bluuebunny/crossref_metadata_2025 huggingface dataset:
A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation
Authors: Goshi Noah , Morgan Rhianna K. , Lein Pamela J. , Seker Erkin
Published: May 2020

Background

Interactions between neurons, astrocytes, and microglia critically influence neuroinflammatory responses to insult in the central nervous system. In vitro astrocyte and microglia cultures are powerful tools to study specific molecular pathways involved in neuroinflammation; however, in order to better understand the influence of cellular crosstalk on neuroinflammation, new multicellular culture models are required.

Methods

Primary cortical cells taken from neonatal rats were cultured in a serum-free “tri-culture” medium formulated to support neurons, astrocytes, and microglia, or a “co-culture” medium formulated to support only neurons and astrocytes. Caspase 3/7 activity and morphological changes were used to quantify the response of the two culture types to different neuroinflammatory stimuli mimicking sterile bacterial infection (lipopolysaccharide (LPS) exposure), mechanical injury (scratch), and seizure activity (glutamate-induced excitotoxicity). The secreted cytokine profile of control and LPS-exposed co- and tri-cultures were also compared.

Results

The tri-culture maintained a physiologically relevant representation of neurons, astrocytes, and microglia for 14 days in vitro, while the co-cultures maintained a similar population of neurons and astrocytes, but lacked microglia. The continuous presence of microglia did not negatively impact the overall health of the neurons in the tri-culture, which showed reduced caspase 3/7 activity and similar neurite outgrowth as the co-cultures, along with an increase in the microglia-secreted neurotrophic factor IGF-1 and a significantly reduced concentration of CX3CL1 in the conditioned media. LPS-exposed tri-cultures showed significant astrocyte hypertrophy, increase in caspase 3/7 activity, and the secretion of a number of pro-inflammatory cytokines (e.g., TNF, IL-1α, IL-1β, and IL-6), none of which were observed in LPS-exposed co-cultures. Following mechanical trauma, the tri-culture showed increased caspase 3/7 activity, as compared to the co-culture, along with increased astrocyte migration towards the source of injury. Finally, the microglia in the tri-culture played a significant neuroprotective role during glutamate-induced excitotoxicity, with significantly reduced neuron loss and astrocyte hypertrophy in the tri-culture.

Conclusions

The tri-culture consisting of neurons, astrocytes, and microglia more faithfully mimics in vivo neuroinflammatory responses than standard mono- and co-cultures. This tri-culture can be a useful tool to study neuroinflammation in vitro with improved accuracy in predicting in vivo neuroinflammatory phenomena.
Guiding functional reorganization of motor redundancy using a body-machine interface
Authors: De Santis Dalia , Mussa-Ivaldi Ferdinando A.
Published: May 2020

Background

Body-machine interfaces map movements onto commands to external devices. Redundant motion signals derived from inertial sensors are mapped onto lower-dimensional device commands. Then, the device users face two problems, a) the structural problem of understanding the operation of the interface and b) the performance problem of controlling the external device with high efficiency. We hypothesize that these problems, while being distinct are connected in that aligning the space of body movements with the space encoded by the interface, i.e. solving the structural problem, facilitates redundancy resolution towards increasing efficiency, i.e. solving the performance problem.

Methods

Twenty unimpaired volunteers practiced controlling the movement of a computer cursor by moving their arms. Eight signals from four inertial sensors were mapped onto the two cursor’s coordinates on a screen. The mapping matrix was initialized by asking each user to perform free-form spontaneous upper-limb motions and deriving the two main principal components of the motion signals. Participants engaged in a reaching task for 18 min, followed by a tracking task. One group of 10 participants practiced with the same mapping throughout the experiment, while the other 10 with an adaptive mapping that was iteratively updated by recalculating the principal components based on ongoing movements.

Results

Participants quickly reduced reaching time while also learning to distribute most movement variance over two dimensions. Participants with the fixed mapping distributed movement variance over a subspace that did not match the potent subspace defined by the interface map. In contrast, participant with the adaptive map reduced the difference between the two subspaces, resulting in a smaller amount of arm motions distributed over the null space of the interface map. This, in turn, enhanced movement efficiency without impairing generalization from reaching to tracking.

Conclusions

Aligning the potent subspace encoded by the interface map to the user’s movement subspace guides redundancy resolution towards increasing movement efficiency, with implications for controlling assistive devices. In contrast, in the pursuit of rehabilitative goals, results would suggest that the interface must change to drive the statistics of user’s motions away from the established pattern and toward the engagement of movements to be recovered.

Trial registration

ClinicalTrials.gov, NCT01608438, Registered 16 April 2012.
Metastatic non-functional paraganglioma to the lung
Authors: Abou Chaar Mohamad K. , Khanfer Aseel , Almasri Nidal M. , Abu Shattal Mohammad , Alibraheem Abdellatif O. , Al-Qudah Obada
Published: May 2020

Introduction

Paragangliomas are rare endocrine tumors that arise from the extra-adrenal autonomic paraganglia and sympathetic paragangliomas usually secret catecholamines and are located in the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In contrast, most parasympathetic paragangliomas are nonfunctional and located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Such neoplasms, although rare, are clinically important because they may recur after surgical resection and 10% of them give rise to metastases causing death with the lymphatic nodes, bones, liver, and lungs being the most common locations.

Case presentation

We present a case of a 26-year-old male patient that was diagnosed with paraganglioma of the right-frontal lobe infiltrating the falx and frontal bone which was diagnosed after suffering from a headache and abnormal vision. On initial work-up he was found to have right pulmonary nodules that increased in size after follow up and other nodules appeared in the contralateral lung. He underwent subtotal resection of the brain tumor and complete resection of the bilateral pulmonary nodules.

Conclusion

To our knowledge, paraganglioma is considered to be a rare entity in the central nervous system with very few cases being reported in the supratentorial region and no cases were reported of metastatic such paraganglioma to the lung.
Short-term outcomes of on- vs off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: a systematic review and meta-analysis
Authors: Guan Zhiyuan , Guan Xiaoqing , Gu Kaiyun , Lin Xuanqi , Lin Jin , Zhou Wenjun , Xu Ming , Wan Fen , Zhang Zhe , Song Chunli
Published: May 2020

Objectives

Does the manipulation of the off-pump CABG (OPCAB) in patient with depressed left ventricular function is better than on-pump CABG (ONCAB) approach in in-hospital mortality and morbidities? Here we undertook a meta-analysis of the best evidence available on the comparison of primary and second clinical outcomes of the off-pump and on-pump CABG.

Design

Systematic literature reviewer and meta-analysis.

Data sources

PubMed, EMBASE, Web of science and Cochrane Center Registry of Controlled Trials were searched the studies which comparing the use of the off-pump CABG(OPCAB) and on-pump CABG (ONCAB) for patients with LVD during January 1990.1 to January 2018.

Eligibility criteria

All observation studies and randomized controlled trials comparing on-pump and off-pump as main technique for multi-vessel coronary artery disease (defined as severe stenosis (>70%) in at least 2 major diseased coronary arteries) with left ventricular dysfunction(defined as ejection fraction (EF) 40% or less) were included.

Data extraction and synthesis

Authors will screen and select the studies extract the following data, first author, year of publication, trial characters, study design, inclusion and exclusion criteria, graft type, clinical outcome, assess the risk of bias and heterogeneity. Study-specific estimates will pool through the modification of the Newcastle-Ottawa scale for the quality of study and while leave-one-out analysis will be used to detect the impact of individual studies on the robustness of outcomes.

Results

Among the 987 screened articles, a total of 16 studies (32,354 patients) were included. A significant relationship between patient risk profile and benefits from OPCAB was found in terms of the 30-day mortality (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73–0.97; P = 0.02), stroke (OR, 0.69; 95% CI, 0.55–0.86; P = 0.00), myocardial infarction (MI) (OR, 0.71; 95% CI, 0.53–0.96; P = 0.02), renal failure (OR, 0.71; 95% CI, 0.55–0.93; P = 0.01), pulmonary complication (OR, 0.68; 95% CI, 0.52–0.90; P = 0.01), infection (OR, 0.67; 95% CI, 0.49–0.91; P = 0.00),postoperative transfusion (OR, 0.25; 95% CI, 0.08–0.84; P = 0.02) and reoperation for bleeding (OR, 0.56; 95% CI, 0.41–0.75; P = 0.00). There was no significant difference in atrial fibrillation (AF) (OR, 0.96;95%; CI, 0.78–1.41; P = 0.56) and neurological dysfunction (OR, 0.88; 95% CI, 0.49–1.57; P = 0.65).

Conclusions

Compared with the on-pump CABG with LVD, using the off-pump CABG is a better choice for patients with lower mortality, stroke, MI, RF, pulmonary complication, infection, postoperative transfusion and reoperation for bleeding. Further randomized studies are warranted to corroborate these observational data.
Comparing the effects of ketorolac and Paracetamol on postoperative pain relief after coronary artery bypass graft surgery. A randomized clinical trial
Authors: Javaherforooshzadeh Fatemeh , Abdalbeygi Hasan , Janatmakan Farahzad , Gholizadeh Behnam
Published: May 2020

Introduction

Pain management after coronary artery bypass graft (CABG) surgery remains challenging.

Objective

This study aimed to compare the effects of Ketorolac and Paracetamol on postoperative CABG pain relief.

Method

This double-blind randomized clinical trial study was conducted in Ahvaz, Iran, from September 2018–December 2019. Two consecutive groups of 60 patients undergoing elective on-pump coronary artery bypass graft surgery.

Intervention

The patients were divided into 0.5 mg/kg of ketorolac mg/dl and 10 mg/kg of Paracetamol after surgery for pain management. Primary outcomeswere: visual analog pain scale (VAS) at the time point immediately after extubation (baseline) and at 6, 12, 24 and 48 h and the total dose of morphine consumption.Secondary outcomesincluded the hemodynamic variables, weaning time, chest tube derange, in-hospital mortality and myocardial infarction.

Statistical analysis:The data were analyzed using SPSS version 22(SPSS, Chicago, IL). The Mann-Whitney U-test was used to compare demographic data, VAS scores, vital signs, and side effects. Repeated measurements were tested within groups using Friedman’s ANOVA and the Wilcoxon rank-sum test. Values were expressed as means ± standard deviations. Statistical significance was defined as ap-value < 0.05.

Results

Compared with baseline scores, there were significant declines in VAS scores in both groups throughout the time sequence (P< 0.05). The statistical VAS score was slightly higher in the Paracetamol group at most time points, except for the time of 6 h. However, at 24 and 48 h, the VAS score in group Paracetamol was significantly higher than in group Ketorolac. There were no significant differences between groups about hemodynamic variables.

Conclusion

The efficacy of ketorolac is comparable to that of Paracetamol in postoperative CABG pain relief.

Trial registry

IRCT20150216021098N5. Registered at 2019-09-12.
The influence of postoperative albumin levels on the outcome of cardiac surgery
Authors: Berbel-Franco David , Lopez-Delgado Juan Carlos , Putzu Alessandro , Esteve Francisco , Torrado Herminia , Farrero Elisabet , Rodríguez-Castro David , Carrio Maria Lluïsa , Landoni Giovanni
Published: May 2020

Background

The prognostic role of low postoperative serum albumin levels (SAL) after cardiac surgery (CS) remains unclear in patients with normal preoperative SAL. Our aim was to evaluate the influence of SAL on the outcome of CS.

Methods

Prospective observational study. Patients undergoing CS with normal preoperative SAL and nutritional status were included and classified into different subgroups based on SAL at 24 h after CS. We assessed outcomes (i.e., in-hospital mortality, postoperative complications and long-term survival) and results were analyzed among the different subgroups of SAL.

Results

We included 2818 patients. Mean age was 64.5 ± 11.6 years and body mass index 28.0 ± 4.3Kg·m− 2. 5.8%(n = 162) of the patients had normal SAL levels(≥35 g·L− 1), 32.8%(n = 924) low deficit (30–34.9 g·L− 1), 44.3%(n = 1249) moderate deficit (25–29.9 g·L− 1), and 17.1%(n = 483) severe deficit(< 25 g·L− 1). Higher SAL after CS was associated with reduced in-hospital (OR:0.84;95% CI:0.80–0.84; P = 0.007) and long-term mortality (HR:0.85;95% CI:0.82–0.87;P < 0.001). Subgroups of patients with lower SAL showed worst long-term survival (5-year mortality:94.3% normal subgroup, 87.4% low, 83.1% moderate and 72.4% severe;P < 0.001). Multivariable analysis showed higher in-hospital mortality, sepsis, hemorrhage related complications, and ICU stay in subgroups of patients with lower SAL. Predictors of moderate and severe hypoalbuminemia were preoperative chronic kidney disease, previous CS, and longer cardiopulmonary bypass time.

Conclusions

The presence of postoperative hypoalbuminemia after CS is frequent and the degree of hypoalbuminemia may be associated with worst outcomes, even in the long-term scenario.
The effect of music therapy on pain, anxiety and depression in patients after coronary artery bypass grafting
Authors: Dai Wang-Sheng , Huang Shu-Ting , Xu Ning , Chen Qiang , Cao Hua
Published: May 2020

Objective

The purpose of this study was to explore the effects of music therapy on pain, anxiety and depression in patients after coronary artery bypass grafting.

Methods

A retrospective study of 99 patients after coronary artery bypass from January 2017 to January 2019 was conducted in a cardiac center in China. According to the different interventions, all the participants were divided into 3 groups: group A: music therapy; group B: rest without music therapy; and group C: conventional treatment. The Numerical Rating Scale (NRS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to measure the patient’s pain, anxiety and depression before and after 30 min of the intervention.

Results

There were no significant differences in the NRS, SDS and SAS scores between the three groups of patients before the intervention. After 30 min of music therapy, the NRS, SDS and SAS scores of patients in group A were significantly lower than those before music therapy, and the differences were statistically significant. However, before and after the intervention in groups B and C, the NRS, SDS and SAS scores were not statistically significant. By comparison among the three groups after 30 min of intervention, the NRS, SDS and SAS scores in patients in group A were significantly lower than those in groups B and C, and the differences were statistically significant. The scores were not significantly different between groups B and C.

Conclusion

Music therapy can effectively alleviate the pain, anxiety and depression of patients after coronary artery bypass grafting.
Altered behavior in mice overexpressing soluble ST2
Authors: Kikuchi Motoshi , Takase Kenkichi , Hayakawa Morisada , Hayakawa Hiroko , Tominaga Shin-ichi , Ohmori Tsukasa
Published: May 2020

Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior.
Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells
Authors: Liu Kai , Zheng Minying , Zhao Qi , Zhang Kexin , Li Zugui , Fu Fangmei , Zhang Hao , Du Jiaxing , Li Yuwei , Zhang Shiwu
Published: May 2020

Background

Our previous studies have confirmed that cobalt chloride (CoCl2) can induce the formation of polyploid giant cancer cells (PGCCs), which is the key to the heterogeneity of solid tumors. PGCC formation is closely related to the abnormal expression of cell cycle-related proteins and cell fusion. In this study, we investigated the molecular mechanism of PGCCs formation by detecting the expression of cell cycle-related proteins in mutant and wild-type p53 cancer cell lines.

Methods

HEY, BT-549, SKOv3 and MDA-MB-231 cells were treated with CoCl2 and the cell cycle was detected by flow cytometry. The expression and subcellular localization of cell cycle-related proteins, kinases, and P53 were compared before and after CoCl2 treatment. Immunoprecipitation was used to analyze the interacting proteins of pCDC25C-Ser216 and pCDC25C-Ser198. The clinicopathologic significances of these cell cycle-related proteins and protein kinases expression were studied.

Results

CoCl2 induced the formation of PGCCs and G2/M arrest. CDC25C, cyclin B1, and CDK1 expressions after CoCl2 treatment were lower than that in control cells. Cytoplasmic CDC25C was degraded by ubiquitin-dependent proteasome. The expression of P53 and phosphokinases including CHK1, CHK2, PLK1, and Aurora A increased after CoCl2 treatment. The expression of pCDC25C-Ser216 and pCDC25C-Ser198 depended upon the genotype of p53. The expressions of cell cycle-related proteins and kinases gradually increased with the development of ovarian cancer and breast cancer.

Conclusion

CHK1, CHK2–pCDC25C-Ser216–cyclin B1–CDK1, and Aurora A–PLK1–pCDC25C-Ser198–cyclin B1–CDK1 signaling pathways may participate in the formation of PGCCs and different phosphorylation sites of CDC25C may be associated with the genotype of p53.
Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study
Authors: Ambrosini Giovanna , Vorontsov Ilya , Penzar Dmitry , Groux Romain , Fornes Oriol , Nikolaeva Daria D. , Ballester Benoit , Grau Jan , Grosse Ivo , Makeev Vsevolod , Kulakovskiy Ivan , Bucher Philipp
Published: May 2020

Background

Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or in vitro data are stored in many databases and used in a plethora of biological applications. This calls for comprehensive benchmarking of public PWM models with large experimental reference sets.

Results

Here we report results from all-against-all benchmarking of PWM models for DNA binding sites of human TFs on a large compilation of in vitro (HT-SELEX, PBM) and in vivo (ChIP-seq) binding data. We observe that the best performing PWM for a given TF often belongs to another TF, usually from the same family. Occasionally, binding specificity is correlated with the structural class of the DNA binding domain, indicated by good cross-family performance measures. Benchmarking-based selection of family-representative motifs is more effective than motif clustering-based approaches. Overall, there is good agreement between in vitro and in vivo performance measures. However, for some in vivo experiments, the best performing PWM is assigned to an unrelated TF, indicating a binding mode involving protein-protein cooperativity.

Conclusions

In an all-against-all setting, we compute more than 18 million performance measure values for different PWM-experiment combinations and offer these results as a public resource to the research community. The benchmarking protocols are provided via a web interface and as docker images. The methods and results from this study may help others make better use of public TF specificity models, as well as public TF binding data sets.
Sampling time-dependent artifacts in single-cell genomics studies
Authors: Massoni-Badosa Ramon , Iacono Giovanni , Moutinho Catia , Kulis Marta , Palau Núria , Marchese Domenica , Rodríguez-Ubreva Javier , Ballestar Esteban , Rodriguez-Esteban Gustavo , Marsal Sara , Aymerich Marta , Colomer Dolors , Campo Elias , Julià Antonio , Martín-Subero José Ignacio , Heyn Holger
Published: May 2020

Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample acquisition can hinder solid, reproducible results, and a systematic benchmarking is required before entering large-scale data production. Here, we report the existence and extent of gene expression and chromatin accessibility artifacts introduced during sampling and identify experimental and computational solutions for their prevention.
Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain
Authors: Liu Shuxian , Wu Mimi , Hua Qianqian , Lu Daiqiang , Tian Yuan , Yu Helin , Cheng Linyan , Chen Yinqi , Cao Jiaxin , Hu Xin , Tan Feng
Published: May 2020

Background

Toxoplasma gondii is a zoonotic pathogen that causes toxoplasmosis and leads to serious public health problems in developing countries. However, current clinical therapeutic drugs have some disadvantages, such as serious side effects, a long course of treatment and the emergence of drug-resistant strains. The urgent need to identify novel anti-Toxoplasma drugs has initiated the effective strategy of repurposing well-characterized drugs. As a principled screening for the identification of effective compounds against Toxoplasma gondii, in the current study, a collection of 666 compounds were screened for their ability to significantly inhibit Toxoplasma growth.

Methods

The inhibition of parasite growth was determined using a luminescence-based β-galactosidase activity assay. Meanwhile, the effect of compounds on the viability of host cells was measured using CCK8. To assess the inhibition of the selected compounds on discrete steps of the T. gondii lytic cycle, the invasion, intracellular proliferation and egress abilities were evaluated. Finally, a murine infection model of toxoplasmosis was used to monitor the protective efficacy of drugs against acute infection of a highly virulent RH strain.

Results

A total of 68 compounds demonstrated more than 70% parasite growth inhibition. After excluding compounds that impaired host cell viability, we further characterized two compounds, NVP-AEW541 and GSK-J4 HCl, which had IC50 values for parasite growth of 1.17 μM and 2.37 μM, respectively. In addition, both compounds showed low toxicity to the host cell. Furthermore, we demonstrated that NVP-AEW541 inhibits tachyzoite invasion, while GSK-J4 HCl inhibits intracellular tachyzoite proliferation by halting cell cycle progression from G1 to S phase. These findings prompted us to analyse the efficacy of the two compounds in vivo by using established mouse models of acute toxoplasmosis. In addition to prolonging the survival time of mice acutely infected with T. gondii, both compounds had a remarkable ability to reduce the parasite burden of tissues.

Conclusions

Our findings suggest that both NVP-AEW541 and GSK-J4 could be potentially repurposed as candidate drugs against T. gondii infection.
Potential therapeutic effects of endothelial cells trans-differentiated from Wharton’s Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model
Authors: Motawea Shaimaa M. , Noreldin Rasha I. , Naguib Yahya M.
Published: May 2020

Background

Diabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events. As aging, diabetes mellitus and hypertension share common pathways, an ideal treatment should possess the ability to counter more than one of, if not all, the underlying mechanisms. Stem cells emerged as a potential approach for complicated medical problems. We tested here the possible role of trans-differentiated endothelial cells (ECs) in the treatment of diabetes mellitus in old rats.

Methods

Mesenchymal stem cells where isolated from umbilical cord Wharton’s Jelly and induced to differentiate into endothelial like-cells using vascular endothelial growth factor-enriched media. Thirty aged male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection as well as single intravenous injection via tail vein of the vehicles), aged diabetic group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of saline via tail vein), and aged diabetic + ECs group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of 2*106 MSC-derived ECs in 0.5 ml saline via tail vein) groups. Assessment of SBP, aortic PWV, and renal artery resistance was performed. Serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF were evaluated, as well as the aortic NO tissue level and eNOS gene expression. Histopathological and immunostaining assessments of small and large vessels were also performed.

Results

Induction of diabetes in old rats resulted in significant increase in SBP, aortic PWV, renal artery resistance, and serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF. While there was significant decrease in aortic NO tissue level and eNOS gene expression in the aged diabetic group when compared to aged control group. ECs treatment resulted in significant improvement of endothelial dysfunction, inflammation and oxidative stress.

Conclusion

We report here the potential therapeutic role of trans-differentiated ECs in aged diabetics. ECs demonstrated anti-inflammatory, antioxidant, gene modifying properties, significantly countered endothelial dysfunction, and improved vascular insult.
Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis
Authors: Broere-Brown Zoe A. , Adank Maria C. , Benschop Laura , Tielemans Myrte , Muka Taulant , Gonçalves Romy , Bramer Wichor M. , Schoufour Josje D , Voortman Trudy , Steegers Eric A. P. , Franco Oscar H. , Schalekamp-Timmermans Sarah
Published: May 2020

Background

Since the placenta also has a sex, fetal sex–specific differences in the occurrence of placenta-mediated complications could exist.

Objective

To determine the association of fetal sex with multiple maternal pregnancy complications.

Search strategy

Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies.

Selection criteria

Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies.

Data collection and analyses

Data were extracted by 2 independent reviewers using a predesigned data collection form.

Main results

From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition.

Conclusion

This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus.

Funding

None.
Trust in the referring physician reduces anxiety in an integrated community-to-hospital care system
Authors: Flugelman Moshe Y. , Jaffe Ronen , Luria Gil , Yagil Dana
Published: May 2020

Background

Continuity of care between the community and hospital is considered of prime importance for quality of care and patient satisfaction, and for trust in the medical system. In a unique model of continuity of care, cardiologists at our hospital serve as primary, community-based cardiologists one day a week. They refer patients from the community to our hospital for interventional procedures such as coronary angiography and angioplasty. We examined the hypotheses that patient anxiety during hospital-based coronary angiography is lower when a patient trusts the referring cardiologist and when the performing cardiologist also treated him/her in the community.

Methods

We administered questionnaires to 64 patients in our cardiology department within 90 min of completion of coronary angiography. The questions assessed anxiety, trust in the medical system and trust in the referring physician. Data were also collected regarding patients’ demographic variables, the number of visits to the referring physician, and whether the physician who performed the coronary angiography was the physician who referred the patient to the hospital.

Results

Mean levels (on 7-point Likert scales) were 2.1, 5.6 and 6.7 for patient anxiety, trust in the medical system and trust in the referring physician, respectively. Multivariate regression analysis showed that trust in the referring physician was significantly and negatively correlated with anxiety level. The number of visits to referring physicians, patients’ demographic characteristics and whether the physician who performed the angiography was the same physician who referred the patient from the community were not found to be associated with patient anxiety.

Conclusion

In this study, trusting the referring physician was associated with lower anxiety among patients who underwent coronary angiography. This trust seemed to have more positive impact than did previous contact with the physician who performed the procedure.
Predictive side decoding for human-centered multiple description image coding
Authors: Xu Yuanyuan
Published: May 2020

Multiple description coding (MDC) provides a favorable solution for human-centered image communication, which takes into account people’s varying watching situations as well as people’s demand for real-time image display. As an effective technique for MDC, three-description lattice vector quantization (3D-LVQ) is considered for image coding in this paper. Based on intra- and inter-correlation in the 3D-LVQ index assignment as well as wavelet intra-subband correlation, a novel predictive decoding method for 3D-LVQ-based image coding is proposed to enhance side decoding performance, which attempts to predict lost descriptions (sublattice points) in a good way for better reconstructions of wavelet vectors (fine lattice points) in the side decoding. Experimental results validate effectiveness of the proposed decoding scheme in terms of rate-distortion performance.
New proofs on two recent inequalities for unitarily invariant norms
Authors: Yang Junjian , Lu Linzhang
Published: May 2020

In this short note, we provide alternative proofs for several recent results due to Audenaert (Oper. Matrices 9:475–479, 2015) and Zou (J. Math. Inequal. 10:1119–1122, 2016; Linear Algebra Appl. 552:154–162, 2019).
Clinical impact of endemic NDM-producing Klebsiella pneumoniae in intensive care units of the national referral hospital in Jakarta, Indonesia
Authors: Saharman Yulia Rosa , Karuniawati Anis , Sedono Rudyanto , Aditianingsih Dita , Goessens Wil H. F. , Klaassen Corné H. W. , Verbrugh Henri A. , Severin Juliëtte A.
Published: May 2020

Objective

A prospective observational study was performed to assess the epidemiology and clinical impact of carbapenem-non-susceptible Klebsiella pneumoniae (CNKP) in intensive care units (ICUs) of the national referral hospital in Jakarta, Indonesia.

Materials/methods

Adult patients consecutively hospitalized for > 48 h in two ICUs of the national referral hospital were included from April until October 2013 and from April until August 2014. K. pneumoniae from clinical cultures and standardized screening of rectum and throat on admission, discharge and weekly if hospitalized > 7 days were collected. Environmental niches and healthcare workers (HCWs) were also screened. Susceptibility was determined phenotypically and the presence of carbapenemase genes by PCR. Raman spectroscopy as well as multiple-locus variable number tandem repeat analysis (MLVA) were used for typing.

Results

Twenty-two out of 412 (5.3%) patients carried CNKP on admission and 37/390 (9.5%) acquired CNKP during ICU stay. The acquisition rate was 24.7/1000 patient-days at risk. One out of 31 (3.2%) environmental isolates was a CNKP. None of the HCWs carried CNKP. Acquisition of CNKP was associated with longer ICU stay (adjusted Hazard Ratio: 2.32 [CI99: 1.35–3.68]). ICU survival was lower among patients with CNKP compared to patients with carbapenem-susceptible K. pneumoniae (aHR 2.57, p = 0.005). Ninety-six of the 100 (96%) CNKP isolates carried a carbapenemase gene, predominantly blaNDM. Raman typing revealed three major clusters among 48 Raman types identified, whereas MLVA distinguished six major clusters among a total of 30 different genotypes.

Conclusions

NDM-producing CNKP are introduced into these ICUs and some strains expand clonally among patients and the environment, resulting in endemic CNKP. CNKP acquisition was associated with prolonged ICU stay and may affect ICU survival.

Trial registration

The study was registered at Netherlands Trial Register http://www.trialregister.nl. Candidate number: 23527, NTR number: NTR5541, NL number: NL5425 (https://www.trialregister.nl/trial/5424), Retrospectively registered: NTR: 22 December 2015.
The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases
Authors: Song Qiaoyun , Meng Bo , Xu Haidong , Mao Zixu
Published: May 2020

Background

Lysosomes digest extracellular material from the endocytic pathway and intracellular material from the autophagic pathway. This process is performed by the resident hydrolytic enzymes activated by the highly acidic pH within the lysosomal lumen. Lysosome pH gradients are mainly maintained by the vacuolar (H+) ATPase (or V-ATPase), which pumps protons into lysosomal lumen by consuming ATP. Dysfunction of V-ATPase affects lysosomal acidification, which disrupts the clearance of substrates and leads to many disorders, including neurodegenerative diseases.

Main body

As a large multi-subunit complex, the V-ATPase is composed of an integral membrane V0 domain involved in proton translocation and a peripheral V1 domain catalyzing ATP hydrolysis. The canonical functions of V-ATPase rely on its H+-pumping ability in multiple vesicle organelles to regulate endocytic traffic, protein processing and degradation, synaptic vesicle loading, and coupled transport. The other non-canonical effects of the V-ATPase that are not readily attributable to its proton-pumping activity include membrane fusion, pH sensing, amino-acid-induced activation of mTORC1, and scaffolding for protein-protein interaction. In response to various stimuli, V-ATPase complex can reversibly dissociate into V1 and V0 domains and thus close ATP-dependent proton transport. Dysregulation of pH and lysosomal dysfunction have been linked to many human diseases, including neurodegenerative disorders such as Alzheimer disease, Parkinson’s disease, amyotrophic lateral sclerosis as well as neurodegenerative lysosomal storage disorders.

Conclusion

V-ATPase complex is a universal proton pump and plays an important role in lysosome acidification in all types of cells. Since V-ATPase dysfunction contributes to the pathogenesis of multiple neurodegenerative diseases, further understanding the mechanisms that regulate the canonical and non-canonical functions of V-ATPase will reveal molecular details of disease process and help assess V-ATPase or molecules related to its regulation as therapeutic targets.
Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
Authors: Zhou Juan , Ma Chuanchuan , Wang Ke , Li Xiuli , Jian Xuemin , Zhang Han , Yuan Jianmin , Yin Jiajun , Chen Jianhua , Shi Yongyong
Published: May 2020

Background

Schizophrenia is a chronic and severe mental disorder, and it has been predicted to be highly polygenic. Common SNPs located in or near BNIP3L were found to be genome-wide significantly associated with schizophrenia in recent genome-wide association studies. The purpose of our study is to investigate potential causal variants in BNIP3L gene.

Results

We performed targeted sequencing for all exons and un-translated regions of BNIP3L gene among 1806 patients with schizophrenia and 998 healthy controls of Han Chinese origin. Three rare nonsynonymous mutations, BNIP3L (NM_004331): c.52A>G, c.167G>A and c.313A>T, were identified in schizophrenia cases, and two of them were newly reported. The frequencies of these rare nonsynonymous mutations were significantly different between schizophrenia cases and healthy controls. For the common variants, rs147389989 achieved significance in both allelic and genotypic distributions with schizophrenia. Rs1042992 and rs17310286 were significantly associated with schizophrenia in meta-analyses using PGC, CLOZUK, and our new datasets in this study.

Conclusions

Our findings provided further evidence that BNIP3L gene is a susceptibility gene of schizophrenia and revealed functional and potential causal mutations in BNIP3L. However, more functional validations are suggested to better understand the role of BNIP3L in the etiology of schizophrenia.
Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: a prospective observational cohort study in Japan
Authors:   on behalf of the CRITICAL Study Group Investigators, Okada Yohei , Kiguchi Takeyuki , Irisawa Taro , Yoshiya Kazuhisa , Yamada Tomoki , Hayakawa Koichi , Noguchi Kazuo , Nishimura Tetsuro , Ishibe Takuya , Yagi Yoshiki , Kishimoto Masafumi , Shintani Hiroshi , Hayashi Yasuyuki , Sogabe Taku , Morooka Takaya , Sakamoto Haruko , Suzuki Keitaro , Nakamura Fumiko , Nishioka Norihiro , Matsuyama Tasuku , Sado Junya , Matsui Satoshi , Shimazu Takeshi , Koike Kaoru , Kawamura Takashi , Kitamura Tetsuhisa , Iwami Taku
Published: May 2020

Background

We aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR).

Methods

We retrospectively analyzed the database of a multicenter prospective observational study on OHCA patients in Osaka prefecture, Japan (CRITICAL study), from July 1, 2012 to December 31, 2016. We included adult OHCA patients treated by ECPR. Patients with OHCA from external causes such as trauma were excluded. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the pH value for 1 month favorable neurological outcome adjusted for potential confounders including sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival.

Results

Among the 9822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥ 7.030, Tertile 2: pH 6.875–7.029, and Tertile 3: pH < 6.875. The adjusted OR of Tertiles 2 and 3 compared with Tertile 1 for 1 month favorable neurological outcome were 0.26 (95% CI 0.10–0.63) and 0.24 (95% CI 0.09–0.61), respectively.

Conclusions

This multi-institutional observational study showed that low pH value (< 7.03) before the implementation of ECPR was associated with 1 month unfavorable neurological outcome among OHCA patients treated with ECPR. It may be helpful to consider the candidate for ECPR.
Gamma detector dead time correction using Lambert W function
Authors: Heemskerk Jan W. T. , Defrise Michel
Published: May 2020

Background

For therapeutic applications of several isotopes (e.g.,131I,153Sm,177Lu) in nuclear medicine, the high activities typically applied require accurate dead time correction in early time point imaging. We present a novel, straightforward dead time correction method using the LambertWfunction, which is in principle exact for the paralyzable detector model with a single parameter τ (i.e., dead time).

Results

As a proof of concept, the method is validated with a simple model: a commonly used isotope,99mTc, with a single photopeak. We measured count rates of a gamma camera both intrinsically and extrinsically (i.e., with collimators) with point sources in air and in a scatter phantom (extrinsic only). τ was estimated for both open window (τOW) and a99mTc photopeak window (τTc), using a “graphical” method for fitting the count rate of decaying sources. These values for τ were subsequently used for dead time correction.

τ varied significantly between the different geometries for both energy windows, but τOWwas more reproducible than τTc, particularly for the scatter phantom measurements.

τOWmeasured from the phantom measurements was approximately 30% lower than τOWfrom the intrinsic measurement but corresponded within 15% with the extrinsic point source measurements. Accordingly, using the intrinsic τOWled to an overcorrection of 8% at high count rates; τOWfrom the extrinsic point source measurements corrected the phantom measurement to within 2%.

However, significant differences were observed between τTcvalues. All measured τTcvalues underestimated dead time losses in a second independent phantom measurement, with even τTcfrom the first phantom measurement underestimating activity with 5–10% at the highest count rates. Based on measurements of the effect of energy window settings and geometry, we tentatively attribute the added dead time losses to pulse pile-up.

Conclusions

Analytic dead time correction based on the LambertWfunction is accurate for the range in which gamma detectors behave as paralyzable systems. However, further investigation indicated measured τ values to be variable with geometry as well as window fraction. We propose that dead time correction should be based on the open window value, τOW, corrected for window fraction.
Laparoscopic and endoscopic cooperative surgery for gastric cancer mimicking a submucosal tumor
Authors: Ozawa Hiroki , Kawakubo Hirofumi , Matsuda Satoru , Mayanagi Shuhei , Irino Tomoyuki , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Kitagawa Yuko
Published: May 2020

Background

Gastric cancer that mimics a submucosal tumor (SMT) is infrequently encountered in routine clinical settings, and histopathological analysis is often negative for malignant cells. In such cases, excisional biopsy of the entire tumor may be necessary to make a definitive pathological diagnosis, and laparoscopic and endoscopic cooperative surgery (LECS) is a viable method of excisional biopsy.

Case presentation

An 80-year-old male patient diagnosed with stomach wall irregularities at routine medical check-up was referred to our facility, and consequent endoscopic examination detected a 20-mm protruded lesion in the greater curvature at the middle third of the stomach. Endoscopic ultrasound (EUS) showed a thick, low echoic lesion with an irregular margin in the second layer of the gastric wall. Further, a nodular part of the lesion had infiltrated into the submucosa, with an appearance similar to that of linitis plastica of the stomach. The lesion was highly suspected to be a gastric carcinoma with submucosal invasion. However, mucosal-incision-assisted biopsy revealed no malignant cells. Computed tomography (CT) identified no metastatic lymph nodes. Therefore, an excisional biopsy using LECS was performed, and to avoid peritoneal dissemination, we used a modified version, namely, combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET). The procedure ended without any complications, and post-operative course was uneventful. As histopathology returned a diagnosis of adenocarcinoma pT4a, we performed radical gastrectomy and D2 lymphadenectomy. Post-operative course was unremarkable and the patient underwent follow-up examinations without adjuvant chemotherapy because of old age.

Conclusions

Local resection using LECS for gastric tumors with a high suspicion of malignancy is useful and feasible. LECS could be used in similar cases.
Integrating automatic question generation with computerised adaptive test
Authors: Susanti Yuni , Tokunaga Takenobu , Nishikawa Hitoshi
Published: May 2020

The present study focuses on the integration of an automatic question generation (AQG) system and a computerised adaptive test (CAT). We conducted two experiments. In the first experiment, we administered sets of questions to English learners to gather their responses. We further used their responses in the second experiment, which is a simulation-based experiment of the AQG and CAT integration. We proposed a method to integrate them with a predetermined item difficulty that enables to integrate AQG and CAT without administering the items in a pretesting. The result showed that all CAT simulations performed better than the baseline, a linear test, in estimating the test taker’s true proficiency.