients (30.8%) showed hypernatremia. Based on propensity score matching, 290 pairs were included in the analysis. The hypernatremia group had higher rates of in-hospital mortality and 28-day mortality in both overall and matched population (both p < 0.001 and p = 0.001, respectively). In multivariable analysis of propensity score-matched population, moderate and severe hypernatremia were significantly associated with in-hospital mortality (adjusted odds ratio [OR]: 4.58, 95% confidence interval [CI]: 2.15 – 9.75 and adjusted OR: 6.93, 95% CI: 3.46 – 13.90, respectively) and 28-day mortality (adjusted OR: 3.51, 95% CI: 1.54 – 7.98 and adjusted OR: 10.60, 95% CI: 5.10 – 21.90, respectively) compared with the absence of hypernatremia. However, clinical outcomes, including in-hospital mortality and 28-day mortality, were not significantly different between the group without hypernatremia and the group with mild hypernatremia (p = 0.720 and p = 0.690, respectively). The mortality rates of patients with moderate and severe hypernatremia were significantly higher in both overall and matched population. Interestingly, the mild hypernatremia group of matched population showed the best survival rate.Conclusions: Moderate and severe hypernatremia were associated with poor clinical outcomes in neurocritically ill patients. However, the prognosis of patients with mild hypernatremia was similar with that of patients without hypernatremia. Therefore, mild hypernatremia may be allowed during treatment of intracranial hypertension using hyperosmolar therapy.
The role of eosinophils and corresponding cytokines and chemokines asthma-COPD overlap (ACO) patients
Authors: Li Qinglan , Lu Liang , Geng Shiyang , Zhang Huiyun , Li Xin , Lu Sijing
Published: November 2020

Background: ACO has been characterized as a kind of clinical disease with overlap symptoms of asthma and COPD. However, little is known of the role of eosinophils and corresponding cytokines and chemokines in ACO patients with different treatment responses. Methods: To evaluate factors which associates with different treatment responses in patients with ACO. In the present study, we investigated the eosinophils proportion of peripheral blood from ACO patients with acute exacerbation (AE) after treatment, ACO patients with clinical response (CR) after treatment, and healthy volunteers (HV) by using flow cytometry analysis. The plasma levels of corresponding cytokines and chemokines from the three groups were evaluated by ELISA.Results: The results showed that ACO patients that had acute exacerbation have relatively lower eosinophils proportions compared to healthy volunteers but have higher eosinophils inflammation compared with patients with clinical response. The percentage of NK1R+ expression population eosinophils was also decreased. Further analysis revealed ACO patients that had acute exacerbation also have relatively higher plasma levels of cytokines and chemokines compared to patients with clinical response after treatments and healthy volunteers.Conclusion: ACO patients from AE group have relatively lower eosinophil proportion and NK1R+ expression population eosinophil proportion, but higher plasma levels of cytokines and chemokines. Inhibitors of cytokines and chemokines are likely useful agents for treatment of ACO patients which had acute exacerbations.
Reinfection with SARS-CoV-2 in a splenectomized patient from Kocaeli, Turkey
Authors: Deniz Müge Toygar , Akhan Sıla , Esgin Melih Berkay , Sayan Murat , Barış Serap Argun
Published: November 2020

Background: The COVID-19 pandemic has resulted in more than 31 million cases diagnosed and 965,000 deaths as of September 21, 2020. As the number of cases increases, clinical conditions such as prolonged viral release, reinfection, and reactivation are being encountered more frequently.Case presentation: This article presents a case who was reinfected with COVID-19 and developed a more severe second disease unlike other cases in the literature.Conclusions: Reinfection in a splenectomy case may help researchers understand the pathogenesis of the disease and can be a guide for the development of vaccines and new treatments.
Brine-Shrimp Lethality Bioassay of different extracts of the medicinal plant matricaria (chamomilla) flowers
Authors: Ali Amal Elnour , Ali Shayob Mohammed El Hassan , EL-Rhman Suad Abd Elgadir Abdo , Mohamed Mona Abd ELmoneim , Khider Tarig Osman
Published: November 2020

The present study aimed to throw some light on phytochemical constituents of Matricaria (cammomile) flowers. The grinded flowers were extracted successively by petroleum ether (40-60°C), chloroform, 95% ethanol, and ethyl acetate; using soxhlet apparatus respectively. The extracts were concentrated under vacuum (rotatory evaporator).Phytochemical screening of matricaria flowers, were performed using standard methods, showed the presence of alkaloids, flavonoids, terpenoids, saponins, and anthraquinone. The 95% ethanolic crude extract was subjected to column chromatography and nine fractions were collected. Fractions 1-6 have the same Rf value, (using thin layer pre-coated silica gel (0.25cm). were combined and subjected to spectroscopic analysis; infrared spectra showed absorption at 1860, 1637 and 805 cm’ indicating the presence of c=o, c=c, and c-o groups respectively. Ultra violet absorption at 250-283nm assign for the presence of flavonoids, (lit. 250-280). Finally GC/MS spectra performed the presence flavonoids.Crude extracts (ethanol, methanol, petroleum ether, and chloroform) were investigated for antimicrobial activities against four strains of bacteria (Staphylococcus aureus, Escherichia coli, Bacillus sub tills, Pseudomonas aeruginosa, and two fungi: Asperigillus niger, and Candida albican) with disc diffusion method, the diameter of growth inhibition zone ranged 15-22mm.The distilled essential oil (hydro distillation) of matricaria flowers was subjected to GC/MS, a Number of aliphatic compounds were detected e.g. 2, 3 heptadione and 3-hexa none, 2, 5 dimethyl.
p53+/-Rb1-ASCL1low phenotype predicts better prognosis after surgical resection in large cell neuroendocrine carcinoma: a molecular characteristic and clinical-pathological investigation of lung neuroendocrine tumors
Authors: Dong Yuting , Zhang Qian , Wang Guoping , Duan Yaqi , Huo Zitian
Published: November 2020

Background: Based on morphology, necrosis degree, and proliferation status, lung neuroendocrine tumors (NETs) are commonly divided into four subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). However, cases difficult to classify still exist in diagnosis. Methods: We immunohistochemically investigated the molecular phenotypes in lung NETs and assessed their prognostic value. Results: After morphological re-analysis of 179 NETs, 19 cases were classified as undefined, which included 3 cases showing carcinoid morphology with high proliferation (Ki67>20% or mitotic count>10/2mm2), and 16 cases showing intermediate differentiated morphology with Ki67 among 20% to 60%. Furthermore, molecular phenotypes were determined by expression of p53, Rb1, ASCL1, STK11, and gene mutation status of KRAS. Interestingly, p53wtRb1+ distinguished an unique subcategory from undefined lung NET cases which differ from SCLC or LCNEC in prognosis, indicating WD-NET G3 existed in lung NETs. Additionally, in LCNEC, high ASCL1 expression was only relevant to lymph node metastasis rather than overall survival. However, in p53+/-Rb1- LCNEC phenotype, low ASCL1 predicted better outcomes, along with less risk of lymph node metastasis. Conclusion: This study provided evidence for existence of WD-NET G3 in NETs and revealed promising prognosis of p53+/-Rb1- ASCL1low subcategory in LCNEC, which could be beneficial to the evaluation of patient status in future clinic practice.
A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir vs Currently Used Therapy in Severe COVID-19 Adults. “COMVIVIR” Trial.
Authors: Pérez-García Adolfo , Villalobos-Osnaya Alma , Hernández-Medel Maria Luisa , Perez-Navarro Lucia Monserrat , Medina-Hernandez Elba O. , Cabrera-Orejuela Diana Sofia , Espinoza-Garcia Ana Maria , Solleiro-Villavicencio Helena , Leon-Hernandez Mireya , Mayor Arianna Rodriguez-Cal Y , Servin-Murillo Manli M. , Carillo-Ruiz Jose Damian , Serrano-Loyola Raul , Guerrero-Avendaño Guadalupe Mercedes Lucia , Reyes-Teran Gustavo , Sierra-Madero Juan , de Oca Gonzalo Salgado-Montes , Avila-Rios Santiago , Lopez-Alvarenga Juan Carlos , Hernandez-Ruiz Joselin
Published: November 2020

Multiple studies have established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of T cells, monocytes/macrophages and neutrophils, thus mitigating the cytokine dysregulation and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients should combine a modulator of the immune response plus a direct antiviral drug against SARS-CoV-2, in order to address both the hyperinflammatory effects of the immune dysregulation and the viral load. Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México Dr. Eduardo Liceaga for severe COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groups. Discussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-β; nevertheless, to our best knowledge, only one study explores chemotaxis control. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomes.
Perceived changes of specific attitudes, perceptions and behaviors during the Corona pandemic and their relation to wellbeing
Authors: Büssing Arndt , Recchia Daniela Rodrigues , Hein Rudolf , Dienberg Thomas
Published: November 2020

Background During the COVID-19 pandemic, most people had to cope with the restrictions of the lockdown, leaving them to their fears, insecurity and isolation. On the other hand, due to the unexpected ‘extra time’ there was room for new experiences and for personal reflections on what is essential in life, to perceive nature and relations more consciously etc. We, therefore, intended to analyze perceived changes of attitudes and behaviors during the time of lockdown, and whether these perceptions would contribute to personal wellbeing during the pandemic.Method An anonym cross-sectional online survey was performed for data collection, using standardized questionnaires, i.e., the WHO-Five Well-being Index (WHO-5), Brief Multidimensional Life Satisfaction Scale (BMLSS), Awe/Gratitude scale (GrAw-7), and the newly developed Perceived Changes Questionnaire (PCQ).Results Within the number of respondents (n=1,277), women were predominating (67.5%). Participants´ mean age was 50.9 ± 14.9 years. Exploratory factor analyses showed that the 24-item Perceived Changes Questionnaire differentiated five factors that would account for 61% of variance: 1) Nature / Silence / Contemplation (Cronbach´s alpha =.87), 2) Spirituality (Cronbach´s alpha =.83), 3) Relationships (Cronbach´s alpha =.80), 4) Reflection on life (Cronbach´s alpha =.74), 5) Digital media usage (Cronbach´s alpha =.74). Strongest changes were observed for Relationships and Nature / Silence / Contemplation. Perceived changes were stronger among older persons, among persons with higher wellbeing, and among those who relied on their faith as a resource. These changes were predicted best by a person´s perception of wondering awe in distinct situations with subsequent feelings of gratitude. Stepwise regression analyzes revealed that participants´ wellbeing was explained best by low perceived burden and high life satisfaction (R2=.46). Awe/gratitude, perceived changes in terms of Nature / Silence / Contemplation and low Reflections of live are further variables that would predict a person´s wellbeing among the COVID-19 pandemic,Conclusions During the Corona pandemic, people tried to find ways to adapt to the outcomes of the restrictions. The perceived changes of attitudes and behaviors can be interpreted in terms of a reappraisal strategy. These can be measured with the extended version of the PCQ which was found to have good quality indices and a plausible factor structure. The reported changes contribute to persons´ wellbeing only to some extend, indicating that they represent an independent quality of relevance in peoples´ life.
Multidisciplinary Approach to Enhancing Provider Well-Being in a Metropolitan Medical Group in the United States
Authors: Shields Lisa Barbara , Jennings James T. , Honaker Joshua T.
Published: November 2020

Background: Physician burnout refers to depersonalization, emotional exhaustion, and a sense of lower personal accomplishment. Affecting approximately 50% of physicians in the United States, physician burnout negatively impacts both the physician and patient. Over a 3-year-period, this prospective study evaluated the multidisciplinary approach to decreasing provider burnout and improving provider well-being in our metropolitan community. Methods: A multidisciplinary Well-Being Task Force was established at our Institution in 2017 to assess the myriad factors that may play a role in provider burnout and offer solutions to mitigate the stressors that may lead to decreased provider well-being. Four multifaceted strategies were implemented: (1) provider engagement & growth; (2) workflow/office efficiencies; (3) relationship building; and (4) communication. Providers at our Institution took the Mayo Clinic’s well-being index survey on 3 occasions over 3 years. Their scores were compared to those of providers nationally at baseline and at 1 and 2 years after implementing organizational and individualized techniques to enhance provider well-being. Lower well-being index scores reflected better well-being. Results: The average overall well-being index scores of our Institution’s providers decreased from 1.76 at baseline to 1.32 2 years later compared to an increase in well-being index scores of physicians nationally (1.73 to 1.85). Both male and female providers’ average well-being index scores at our Institution decreased over the 3 years of this study, from 1.72 to 1.58 for males and 1.78 to 1.21 for females, while physicians’ scores nationally increased for both genders. The average well-being index scores were highest for providers at our Institution who graduated from medical school less than 5 years earlier (2.0) and who graduated 15-24 years earlier (2.3), whereas the average lowest scores were observed in providers who graduated ³ 25 years earlier (1.37). Obstetricians/gynecologists and internal medicine physicians had the highest average well-being index scores (2.48 and 2.4, respectively) compared to other medical specialties. The turnover rate of our Institution’s providers was 5.6% in 2017 and 3.9% in 2019, reflecting a 30% decrease. Conclusion: This study serves as a model to reduce provider burnout and enhance well-being through both organizational and individual interventions.
Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre
Authors: Bailo Paula Sienes , Lahoz Raquel , Marín Juan Pelegrín Sánchez , Álvarez Silvia Izquierdo
Published: November 2020

Background: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases.Methods: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100 000 inhabitants per year during the period 2007-2019 in Aragon (Spain).Results: 50 (27.9%) incident cases of HD (CAG repeat length ≥36) were identified from a total of 179 persons studied. The remaining 129/179 (73.4%) were HD negative (CAG repeat length <36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 64.8 per 100 000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 10 and the most common CAG length among HD negative individuals was 16.Conclusions: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.
Metatranscriptomic analyses reveal ruminal pH regulates fiber degradation and fermentation by shifting the microbial community and gene expression of carbohydrate-active enzymes
Authors: Li MengMeng , White Robin R. , Guan Le Luo , Harthan Laura , Hanigan Mark D.
Published: November 2020

Background: Volatile fatty acids (VFA) generated from ruminal fermentation by microorganisms provide up to 75% of total metabolizable energy in ruminants. Ruminal pH is an important factor affecting the profile and production of VFA by shifting the microbial community. However, how ruminal pH affects the microbial community and its relationship with expression of genes encoding carbohydrate-active enzyme (CAZyme) for fiber degradation and fermentation are not well investigated. To fill in this knowledge gap, six cannulated Holstein heifers were subjected to a continuous 10-day intraruminal infusion of distilled water or a dilute blend of hydrochloric and phosphoric acids to achieve a pH reduction of 0.5 units in a cross-over design. RNA-seq based transcriptome profiling was performed using total RNA extracted from ruminal liquid and solid fractions collected on day 9 of each period, respectively.Results: Metatranscriptomic analyses identified 19 bacterial phyla with 156 genera, 3 archaeal genera, 11 protozoal genera, and 97 CAZyme transcripts in sampled ruminal contents. Within these, 4 bacteria phyla (Proteobacteria, Firmicutes, Bacteroidetes, and Spirochaetes), 2 archaeal genera (Candidatus Methanomethylophilus and Methanobrevibacter), and 5 protozoal genera (Entodinium, Polyplastron, Isotricha, Eudiplodinium, and Eremoplastron) were considered as the core active microbes, and genes encoding for cellulase, endo-1,4-beta- xylanase, amylase, and alpha-N-arabinofuranosidase were the most abundant CAZyme transcripts distributed in the rumen. Rumen microbiota is not equally distributed throughout the liquid and solid phases of rumen contents, and ruminal pH significantly affect microbial ecosystem, especially for the liquid fraction. In total, 21 bacterial genera, 4 protozoal genera, and 6 genes encoding CAZyme were regulated by ruminal pH. Metabolic pathways participated in glycolysis, pyruvate fermentation to acetate, lactate, and propanoate were downregulated by low pH in the liquid fraction.Conclusions: The ruminal microbiome changed the expression of transcripts for biochemical pathways of fiber degradation and VFA production in response to reduced pH, and at least a portion of the shifts in transcripts was associated with altered microbial community structure.
LncRNA-SNHG6 promotes the progression of hepatocellular carcinoma by targeting miR-6509-5p and HIF1A
Authors: Fan Xiaoxi , Zhao Zhongwei , Song Jingjing , Zhang Dengke , Wu Fazong , Tu Jianfei , Xu Min , Ji Jiansong
Published: November 2020

Background: Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied. Methods: In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels. Also, we performed the xenograft assay to investigate the function of SNHG6 during the tumor growth in vivo. Results: We found SNHG6 was highly expressed in HCC tissues. Next, using Hep3B and Huh7 cells, we confirmed knockdown of SNHG6 reduced the proliferation, migration and invasion abilities in vitro. Also, by bioinformatics analysis, further molecular and cellular experiments, we found miR-6509-5p bound to SNHG6 directly, and the expression level of HIF1A was regulated through SNHG6/miR-6509-5p axis. Finally, we found that down-regulation of SNHG6 dramatically reduced the tumor growth ability of Huh7 cells in vivo. Conclusions: We concluded that SNHG6/miR-6509-5p/HIF1A axis functioned in the progression of hepatocellular carcinoma, and could be the promising therapeutic targets during the development of hepatocellular carcinoma drugs.
Assessment of irreducible aspects in developmental hip dysplasia by magnetic resonance imaging
Authors: Jia Huihui , Wang Liang , Chang Yan , Song Yongrui , Liu Yuqi , Zhang Fuyong , Feng Jie , Yang Xiaodong , Sheng Mao
Published: November 2020

Background: The developmental dysplasia of the hip (DDH) can cause a wide range of pathological changes, and often requires surgical treatment. Preoperative evaluation is very important for DDH. We aimed to assess the diagnostic capability of magnetic resonance imaging (MRI) for irreducible aspects preventing hip reduction in DDH. Methods: A total of 39 pediatric patients who received DDH evaluation in pediatric orthopedics from January 2015 to December 2019 were included. The samples included 4 cases of bilateral DDH and 35 cases of unilateral DDH, a total of 43 hip joint samples. All patients underwent surgical treatment, pathological examination and MRI of hip joint. Results: With pathological results or intraoperative findings as the gold standard, the sensitivity and specificity of MRI were 90.3% and 83.3% for the affected labrum, 92% and 83.3% for thickening of the round ligament, 90.0% and 91.3%for atrophy of the iliopsoas muscle, and 100% and 100% for fibrofatty pulvinar tissue and joint effusion, respectively. Conclutions: The MRI showed an extraordinary capability of detecting these irreducible factors and helped surgeon choose the appropriate treatment strategies.
Preconceptional and prenatal exposure to diurnal temperature variation increases the risk of childhood pneumonia
Authors: Zheng Xiangrong , Kuang Jian , Lu Chan , Deng Qihong , Wu Haiyu , Murithi Rachael Gakii , Johnson McSherry Brownel , Peng Wang , Wu Maolan
Published: November 2020

Background: Pneumonia is the leading cause of death and hospitalization among young children worldwide, but its risk factors remain unclear. Objective: To evaluate the effect of maternal exposure to diurnal temperature variation (DTV) during preconceptional and prenatal periods on childhood pneumonia. Methods: A retrospective cohort study by case-control design was conducted for pneumonia (N=699) and normal (N=811) children under age of 14 who were enrolled in XiangYa Hospital, Changsha, China from May 2017 to April 2019. Demographic data including gender, age, birth season, gestational age, parity, mode of delivery, and parental atopy were collected from the electronic medical records in the hospital system. We obtained the data of daily DTV in Changsha during 2003-2019 from China Meteorological Administration. Maternal exposure to DTV during preconceptional and prenatal periods was respectively calculated by the average of daily DTV during one year and three months before conception and entire pregnancy as well as the three trimesters. The association between maternal exposure to outdoor DTV and childhood pneumonia was analyzed by multiple logic regression model. Results: We found that childhood pneumonia was significantly associated with exposure to an increase in DTV during one year before conception and entire pregnancy, with ORs (95% CI) = 2.53 (1.56-4.10) and 1.85 (1.24-2.76). We further identified a significant risk of pneumonia due to DTV exposure during the first and second trimester of pregnancy. Sensitivity analysis showed that boys were more susceptible to the effect of prenatal exposure to outdoor DTV during pregnancy particularly in the first two trimesters compared to girls. Conclusions: Preconceptional and prenatal exposure to DTV plays an important role in development of childhood pneumonia, especially during the first and second trimesters of pregnancy.
New view on the organization and evolution of Palaeognathae mitogenomes poses the question on the ancestral gene rearrangement in Aves
Authors: Urantowka Adam Dawid , Kroczak Aleksandra , Mackiewicz Pawel
Published: November 2020

BackgroundBird mitogenomes differ from other vertebrates in gene rearrangement. The most common avian gene order, identified first in Gallus gallus, is considered ancestral for all Aves. However, other rearrangements including a duplicated control region and neighboring genes have been reported in many representatives of avian orders. The repeated regions can be easily overlooked due to inappropriate DNA amplification or genome sequencing. This raises a question about the actual prevalence of mitogenomic duplications and the validity of the current view on the avian mitogenome evolution. In this context, Palaeognathae is especially interesting because is sister to all other living birds, i.e. Neognathae. So far, a unique duplicated region has been found in one palaeognath mitogenome, that of Eudromia elegans. ResultsTherefore, we applied an appropriate PCR strategy to look for omitted duplications in other palaeognaths. The analyses revealed the duplicated control regions with adjacent genes in Crypturellus, Rhea and Struthio as well as ND6 pseudogene in three moas. The copies are very similar and were subjected to concerted evolution. Mapping the presence and absence of duplication onto the Palaeognathae phylogeny indicates that the duplication was an ancestral state for this avian group. This feature was inherited by early diverged lineages and lost two times in others. Comparison of incongruent phylogenetic trees based on mitochondrial and nuclear sequences showed that two variants of mitogenomes could exist in the evolution of palaeognaths. Data collected for other avian mitogenomes revealed that the last common ancestor of all birds and early diverging lineages of Neoaves could also possess the mitogenomic duplication.ConclusionsThe duplicated control regions with adjacent genes are more common in avian mitochondrial genomes than it was previously thought. These two regions could increase effectiveness of replication and transcription as well as the number of replicating mitogenomes per organelle. In consequence, energy production by mitochondria may be also more efficient. However, further physiological and molecular analyses are necessary to assess the potential selective advantages of the mitogenome duplications.
Propensity score-matched analysis of systemic chemotherapy versus salvage hysterectomy for persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy.
Authors: TAKEKUMA MUNETAKA , Takahashi Fumiaki , Mabuchi Seiji , Kudaka Wataru , Horie Koji , Ikeda Mariko , Shikama Ayumi , Mitsuhashi Akira , Nagao Shoji , Suzuki Shiro , Mizuno Mika , Nishio Shin , Tokunaga Hideki , Ota Yukinobu , Kasamatsu Takahiro , Kitagawa Ryo , Toita Takafumi , Kobayashi Hiroaki , Ishikawa Mitsuya , Yaegashi Nobuo
Published: November 2020

Background: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT).Methods: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005–2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched–cohort analysis were compared.Results: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p= 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23–0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort.Conclusion: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.
Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Gastrodin from Glucose
Authors: Yin Hua , Hu Tian Dong , Zhuang Yi Bin , Liu Tao
Published: November 2020

Background: The natural phenolic glycoside gastrodin is the major bioactive ingredient in the well-known Chinese herb Tianma and is widely used as a neuroprotective medicine in the clinic. Microbial production from sustainable resources is a promising method to replace plant extraction and chemical synthesis which were currently used in industrial gastrodin production. Saccharomyces cerevisiae is considered as an attractive host to produce natural plant products used in the food and pharmaceutical fields. In this work, we intended to explore the potential of S. cerevisiae as the host for high-level production of gastrodin from glucose.Results: Here, we first identified the plant-derived glucosyltransferase AsUGT to convert 4-hydroxybenzyl alcohol to gastrodin with high catalytic efficiency in yeast. Then, we engineered de novo production of gastrodin by overexpressing codon-optimized AsUGTsyn, the carboxylic acid reductase gene CARsyn from Nocardia species, the phosphopantetheinyl transferase gene PPTcg-1syn from Corynebacterium glutamicum, the chorismate pyruvate-lyase gene UbiCsyn from Escherichia coli, and the mutant ARO4K229L. Finally, we achieved an improved product titer by a chromosomal multiple-copy integration strategy and enhancement of metabolic flux toward the aglycon 4-hydroxybenzyl alcohol. The best optimized strain produced 2.1 g/L gastrodin in mineral medium with glucose as the sole carbon source by flask fermentation, which was 175 times higher than that of the original gastrodin-producing strain.Conclusions: The de novo high-level production of gastrodin was first achieved. Instead of chemical synthesis or plants extraction, our work provides an alternative strategy for the industrial production of gastrodin by microbial fermentation from a sustainable resource.
Linkage analysis, GWAS, transcriptome analysis to identify candidate genes for rice seedlings in response to high temperature stress
Authors: Wei Zhaoran , Yuan Qiaoling , Lin Hai , Li Xiaoxia , Zhang Chao , Gao Hongsheng , Zhang Bin , He Huiying , Liu Tianjiao , Zhang Jie , Gao Xu , Shi Shandang , Wang Bo , Gao Zhenyu , Kong Lingrang , Qian Qian , Shang Lianguang
Published: November 2020

Background: With the increase of global temperature, rice yield decline caused by the rising temperature is becoming more and more prominent. Mining heat-resistant genes and applying them to rice breeding is a feasible and effective way to solve the problem.Result: Three main biomass traits, including shoot length, dry weight, and fresh weight, changed after abnormally high temperature treatment in the seedling stage of a recombinant inbred line and natural groups. Based on a comparison of the results of linkage analysis and genome-wide association analysis, the presence of two sections with lengths of 57 kb and 69 kb in qDW7 and qFW6, respectively, was associated with the rice response to abnormally high temperatures in the seedling stage. Meanwhile, based on integrated transcriptome analysis, some genes are considered as candidate genes for subsequent research and analysis. Combining with reports of known genes and analysis of homologous genes, it was found that there are 8 genes in candidate genes that need to be focused in subsequent research.Conclusions: The results indicated several relevant loci, which would help researchers to further discover excellent heat-resistant genes that can be applied to rice heat-resistant breeding.
Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection
Authors: Hu Zhi-Qiang , Zhou Zheng-Jun , Luo Chu-Bin , Xin Hao-Yang , Li Jia , Yu Song-Yang , Zhou Shao-Lai
Published: November 2020

Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.
Excessive Amounts of Salt Consumption and Atheroma Formation Among Patients Awaiting Coronary-Artery-Bypass-Grafting at A Tertiary Care Hospital in Sri Lanka
Authors: Amadoru Harischandra , Dias Ashini R , Wijesiri Nuwan , Gamage Pasan , Perera Thilini , Goonawardana Vas , Liyanage Nisansala , Malwatta Arunie , Anthonipille Ravikaran , Mahesh Buddhika , Alles Randara , Suriyarachchi Vasana , Siriwardana Sumudu , Jayasekara Prasanna , Jayatissa Renuka , Silva Rajitha De , Kapuruge Aruna
Published: November 2020

Background:Ischemic Heart Disease(IHD) characterized by atheroma formation, is a leading contributor for the rising disease burden of chronic non-communicable diseases in Sri Lanka. Even though excessive salt-consumption has been attributed with hypertension, documented literature is scarce on exploring its direct association with atheroma formation with primary data. Coronary-Artery- Bypass-Grafting(CABG) is done as a tertiary preventive measure for IHDs. The aim was to estimate the sodium-intake and to describe the association of salt consumption and atheroma formation among preoperative patients undergoing CABG at Sri Jayewardenepura General Hospital, Sri Lanka.MethodsA descriptive cross-sectional study was done on a calculated sample size of 213 participants who were awaiting CABG at SJGH. An interviewer-administered Additional file 1 was used, and dietary intake of sodium was calculated with food-frequency tables and web-based tools. A data extraction form was used and details regarding Coronary arterial segments with atheroma formation were obtained from angiogram reports. After exploring the normality, Spearman-correlation-coefficient and Mann-Whitney-U tests were used to explore associations of atheroma formation. Independent association of sodium-intake and Coronary arterial segments affected with atheroma was explored with multiple-logistic regression. ResultsThe sample was with a male preponderance(male to female ratio=3:1). Comorbidities were observed in a notable proportion: diabetes(47%), dyslipidemia(40%), hypertension(56%). The median(IQR) of BMI and waist circumference were 25.00(23.00-27.00)kg/m2 and 87.00(82.00-91.00)cm. The median(IQR) sodium-intake was 5875.50(4905.25-7091.25)mg. All participants (n=210) had a sodium intake of more than 2000mg/day. Sodium intake(rs=0.599,p<0.001) and BMI(rs=0.634,p=0.034) were significantly associated with atheroma segments whereas age, gender, diabetes, hypertension, dyslipidemia, waist circumference was not(p>0.05). Sodium intake was found to be an independent predictor of affecting “5 or more segments” when multiple logistic regression was applied(OR= 2.25,CI=1.41 to 3.61). Conclusions and RecommendationsThe daily intake of sodium by a regular person is more than the dietary recommendations in the study sample. Salt intake reflected by sodium intake seemingly increase the risk of atheroma formation in more coronary segments irrespective of age, sex as well as several known disease conditions and risk factors. More research must be promoted with analytical approaches in proving this hypothesis.
IL-17A in COVID-19: a meta-analysis
Authors: Fadlallah Sukayna , Eddin Marcel Shams , Rahal Elias
Published: November 2020

IL-17A is a proinflammatory cytokine attributed with homeostatic roles but that is also involved in autoimmune disease pathogenesis. While some studies have reported an increase in IL-17A in subjects affected by COVID-19, no significant associations were found by others. Hence, we undertook this meta-analysis to examine whether serum IL-17A increases in COVID-19 patients. We report here that IL-17A increases in COVID-19 subjects irrespective of disease severity. It is also higher in patients with moderate disease compared to controls as well as higher in patients with severe COVID-19. While the increase in serum levels in subjects with severe disease over those with moderate disease was statistically significant, the association was not as robust as the other comparisons. Hence, IL-17A may be of relevance when considering management approaches to COVID-19; however, therapeutic approaches that target IL-17A should consider whether alleviation of inflammation outweighs eliminating the possible anti-viral roles of this cytokine.