bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic value of the SOFA score in patients with COVID-19: a retrospective, observational study
Authors: Yang Zheng , Hu Qinming , Huang Fei , Xiong Shouxin , sun yi
Published: October 2020

Background
Patients with Coronavirus disease 2019 (COVID-19) have a high mortality rate, and thus, it is particularly important to predict the severity and prognosis of COVID-19. The Sequential Organ Failure Assessment (SOFA) score has been used to predict the clinical outcomes of patients with multiple organ failure requiring intensive care. Therefore, we retrospectively analyzed the clinical characteristics, risk factors, and relationship between the SOFA score and the prognosis of COVID-19 patients.
Methods
Clinical variables were compared between patients with mild and severe COVID-19. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for severe COVID-19. The Cox proportional hazards model was used to analyze risk factors for hospital-related death. Survival analysis was performed by the Kaplan-Meier method, and survival differences were assessed by the log-rank test. Receiver operating characteristic (ROC) curves of the SOFA score in different situations were drawn, and the area under the ROC curve was calculated.
Results
The median SOFA score of all patients was 2 (IQR, 1–3). Patients with severe COVID-19 exhibited a significantly higher SOFA score than patients with mild COVID-19 [3 (IQR, 2–4) vs 1 (IQR, 0–1); P < 0.001]. The SOFA score increased the risk of severe COVID-19, with an odds ratio of 5.851 (95% CI: 3.044–11.245; P < 0.001). The area under the ROC curve (AUC) was used to evaluate the diagnostic accuracy of the SOFA score in predicting severe COVID-19 [cutoff value = 2; AUC = 0.908 (95% CI: 0.857–0.960); sensitivity: 85.20%; specificity: 80.40%] and the risk of death in COVID-19 patients [cutoff value = 5; AUC = 0.995 (95% CI: 0.985-1.000); sensitivity: 100.00%; specificity: 95.40%]. Regarding the 60-day mortality rates of patients in the two groups classified by the optimal cutoff value of the SOFA score (5), patients in the high SOFA score group (SOFA score ≥ 5) had a significantly greater risk of death than those in the low SOFA score group (SOFA score < 5).
Conclusion
The SOFA score could be used to evaluate the severity and 60-day mortality of COVID-19. The SOFA score may be an independent risk factor for in-hospital death.
Incidence and Outcome of Acute Myocardial Infarction in Patients with Aortic Dissection and Risk Factor Control
Authors: Liu Fang , Qian Si-Chong , Chen Mu-Lei , Wang Zhe , Yang Xin-Chun
Published: October 2020

Background
The contradiction of management modality between acute myocardial infarction(AMI) and aortic dissection(AD) may result in clinical catastrophe. Data on risk factors, incidence and outcome of AD and AMI are limited, and there have been no studies on the long-term outcomes of AMI in patients with AD. So we aimed to investigate long-term outcomes after AMI in patients with AD, and propose a useful diagnostic paradigm.
Methods
Consecutively enrolled patients with AD and AMI who were referred to our center from 2010 to 2017. Baseline patient characteristics, risk factors, all medical treatments, echocardiographic parameters, laboratory data and treatment were recorded. All patients were followed up from the first hospitalization until a first heart event, death or 17 March, 2018.
Results
0.13% in AMI and 7.49% in AD patients had a concomitant diagnosis of AD and AMI. The average patient age was 53.3 ± 12.1 years and 84.6% were male. The most prevalent vascular risk factors were hypertension (69.2%) and current smoker (64.1%). Of all the 39 patients, 66.7% were managed surgically. Overall in-hospital mortality was 10.3%. The 30-day and 5-year fatality rates were 23.1% and 35.9%, but were higher for female than for male(66.7% vs 30.3%, log-rank P = 0.045) on 5-year mortality. The overall survival of females was inferior to the males (log-rank P = 0.045).
Conclusions
Patients with AMI and AD exhibit high 5-year fatality rates. For these patients, surgical management tend to have lower mortality. Improved management of hypertension and smoking, may reduce future incidence rates.
Human-mouse chimeric Fragile X syndrome model reveals FMR1-dependent neuronal phenotypes
Authors: Krzisch Marine , Wu Hao , Yuan Bingbing , Whitfield Troy , Liu Shawn , Fu Dongdong , Garrett-Engele Carrie , Chang Aaron , Warren Stephen , Cacace Angela , Andrykovich Kristin , Rietjens Rosalie , Jain Bhav , Wallace Owen , Jaenisch Rudolf
Published: October 2020

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The cells populated the brain and differentiated into neurons and astrocytes. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons, an increased proportion of Arc-positive FXS neurons and increased dendritic protrusion width of FXS striatal medium spiny neurons. Our data show faster maturation and suggest increased synaptic activity and synaptic strength of FXS transplanted neurons. This model provides new insights into the alterations in FXS neuronal development.
Development of a versatile and efficient C-N lyase platform for asymmetric hydroamination via computational enzyme redesign
Authors: Cui Yinglu , Wang Yinghui , Tian Wenya , Bu Yifan , Li Tao , Cui Xuexian , Zhu Tong , Li Ruifeng , Wu Bian
Published: October 2020

Although C-N bonds are ubiquitous in natural products, pharmaceuticals, and agrochemicals, biocatalysts that forge these bonds with high atom efficiency and enantioselectivity have primarily been limited to a few select enzymes. In particular, the use of ammonia lyases has emerged as a powerful strategy to access C-N bond formation through hydroamination reactions, which has no counterpart in traditional synthetic chemistry. However, the broad utility of ammonia lyases is rather restricted due to their narrow synthetic scope, and the conjugate addition of a matrix of nucleophilic donors to electrophilic acceptors remains a longstanding challenge. Herein, we report the computational redesign of aspartase, a highly specific ammonia lyase, to yield C-N lyases with unprecedented cross-compatibility of nonnative nucleophiles and electrophiles. A wide range of noncanonical amino acids (ncAAs) are afforded with excellent conversion (up to 99%), regioselectivity > 99%, and product enantiomeric excess > 99%, and the process is scalable under industrially relevant protocols (demonstrated in kilogram-scale synthesis). Furthermore, the redesigned enzymes can be facilely integrated in cascade reactions, as we demonstrated the synthesis of β-lactams with different substitution patterns at the N-1 and C-4 positions in a one-pot reaction. This versatile and efficient C-N lyase platform supports the preparation of diverse libraries of ncAAs and their derivatives and will present opportunities in medicinal chemistry and synthetic biology.
Divergent Rhodium-Catalyzed Electrochemical Vinylic C–H Annulation of Acrylamides with Alkynes
Authors: Xing Yi-Kang , Chen Xin-Ran , Yang Qi-Liang , Zhang Shuoqing , Guo Haiming , Hong Xin , mei Tian-Sheng
Published: October 2020

A Rh-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes has been developed in an undivided cell, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C–H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C–H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates.
COVID-19 Lockdown in Spain: Psychological impact is greatest on younger and vulnerable children.
Authors: Matalí-Costa Josep , Camprodon-Rosanas Ester
Published: October 2020

In 2020, quarantine home confinement measures were implemented in Spain to control a pandemic for the first time. The objective of this study is to assess both the psychological and social impact of that “lockdown” on different age groups of children and adolescents, and also the different strategies adopted by families in that situation. We collected data via an online questionnaire answered by 850 participants, parents of young people aged between 4 and 18, between 24th April and 8th May 2020. Our results show that living in a home smaller than 80 m2 is associated with an increased risk of presenting clinical symptoms of emotional or behavioural distress, with an odds ratio of 2.54 (95%CI: 1.07 - 6.02), p = 0.034; while increased age is a predictor of better psychological functioning during lockdown: coefficient of 0.25 (95%CI: 0.07 - 0.41), p = 0.004. Moreover, age is also a marker of higher scores on the scale of psychological symptoms, with a coefficient of 0.02 (95%CI: 0.01 - 0.04), p = 0.005. To conclude, younger children present poorer behavioural and emotional functioning and more symptoms of emotional distress than adolescents during lockdown. Living in a small home is a risk factor for presenting clinical symptoms. These findings should be taken into consideration when planning for future home confinement episodes and when considering preventative strategies in the realm of mental healthcare.
SLAM Negatively Regulates IL-21 Production in Tfh-Like Cells from Allergic Rhinitis Patients
Authors: Yang Jun , Geng Lina , Ma Yongming , Tang Xinyi , Peng Huiyong , Tian Jie , Xu Huaxi , Wang Shengjun
Published: October 2020

Background: Allergic rhinitis (AR) is characterized by type Ⅰ hypersensitivity that is mediated by IgE-induced humoral responses. It is known that follicular helper T cells (Tfh) comprise the key Th cell subset that promotes antibody production. Signaling lymphocytic activation molecule (SLAM) participates in the regulation of the differentiation and function of Tfh cells, but whether this regulation is involved in the pathogenesis of AR is unknown.Methods: CD4+CXCR5+ Tfh-like cells from peripheral blood were detected by flow cytometry. The levels of IL-21 and IgE in serum were tested by ELISA. Blood CD4+CXCR5+ Tfh-like cells were sorted and cultured with anti-SLAM mAb in vitro.Results: The frequencies of circulating CD4+CXCR5+ Tfh-like cells appeared virtually unchanged in AR patients, but the expression of SLAM and SLAM-associated protein (SAP) on circulating Tfh-like cells was significantly decreased. Meanwhile, the level of serum IL-21 was increased in AR patients, and there was a negative correlation between the levels of IL-21 and the expression of SLAM or SAP in CD4+CXCR5+ T cells. Treatment with anti-SLAM mAb resulted in the reduced production of IL-21 by Tfh-like cells in vitro. Additionally, the expression of SLAM on B cells significantly decreased, although the percentages of B cells were increased in AR patients.Conclusions: SLAM negatively regulates the production of IL-21 in CD4+CXCR5+ Tfh-like cells, which contributes to the pathogenesis of AR.
The Optimal Changing Frequency of Hospital Privacy Curtains Based on Contamination Rates: A Prospective Culture Study
Authors: Lee Chan Mi , Goh Hye Yeon , Lee Hyo Yeon , Oh Young Rok , Park Wan Beom , Kim Nam Joong
Published: October 2020

To estimate contamination rates over time, we obtained cultures from 34 hospital privacy curtains and two control curtains over 8 weeks. If cultures revealed microorganisms over 2.5 colony forming unit (CFU)/cm2, we defined the curtains as contaminated. The burden of microorganisms of control curtains remained under 0.2 CFU/cm2 over the study period. The cumulative contamination rate of hospital privacy curtains increased over time (15.6% at week 2, 37.0% at week 4, and 55% at week 8). Contamination rates showed a tendency to increase as the number of beds in a room increased. We suggest that hospital curtains should be changed every 4 weeks, or less if the number of beds is high.
Impact of the COVID-19 Pandemic on Residents’ Clinical Training and Psychosocial Well-Being in Saudi Arabia’s Western Region
Authors: Alshareef Reem , Zahrani Abdullah Al , Alzhrani Meshari , Suwaidi Abdulaziz , Alamry Bander
Published: October 2020

Background: The novel COVID-19 pandemic has imposed a significant burden on healthcare systems. Similarly, it has also affected the performance and well-being of the medical staff working during the pandemic. However, to what extent COVID-19 is affecting medical staff is still unclear, especially among physicians.This study aims to evaluate the negative effect of the COVID-19 pandemic on the medical training and psychological well-being of resident doctors practicing in the western region in Saudi Arabia.Methods: This is a quantitative cross-sectional study that included a survey distributed to resident physicians working in the western region in Saudi Arabia. The survey included questions on demographic data and factors influencing the academic training, attitude, and daily habits of the residents during the pandemic. Psychological impact was assessed using the Kessler Psychological Distress Scale. Data analysis was executed using IBM SPSS version 26. Results: A total of 121 residents responded to this survey. Of all respondents, 71.1% were junior residents, 66.9% had a medical specialty; and 33% were family medicine doctors, followed by 17% from general surgery. In regards to work amid the pandemic, 36.1% were in contact with confirmed COVID-19 patients, and 35.5% had to work overtime during the pandemic. Of the respondents, 44% described their training as extremely affected, and 32% strongly agreed and 53% agreed that their psychological well-being was negatively affected. Further, 39.6% were smoking more than they used to. Female and junior residents’ training was significantly more negatively affected than their peers’ (p=0.039 and 0.011, respectively). There was a non-significant difference detected between the residents regarding the factors negatively affecting their psychological well-being. Conclusion: Residents working during the pandemic in the western area of Saudi Arabia were significantly affected by the pandemic from both professional and psychological perspectives. Further research on how the pandemic is affecting doctors in other areas in Saudi Arabia is needed.
Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin
Authors: Pothapragada Shilpa , Gupta Praver , Mukherjee Soumi , Das Tamal
Published: October 2020

In epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against activated HRasV12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell interface to initiate transformed cell-extrusion. But, on stiff matrix mimicking fibrotic epithelium, filamin redistributes into two dynamically distinct populations, including a new perinuclear pool, which cannot move to the cell-cell interface. A tug-of-war between filamin-Cdc42 and filamin-perinuclear cytoskeleton interactions controls this differential filamin localization and hence, determines the success or failure of epithelial defence on soft versus stiff matrix. Together, our study reveals how pathological matrix stiffening leads to a failed epithelial defence at the initial stage of oncogenesis.
A hot Jupiter spectral sequence with evidence for compositional diversity
Authors: Mansfield Megan , Line Michael , Bean Jacob , Fortney Jonathan , Parmentier Vivien , Kempton Eliza , Sing David , Lopez-Morales Mercedes , Baxter Claire , Désert Jean-Michel , Swain Mark , Roudier Gael
Published: October 2020

The emergent spectra of close-in, giant exoplanets ("hot Jupiters") are believed to be distinct from those of young gas giants and brown dwarfs with similar effective temperatures because these objects are primarily heated from above by their host stars rather than internally from the release of energy from their formation (Showman et al. 2020). Theoretical models predict a continuum of dayside spectra for hot Jupiters as a function of irradiation level, with the coolest planets having absorption features in their spectra, intermediate-temperature planets having emission features due to thermal inversions, and the hottest planets having blackbody-like spectra due to molecular dissociation and continuum opacity from the H- ion (Fortney et al. 2008, Parmentier et al. 2018, Arcangeli et al. 2018). Absorption and emission features have been detected in the spectra of a number of individual hot Jupiters (Kreidberg et al. 2014, Mikal-Evans et al. 2020), and population-level trends have been observed in photometric measurements (Keating et al. 2019, Baxter et al. 2020, Garhart et al. 2020, Dransfield et al. 2020). However, there has been no unified, population-level study of the thermal emission spectra of hot Jupiters such as has been done for brown dwarfs (Manjavacas et al. 2019) and transmission spectra of hot Jupiters (Sing et al. 2016). Here we show that hot Jupiter secondary eclipse spectra centered around a water absorption band at 1.4 microns follow a common trend in water feature strength with temperature. The observed trend is broadly consistent with the predictions of self-consistent one-dimensional models for how the thermal structures of solar composition planets vary with irradiation level. Nevertheless, the ensemble of planets exhibits significant scatter around the mean trend. The spread can be accounted for if the planets have modest variations in metallicity and/or elemental abundance ratios, which is expected from planet formation models (Mordasini et al. 2016, Ali-Dib et al. 2017, Madhusudhan et al. 2017, Cridland et al. 2019).
Parent Child Relationship During COVID-19 in Saudi Arabia
Authors: Andejany Najwa , Qutah Karimah , Alwajeeh Sultan , Msallam Reem , Alyamani Dalia
Published: October 2020

Background: Coronavirus disease in 2019, also known as COVID-19, is a respiratory disease that is cause by Severe Acute Respiratory Coronavirus 2. In March 2020, the World Health Organization Declared the disease as a pandemic. Social Distancing is to prevent the transmission of the virus from the asymptomatic persons, who are not yet isolated. Aim: To measure the parent-child relationship during the COVID-19 Social Distancing in Saudi Arabia. Method: A cross sectional survey study, done from 2020 April to July and shortly after the quarantine was stopped. Questionnaire used was the short version of a validated survey created by Robert Pianta to assess the parents-child relationship during and before the quarantine period in the western part of Saudi Arabia, mainly Jeddah and adjacent cities. Result: Total participants were 377, and the mean age of the parents is 37 years. On average, parents have from 1-3 children. The mean average number of hours parent stayed with their children before the Social Distancing was 8 hours and this increased to 12 hours after Social Distancing. Women tend to have average number of hours stayed with children higher than men. Comparing the closeness score and conflict score between before the Quarantine and after it showed a statistically significant more conflict before the Quarantine than after it. It was higher among female parents compared to male parents. For closeness there was no statistical significance as both scores were close to 31. Conclusion: There is a statistical significance improve in the closeness between parents and their children after the COVID-19 social distancing and more time spent with them. However, the conflict between mothers and their children were less comparing before and during the quarantine.
High Rate of Bleeding and Arterial Thrombosis in COVID-19: Saudi Multicenter Study
Authors: Raizah Abdulrahman Al , AlAskar Ahmed , Shaheen Naila , Aldosari Khalid , Alnahdi Mohamed , Luhanga Musumadi , Alshuaibi Turki , Bajhmoum Wail , Alharbi Khaled , Alsahari Ghaida , Algahtani Hadeel , Alrayes Eunice , Basendwah Abdulrahim , Abotaleb Alia , Almegren Mosaad
Published: October 2020

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic with a substantial impact on mortality, the health system and the economy8,9. Several observational studies reported the rate of venous and arterial thrombotic events in patients infected with COVID-19, with conflicting results . The aim of this multicentre study was to estimate the rate of thrombotic and bleeding events in hospitalized patients diagnosed with COVID-19 in Saudi Arabia. Method: multicenter study of 636 hospitalized patients with COVID-19.﻿Result: Twelve patients were diagnosed with VTE 1.89% (95% CI, 1.18–3). The rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84) compared to 10.38% (95% CI, 6.45–16.27) in the ICU group. Fourteen patients were diagnosed with an arterial event with an overall rate of 2.20% (95% CI, 1.43–3.38). The rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 8.49% (95% CI, 5.01–14.04) in the ICU group. The overall composite events rate was 2.99% (95% CI, 2.06–4.31). The composite events rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 13.21% (95% CI, 8.7–19.54) in the ICU group. Eleven patients developed bleeding with an overall rate of 1.73% (95% CI, 1.06–2.81). The bleeding rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84), and 9.43% (95% CI, 5.72–15.16) in the ICU group. Of the selected risk factors, the only risk factor that predicted VTE and the composite outcome, was the baseline D-dimer. (OR 1.31, 95% CI, 1.084-1.573, p=0.005) and composite events (OR 1.32, 95% CI, 1.126-1.555, p=0.0007).Conclusion: Of 636 adults with COVID-19, the rate of VTE was similar to the rate of hospitalized patients with a similar degree of critical illness. In contrast to the risk of VTE, we found a high rate of arterial and bleeding complications in patients admitted to ICU. An elevated D-dimer at baseline could predict a thrombotic complication in the COVID-19 patients, which may assist in the identification of these patients. Given the high rate of bleeding, the current study suggests that the intensification of anticoagulation in COVID-19 patients beyond the standard of care, should be pursued with caution and is best evaluated in a randomised controlled study.
Detailed molecular cytogenetic characterisation of the myeloid cell line U937 reveals the fate of homologous chromosomes and shows that centromere capture is a feature of genome instability
Authors: MacKinnon Ruth , Peverall Joanne , Campbell Lynda J. , Wall Meaghan
Published: October 2020

BackgroundThe U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements. ResultsSNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances.Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified.There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss.Conclusions Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.
Di(2-ethylhexyl)phthalate Impairs Erythropoiesis via Inducing Klotho Expression and Not via Bioenergetic Reprogramming
Authors: Tsai Chang-Yi , Fang Te-Ping , Chen Shuoh-Wen , Chen Hsiao-Wen , Lin Eric Chang-Yi , Lin Ting-An , Tarng Der-Cherng , Chang Yuan-I
Published: October 2020

Background: Di(2-ethylhexyl)phthalate (DEHP) is one of the phthalates most widely used to manufacture various plastic products. However, the potential effects of DEHP on erythropoiesis have not been investigated comprehensively. Here, we aimed to investigate whether DEHP modulate the function of haematopoietic stem and progenitor cells (HSPCs) to influence erythropoiesis, and to explore the associated mechanisms.Results: In the present study, human cell lines with a capacity to differentiate into erythroid cells and murine bone marrow cells were treated with DEHP. DEHP not only impaired HSPC function but also suppressed erythroid differentiation in a dose-dependent manner. In addition, DEHP removal restored HSPC activity. To explore how DEHP interferes with erythroid differentiation, we focused on energy metabolism and Klotho expression. DEHP suppressed erythroid differentiation via upregulation of Klotho expression in erythroblasts and not via cellular bioenergetic modulation.Conclusions: Here, we have demonstrated a novel pathophysiological role of DEHP in erythroid differentiation. DEHP impaired erythroid differentiation by inducing Klotho expression and not by reprogramming cellular bioenergetic profiles during differentiation.
Clinical Outcomes of COVID-19 Cases and Influencing Factors of Severe Cases in Qingdao City: A Retrospective Cohort Study
Authors: Jia Jing , Dai Xiaoqi , Jiang Xiaolin , Li Shuo , Wang Xia , Gao Ruqin , Jiang Fachun , Qi Fei , Kang Dianmin
Published: October 2020

BackgroundTo analyze the clinical outcomes of COVID-2019 cases and the influencing factors of severe cases in Qingdao City and provide theoretical reference basis for optimizing medical treatment and the strategies of epidemic prevention and control. MethodsThe demographical, epidemiological, clinical data of 81 confirmed COVID-2019 cases in Qingdao City were collected via epidemiological investigation and clinical process tracking. The status of cure, discharge, clinical outcome and influencing factors were analyzed in our study. ResultsAmong the 81 cases，12(14.81%) and 55(67.90%) were mild and ordinary, 9(11.11%) and 4(4.94%) were severe and critical, and 1 critical cases (1.23%) developed into fatal, with the fatality rate 1.23%. The median time from onset of symptoms to hospital admission were 3.67 days (IQR, 1.75 to 6.71). The median duration of illness were 21.00 days (IQR, 16.00 to 26.00) and the median length of hospitalization were 15.63 days (IQR, 11.60 to 20.50). The median time for progression to severe cases was 6.00 days after onset (IQR, 5.00-10.00). The median duration of severe cases was 8.00 days (IQR, 6.25-14.00). Age older than 40 years old (OR=5.797, 95%CI: 1.064~31.568) and first chest CT abnormal (OR=0.1140, 95%CI: 0.014~0.923) were the influencing factors of COVID-2019 severe cases. ConclusionsOlder age and first chest CT normal would be more prone to develop to severe cases of COVID-2019. During the epidemic period, it was necessary to classify and manage cases according to the needs of prevention and control in order to ensure the rational allocation of medical resources.
WITHDRAWN: Numerical Visualization of Grease Flow in a Gearbox
Authors: Liu Hua , Dangl Florian , Lohner Thomas , Stahl Karsten
Published: October 2020

Gearbox lubrication plays a decisive role in both load capacity and efficiency. It is necessary for the formation of a lubricant film in tribological contacts, and for heat dissipation. Grease lubrication is often applied to gearboxes at a low operating speed and means that, for example, less effort is required in sealing design compared to oil lubrication. Over the years, the computational fluid dynamics (CFD) method has frequently been applied to support the lubrication-related design of gearboxes. However, very few studies have focused on grease lubrication. Whereas oil can generally be considered as Newtonian fluid, grease displays complex non-Newtonian flow behavior. In this study, the grease lubrication of a single-stage test gearbox is investigated by means of a finite-volume based CFD model. The numerical results on the grease flow show good accordance with high-speed camera recordings, and clearly display the lubrication mechanisms of “channeling” and “circulating”. These first results on grease flow simulation in gearboxes offer a starting point for further numerical studies.
Design and Analysis of Jittering Mitigator for Robot Arm-tip
Authors: Duan Shuyong , Li Chunlu , Xu Pengfei
Published: October 2020

To tackle the jittering of a robot arm-tip, a novel method of the jittering mitigation is proposed. The key idea is to transmit the jittering to vibration of a mass block nested inside the jittering-mitigator. This method only requires the frequency of the jittering at the arm-tip. To verify the practicability of the method, a practical robot was applied through simulations and physical experiments. The jittering mitigator device can be directly attached to or detached from the arm-tip. The jittering at the arm-tip was first measured through experiments using accelerometers connected to the vibration and noise testing system. Then, the dominant frequency was identified through fast Fourier transform analysis. The theoretical parameters of the jittering mitigator were calculated accordingly. A model was established to simulate the jitter reduction effect of the mitigator. The results revealed a 68% reduction in the average amplitude of the jittering vibration at the arm-tip, which is corroborated by the experiment results. The proposed method could be applicable to all types of robot because it only requires computing the frequency of jitter.
Evaluation of Short-term Outcomes of Laparoscopic Heller Cardiomyotomy with Dor Fundoplication Versus Pneumatic Dilatation for Treatment of Achalasia
Authors: Khaled Islam , Behairy Gad M. , Saeed Mohamed , Abdulaziz Sara , Omar Leena S. , Alshafie Somia , Elhaj Mugahid , Faisal Mohammed
Published: October 2020

Background: Achalasia is a rare esophageal motility disorder of unknown cause. However, the best treatment modality for achalasia is controversial. Treatment consists of disruption of the lower esophageal sphincter, classically either by endoscopic pneumatic dilation or laparoscopic Heller’s myotomy combined with an anti-reﬂux procedure. The study aim was to compare laparoscopic Heller cardiomyotomy plus Dor Fundoplication with pneumatic dilatation for treatment of achalasia.Methods: In this interventional study, we included 50 adult patients diagnosed as having achalasia by performing either a barium study or by the absence of peristalsis and impaired relaxation of the lower esophageal sphincter on esophageal manometry. The patients were randomly classified into two groups according to the intervention performed: pneumatic dilation or laparoscopic Heller’s cardiomyotomy with Dor’s fundoplication(LHCM). Follow-up evaluations were performed after 8 and 16 months.Results: In total, 50 patients with achalasia and an Eckardt symptom score > 3 were managed by two different interventions according to their groups.After 16 months of follow up the height of a barium-contrast column after 5 min was significantly lower in the LHCM group than in the pneumatic dilation group. There were no other statistically significant differences in the primary or secondary outcomes(Eckardt score, lower esophageal sphincter, and quality of life) between the two groups.Conclusion: After 16 months of follow-up, the rates of therapeutic success and number of complications were nearly similar between LHCM and pneumatic dilation. We conclude that either treatment is suitable as an initial treatment for achalasia.
Safety of Stoma Closure within 90 Days after Low Anterior Resection and Diverting Ileostomy
Authors: Fukudome Ian , Maeda Hiromichi , Okamoto Ken , Kuroiwa Hajime , Yamaguchi Sachi , Fujisawa Kazune , Shiga Mai , Dabanaka Ken , Kobayashi Michiya , Namikawa Tutomu , Hanazaki Kazuhiro
Published: October 2020

Background This study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection.MethodsWe retrospectively reviewed 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed. ResultsAmong 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher’s exact test). ConclusionsNo association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.
ANLN Promotes Carcinogenesis in Oral Cancer by Regulating PI3K/mTOR Signaling Pathway
Authors: Wang Bing , Zhang Xiaoli , Li Chenxi , Liu Ningning , Hu Min , Gong Zhongcheng
Published: October 2020

Background: Oral cancer is a malignant disease threatening human’s life and greatly reduces human’s life quality. ANLN was reported to promote progression in cancer. This study aims at investigating the role of ANLN and the molecular mechanism in oral cancer. Methods: ANLN was down-regulated by RNAi technology. The effect of ANLN on cell behaviors including proliferation, cycle distribution, invasion, and apoptosis was detected. Western blotting analysis was used to explore the mechanism of ANLN in oral cancer. Results: Based on data from TCGA database, ANLN was shown to be expressed significantly higher in tumor tissues than the normal control. Patients with higher ANLN expression exhibited shorter survival time. ANLN was also expressed abundantly in cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation ability was downregulated. Cell invasion ability was also suppressed. But cell apoptosis rate was induced reversely. In addition, the level of critical members in PI3K signaling pathway including PI3K, mTOR, Akt, and PDK-1 were significantly reduced after ANLN was knocked down in CAL27 cells. Conclusions: ANLN contributes to progression in oral cancer and affects activation of PI3K/mTOR signaling pathway. This study provides a new potential target for therapy and drug development in oral cancer.
Zinc and Vitamin a Deficiency Predisposes to the Need for Intubation and Icu Admission in Patients With COVID-19. An Observational Study
Authors: Berrocal Lara Bielsa , Irriguible Teresa Tomasa , Philibert Viridiana , Llàcher Cristina Tural , Osaba Jaume Barallat Martínez de , Domínguez Josep Maria Manresa , Monserrat Pere Torán
Published: October 2020

Objective: To analyse whether the micronutrient deficit predicts a worse prognosis in patients infected by SARS-CoV-2 who developed the COVID-19 disease.Methods: We carried out an observational and retrospective study with 120 patients admitted for COVID-19 in the ICU and in the Internal Medicine ward of a tertiary hospital. In the nutritional admission analysis of these patients, we analysed plasmatic levels of vitamins A, B6, C, D, E and zinc. In addition, different variables of interest were collected, such as the need for orotracheal intubation, hospital stay, mortality and multi-organ failure.Results: One hundred and twenty patients were included. The independent variables associated with the need for ICU admission were low levels of zinc (standard error 0.566, 95% CI 0.086 to 0.790, p = 0.017), low levels of vitamin A (standard error 0.582, 95% CI 0.061 to 0.594, p = 0.004), age over 65 (standard error 0.018, 95% CI 0.917 to 0.985, p = 0.005) and male gender (standard error 0.458, 95% CI 1.004 to 6.040, p = 0.049). The only variable that was independently associated with the need for orotracheal intubation was vitamin A deficiency (standard error 0.58, 95% CI 0.042 to 0.405, p = 0.000).Conclusions: Low levels of vitamin A and zinc are associated with a greater need for admission to the ICU and orotracheal intubation. Patients older than 65 years had higher mortality. Randomized clinical trials are needed to examine whether micronutrient supplementation could be beneficial as an adjunctive treatment in COVID-19.
Mesenchymal Stromal Cells as Prophylaxis for Graft-versus-host Disease in Haplo-identical Hematopoietic Stem Cell Transplantation Recipients With Severe Aplastic Anemia? - A Systematic Review and Meta-analysis
Authors: Li RuoNan , Tu Jingke , Zhao Jingyu , Pan Hong , Fang Liwei , Shi Jun
Published: October 2020

Background: Mesenchymal stromal cells (MSCs) are an emerging prophylaxis option for graft-versus-host disease (GVHD) in haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) recipients with severe aplastic anemia (SAA), but studies have reported inconsistent results. This systematic review and meta-analysis evaluates the efficacy of MSCs as prophylaxis for GVHD in SAA patients with haplo-HSCT. Methods: Studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science and http://clinicaltrials.gov from establishment to February 2020. Twenty-nine single-arm studies (n = 1456) were included, eight (n = 241) studies combined with MSCs and eleven (n = 1215) reports without MSCs in haplo-HSCT for SAA patients. The primary outcomes were the incidences of GVHD. Other outcomes included 2-year overall survival (OS) and the prevalence of cytomegalovirus viremia (CMV). Odds ratios (ORs) were calculated to compare the results pooled through random or fixed effects models. Results: Between MSCs and no MSCs groups, no significant differences were found in the pooled incidences of acute GVHD (56.0%, 95%CI: 48.6%-63.5% vs. 47.2%, 95%CI: 29.0%-65.4%; OR 1.43, 95%CI: 0.91-2.25; p = 0.123), grade II-IV acute GVHD (29.8%, 95%CI: 24.1%-35.5% vs. 30.6%, 95%CI: 26.6%-34.6%; OR 0.97, 95%CI: 0.70-1.32; p = 0.889), chronic GVHD (25.4%, 95%CI: 19.8%-31.0% vs. 30.0%, 95%CI, 23.3%-36.6%; OR 0.79, 95%CI 0.56-1.11; p = 0.187). Furtherly, there was no obvious differences in 2-year OS (OR 0.98, 95%CI 0.60-1.61; p = 1.000) and prevalence of CMV (OR 0.61, 95%CI 0.40-1.92; p = 0.018).Conclusions: Our meta-analysis indicates that the prophylactic use of MSCs co-transplantation is not an effective option for SAA patients undergoing haplo-HSCT. Hence, the general co-transplantation of MSCs for SAA haplo-HSCT recipients may lack of evidence-based practice.
TAZ Regulates Bladder Cancer Cell Proliferation and Apoptosis via p38 Activity
Authors: Sun Yangyang , Hu Lianxin , Liu Chengxi , Su Ganglin , Yang Lina , Huang Weiren , Chen Wei
Published: October 2020

Background The progression of cancer is driven by the deregulation of various signaling pathways, especially Hippo and p38 MAPK pathway. TAZ, a downstream target of Hippo pathway, has been demonstrated to promote tumorigenesis in various cancers, but the functions of both Hippo and p38 signaling in bladder cancer cells are still unclear. Methods T24 and 5637 cells with knockdown of TAZ were constructed. EdU cell proliferation assay and western blot were used to illustrate the effects of TAZ on the proliferation and apoptosis of bladder cancer cells and the expression of p38 protein and phosphorylation. We overexpressed Flag-tagged TAZ in 293T cells. Western blot and RT-qPCR were used to further illustrate the effect of TAZ on the expression level of p38. The p38 inhibitor (PH-797804) combined with western blot and EDU cell proliferation assay were used to show whether TAZ affects the proliferation and apoptosis of bladder cancer cells by regulating the activity of p38.Results The shTAZ contained in T24 and 5637 cells significantly inhibited bladder cancer cells proliferation, in addition, the knockdown of TAZ-induced apoptosis of T24 and 5637 cells was found out. The loss of TAZ led to the upregulation of p38 protein as well as phosphorylation. The over-expression of Flag-TAZ had no obvious effect on p38 mRNA level, but p38 protein was reduced clearly in 293T cells. ShTAZ induced the upregulation of cleaved-caspase 3, which disappeared when treated with PH-797804, a p38 inhibitor, and the reduction to EdU positive cells induced by shTAZ was reversed by PH-797804 treatment, which suggested that p38 activity could mediate both cell proliferation and apoptosis regulated by TAZ knockdown. Conclusions In this study, it was demonstrated that TAZ could regulate the proliferation and apoptosis of bladder cancer cells by regulating the stability of p38 protein. Our finding uncovered the novel functional interaction between Hippo and p38 MAPK pathway. An in-depth understanding of this question may indicate a new direction of diagnosis or treatment for bladder cancer.
Application of Fluorescence in Situ Hybridization to Detect MYCN Amplification on Paraffin-embedded Tissue Sections of Neuroblastoma - Single Institute Study.
Authors: Winnicka Dorota , Babicz Mariusz , Styka Borys , Skowera Paulina , Zawitkowska Joanna , Lejman Monika
Published: October 2020

BackgroundNeuroblastoma is the most common extracranial solid tumour in children. Amplification of the MYCN gene was observed in approximately 20-30% of tumours. It is strongly correlated with advanced stage of disease, rapid tumour progression, resistant to chemotherapy and poor outcome independent of patient age and stage of advanced disease. Amplification of the MYCN identify high-risk patients.MethodsTo assess neuroblastoma tumours with MYCN amplification we used paraffin-embedded tissue sections in 57 patients by fluorescent in situ hybridization (FISH). ResultsTwenty-eight (49,1%) of patients had localized neuroblastoma (1–3 stages), 5,3% stage 4S, and 45,6% stage 4 disease. Thirty-eight (66,7%) of patients had got abdominal/adrenal mass at diagnosis. Twenty-seven (47,4%) patients were <18 month of age, thirty (52,6%) patients were >18 month of age. MYCN amplification appeared in 12 (21%) tumour specimens. ConclusionsFluorescent in situ hybridization is a high-sensitive, useful technique for detecting MYCN amplification on paraffin- embedded tissue section of neuroblastoma tumours thus facilitating therapeutic decisions based on the presence or absence of this important biologic marker.
Extended Ischiopubic Fixation Using Porous Metal Augments In Cementless Acetabular Reconstruction During Revision Total Hip Arthroplasty
Authors: Huang Yong , Zhou Yixin , Shao Hongyi , Tang Hao , Yang Dejin , Zhou Baochu
Published: October 2020

Background: As opposed to rim fixation, 3-point fixation provides sufficient primary stability for cememless cups in the presence of massive bony deficiency. While several methods, including doming augments or flying buttress augments, have been introduced to reconstruct superior supportive points, good methods to establish supportive ischiopubic points are currently lacking. The aims of this study were to introduce the definition, indication and surgical technique of extended ischiopubic fixation (EIF) and to investigate the early clinical and radiographic results and complications of hips revised with EIF.Methods: Patients who underwent revision THA utilizing the technique of EIF with porous metal augments secured in the ischium and/or pubis in a single institution from February 2015 to February 2020 were retrospectively reviewed. 25 patients were included based on the criteria of minimum 2-year follow-up. The median duration of follow-up was 48.06 months (interquartile range: 41.37-62.20 months). The patients’ clinical results were assessed using of the Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis index and any complications including infection, intraoperative fracture, dislocation, postoperative nerve palsy, hematoma, wound complication and/or any subsequent reoperation(s) were documented. The radiographic results were assessed with the construct stability, the position of the center of rotation and cup orientoration. Results: At the most recent follow-up, 20 (80%) patients rated their satisfaction level as “very satisfied”, 5 (20%) were “satisfied”. The median HHS score improved from 36.00 preoperatively to 81.00 (p＜0.001) while the median WOMAC index score decreased from 74.50 preoperatively to 16.50 at the latest follow-up (p＜0.001). No intraoperative or postoperative complications were identified. All constructs were considered to have obtained stable fixation. The median vertical and horizontal distance between the latest postoperative center of rotation to the anatomic center of rotation improved from 13.62 mm and 8.68 mm preoperatively to 4.42 mm and 4.19 mm, at final follow-up (p<0.001), respectively.Conclusions: Early follow-up of patients reconstructed with porous metal augments using the EIF technique demonstrated satisfactory clinical results with no particular complications, stable fixation and restoration of the center of rotation.