bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of Pgi Gene in E. coli Increases Tolerance to Furfural and 5-Hydroxymethyl Furfural in Media Containing Glucose-Xylose Mixture
Authors: Jilani Syed Bilal , Dev Chandra , Eqbal Danish , Jawed Kamran , Prasad Rajendra , Yazdani Syed Shams
Published: May 2020

Background: Furfural and 5-hydroxymethyl furfural (5-HMF) are key furan inhibitors that are generated due to breakdown of lignocellulosic sugars at high temperature and acidic treatment conditions. Both furfural and 5-HMF act in a synergistic manner to inhibit microbial metabolism and resistance to both is a desirable characteristic for efficient conversion of lignocellulosic carbon to ethanol. Genetic manipulations targeted toward increasing cellular NADPH pools have successfully imparted tolerance against furfural and 5-HMF. In present study, deletion of pgi gene as a strategy to augment carbon flow through pentose phosphate pathway (PPP) was studied in ethanologenic Escherichia coli strain SSK101 to impart tolerance towards either furfural or 5-HMFor both inhibitors together.Results: A key gene of EMP pathway, pgi, was deleted in an ethanologenic E. coli strain SSK42 to yield strain SSK101. In presence of 1 g/L furfural in minimal AM1 media, the rate of biomass formation for strain SSK101 was up to 1.9-fold higher as compared to parent SSK42 strain, and it was able to clear furfural in half the time. Tolerance to inhibitor was associated with glucose as carbon source and not xylose, and the tolerance advantage of SSK101 was neutralized in LB media. Bioreactor studies were performed under binary stress of furfural and 5-HMF (1 g/L each) and different glucose concentrations in a glucose-xylose mixture with final sugar concentration of 5.5%, mimicking major components of dilute acid treated biomass hydrolysate. In the mixture having 6 g/L and 12 g/L glucose, SSK101 strain produced ~ 18 g/L and 20 g/L ethanol, respectively. Interestingly, the maximum ethanol productivity was better at lower glucose load with 0.46 g/(L.h) between 96–120 h, as compared to higher glucose load where it was 0.33 g/(L.h) between 144–168 h. Importantly, parent strain SSK42 did not exhibit significant metabolic activity under similar conditions of inhibitor load and sugar concentration.Conclusions: E. coli strain SSK101 with pgi deletion had enhanced tolerance against both furfural and 5-HMF, which was associated with presence of glucose in media. Strain SSK101 also had improved fermentation characteristics under both hyperosmotic as well as binary stress of furfural and 5-HMF in media containing glucose-xylose mixture.
Dynamics and Transcriptome Analysis of Starch and Sucrose Metabolism During Corm Development in Freesia Hybrida
Authors: Ma Li , Ding Suqin , Yan Zi , Tang Dongqin
Published: May 2020

Background Starch and sucrose metabolism plays a crucial role in the formation and development of bulbs in bulbous plants, which, however, remains unclear and unexplored in the corms of Freesia hybrida, one kind of famous bulbous flower. Herein, we investigated the dynamics of the major form of carbohydrates and related enzyme activities and profiled the transcriptome of freesia corms at four developmental stages with the aim to reveal the relation of starch and sucrose metabolism to corm development and the transcriptional regulation of this metabolic process.Results The content of starch, sucrose and soluble sugars followed an overall upward trend across the corm developmental stages. Activities of the adenosine diphosphoglucose pyrophosphorylase, starch branching enzyme and β-amylase generally followed the pattern of the starch and sucrose level. Activities of sucrose phosphate synthase increased from corm formation till the initial swelling stage and subsequently reached a plateau. Activities of invertase and sucrose synthase peaked at the later rapid swelling stage. Transcriptome analysis revealed a total of 100,999 unigenes, out of which 44,405 unigenes were annotated. Analysis based on Clusters of Orthologous Groups suggested that carbohydrate transport and metabolism (9.34% of the sequences) was prominent across the corm developmental process. Totally 3427 differentially expressed genes were identified and the enrichment analysis directed starch and sucrose metabolism a critical pathway in corm development especially at the rapid swelling stage. Genes encoding key carbohydrate-metabolizing enzymes were identified and their differential expression related to corm development was explored.Conclusions The comparative transcriptome analysis discloses essential roles of starch and sucrose metabolism and the genetic mechanism related to the corm development. The results construct a valuable resource pool for further molecular-level studies, which are helpful for metabolic regulation of carbohydrates and improvement in molecular breeding of Freesia hybrida.
High prevalence of cardiovascular risk factors in adults living in Greece: The EMENO National Health Examination Survey
Authors: Touloumi Giota , Karakosta Argiro , Kalpourtzi Natasa , Gavana Magda , Vantarakis Apostolos , Kantzanou Maria , Hajichristodoulou Christos , Chlouverakis Grigoris , Trypsianis Grigoris , Voulgari Paraskevi V. , Alamanos Yannis , Makrilakis Konstantinos , Liatis Stavros , Chatzipanagiotou Stylianos , Stergiou George
Published: May 2020

Background
Nationwide data on cardiovascular risk factors prevalence is lacking in Greece. This work presents the findings of the national health examination survey EMENO regarding the prevalence of hypertension, hypercholesterolemia, diabetes, obesity and smoking.
Methods
A random sample of adults (≥ 18 years) was drawn by multistage stratified random sampling based on 2011 Census. All EMENO participants with ≥ 1 measurement of interest [blood pressure (BP), fasting glucose, HbA1c, total cholesterol (TC), Body Mass Index (BMI)] were included. Hypertension was defined as BP ≥ 140/90 mmHg and/or antihypertensive treatment; diabetes as fasting glucose ≥ 126 mg/dL and/or HbA1c ≥ 6.5% or self-reported diabetes; hypercholesterolemia as TC ≥ 190 mg/dL. Sampling weights were applied to adjust for study design and post-stratification weights to match sample age and sex distribution to population one. Non-response was adjusted by inverse probability weighting.
Results
Of 6,006 EMENO participants, 4,822 were included (51.5% females, median age:47.9 years). The prevalence of hypertension was 40.5%, higher in men (44.6%) than in women (36.6%); of hypercholesterolemia 60.2%, similar in men (59.5%) and women (60.9%); of diabetes 11.6%, similar men (12.4%) and women (10.9%); of obesity 32.1%, higher in women (33.5% vs 30.2%), although in subjects aged 18–40 year it was higher in men; of current smoking 38.2%, higher in men (44.0%) than in women (32.7%). The prevalence of all risk factors increased substantially with age, except smoking, which followed an inverse U shape.
Conclusions
The burden of cardiovascular risk factors among Greek adults is alarming. There is considerable preventive potential and actions at health care and societal level are urgently needed.
TNFAIP8 variants as a potential epidemiological and predictive biomarker in ovarian cancer
Authors: Gao Hongyu , Zhang Zhiran , Jiang Liangliang , Zhang Lei , Qin Ling , Yang Shanshan , Liu Tianbo
Published: May 2020

Background
This research aimed to investigate the association between tumor necrosis factor-a-induced protein 8 (TNFAIP8) polymorphisms and ovarian cancer (OC) susceptibility.
Methods
A case-control study of 210 patients with OC and 231 healthy controls was conducted to assess the association between TNFAIP8 polymorphisms (rs11064, rs1045241, and rs1045242) and OC risk in Heilongjiang Province of China. Logistic regression analysis was applied to illustrate the underlying association.
Results
Our research found that TNFAIP8 rs11064 and rs1045242 were significantly connected with the susceptibility of OC. Additionally, rs1045242 increased the risk of OC, while rs11064 performed a protective role in the risk of OC. Data revealed that rs1045242 strongly related with advanced FIGO stage, larger residual tumor, and the presence of recurrence.
Conclusions
TNFAIP8 genetic variants, which may play difference roles, were significantly associated with OC susceptibility. The underlying molecular mechanism needs be clarified with scientific evidence.
Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling
Authors: Jiang Hao , Tang Jing-Yuan , Xue Dong , Chen Yi-Meng , Wu Ting-Chun , Zhuang Qian-Feng , He Xiao-Zhou
Published: May 2020

Background
RCC is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. APOC1 has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism.
Methods
Differential levels of APOC1 in RCC samples and controls in a downloaded TCGA profile and clinical samples collected in our center were detected by qRT-PCR. The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After transfection of sh-APOC1 or oe-APOC1, cell phenotypes were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of Wnt3a in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a xenograft model was generated in nude mice for clarifying the in vivo function of APOC1 in RCC process.
Results
APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative and metastatic abilities in RCC cells. Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 slowed down the growth of RCC.
Conclusions
APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.
N-α-Acetyltransferase 10 protein inhibits invasion and metastasis of oral squamous cell carcinoma via regulating Pirh2-p53 signaling pathway
Authors: Wang Fazhan , Zheng Jun , Yang Yongyong , Yang Jie , Luo Ting , Xu Jiang , Gu Yongqing , Zeng Yan
Published: May 2020

Background

Naa10p (N-α-Acetyltransferase 10 protein) was reported to be involved in tumor invasion and metastasis in several of tumors. However, the role and mechanism of Naa10p mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined.
Methods

The functional role of Naa10p in OSCC cells were determined using Transwell assay in vitro and xenograft tumorigenesis in nude mice. Immunoprecipitation, GST-pull down assays and immunofluorescence were performed to confirm the interaction between Naa10p and RelA/p65 in OSCC cells. Lastly, luciferase reporter assays, chromatin immunoprecipitation (ChIP) and western blot were used to evalute the effect of Naa10p expression on the Pirh2-p53 signaling pathway.
Results

Naa10p inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, there is a physical interaction between Naa10p and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, MMP-2 and MMP-9.
Conclusion

Naa10p function as a tumor metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis, and might be a prognostic marker as well as a therapeutic target for OSCC.
Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model
Authors: Sheng Yan Xiao , Yang Yuan Shui , Wen Min Xiao , Zhang Xin , Ye Feng Yong , Zhao Peng , Zang Min Li , Peng Kang , Du Ming En , Li Sai
Published: May 2020

Background
Shende’an tablet (SDA) is a newly developed Chinese herbs formula derived from the chinese traditional medicine Zhenganxifeng Decoction, which is approved for treatment of neurasthenia and insomnia in China. The aim of this study was to investigate the in vitro and in vivo neuroprotective effects of SDA against Parkinson’s disease (PD).
Methods
In the present work, PC12 cells transfected with or without A53T α-syn genes and MPTP-induced PD mice were used as models to elucidate protective effects of SDA on dopamine (DA) neurons, and the involvement of PGC-1α/Nrf2 signaling in α-syn clearance in PC12/α-syn cells stimulated with Doxycycline (Dox) and reversal of MPTP-induced toxicity in PD mice.
Results
Our results demonstrated that SDA had neuroprotection effect in dopaminergic PC12 cells with 6-OHDA. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12/α-syn cells and MPTP-induced PD animal models, SDA was highly efficacious in α-syn clearance associated with activation of PGC-1α/Nrf2 signal pathway.
Conclusion
The results of our study suggest that SDA could be a potential therapeutic drug for PD through protecting dopamine neurons and alleviating the motor symptoms, and the mechanism might be related to the activation of PGC-1α/Nrf2 signal pathway.
Association Between Training Experience and Attitudes Toward Advance Care Planning Among Healthcare Professionals: A Cross-Sectional Study
Authors: Chan Helen Yue-lai , Kwok Annie Oi-ling , Yuen Kwok-keung , Au Derrick Kit-sing , Yuen Jacqueline Kwan-yuk
Published: May 2020

Background: Training has been found effective in improving healthcare professionals’ knowledge, confidence, and skills in conducting advance care planning (ACP). However, its association with their attitudes toward ACP, which is crucial to its implementation, remained unclear. To fill this gap, this paper examines the association between their attitudes toward ACP and relevant training experiences.Methods: An online survey about attitudes toward ACP of healthcare professionals, including physicians, nurses, social workers, and allied healthcare professionals, currently working in hospital and community care in Hong Kong was conducted.Results: Of 250 respondents, approximately half (51.6%) had received ACP-related training. Those with relevant training reported significantly more positive in the perceived clinical relevance, willingness, and confidence in conducting ACP and levels of agreement with 19 out of the 25 statements in a questionnaire about attitudes toward ACP than those without (ps ≤ 0.001–0.05). Respondents who received training only in a didactic format reported a significantly lower level of confidence in conducting ACP than did others who received a blended mode of learning (p = 0.012). Notwithstanding significant differences between respondents with and without relevant training, respondents generally acknowledged their roles in initiating conversations and appreciated ACP in preventing decisional conflict in surrogate decision-making regardless of their training experience.Conclusions: This paper revealed the association between training and positive attitudes toward ACP among healthcare professionals. The findings showed that training is a predictor of their preparedness for ACP in terms of perceived relevancy, willingness, and confidence. Those who had received training were less likely to consider commonly reported barriers such as time constraints, cultural taboos, and avoidance among patients and family members as hindrances to ACP implementation.
Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis
Authors: Carter John A , Black Libby K , Sharma Dolly , Bhagnani Tarun , Jahr Jonathan
Published: May 2020

BACKGROUND
The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain.
METHODS
We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000–2019, adult human subjects) of IV nonopioids (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v13.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360).
RESULTS
Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory).
CONCLUSIONS
MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.
Reliable and rapid smooth extubation after Ketofol for induction of general anesthesia in Laparoscopic Drilling of polycystic ovary: A randomized controlled trial
Authors: Mahmoud Atef Mohamed Sayed , Botros Joseph Makram , Ragab Safaa Gaber
Published: May 2020

Background

the outcome of ketofol on the hemodynamics and the airway response during induction of general anesthesia has been studied before. Its effect on smoothness of extubation has not been studied before. So, we aimed to assess the effect of ketofol on the smoothness of extubation and compare it with propofol only for induction of general anesthesia.
Methods

This double-blind, randomized, and controlled study was conducted on one hundred and six American Society of Anesthesiologists Physical status ''ASA PS'' class I and II female patients aged 18–40 years old and scheduled for laparoscopic drilling for polycystic ovary disease under general anesthesia. The patients were assigned into one of two groups (53) patients each; group KP = ketofol and group P = propofol.
Results

There was good sedation score during suction and extubation in the ketofol group. Airway response and smoothness of extubation were better in the ketofol group better than the propofol group.
Conclusion

Ketofol as an induction anesthetic agent was effective in attenuating the airway response during extubation more than profofol only.
Trial registration:

This trial was retrospectively registered at the Clinical Trial.gov with the Identification Number: NCT04365686.
The Association Between Male Infertility and Cardiometabolic Disturbances: A Population Based Study
Authors: Behboudi-Gandevani Samira , Yarandi Razieh Bidhendi , Dovom Marzieh Rostami , Azizi Fereidoun , Tehrani Fahimeh Ramezani
Published: May 2020

Aim: Studies focusing of male infertility and cardio-metabolic disorders is insufficient and controversial. The aim of this study was to evaluate the association between male infertility and cardiometabolic disturbances in a population based Tehran lipid and glucose study. Material and methods: For the purpose of the present study, we used data collected in 3rd follow up visit of Tehran Lipid and Glucose Study, which included comprehensive data on reproductive status of participants. All those who were never married, were unwillingness to have a child, had documented female infertility were excluded from the study. A total of 1611 remaining participants were further classified as two groups: men who had documented male infertility as infertile group (n = 88) and those had at least one live birth and did not have a history of primary infertility as the fertile group (n = 1523). Generalized Linear Regression model (GLM) with logit link were applied to assess the to explore the association between male infertility and cardiometabolic disturbances including diabetes mellitus, pre-diabetes, hypertension, metabolic syndrome, dyslipidemia, obesity, central obesity and chronic kidney disease after further adjustment for age and BMI.Results: Compared to fertile controls, infertile men were more likely to be older, [58 (13.3) versus 53 (10.2) years (P = 0.003)]. The results of unadjusted model revealed that infertility were significantly associated with hypertension and CKD, OR = 1.8 (95%CI: 1.2, 2.9, P-value = 0.006) and OR = 1.9 (95%CI: 1.1, 3.6, P-value = 0.033), respectively. However, the significant association, which were found in crude analyses, were disappeared after adjusting for potential confounders of age and BMI. Moreover, infertility did not have any association with other cardiometabolic disturbances including diabetes and pre-diabetes, metabolic syndrome, dyslipidemia, obesity and central obesity in unadjusted and adjusted analysis. Conclusion: Our study revealed that there were not any association between male infertility and cardiometabolic disturbances in a population based setting. This study is an incentive to initiate more explicit surveys concerning this topic in order to provide more accurate data on male infertility. More population-based studies with large sample size are still warranted to confirm these findings.
‘Recoupling’ the attentional and motor control of preparatory postural adjustments to overcome Freezing of Gait in Parkinson’s
Authors: Maslivec Amy , Fielding Anna , Wilson Mark , Norris Meriel , Young William
Published: May 2020

Objectives
This study examined if people with Parkinson’s and freezing of gait pathology (FoG) could be trained to increase preparatory weight-shift amplitude, and facilitate step initiation during FoG.
Methods
Thirty-five people with Parkinson’s and FoG attempted to initiate forward stepping either during a FoG event (n = 17, FoG-F) or following a voluntary stop (n = 18, FoG-NF) in a Baseline condition and two conditions where an increased weight-shift amplitude was trained via: i) Explicit verbal instruction, and ii) Implicit movement analogies.
Results
At Baseline, weight-shift amplitudes were smaller during: i) unsuccessful, compared to successful step initiations (FoG-F group), and ii) successful step initiations in the FoG-F group compared to FoG-NF. Both Verbal and Analogy training resulted in significant increases in weight-shift amplitude in both groups, and a corresponding pronounced reduction in unsuccessful attempts to initiate stepping (FoG-F group).
Conclusions
Hypometric preparatory weight-shifting is associated with failure to initiate forward stepping in people with Parkinson’s and FoG. However, impaired weight-shift characteristics are modifiable through conscious strategies. This current study provides a novel and critical evaluation of preparatory weight-shift amplitudes during FoG events. The intervention described represents an attractive ‘rescue’ strategy and should be further scrutinised regarding limitations posed by physical and cognitive deficits.
SLC40A1 mediates ferroptosis and cognitive dysfunction in type 1 diabetes
Authors: Hao Lijun , Mi Jun , Song Liping , Guo Yinnan , Li Yanli , Yin Yiru , Zhang Ce
Published: May 2020

Objective: Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. Recent evidence show that ferroptosis primarily triggers nerve cell death, Alzheimer's disease (AD), Huntington’s disease (HD), and Parkinson's disease (PD). We purposed to investigate whether ferroptosis is a vital pathogenic pathway in diabetes-induced cognitive dysfunction. Methods and results: Type 1 diabetic rat model was created by intraperitoneal injection of streptozotocin (STZ). Significant cognitive dysfunction was observed in the diabetic rats as evidenced by increase in latency period to find a hidden platform and decreased cumulative time spent in the target quadrant in the Morris water maze test. We detected the amplitude of low-frequency fluctuation (ALFF) of the BOLD (Blood Oxygenation Level-Dependent) signal using resting-state functional magnetic resonance imaging (rs-fMRI). Consequently, we found that the ALFF values, as well as the T2 relaxation time of the bilateral hippocampus, were reduced in Type 1 diabetic rats. We detected Fe2+ level and lipid peroxidation products (MDA and 4-HNE) in the hippocampus. Mitochondria and neuron injury in the STZ-induced diabetic rats were determined using a Transmission Electron Microscope and Nissl body staining. Iron overload and ferroptosis were detected in the hippocampus. Furthermore, mRNA microarray analysis revealed 201 dysregulated mRNAs in STZ-induced type 1 diabetes (T1D). Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated.Conclusion: We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in Type 1 diabetes.
Pose estimation by extended Kalman filter using noise covariance matrices based on sensor output
Authors: SAITO AYUKO , Kizawa Satoru , Kobayashi Yoshikazu , Miyawaki Kazuto
Published: May 2020

This paper presents an extended Kalman filter for pose estimation using noise covariance matrices based on sensor output. Compact and lightweight nine-axis motion sensors are used for motion analysis in widely various fields such as medical welfare and sports. A nine-axis motion sensor includes a three-axis gyroscope, a three-axis accelerometer, and a three-axis magnetometer. Information obtained from the three sensors is useful for estimating joint angles using the Kalman filter. The extended Kalman filter is used widely for state estimation because it can estimate the status with a small computational load. However, determining the process and observation noise covariance matrices in the extended Kalman filter is complicated. The noise covariance matrices in the extended Kalman filter were found for this study based on the sensor output. Postural change appears in the gyroscope output because the rotational motion of the joints produces human movement. Therefore, the process noise covariance matrix was determined based on the gyroscope output. An observation noise covariance matrix was determined based on the accelerometer and magnetometer output because the two sensors’ outputs were used as observation values. During a laboratory experiment, the lower limb joint angles of three participants were measured using an optical 3D motion analysis system and nine-axis motion sensors while participants were walking. The lower limb joint angles estimated using the extended Kalman filter with noise covariance matrices based on sensor output were generally consistent with results obtained from the optical 3D motion analysis system. Furthermore, the lower limb joint angles were measured using nine-axis motion sensors while participants ran on a treadmill for about 90 seconds. The experiment results demonstrated the effectiveness of the proposed method for human pose estimation.
Evaluation of NaCl and MgCl2 heat exchange fluids in a deep binary geothermal system in a sedimentary halite formation
Authors: Moore Kayla R , Holländer Hartmut M.
Published: May 2020

Halite formations are attractive geothermal reservoirs due to their high heat conductivity, resulting in higher temperatures than other formations at similar depths. However, halite formations are highly reactive with undersaturated water. An understanding of the geochemical reactions that occur within a halite-saturated formations can inform decision making regarding well construction, prevention of well clogging, formation dissolution, and thermal short-circuiting. Numerical 1-D and 3-D flow and equilibrium reactive transport modeling were used to characterize the produced NaCl-brine in a well targeting a halite-saturated formation. The potential for inhibition of precipitation and dissolution using an MgCl2-brine and NaCl+MgCl2-brine were also investigated. Within the injection well, with heating from 60 to 120°C, the solubility of halite decreases resulting in the potential dissolution of 0.57 mol L-1 at the formation. Cooling from 120 to 100°C in the production well results in precipitation of 0.20 mol L-1 halite as well as anhydrite, brucite, carnallite, goergeyite, gypsum, halite, kieserite and polyhalite. Introduction of Mg2+ into the heat exchange brine resulted in a decreased potential for dissolution by 0.35 mol L-1 as the heat exchange fluid entered the formation and within the formation itself, as well as decreased precipitation within the production well, compared to the NaCl-brine. The NaCl-brine solubility was altered by changes in pressure up to 0.18 mol L-1. This indicates that designing and monitoring the composition of heat exchange fluids in highly saline environments is an important component in geothermal project design.
E -learning during Covid 19 Pandemic.
Authors: Gohiya Poorva , Gohiya Ashish
Published: May 2020

Introduction: Teaching learning in the times of Covid 19 pandemic needs to be revamped in order to follow norms of social distancing. Therefore, online classes are a necessity now.Methodology: We registered our institution on Microsoft Teams under educational institutes. Entire college faculty was registered along with undergraduates and post graduate students. E- classes were planned after a professional demonstration.Results: The feedback of e classes given by students was encouraging. They were satisfied by the teacher’s way of delivering lecture. The students felt, on line classes are almost similar to offline classes. The main hinderance in e-classes was internet connection.Conclusion: The e classes helped to continue the teaching learning activities during restrictions because of Covid19 pandemic
Mer regulates microglial M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
Authors: wu haijian , zheng jingwei , xu shenbin , fang yuanjian , shao anwen , shi ligen , lu jianan , wang xiaoyu , wang yirong , zhao zhen , Zhang Jianmin
Published: May 2020

Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial physiology. However, its function in regulating the innate immune response and microglial M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial M1/M2 polarization and neuroinflammation following TBI. Methods: The controlled cortical impact (CCI) mouse model was established. Mer siRNA was intracerebroventricularly administered and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed. Results: Mer is upregulated and regulates microglial M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial M2 polarization while increases M1 polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation. Conclusions: Mer is an important regulator of microglial M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors
Authors: Dyrstad Sissel Elisabeth , Lotsberg Maria Lie , Tan Tuan Zea , Pettersen Ina Katrine Nitschke , Hjellbrekke Silje , Tusubira Deusdedit , Engelsen Agnete Svensen Tenfjord , Daubon Thomas , Mourier Arnaud , Thiery Jean Paul , Dahl Olav , Lorens James , Tronstad Karl Johan , Røsland Gro
Published: May 2020

Background Non-small cell lung cancer (NSCLC) patients harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) inevitably develop resistance to targeted therapy. Drug resistance is an example of cancer cell plasticity where cells change according to diverse microenvironmental pressure, which can be described as a way of evolution by natural selection. Metabolic rewiring during cancer development may support several malignant features and facilitate emergence of therapy resistant clones. Results Analysis of transcriptome data from two independent NSLSC patient cohorts identified upregulated markers of glucose metabolism and ROS defense in tumors compared to normal tissue. We show that these alterations were associated with increased expression of pyruvate dehydrogenase kinase 1 (PDK1). We established relevant in vitro models to study metabolic alterations in the context of resistance to EGFR TKIs to determine if targeted metabolic intervention would prevent development of resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) in NSCLC cells. The PDK inhibitor dichloroacetate (DCA) was shown to reduce cell growth. This mechanism was associated with redirected metabolism towards pyruvate and lactate oxidation, and reduced lactate production, both in EGFR TKI sensitive and resistant NSCLC cells. Conclusion We propose that the intracellular stress created by redirecting pyruvate metabolism can prevent EGFR TKI resistance in NSCLC.
Crime and physical activity measures from the Safe and Fit Environments Study (SAFE) Psychometric properties across age groups
Authors: Roesch Scott C. , Patch Christina M. , Roman Caterina G. , Conway Terry L. , Taylor Ralph B. , Saelens Brian E. , Adams Marc A. , Cain Kelli L. , Natarajan Loki Loki , Sallis James F.
Published: May 2020

Valid and reliable measures are needed to better understand the relationship between physical activity and crime. This paper provides a comprehensive psychometric evaluation of measures developed in the Safe and Fit Environments (SAFE) Study to assess a conceptual framework. In addition to assessing the basic psychometric properties of each measure (e.g., variable distributions [item/scale level], internal consistency reliability), this study formally examined the measurement validity and invariance of measures across four age groups using confirmatory factor analysis. The sample (n=2,173) included 336 Adolescents (aged 12-17), 532 Young adults (aged 18-39), 838 Middle Adults, and 467 Older Adults (aged 66+). The psychometric evaluation of (sub)scales showed consistent factorial validity and internal consistency reliability across the majority of the measures and across the four age groups. Specifically, 14 of the 17 measures subjected to a test of factorial validity displayed statistically and practically significant factor loadings and internal consistency values in the overall sample and across the age groups. The pattern of correlations for each (sub)scale with other (sub)scales/indexes largely did not exhibit redundancy across measures. The findings expanded upon the test-retest reliability evaluation reported in Patch et al. (2019) and suggest these measures can be used in predictive models.
Collagen-dependent platelet dysfunction and its relevance to either mitochondrial ROS or cytosolic superoxide generation: a question about the quality and functional competence of long-stored platelets
Authors: Hosseini Ehteramolsadat , Hojjati Saba , gashti Safoora Afzalniaye , Ghasemzadeh Mehran
Published: May 2020

Upon vascular damage, the exposure of sub-endothelial matrix to circulating platelets causes their firm adhesion and spreading on the site of injury mainly via GPVI-collagen interaction. Whilst reactive oxygen species (ROS) modulate this stage of thrombosis, augmented oxidant stress also disturbs platelet functions. Stored-dependent platelet lesion is associated with the increasing levels of ROS. Whether ROS accumulation is also relevant to collagen-dependent platelet dysfunction is the main interest of this study. Here, fresh PRP-PCs (platelet concentrates) were either stimulated with PMA and CCCP or stored for 5 days. Intra-platelet superoxide or mitochondrial-ROS was detected by flowcytometery. GPVI shedding, platelet aggregation and spreading/adhesion to collagen were analyzed by western blot, aggregometry and fluorescence-microscopy respectively. Mitochondrial-ROS levels in 5 days-stored PCs were comparable to those induced by mitochondrial uncoupler, CCCP while O2-- generations were higher than those achieved by PMA. Shedding levels in 5 days-stored PCs were also higher than those induced by these potent stimuli. Platelet adhesion surface area in 5 days-stored PCs was tremendously reduced compared to that of fresh ones. Whereas platelet spreading/adhesion and aggregation in response to collagen showed reverse correlations with both O2-- and mitochondrial-ROS formations, total number of adhesion was only relevant to O2-- generations. Conclusively, ROS accumulations in 5 days-stored platelets were at the levels comparable to those induced by potent stimuli. Direct correlation of accumulating ROS with collagen-dependent platelet spreading/adhesion and aggregation is a striking sign of an oxidant-induced lesion that may raise serious question about the post-transfusion quality and competence of longer stored products.
A 5-step systematic therapy (FSST) for treating plugged ducts and mastitis in breastfeeding women
Authors: Yao Yuzhi , Long Tianzhu , Pan Yuhong , Li Yin , Wu Ling , Fu Benjie , Ma Hongmin
Published: May 2020

Introduction: Plugged ducts and mastitis are common conditions in lactating women. Milk excretion and relief of local symptoms are equally important for the treatment of plugged ducts and mastitis.This study aimed to describe clinical response to 5-step systematic therapy (FSST) in the management of plugged ducts and mastitis. FSST was a comprehensive milk stasis dredging treatment, which contained five steps to make the milk out of the plugged duct. Materials and Methods: This retrospective study included 922 breastfeeding women, 714 with plugged ducts and 208 with mastitis who received FSST at the breast nursing outpatient department from June to September 2017. The breast pain score, swelling degree and range of breast induration were recorded pre-FSST and post-FSST. Results: After a single FSST, pain score and degree of swelling were significantly improved (both, p < 0.001) in all cases. After receiving FSST, the mean breast pain relief score was 1.7±0.7, while the mean swelling fade-away degree was 1.6±0.6. In subgroup analysis, pain score and degree of swelling were significantly improved (both, p < 0.001) in the plugged ducts group and the mastitis group. The score of pain relief in the plugged ducts group was less than that in the mastitis group (1.6±0.7 vs. 1.9±0.7, t=-5.301, p=0.000), while improvement of swelling fade-away was greater in the plugged ducts group than the mastitis group (1.7±0.6 vs. 1.5±0.6, t=3.488, p=0.001). The composition ratio of the changes in induration range between the two groups was statistically different (Pearsonχ2=137.865, p = 0.000), of which more obvious improvement in the plugged ducts group than the mastitis group (χ2=25.653, p = 0.000). Conclusion: FSST can relieve pain, reduce breast swelling and range of induration, and for plugged ducts or mastitis varied degree differently.
Socioeconomic Factors Affecting Exclusive Breastfeeding in the First 6 Months of Life
Authors: Nazari Javad , Esmaili Abbas , Mousavi Eshrat-Sadat , Mirshafiei Pari , Amini Saeed
Published: May 2020

The authors have requested that this preprint be removed from Research Square.
Toe flexor strength is associated with mobility in older adults with pronated and supinated feet but not with neutral feet
Authors: Kusagawa Yuki , Kurihara Toshiyuki , Imai Aiko , Maeo Sumiaki , Sugiyama Takashi , Kanehisa Hiroaki , Isaka Tadao
Published: May 2020

Background
Older adults are known to have more pronated foot posture and decreased toe flexor strength (TFS), as well as decreased mobility compared to young adults. Although foot posture is reported to be an influential factor for walking biomechanics in young adults, there is less information on this subject in older adults. Age-related reduction in TFS is shown to be associated with impairments of functional performance, but it is poorly understood whether foot posture influences the relationships between TFS and functional performances. Therefore, the present study aimed to elucidate this concern by examining older women.
Methods
Seventy community-dwelling older women (76.8 ± 4.4 years) voluntarily participated in this study. Foot posture was evaluated by the 6-item foot posture index (FPI). On the basis of the FPI score, participants were allocated to pronated, neutral, or supinated group (n = 33, 26, and 11, respectively). TFS was assessed using a toe grip dynamometer in a seated position. Scores of 30-second chair stand, timed up-and-go, 5-m comfortable-speed walking, and static balance tests were determined to evaluate functional performances. Pearson’s correlation coefficients were computed to examine the relationships between TFS and functional performances in each group.
Results
TFS positively correlated with comfortable walking speed in the pronated (r = 0.37, p = 0.03) and supinated (r = 0.76, p < 0.001) groups, but not in the neutral group (r = 0.17, p = 0.42). For the two significant relationships, an analysis of covariance showed that there was no significant difference between the pronated and supinated groups in the slopes of the regression lines, suggesting a similar relative contribution of TFS to comfortable walking speed between the two groups. In addition, TFS tended to negatively correlate with timed up-and-go time in the pronated (r = -0.32, p = 0.07) and supinated (r = -0.56, p = 0.08) groups, and positively correlate with 30-second chair stand score in the pronated group (r = 0.31, p = 0.08).
Conclusions
The present study indicates that TFS would be associated with mobility, walking performance in particular, in older women with pronated and supinated feet but not with neutral feet.
Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia
Authors: Fang Tingting , Liu Lanqin , liu wenjun
Published: May 2020

Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore，this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology.Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database.Key findings. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway.Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.
Combination of interferon-gamma and autophagy inhibitor as a therapeutic approach in oral squamous cell carcinoma
Authors: Zhou Zhi-hang , Zhao Tong-Chao , Liang Si-yuan , Zhu Dong-wang , Zhang Zhi-yuan , Ju Wu-tong , Zhong Lai-ping
Published: May 2020

Background: Former clinical trials and experimental research have indicated that interferon-gamma (IFNγ) therapy does not achieve an ideal effect in solid tumors. Autophagy has been associated with tumor chemoresistance. The aim of this study was to explore the efficacy of IFNγ and autophagy inhibitor in the combination treatment of oral squamous cell carcinoma (OSCC). Method: IFNγ-induced apoptosis was evaluated by the expression of relative proteins (cleaved-PARP and caspase-3) and flow cytometry. IFNγ-induced autophagy was assessed by the expression of Beclin1, LC3B, and P62. The synergistic effect of IFNγ and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo.Findings: IFNγ induced anti-proliferation, apoptosis, and autophagy in OSCC cells. Autophagy-related protein 5 (ATG5) was a key feature in IFNγ-induced autophagy flux. IFNγ and chloroquine had obvious synergistic effects on cellular growth inhibition and apoptosis promotion in OSCC cells and xenograft models. Interpretation: Our findings suggest that IFNγ-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote IFNγ-mediated OSCC cell apoptosis. The combination of IFNγ and autophagy inhibitors represents a novel strategy for OSCC therapy.