bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the experiences of stroke patients treated with transcranial magnetic stimulation for upper limb recovery: a qualitative study
Authors: Lieshout Eline CC van , Jacobs Lilliane D , Pelsma Maaike , Dijkhuizen Rick M , Visser-Meily Johanna MA
Published: September 2020

Background: Transcranial magnetic stimulation (TMS) treatments have shown promise in improving arm recovery in stroke patients. Currently, little is known about patients’ experiences with TMS treatment, and this lack of knowledge may affect optimal implementation in clinical practice. The aim of this explorative study was to gain insight in the perceived effects and experiences of the design and delivery of a TMS treatment for upper limb recovery from the perspectives of stroke patients.Methods: This qualitative study was conducted as part of a randomized controlled trial (RCT) in a specialized rehabilitation center. Data were collected through face-to-face semi-structured interviews with 13 stroke patients who completed a 10-day TMS intervention for upper limb recovery. The interviews were recorded, transcribed verbatim and analyzed using thematic analysis.Results: The major themes that emerged from the patients’ feedback were the following: positive experiences of the treatment (experienced physical effects, comfort, therapeutic relationship, receiving information, learning about the brain, no burden of added rTMS treatment session, no unpleasant aspects), concerns (effects of stimulation of the brain, equipment, logistics), general experience of recovery, experienced psychological effects (grateful, sense of purpose, recovery as extra motivation to exercise, disappointment and hope of group allocation), and motivation to participate (personal benefit and cognitions, altruism). Important components related to the positive experience of the design and delivery of the treatment included comfort (i.e. moment of relaxation) and the sensation of a painless treatment without side-effects. Key concerns included uncertainty and anxiety about possible negative consequences and group allocation.Conclusions: This study demonstrates that TMS is well accepted by stroke patients with an upper limb paresis. Besides the expectation of a therapeutic benefit, the patients reported various psychological effects. Positive experiences, such as the provision of a short moment of relaxation each day, could have practical implications for clinical stroke rehabilitation settings aimed at improving patient satisfaction. Explanation about and feedback from routine motor recovery progression monitoring at fixed times post-stroke is also valued by patients. Negative emotions may be limited or avoided by transparent and recurrent information delivery in future trials.
Clinical Phenotypes and Heath-Related Quality of Life of COPD Patients in a Rural Setting in Malaysia – A Cross-Sectional Study
Authors: Chai Chee-Shee , Mos Sumastika Bt , Ng Diana-Leh-Ching , Goh Greta-Miranda-Kim-Choo , Su Anselm-Ting , Ibrahim Muhammad Amin Bin , Musa Aisya Natasya Bt , Tan Seng-Beng , Pang Yong-Kek , Liam Chong-Kim
Published: September 2020

Background

The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients’ health-related quality of life (HRQoL) according to their COPD phenotypes.

Methods

This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23 th January 2018 to 22 th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).

Results

Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the COPD patients, 65.9% had exposure to biomass fuel.

The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p < 0.001). There were significantly more patients with mMRC 2 – 4 among AE (68.6%) (p < 0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p < 0.001) and SGRQ-c (both p < 0.001) scores than those with ACO and NON-AE. Patients with ACO also had significantly higher total CAT and SGRQ-c (both p < 0.001) scores than those with NON-AE.

AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p < 0.001), and ACO [(p = 0.003 – 0.016; p = < 0.001 – 0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001 – 0.040; p < 0.001) except CAT 2 and activity components of SGRQ-c.

Conclusions

The HRQoL of COPD patients was significantly different across COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.
Evaluation of the standard procedure for the treatment of periprosthetic joint infections (PJI) in Germany - Results of a survey within the EndoCert initiative
Authors: Rimke Christina , Enz Andreas , Bail Hermann Josef , Heppt Peter , Kladny Bernd , von Lewinski Gabriela , Lohmann Christoph H. , Osmanski-Zenk Katrin , Haas Holger , Mittelmeier Wolfram
Published: September 2020

Background: The periprosthetic joint infection (PJI) is a severe complication in the field of arthroplasty. Despite the rising number of primary joint replacements, no unified therapeutic standard has been established for the treatment of PJI yet.Methods: A survey on the principles of treatment of PJI in Germany wasconducted. A total of 515 EndoProthetikZentren (EPZ) were included, resulting in a response rate of 100%.Results: For early infections 97.6% of the centers use prosthesis-preserving procedures (DAIR). A one-stage exchange was implemented by less than 50% of the centers. If implemented, this treatment entails a prior selection of patients for a successful treatment. The two-stage exchange is performed in all centers, and most centers proceed with the implantation of a cemented spacer between stages. 75% of the centers proceed with a center-based concept for the treatment of PJI.Conclusion: The aim of a uniform PJI standard at the centers has not yet been fully achieved. Further improvements within the certification were initiated. The most relevant treatment options in Germany are displayed. The two-stage revision with a cemented spacer is the most widely implemented treatment. This exposition of principles could help for the further development of standardized treatment guidelines and definitions.
Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti
Authors: Daniels Rachel , Chenet Stella , Rogier Eric , Lucchi Naomi , Herman Camelia , Pierre Baby , Lemoine Jean Frantz , Boncy Jacques , Wirth Dyann , Chang Michelle , Udhayakumar Venkatachalam , Volkman Sarah
Published: September 2020

Background: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian populace remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity­­—at least 20 of 21 SNPS—with at least one other sample in the dataset. Conclusions: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.
Cutaneous Anthrax Outbreak Associated with Handling Dead Animals, Rhino Camp Sub-county: Arua District, Uganda, January-May2018
Authors: Ntono Vivian , Eurien Daniel , Bulage Lilian , Kadobera Daniel , Harris Julie , Ario Alex Riolexus
Published: September 2020

Background: On the 9 February 2018, Arua District notified Uganda Ministry of Health of a confirmed anthrax outbreak among humans in Rhino Camp sub-county. Many persons fell ill after reported contact with livestock that died suddenly. We investigated to determine the scope, mode of transmission and exposures associated with identified anthrax, to guide control and prevention measures. Methods: We defined a suspected cutaneous anthrax case as onset of skin lesions (e.g., papule, vesicle, or eschar) in a person residing in Rhino Camp sub-county, Arua District from 25 December, 2017 to 31 May, 2018. A confirmed case was a suspected case with PCR-positivity for Bacillus anthracis from a clinical sample. We identified cases by reviewing medical records at Rhino Camp Health Centre. We also conducted additional case searches in the affected community with support from Community Health Workers. In a retrospective cohort study, we interviewed all members of households in which at least one person had contact with the carcasses of or meat from animals suspected to have died of anthrax. We collected and tested hides of implicated animals using an anthrax rapid diagnostic test.Results: We identified 14 case-patients (1 confirmed, 13 suspected); none died. Only males were affected (AR: 12/10,000). Mean age of case-persons was 33years (SD: 22).The epidemic curve shows that the outbreak lasted for 5 months, from January 2018-May 2018, peaking in February.Skinning(RR=2.7, 95%CI=1.1-6.7), dissecting (RR=3.0, 95%CI=1.2-7.6), and carrying the dead animals (RR=2.7, 95%CI=1.1-6.7) were associated with increased risk of illness, as were carrying dissected parts of the animal (RR=2.9, 95%CI 1.3-6.5) and preparing and cooking the meat (RR=2.3, 95%CI 2.7-8.1). We found evidence of animal remains on pastureland.Conclusion: Multiple exposures to the hides and meat of animals that died suddenly were associated with this cutaneous anthrax outbreak in Arua District. We recommended public education about safe disposal of carcasses of livestock that die suddenly.
Development and validation of an RNA binding protein-associated prognostic model for hepatocellular carcinoma
Authors: wang Min , Huang Shan , Chen Zefeng , Han Zhiwei , Li Kezhi , Chen Chuang , Wu Guobin , Zhao Yinnong
Published: September 2020

Background: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized.Methods: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network.Results: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS.Conclusion: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.
Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis
Authors: Takasaka Naoki , Seki Yoshitaka , Fujisaki Ikumi , Uchiyama Shota , Matsubayashi Sachi , Sato Akihito , Yamanaka Yumie , Odashima Kyuto , Kazuyori Taisuke , Seki Aya , Takeda Hiroshi , Ishikawa Takeo , Kuwano Kazuyoshi
Published: September 2020

Background Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB). Methods We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥1 based on low attenuation area < -950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment. Results Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [ interquartile range (IQR) 29.0–66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0–42.0 days) (p<0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [ hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18–4.97; p=0.015), cavities (HR: 2.15; 95% CI: 1.83–3.89; p=0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64–5.31; p<0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p=0.015 and 84.21% vs 60.98%; p=0.021, respectively). Conclusions This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.
The predictive value of D-dimer test for venous thromboembolism during puerperium in women age 35 or older：A prospective cohort study
Authors: Hu Wen , Xu Dong , Li Juan , Chen Cheng , Chen Yuan , Xi Fangfang , Zhou Feifei , Guo Xiaohan , Zhao Baihui , Luo Qiong
Published: September 2020

Background: This study aimed to investigate the predictive value of the D-dimer level for venous thromboembolism (VTE) events during puerperium of women age at 35 years or older, as well as to identify other risk factors associated with the occurrence of VTE. Methods: It was a prospective observational cohort study, from January 2014 to December 2018, which involved 12451 women age 35 or older who delivered at least 28 weeks of gestation at Women’s Hospital of Zhejiang University, School of Medicine. The maternal and fetal demographic characteristics, pregnancy complications, imaging finding and results of laboratory test within postpartum 24 hours including D-dimer level, platelet counts and fibrinogen level were collected for analyses. Results: 30(2.4‰) women were identified as VTE, including 1 pulmonary embolism event and 29 deep venous thrombosis events. The receiver operating characteristic (ROC) curve analysis suggested the best cutoff point for D-dimer level within postpartum 24 hours of women age 35 or older was 5.545 mg/L, with a specificity of 70.0% and a sensitivity of 75.4%. Besides, there was no statistical correlation between platelet counts and VTE, as well as between fibrinogen level and VTE. On multivariate analysis, D-dimer≥5.50 mg/L (OR=5.874, 95%CI: 2.678-12.886) and emergency cesarean section (OR=11.965, 95%CI: 2.732-52.401) were independently associated with VTE in puerperium of women age 35 or older.Conclusions: We concluded that D-dimer≥5.50 mg/L was an independent predictor of VTE in puerperium with maternal age 35 or older and D-dimer testing was a necessary examination for perinatal women.
Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends
Authors: Sgalla Giacomo , Larici Anna Rita , Golfi Nicoletta , Calvello Mariarosaria , Farchione Alessandra , Ciello Annemilia Del , Varone Francesco , Iovene Bruno , Manfredi Riccardo , Richeldi Luca
Published: September 2020

Background and objectives
Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients.

Methods
This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models.

Results
152 IPF patients were included in the analysis, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p≤0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p=0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time.

Conclusions
Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.
Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9
Authors: Zhang Ting , Lu Rui , Chen Yibing , Yuan Yuguo , Song Shaozheng , Yan Kunning , Zha Yiwen , Zhuang Wenwen , Cheng Yong , Liang Jingyan
Published: September 2020

Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS. Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed. Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals. Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.
Recommendations for hemodynamic Monitoring for Critically Ill Children – Expert Consensus Statement issued by the Cardiovascular Dynamics Section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)
Authors: Singh Yogen , Villaescusa Javier Urbano , Cruz Eduardo M. da , Tibby Shane M , Bottari Gabriella , Saxena Rohit , Guillén Marga , Herce Jesus Lopez , Nardo Matteo Di , Cecchetti Corrado , Brierley Joe , de Boode Willem , Lemson Joris
Published: September 2020

Background: Cardiovascular instability is common in critically-ill children. There is scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children.Methods: Creation of a panel of experts in cardiovascular hemodynamic assessment and hemodynamic monitoring and review of relevant literature - a literature search was performed, and recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. The AGREE statement was followed to prepare this document.Results: Of 100 suggested recommendations across 12 subgroups concerning hemodynamic monitoring in critically ill children, 72 reached “strong agreement”, 20 “weak agreement” and 2 had “no agreement”. Six statements were considered as redundant after rephrasing of statements following first round of voting. The agreed 72 recommendations were then coalesced into 36 detailing four key areas of hemodynamic monitoring in the main manuscript. Due to lack of published evidence to develop evidence-based guidelines, most of the recommendations are based upon expert consensus.Conclusions: These expert consensus-based recommendation may be used to guide clinical practice for hemodynamic monitoring in critically-ill children and they may serve as a basis for highlighting gaps in the knowledge base to guide further research in hemodynamic monitoring.
Ammonia Induced Microglial Activation Modulates Connexin 43 and Aquaporin 4 Expression in Astrocyte-microglia Co-culture Model
Authors: Ismail Fatme Seval , Faustmann Timo Jendrik , Tsvetanova Anamariya , Moinfar Zahra , Faustmann Pedro M.
Published: September 2020

Background Hepatic encephalopathy (HE) is a neurological complication resulting from acute or chronic liver disease. Hyperammonemia leading to astrocyte swelling and cerebral edema in combination with neuroinflammation including microglia activation, mainly contribute to the pathogenesis of HE. However, little is known about microglia and their inflammatory response, as well as their influence on astrocytic channels and astrocyte swelling under hyperammonemia.Objective To investigate the effects of ammonia on the microglial activation, glial viability, connexin 43 (Cx43) and aquaporin 4 (AQP4) expression in astrocytes in in vitro astrocyte-microglia co-culture model.Methods Primary rat glial cocultures of astrocytes containing 5% (M5, representing "physiological" conditions) or 30% (M30, representing "pathological" conditions) of microglia were incubated with 3 mM, 5 mM, 10 mM and 20 mM ammonium chloride (NH4Cl) for 6 h and 24 h in order to mimic the conditions of HE. An MTT assay was performed to measure the viability, proliferation and cytotoxicity of cells. The microglial phenotypes were analysed by immunocytochemistry. The expression of Cx43 and AQP4 were quantified by immunoblot analysis.Results A significant reduction of glial viability was observed in M30 co-cultures after incubation with 20 mM NH4Cl for 6 h, whereas in M5 co-cultures the viability remained unchanged. Microglial activation was detected by immunocytochemistry after incubation with 3 mM, 5 mM and 10 mM NH4Cl for 6 h and 24 h in M5 as well as in M30 co-cultures. The Cx43 expression was increased significantly in M30 co-cultures after 6 h incubation with 5 mM NH4Cl. The AQP4 expression was increased significantly in M5 co-cultures treated with 10 mM NH4Cl for 6 h.Conclusions Our findings showed a significant microglial activation, decrease of viability and increase in Cx43 and AQP4 expression after NH4Cl incubation in astrocyte-microglia co-culture model. Based on previous in vitro studies suggesting that microglia activation influences astrocytic networks, it can be assumed that the microglial activation under hyperammonemia can modulate the Cx43 and AQP4 expression in astrocytes in a dynamic way and this can contribute to astrocytic dysfunction in HE.
Chromosome segregation in B. subtilis is highly heterogeneous
Authors: Najjar Nina El , Graumann Peter
Published: September 2020

Objective: The bacterial cell cycle comprises initiation of replication and ensuing elongation, concomitant chromosome segregation (in some organisms with a delay termed cohesion), and finally cell division. By quantifying the number of origin and terminus regions in exponentially growing Bacillus subtilis cells, and after induction of DNA damage, we aimed at determining cell cycle parameters at different growth rates at a single cell level.Results: B. subtilis cells are mostly mero-oligoploid during fast growth and diploid during slow growth. However, we found that the number of replication origins and of termini is highly heterogeneous within the cell population at two different growth rates, and that even at slow growth, a majority of cells attempts to maintain more than a single chromosome at all times of the cell cycle. Heterogeneity of chromosome copy numbers may reflect different subpopulations having diverging growth rates even during exponential growth conditions. Cells continued to initiate replication and segregate chromosomes after induction of DNA damage, as judged by an increase in origin numbers per cell, showing that replication and segregation are relatively robust against cell cycle perturbation.
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Authors: Hong Taeui , Kim Moon Young , Ly Dat Da , Park Su Jung , Eom Young Woo , Park Kyu-Sang , Baik Soon Koo
Published: September 2020

Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.
Development and Evaluation of Two-Parameter Linear Free Energy Models for the Prediction of Human Skin Permeability Coefficient of Neutral Organic Chemicals
Authors: Naseem Sana , Zushi Yasuyuki , Nabi Deedar
Published: September 2020

The experimental values of skin permeability coefficients, required for dermal exposure assessment, are not readily available for many chemicals. The existing estimation approaches are either less accurate or require many parameters that are not readily available. Furthermore, current estimation methods are not easy to apply to complex environmental mixtures. We present two models to estimate the skin permeability coefficients of neutral organic chemicals. The first model, referred to here as the 2-parameter partitioning model (PPM), exploits a linear free energy relationship (LFER) of skin permeability coefficient with a linear combination of partition coefficients for octanol-water and air-water systems. The second model is based on the retention time information of nonpolar analytes on comprehensive two-dimensional gas chromatography (GC×GC). The PPM successfully explained variability in the skin permeability data (n = 175) with R2 = 0.82 and root mean square error (RMSE) = 0.47 log unit. In comparison, the US-EPA’s model DERMWIN exhibited an RMSE of 0.78 log unit. The Zhang model a 5-parameter LFER equation based on experimental Abraham solute descriptors (ASDs) performed slightly better with an RMSE value of 0.44 log unit. However, the Zhang model is limited by the scarcity of experimental ASDs. The GC×GC model successfully explained the variance in skin permeability data of nonpolar chemicals (n = 79) with R2 = 0.90 and RMSE = 0.23 log unit. The PPM can easily be implemented in US-EPA’s Estimation Program Interface Suite (EPI Suite™). The GC×GC model can be applied to the complex mixtures of nonpolar chemicals.
Acute exercise in mice transiently remodels the hepatic lipidome in an intensity-dependent manner
Authors: Henderson Gregory C , Tenorio Valeria Martinez , Tuazon Marc A
Published: September 2020

Background: The content of triacylglycerol (TAG) in the liver is known to rapidly increase after a single bout of exercise followed by recovery to sedentary levels. The response of other hepatic lipids, and acyl chain composition of lipid classes, would provide a deeper understanding of the response of hepatic lipid metabolism to acute exercise. Methods: Female mice performed a single bout of continuous exercise (CE), high-intensity interval exercise (HIIE), or no exercise (CON). The total content of various lipids in the liver, and fatty acids within lipid classes, were measured in tissues collected 3 h after exercise (Day 1) and the day following exercise (Day 2). Results: The total concentration of TAG rose on Day 1 after exercise ( P < 0.05), with a greater elevation in HIIE than CE ( P < 0.05), followed by a decline toward CON levels on Day 2. The total concentration of other measured lipid classes was not significantly altered by exercise. However, n-6 polyunsaturated fatty acid relative abundance in diacylglycerol (DAG) was increased by HIIE ( P < 0.05). In CON liver, TAG content was positively correlated with DAG and phosphatidylethanolamine ( P < 0.05), while these statistical associations were disrupted in exercised mice on Day 1. Conclusions: The response of lipid metabolism to exercise involves the coordination of metabolism between various tissues, and the lipid metabolism response to acute exercise places a metabolic burden upon the liver. The present findings describe how the liver copes with this metabolic challenge. The flexibility of the TAG pool size in the liver, and other remodeling of the hepatic lipidome, may be fundamental components of the physiological response to intense exercise.
Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)
Authors: Yu Xiaofei , Megens Hendrik-Jan , Mengistu Samuel B. , Bastiaansen John W.M. , Mulder Han A. , Benzie John A.H. , Groenen Martien A.M. , Komen Hans
Published: September 2020

Background: Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 17th generation of a Genetically Improved Farmed tilapia population. Results: In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.Conclusions: There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.
Comprehensive Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in LGG
Authors: Ding Yiming , Liu Hanjie , Zhang Chuanbao , Bao Zhaoshi , Yu Shuqing
Published: September 2020

Background: Messenger RNA(mRNA) and Long non coding RNA (lncRNA) targets can interact through the ability to compete for microRNA binding. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of low grade glioma (LGG) are still unclear.Methods: This study obtained two types of RNAs sequencing data in Solid Tissue Normal and LGG Primary Tumor from TCGA database. We used a computational method to analyse the relation between mRNAs, lncRNAs and miRNAs. The function enrichment of Go item and KEGG pathway were analyzed to predict the biological process and pathway of the screened gene. Kaplan‐Meier survival analysis was used to evaluate the association with the expression levels of mRNAs, lncRNAs, and micRNAs and the overall survival of the patients. the ceRNA network of mRNA-lncRNA-miRNA was constructed with the version of cycloscape 3.5.1.Results: 2555 DEmRNA, 218 DElncRNA. 192 DEmiRNAs were screened by using the R package. We analyzed the function enrichment of Go item and KEGG pathway of mRNAs and lncRNAs in ceRNA network. The main 10 BP items, 10 CC items, 10 MF items and 48 KEGG pathways were selected.55 survival related lncRNAs, 50 survival related miRNAs and top 10 survival most related mRNAs in LGG. Finally, 59 miRNAs, 235 mRNAs and 17 lncRNAs, a total of 313 nodes and 1046 edges, constructed the ceRNA network of mRNA-lncRNA-miRNA.Conclusions: This study is advantageous to deeply understand the biological mechanism of ceRNA and to clarify the pathogenesis of LGG.
Coaxial Drainage Versus Standard Chest Tube After Pulmonary Lobectomy: A Randomized Controlled Study
Authors: Bassi Massimiliano , Mottola Emilia , Mantovani Sara , Amore Davide , Pagini Andreina , Diso Daniele , Poggi Camilla , Vannucci Jacopo , Giacomo Tiziano De , Rendina Erino Angelo , Venuta Federico , Anile Marco
Published: September 2020

Background

Chest tubes are routinely inserted after major thoracic surgery procedures and usually two drainages are placed. The aim of this study is to assess the efficacy of Smart Drain Coaxial drainage compared with two standard chest tubes in patients undergoing pulmonary lobectomy.
Methods

Ninety-eight patients (57 males and 41 females, mean age 68.3 ± 7.4 years) with lung cancer undergoing pulmonary lobectomy were randomized in two groups: 50 patients received one upper 28 Fr and one lower 32 Fr standard chest tube (ST group) and 48 patients received one 28 Fr Smart Drain Coaxial chest tube (CT group). Hospitalization, quantity of fluid output, air leaks, chest radiograph findings, pain control and costs were assessed.
Results

We performed 33 right upper lobectomies (17 ST, 16 CT), 25 right lower (15 ST, 10 CT), 20 left upper (8 ST, 12 CT) and 19 left lower (10 ST, 9 CT). The CT group showed a significantly shorter hospitalization (7.3 vs 6.1 days, p = 0.03), a significantly lower pain in postoperative day 1 (p = 0.015) and a lower use of analgesic drugs (p = 0.05). Pleural effusion drainage was lower in CT group both in first postoperative day (464 ± 143 ml vs 408 ± 141 ml, p = 0.05) and average of first three days (374 ± 96 ml vs 324 ± 95 ml, p = 0.01). No differences in terms of fluid retention, pneumothorax, subcutaneous emphysema and complications after chest tubes removal were found.
Conclusion

Smart Drain Coaxial chest tube seems an effective option after pulmonary lobectomy. The CT group showed lower hospitalization and use of analgesic drugs and thus a reduction of costs.
An Online Automatic Corona Diagnose System Based on Chest X-ray Images
Authors: Gougeh Reza Amini
Published: September 2020

An outbreak of SARS-CoV-2 shocked healthcare systems around the world. It began in December 2019 in Wuhan, China, and spread out in over 120 countries in less than three months. Imaging technologies helped in COVID-19 fast and reliable diagnosis. CT-Scan and X-ray imaging are popular methods. This study is focused on X-ray imaging, concerning limitations in small cities to access CT-Scan and its costs. Using deep learning models helps to diagnose precisely and quickly. We aimed to design an online system based on deep learning, which reports lung engagement with the disease, patient status, and therapeutic guidelines. Our objective was to relieve pressure on radiologists and minimize the interval between imaging and diagnosing. VGG19, VGG16, InceptionV3, and ResNet50 were evaluated to be considered as the main code of the online diagnosing system. VGG16, with 98.92% accuracy, achieved the best score. VGG19 performed quite similarly to VGG16. VGG19, InceptionV3 and ResNet50 obtained 98.90, 71.79 and 28.27 subsequently.
A Strategy for Scleroglucan Production in Sclerotium Rolfsii: Lowering pH in Fermentation Process by Manipulating Oxalate Metabolic Pathway With CRISPR/Cas9 Tool
Authors: Bai Tianlong , Wang Teng , Li Yan , Gao Na L , Zhang Lixin , Chen Wei-Hua , Yin Xiushan
Published: September 2020

Background: Sclerotium rolfsii is a potent producer of many secondary metabolites, one of which like scleroglucan is an exopolysaccharide (EPS) appreciated as a multipurpose compound applicable in many industrial fields. Results: We chose AAT1 gene in oxalate metabolic pathway as target of CRISPR/Cas9. When the AAT1 gene is disrupted, oxalate was not converted to α-ketoglutarate (AKG), but accumulated. So AAT1-mutant serves to lower the pH (pH 3-4) to increase the production of the pH-sensitive metabolite scleroglucan to be 21.03 g l-1 with productivity reached 0.25 g/(L·h).Conclusions: We established a platform for gene editing to rapidly generate and select mutants, and provide a new beneficial strain of S. rolfsii as a scleroglucan hyper-producer which could also reduce the cost of controlling optimum pH condition in fermentation industry.
Energy System Assessment in Metastatic Breast Cancer: A Cross-Sectional Study
Authors: Cuesta-Vargas Antonio I , Buchan Jena , Pajares Bella , Sofía Ruiz-Medina , Alba Emilio , Trinidad-Fernandez Manuel , Diaz-Balboa Estibaliz , Roldan-Jimenez Cristina
Published: September 2020

Background: Metastasis breast cancer commonly report physical and psychosocial side effects, which requires a supervised exercise prescription with an individualized assessment. This cross-sectional study examined the feasibility of energy system-based assessment, also generating descriptive values for assessment performance in this population.Methods: This cross-sectional study recruited 70 women diagnosed with metastatic breast cancer. After baseline assessment, participants attempted up to three energy system assessments: submaximal aerobic (multi-stage treadmill); anaerobic alactic (30-second sit-to-stand [30-STS]); and anaerobic lactic (adapted burpees). Heart rate and rating of perceived exertion (RPE) were recorded. Secondary outcomes included body composition, CRF and upper- and lower-limb functionality. Results: 64 and 70 of the participants performed the submaximal aerobic test and the 30-STS, respectively, and 5 completed the adapted burpees task. Heart rate and RPE specific to each task were correlated, reflecting increased intensity. Women reported low-moderate levels of CRF [3(2.1)] and moderate-high functionality levels [upper-limb: 65.8% (23.3); lower-limb: 63.7% (34.7)]. Conclusions: Using a combination of heart rate and RPE, as well as baseline assessment of each energy system, clinicians may improve ability to prescribe personalized exercise and give patients greater ability to self-monitor intensity and progress.Trial registration: ClinicalTrials.gov ID NCT03879096
Dexmedetomidine Provides Protection to Neurons Against OGD/R-Induced Oxidative Stress and Neuronal Apoptosis
Authors: Xu Deming , Zhou Changbi , Lin Juanyun , Cai Wenhui , Lin Wei
Published: September 2020

Background: Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has applied in several diseases. However, the precise role of dexmedetomidine in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated neurons, and the mechanisms underlying its effect, has yet to be elucidated. Methods: OGD/R-treated neurons served as a cellular model in our study. Western blotting was used to investigate the protein levels of α-adrenergic receptor (α-AR) in OGD/R-treated neurons, apoptosis related proteins (Bcl-2, Bax and Cleaved Caspase 3) and a range of proteins associated with the Nrf2/ARE pathway (Nrf2, HO-1, NQO-1, SOD). The CCK-8 assay was used to determine cell survival rates while Co-IP was used to determine the interactions between α2-AR and Nrf2. The TUNEL assay was used to detect the levels of apoptosis in neurons. Results: OGD/R treatment reduced the level of α2-AR protein in neurons and reduced neuronal survival in a time-dependent manner. However, treatment with dexmedetomidine led to an elevation of α2-AR protein expression in OGD/R-treated neurons and the survival rate of OGD/R-treated neurons. These results indicated that dexmedetomidine treatment promoted the viability of OGD/R-treated neurons but inhibited OGD/R-mediated oxidative stress and neuronal apoptosis. From a mechanistic point-of-view, Nrf2 can bind effectively with α2-AR. We believe that dexmedetomidine exerted effect on the Nrf2/ARE pathway in OGD/R-treated neurons. Silencing the expression of Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons.Conclusion: Collectively, our data indicate that elucidated that the activation of α2-AR by dexmedetomidine had a protective effect in neurons against OGD/R-triggered oxidative stress and neuronal apoptosis by modulating the Nrf2/ARE pathway, thus providing a novel way forward to develop clinical therapies to reduce oxidative stress induced by neuronal injury.
Evaluating Common Variants in NOS1AP in Patients with Implantable Cardioverter Defibrillator for Secondary Prevention
Authors: Zang Xiaobiao , Shulong Zhang , Li Sisi , Wang Xianqing , Song Weifeng , Chen Ke , Ma Jifang , Tu Xin , Xia Yunlong , Yonghui Zhao , Chuanyu Gao
Published: September 2020

Background

Contemporary researchers found single nucleotide polymorphisms (SNPs) in nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with altered QT intervals and SCD. However, the clinical utility and implications of these SNP have not been described. This study aims to explore the clinical utility and implications of SNPs in nitric oxide synthase 1 adaptor protein (NOS1AP) in patients with implantable cardioverter defibrillator (ICD) for secondary prevention.
Methods

We firstly conducted a case-control study to evaluate the associations between hot-spot SNPs in NOS1AP (rs12143842, rs10494366, rs12567209 and rs16847548) and patients with ICD for secondary prevention. Then the clinical values of the positive SNPs were further evaluated in these patients. All patients were divided into three groups according to different genotypes of the positive SNPs. ICD interrogation data at 3, 12 months, and 3 years after implantation, which include rapid ventricular arrhythmia episodes and appropriate therapies, were analyzed in three genotypes.
Results

Case-control study revealed significant allelic association between rs10494366 and ICD recipients who experienced appropriate therapies. After a mean follow-up time of 31.70 ± 9.15 months, we detected not only significant difference among three genotypes on the distribution of ICD shocks and appropriate therapies, but apparently also the correlation of rs10494366 and ICD shocks. Furthermore, under kaplan-meier and cox regression analysis, TT genotype both showed higher risk for sudden cardiac death (SCD) compared with GG genotype.
Conclusions

The present study revealed that SNP rs10494366 was associated with appropriate therapies and SCD in patients with ICD for secondary prevention for the first time.