bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic of SOFA Score Predicts Functionality after ARDS Therapy
Authors: Bernard Alice , Higuita Lina Maria Serna , Martus Peter , Mirakaj Valbona , Koeppen Michael , Zarbock Alexander , Marx Gernot , Putensen Christian , Rosenberger Peter , Haeberle Helene Anna
Published: November 2022

Rationale: Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic.
Objectives: A total of 143 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial.
Methods: Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180.
Measurements: Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression.
Main Results: Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19. The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group.
Conclusions: Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity. Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity and emphasizes the importance of timely initiation of treatment in these critically ill patients.
Development and validation of machine learning models for the prediction of overall survival and cancer-specific survival in endometrial cancer
Authors: Akazawa Munetoshi , Hashimoto Kazunori
Published: November 2022

Background
Accurate prediction of prognosis is essential for the management of patients with cancer. We aimed to predict the prognosis of endometrial cancer using machine learning.
Methods
We included patients with endometrial cancer in the Surveillance, Epidemiology, and End Results database. We constructed four machine learning models including logistic regression, random forest, gradient boosting machine (XGBoost), and artificial neural network to predict 5-year overall survival (OS) and cancer-specific survival (CSS). The variables included patient demographics (age, race, and year of diagnosis), pathologic factors (clinical stage, histological grade, and TNM classification), and therapeutic factors (surgical content).
Results
Overall, 71,506 patients for OS and 66,368 patients for CSS were included in the study. For the prediction of OS, XGBoost showed the best performance, with a class accuracy of 0.862 (95%CI: 0.859–0.866) and area under the curve (AUC) of 0.831 (95%CI: 0.827–0.836). Regarding the prediction of CSS, XGBoost also showed the best performance with a class accuracy of 0.914 (95%CI: 0.911–0.916) and AUC of 0.867 (95%CI: 0.862–0.871).
Conclusion
Using machine learning, we were able to predict the prognosis of endometrial cancer. Future studies should analyze the important variables and suitable algorithms with larger clinical data.
Selective Load Control of Lumbar Muscles in Robot-assisted Isometric Lumbar Stabilization Exercise
Authors: Kim Joowan , Choi Wonje , Park Jaeheung
Published: November 2022

Background: Lumbar stabilization exercise was developed as a rehabilitation therapy to improve the condition of patients with low back pain. However, many patients discontinue performing exercises for several reasons. Basically, the main reason is difficult to provide an appropriate intensity of exercise load to the patient. First, there is no way to provide the desired strength of the load on the target lumbar muscle. Also, it is difficult to precisely control the intensity of exercise for a gradual increase in load. Lastly, especially in calisthenics, there are cases where a large load acts on unexpected parts, such as the upper and lower limbs. Therefore, in order to allow the patient to continuously exercise and recover gradually, there is a need for a method capable of exercising with a desired load on the target lumbar muscles.
Methods: We propose a rehabilitation assistive device to help the patient quantitatively control the lumbar spine load. In isometric lumbar stabilization exercise, our proposed method is to provide compensating gravity precisely. The proposed device applies assist force in the direction opposite to gravity, with a series elastic actuator placed below the patient in a lying posture, enabling precise load control on the lumbar and reducing vertical load on the spine. To validate the effectiveness, we experimented with 20 healthy subjects on three exercises and analyzed electromyography data using non-parametric statistical methods to determine whether the load could be controlled gradually for the target lumbar muscles.
Results: From the statistical analysis with the three exercises, it was verified that for the two exercises with a single degree of freedom, there were significant differences even with a small load change on the target lumbar muscle in the exercise using the device. However, in one exercise with multi degrees of freedom, a load change were different than expected.
Conclusions: It was found that the proposed device can fine-tune the load on the target lumbar muscle for exercise with a single degree of freedom. To control the lumbar muscles that were not controlled in this study, dynamic analysis of various exercise postures and additional experiments are needed.
Gamma-irradiation effect on the chemical composition and antibacterial activity of the Moroccan Tanacetum Annuum L. Essential Oil
Authors: Belcadi Hasna , Aknouch Adil , amrani Soukayna El , Chraka Anas , Lachkar Mohammed , mouhib Mohamed , Zantar Said , Ibnmansour Ahmed
Published: November 2022

The study aims to evaluate the Moroccan Tanacetum annuum L. essential oil by studying the effect of gamma irradiation on both the chemical composition and antibacterial activity, this is done by exposing the oil extracted from the dry aerial parts of the plant by hydrodistillation to irradiation dose of 5kGy and 10kGy.
The obtained results proved that irradiation technology can actually raise the percentage of chemical compounds that would increase the biological activity of the essential oil. This allows to increase the potential of the plant studied and its biological effectiveness, also the irradiation process has proven the ability to raise the quality of the chemical composition both in terms to reduce the risk of contamination it can be microbiological, physical, and chemical of one of the most abundant medicinal plants in northern Morocco.
Effect of chicken gut meal on growth, immune and metabolism in juvenile fat greenling (Hexagrammos otakii)
Authors: Wang Wei , Gu Yixin , Dai Qianliang , Wei Yanchao , Zhang Zheng , Wang Yue , Chen Bojin , Xue Zhuang
Published: November 2022

In modern aquaculture, chicken gut meal (CGM) is reasonably priced and rich in nutrients, and can become a new source of protein in the diets of major aquatic products such as fish and shrimp. An 8-week feeding trial was conducted to comprehensively investigate the beneficial effects of CGM on juvenile fat greenling (Hexagrammos otakii). Juvenile H. otakii (1.58 ± 0.06) g were fed with different levels of CGM in a replacement percentage of fish meal (FM) in the basal diet: 0% (CGM0), 25% (CGM25), 50% (CGM50), 75% (CGM75) and 100% (CGM100). The results showed that the percent weight gain (PWG), specific growth rate (SGR), feeding rate (FR) and feed conversion rate (FCR) were significantly improved among the experimental groups (P < 0.05). Higher hepatosomatic index (HSI) was observed in CGM50, CGM75 and CGM100 groups compared to the control (P < 0.05). The apparent digestibility coefficient (ADC) of dry matter, protein and lipid were significantly increased with CGM inclusion (P < 0.05). Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in CGM25 and CGM50 groups, respectively (P < 0.05). The activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) were significantly decreased in CGM75 and CGM100 groups (P < 0.05). Triglyceride (TG) and total cholesterol (TCHO) were significantly increased in CGM50 and CGM75 groups, respectively (P < 0.05). Fish fed in CGM100 and CGM75 groups had higher activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) than the control (P < 0.05). Moreover, the relative expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase alphα (ACCα) were significantly increased in CGM75 and CGM100 groups, while hormone-sensitive lipase (HSL) and peroxisome proliferator-activated receptor alpha (PPAR-α) were significantly decreased (P < 0.05). In summary, the optimal replacement level of FM with CGM was shown by curve equation analysis to be 61.30%.
Assessment of awareness about wearing contact lenses & methods of care for them among a sample of Syrian private university
Authors: Shebli Mohammad Ibrahim , Basha Ahmad Mousa , Salman Afraa
Published: November 2022

Background:
Contact lenses are an increasingly frequent topic that may cause eye and health problems for individuals of different age groups, especially the youth group, due to their frequent use of them. From this point of view, we conducted our research. To assess the awareness of participating students from different faculties at the Syrian Private University about contact lenses and how to use them in general by studying several demographic factors and their relationship to the knowledge and awareness of students based on their answers to our questionnaire.
Design:
A Cross-Sectional Study conducted at Syrian private university.
Methods:
The study was on 500 students using a questionnaire tool, targeting students at the Syrian Private University in its various faculties
Results:
We studied a sample of the faculties at the Syrian Private University, which numbered 500 students. Males represented more than half of the sample with a percentage of 63.2%, and the most age group was 21-25 years old with a percentage of 90.4%, and most students were from the Faculty of Human Medicine with a percentage of 81%, in the context of our study, they found a correlation between gender, college, school year, and students’ use of contact lenses, where most of them had not used them before, and their percentage was 72.8%. Or wear it while sleeping, or share it with others.
Testing the Charnov-Bull model from the sex determining temperature range
Authors: Ferrando-Bernal Manuel
Published: November 2022

Vertebrates show diversity in their sex determining systems. The main reasons to explain why a species shows a specific system is yet unclear. The Charnov-Bull model predicts that temperature-dependent sex determining system (TSD) evolve when there is a differential fitness between sexes, linking the sex determination system to different environmental temperatures. Here, I observed that TSD species tend to breed inside a specific range that allows them to produce both males and females. Contrary, close species where the sex is controlled by genotypic mechanisms (GSD) tend to breed outside these ranges, suggesting possible complete sex bias if they had TSD systems. I also do not find support for thermal adaptation in 25 TSD reptile species belonging to three different phylogenetic orders. Finally, I test different scenarios to confirm that the Charnov-Bull model is also able to explain why transitions from sex chromosomes to temperature-dependent sex determining systems has never been observed neither in mammals nor in birds.
Serial Viral Load Analysis by Ddpcr to Evaluate Fnc Efficacy and Safety in the Treatment of Moderate Cases of Covid-19
Authors: Cabral Paula , de Souza Sávio , Silva Renato da , Arruda Raul , Cabral Sheila , de Assis Arícia , Júnior Antônio Viana , Degrave Wim , Moreira Aline , Silva Cléber , Chang Junbiao , Lei Pingsheng
Published: November 2022

A highly pathogenic coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 causing coronavirus disease 2019 (COVID-19). Trials have been carried out to find drugs effective in fighting the disease, as COVID-19 is being considered a treatable disease only after we have antivirals. A clinical candidate originally developed for HIV treatment, AZVUDINE (FNC), is a promising drug in the treatment of COVID-19, being able to reduce the patient's viral load leading to cure. In this study, a randomized clinical trial was performed in moderate COVID-19 patients to evaluate the efficacy of FNC added to standard treatment, compared with placebo group added to standard treatment. RT-qPCR and ddPCR were applied to estimate the viral load in samples from patients, which was performed every 48 hours throughout the treatment. Also, the clinical improvement was evaluated as well as the liver and kidney function. Notably, FNC treatment in moderate COVID-19 patients may shorten the time of nucleic acid negativity conversion versus placebo group, accelerates the elimination of the virus, decreasing the viral load significantly, especially in the first days. Due to the lack of specific antiviral drug, the pandemic is not under the control and resurfaces in different waves of infection, which cause a large cumulative expense of medical resources. Fortunately, FNC could reduce treatment time of moderate COVID-19 patients and save a lot of medical resources, making it a strong candidate for the treatment of COVID-19.
Trial registration number: NCT04668235
https://clinicaltrials.gov/ct2/show/NCT04668235?term=azvudine&cond=COVID-19&draw=2&rank=1
Serial Viral Load Analysis by Ddpcr to Evaluate Fnc Efficacy and Safety in the Treatment of Mild Cases of Covid-19
Authors: Cabral Paula , Silva Renato da , de Souza Sávio , Arruda Raul , Cabral Sheila , de Assis Arícia , Martins Yolanda , Tavares Carlos Augusto , Junior Antônio Viana , Chang Junbiao , Lei Pingsheng
Published: November 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has threatened the human population globally as the numbers of reinfection cases even after large-scale vaccination. Trials have been carried out to find drugs effective in fighting the disease, as COVID-19 is being considered a treatable disease only after we have antivirals. A clinical candidate originally developed for HIV treatment, AZVUDINE (FNC), is a promising drug in the treatment of COVID-19, being able to reduce the patient's viral load leading to cure. To predict the clinical outcome of COVID-19, we examined the course of viral load, every 48hs, by RT-PCR, and disease severity using a promising antiviral drug, AZVUDINE (FNC) with 281 participants. A randomized clinical trial was performed to evaluate the efficacy of FNC added to standard treatment, compared with placebo group added to standard treatment, for patients with mild COVID-19. RT-qPCR and ddPCR were applied to estimate the viral load in samples from patients, which was performed every 48 hours throughout the treatment. Also, the clinical improvement was evaluated as well as the liver and kidney function. Notably, the FNC treatment in the mild COVID-19 patients may shorten the time of the nucleic acid negative conversion (NANC) versus placebo group. In addition, the FNC was effective in reducing the viral load of these participants, in the first days (D3, D5, D7, D9). Therefore, the present clinical trial results showed that the FNC accelerate the elimination of the virus in and could reduce treatment time of mild patients and save a lot of medical resources, making it a strong candidate for the outpatient and home treatment of COVID-19.
Trial registration number:NCT05033145
https://clinicaltrials.gov/ct2/show/NCT05033145
Consolidation Deformation Characteristics of Hachirogata Clay with Salt Leaching
Authors: Takahashi Momoe , Kanayama Motohei
Published: November 2022

Thick, soft alluvial clay was deposited in the Hachirogata reclaimed area in Akita Prefecture, Japan. The phenomenon of differential settlements of the irrigation structure occurring at the site lowers the function of the water supply to the irrigation channel. In this study, assuming that the differential settlement of the ground is due to salt leaching of the sediments, the effect of leaching on the physical and mechanical properties of Hachirogata clay was examined. It was confirmed that the liquid limit and plasticity index decreased due to the leaching, which indicates that the leached sample changed the flowability due to changes in the water content. From the consolidation tests, it was found that the leached clay had a delay in consolidation deformation, a decrease in permeability, and remarkable creep behaviour. According to the observations of the clay structure by scanning electron microscope, leaching caused the clay particles to change from a random arrangement to an impermeable parallel arrangement, and the resultant pore area increased. These results show that the changes in the clay structure were due to leaching affect the physicochemical and mechanical properties. Therefore, it can be inferred that the occurrence of localised leaching is one of the factors that accelerates differential settlement.
Combined host depletion and metagenomics sequencing significantly improves the diagnosis of pulmonary tuberculosis.
Authors: Li Shanshan , Ma Liping , Du Juan , Sun Hailin , Zhang Hongbo , Su Hong , Tian Dan , Cheng Changhao , Chen Wangyang , Li Duheng , Wang Yan , Li Liang , Li Lifeng , Pang Yu
Published: November 2022

Rapid and accurate detection of MTB (Mycobacterium tuberculosis) is key to eliminating tuberculosis. Metagenomic sequencing combining host depletion can significantly improve the diagnostic performance for tuberculosis. Here we compared the performance for diagnosis of 98 suspected pulmonary tuberculosis (PTB) among mycobacterial culture, Xpert, metagenomic next-generation sequencing (mNGS), mNGS of depletion human DNA (mNGS-DH), and nanopore sequencing of depletion human DNA (Nanopore-DH). In the 82 cases of PTB, the PPA (Positive percentage agreement) of mNGS-DH was 71.95% (95%CI, 60.77–81.04%,59/82). In the definite PTB groups(n = 50), the sensitivity of mNGS-DH was up to 86.00%, which was superior to the other four methods. Removing host DNA enhanced the sequencing depth and coverage of the MTB and improved tuberculosis detection, increasing the mean coverage of MTB by 16-fold. Our data demonstrated that mNGS-DH significantly improved the sensitivity of tuberculosis detection in the BALF (bronchoalveolar lavage fluid). Thus, it could be used as a promising alternative to assist the diagnosis of pulmonary TB patients.
Structure and composition analysis of painted films unearthed from Pit 2 of Qin Terra-Cotta Warriors
Authors: Wang Chunyan , Zhu Sihong , Hu Daodao , Xia Yin , Lu Wenxian , Li Hua
Published: November 2022

Lacquer is widely used in ancient times. The antiques unearthed from Qin Terra-Cotta Warriors bear traces of lacquer painting massively. The lacquer paintings on the surface of the Qin Terra-Cotta Warriors fully demonstrate the characteristics and development level of lacquer painting at that time. However, the painted films unearthed appear crispy and fragile. In this study, six painted films are chosen from Pit.2 of the Qin Terra-Cotta Warriors and characterized by an ultra-depth-of-field microscope, a metalloscope, a scanning electron microscope, an energy dispersive spectrometer, and infrared spectroscopy. The results show that the painted films are lacquer films on the base layer of Qin terra-cotta warriors. In the wet alkaline environment, a fracture of the polymer chain along polymerization products of urushiol occurs, which produces soluble products containing benzene ring-related molecules, leading to lacquer films’ embrittlement and cracks. Lacquer films have aged.
Improving the production of 9α-hydroxy-4-androstene-3,17-dione from phytosterols by 3-ketosteroid-Δ1- dehydrogenase deficiency and multiple gene regulation in Mycobacterium fortuitum
Authors: Liu Xiangcen , Zhang Jingxian , Yuan Chenyang , Du Guilin , Han Suwan , Shi Jiping , Sun Junsong , Zhang Baoguo
Published: November 2022

Background
9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) refers to a significant intermediate for synthesis of glucocorticoid drugs. Microbial transformation of phytosterols to manufacture 9-OHAD has obvious advantages in terms of lead time, cost control, environmental friendliness, etc. However, the product degradation and the formation of by-products restrict their application. In this study, a combined strategy of blocking Δ1‑dehydrogenation and regulating metabolic flow was investigated to construct a stable high-yield 9-OHAD producer.
Results
Five 3-Ketosteroid-Δ1-dehydrogenase (KstD) were identified in ATCC 35855 and each of them was functionally confirmed by heterologous expression, transcriptional response and knockout analysis. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4 and KstD5. In particular, KstD2 has a much higher catalytic activity for C9 hydroxylated steroids than for C9 non-hydroxylated steroids, whereas KstD3 showed the opposite characteristics. The deletion of kstDs indicated that KstD2 and KstD3 are the main assailants of 9-OHAD degradation. Compared with ATCC 35855, MFΔkstD, the five KstDs deficient train, realized the stable accumulation of 9-OHAD, and its yield increased by 42.57%. The knockout of Opccr or the overexpression of Hsd4A alone could not reduce the metabolic flow of C22 pathway, while the overexpression of Hsd4A based on the knockout of Opccr in MFΔkstD could remarkably reduce the contents of 9-OHHP by-products. The inactivation of FadE28-29 leads to a large amount of accumulation of incomplete side chain degradation products. Therefore, hsd4A and fadE28-29 were co-expressed in MFΔkstDΔopccr successfully eliminated two by-products. Compared with MFΔkstD, the purity of 9-OHAD was improved from 80.24% to 90.14%. Ultimately, 9‑OHAD production reached 12.21 g/L (83.74% molar yield) and the productivity of 9-OHAD was 0.0927 g/L/h.
Conclusions
Five putative KstDs have been identified and functionally confirmed in ATCC 35855. KstD2 and KstD3 were the main murderers of 9-OHAD degradation. Hsd4A and Opccr are key enzymes regulating the metabolic flux of C19 and C22-pathways. The overexpression of fadE28-29 can reduce the accumulation of incomplete degradation products of side chains. According to the findings above, MF-FA5020 transformant was successfully constructed to rapidly and stably accumulate 9-OHAD from phytosterols. These results contribute to understanding the diversity and complexity of steroid catabolism regulation in actinobacteria and providing a theoretical basis for further optimizing industrial microbial catalyst.
A Variable Switching Frequency Space Vector Modulation Method Using Voltage Ripple Prediction
Authors: Ruan Zhihuang , Song Wenxiang
Published: November 2022

Regular space vector pulse width modulation (SVPWM) uses a fixed switching frequency, and this method causes high harmonics to be concentrated around integer multiples of the switching frequency. In this paper, we propose a variable switching frequency SVPWM (VSFSVPWM) method with voltage ripple prediction. By varying the switching frequency in real time according to the voltage ripple prediction model under the time domain, VSFSVPWM can suppress high-frequency harmonics caused by pulse width modulation (PWM). The proposed method was fully compared with the CSFSVPWM method on a 5kW inverter for experimental validation.
Elevated plasma IL-8 as a risk factor for mortality in children presenting with cerebral malaria (NeuroCM study)
Authors: Royo Jade , Vianou Bertin , Accrombessi Manfred , Kinkpé Elisée , Ayédadjou Linda , Dossou-Dagba Ida , Ladipo Yélé , Alao Maroufou Jules , Bertin Gwladys I , Cot Michel , Boumediene Farid , Houzé Sandrine , Faucher Jean-François , Aubouy Agnès , group collaborators NeuroCM
Published: November 2022

Background: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis.
Methods: Children presenting with CM (n = 70) due to P. falciparuminfection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examinationwas complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysedby univariate analysis using the nonparametric Mann‒Whitney U test and Chi2 Pearson test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors.
Results: Univariate analysis revealed that higher plasma levels of TNF, IL-1β, IL-10, IL-8, CXCL9, granzyme B, and angiopoietin-2 and lower urinary levels of PGEM were associated with CM mortality. The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM. Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, CCL17, CCL22, and urinary 15-F2t-isoprostane.
Conclusions: These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.
Technological innovation for the coal industry to achieve carbon neutrality in China
Authors: Wang Siyao , Chen Fu , Wang Yinghong
Published: November 2022

The energy crisis in Europe, triggered by the conflict between Russia and Ukraine, has again drawn attention to the decarbonisation of fossil energy sources. However, few studies have objectively considered coal from an integrated life cycle and its position in the energy system. In the present study, we revealed that (1) Power generation & heating and iron & steel smelting are the highest CO2 emissions sectors. In addition, the coal chemical industry and power generation & heating are the two sectors with the highest contribution rate of CO2 emissions. (2) Based on these, Underground Coal Gasification (UCG) and Underground Coal Gasification-Integrated Gasification Combined Cycle (UCG-IGCC) technologies were introduced to innovate the coal life cycle. The panel threshold model has proved that when the energy intensity falls in the interval 0.363-2.599, UCG-IGCC technology could be the complement in mitigating CO2 emissions. (3) Finally, for the same amount of emission mitigations, the social cost of innovating coal production and utilization processes using UCG-IGCC technology will be lower than the one of phasing out coal-fired power plants using carbon prices. For China, UCG-IGCC and renewable energy should be developed simultaneously.
The TAU isoform 1N4R restores vulnerability of MAPT knockout human iPSC-derived neurons to Amyloid beta-induced neuronal dysfunction
Authors: Buchholz Sarah , Bell-Simons Michael , Kabbani Mhd Aghyad Al , Kluge Lena , Cagkmak Cagla , Klimek Jennifer , Zempel Hans
Published: November 2022

The microtubule-associated protein TAU is a key driver of the neurodegeneration observed in Alzheimer’s disease (AD). Normally, TAU stabilizes neuronal microtubules (MT) and promotes essential MT-associated functions. Alternative splicing of the TAU-encoding MAPT gene results in the expression of six isoforms in the human brain. Models of AD and TAU pathology to date are mostly based on rodents, which differ in their TAU isoform expression and often rely on the overexpression of mutant human TAU to develop hallmarks of AD. Moreover, recent results from murine neurons highlight that TAU isoforms are differentially localized within neurons and may have isoform-specific functions, but human cellular data is scarce. In this study, we generated MAPT KO human induced pluripotent stem cells using CRISPR/Cas9 and induced neuronal differentiation using Ngn2. Differentiated TAU KO neurons show no major abnormalities or changes in neuronal activity but sightly decreased neurite outgrowth and AIS length. Yet, TAU-depleted neurons are protected from AD-like stress, e.g, Amyloid-beta oligomer (AβO)-induced reduction of neuronal activity. Re-expression of most individual TAU isoforms was sufficient to rescue the changes in neurite and AIS development. However, the 1N4R-TAU isoform alone was sufficient to restore neuronal vulnerability to AD-like stress. In sum, we describe here for the first time a human iPSC-based MAPT KO/TAU depletion model to study the function of TAU isoforms and their role in AD pathology. Our results suggest that 1N4R-TAU is involved in early TAU-mediated toxicity and a potential target for future therapeutic strategies for AD.
Effect of lignin and released acid on the gelation and aerogel fabrication of whole biomass in the lithium bromide molten salt hydrate system
Authors: Guo Xu , Cao Xinyu , Xiao Tianyuan , Hou Minjie , Li Changgeng , Sheng Xueru , Guo Yanzhu , Sun Yanning , Fatehi Pedram , Shi Haiqiang
Published: November 2022

Biomass-based aerogels have received attention these days due to their environmentally friendly and easily degradable nature. However, the aerogel production is challenged by the generation of acid in aerogel manufacturing. This work aims at understanding how acid originating from biomass would impact aerogel production. In this study, alkali pre-extraction (APE) was carried out to demonstrate how the acidic substances released from poplar in a green inorganic molten salt hydrate solvent (LiBr·3H2O) would impact the properties of biomass-based aerogels. To understand the impact of lignin on aerogel production, the aerogel production was carried out on lignin-free biomass. The results confirmed that alkali pretreatment of biomass could be an effective method to accelerate the production of biomass-based aerogels. The biomass and particle size primarily affected the properties and microstructure of aerogels. Also, lignin has a substantial adverse effect on such aerogel production. Therefore, selecting suitable alkali treatment conditions, biomass content and particle size have crucial effects on the preparation of lignin-containing aerogels and lignin-free aerogels.
Bis(oxime Palladacyle) Supported on Magnetized SBA-15 as an Efficient and Retriveble Catalyst for the Mizoroki-Heck Reaction
Authors: Ghahremani Fateme , Mansoori Yagoub , Bezaatpour Abolfazl , Esqu Dolores , Navarro M. Angeles
Published: November 2022

Herein, we report the anchoring of a bis(oxime palladacyle) adduct on magnetic mesoporous silica (Fe3O4@SBA-15). Magnetic mesoporous silica was successively treated with (3-aminopropyl) triethoxysilane (APTES), cyanuric chloride (CC), and 4-hydroxyacetophenone oxime-derived palladacycle to give Fe3O4@SBA-AP-CC-bis(oxime palladacycle). The resulting supported complex was characterized by analytical and spectroscopic techniques (FT-IR and CP/MAS 13C NMR). X‐Ray photoelectron spectroscopy (XPS) analysis corroborated the (+2) oxidation number for palladium. The catalytic potential of Fe3O4@SBA-AP-CC-bis(oxime palladacycle) was explored in the Mizoroki-Heck reaction. The effects of different reaction conditions, including the solvent, the base, temperature, and palladium content, were studied in detail. The catalyst shows a wide substrate scope, including aryl halides (I, Br, Cl) and olefins, in the Mizoroki-Heck reaction, using low catalyst loadings viz., Pd 0.09 mol%. The bis(oxime palladacyle) enjoys easy magnetic separation, stability, and recyclability over five runs.
Histopathology of the digestive gland of the snail Cantareus aspersus exposed chronically to cadmium and copper fungicide
Authors: Farfar Khadidja , Bouraiou Chiraz , Youbi Amira , Fetnaci Imene , Khebbeb Mohamed Elhadi , Djebar Mohamed Reda , Bouslama Zihad
Published: November 2022

The presence of unnatural substances in the environment increases in proportion to their use by humans. Thus, the development of agriculture will most certainly result in an increase in the concentration of pesticides and chemicals in the air, water and soil. They will therefore be able to reach ecosystems. In this study, we are interested in the histological effects of a copper-based fungicide Vacomil-Plus (2 g/l), cadmium (800 µg/l) and their mixture (CdCl2 + Copper fungicide, 1/1, V/V) on the digestive gland of bio-accumulators and bio-indicators of pollution: the snail Cantareus aspersus. We have chosen three processing times: Acute (15 days), sub-acute (30 days) and chronic (90 days). After each period, an individual chosen randomly from each batch, is shelled and then dissected to collect the target organ (digestive gland). The histological aspect of the digestive gland of treated snails illustrated tissue damages and alterations after exposure to cadmium, copper fungicide and their mixture, manifested by cellular hypertrophy, decreased epithelial height accompanied by chorion fibrosis confirming the toxicity of these two substances. In the other hand, we noted the appearance of nuclear pyknosis, necrosis and cellular apoptosis to treaties by the mixture (from 30 days of treatment) earlier that cadmium or copper fungicide single (90 days). Moreover, this study revealed that the cocktail was much more toxic to the tested snail than the Cadmium or the fungicide alone, therefore the cadmium have a synergic effect on this copper fungicide.
A picogram BA-ELISA quantification assay for rLj-RGD3, a platelet fibrinogen receptor antagonist, in the rat plasma and its application to a pharmacokinetic study
Authors: Wang Yuping , Liu Zhien , Han Guozhu , Yu Ping , Yang Xiaobo , Wang Jihong , Lv Li
Published: November 2022

Background: rLj-RGD3, a new member of RGD-motif toxin protein family derived from Lampetra japonica by means of DNA recombinant technique, has been demonstrated to be a platelet fibrinogen receptor antagonist. Researches over the years have shown that rLj-RGD3 has great value in developing as a useful antithrombotic and antitumor agent. Therefore, the study of pharmacokinetics is essential, so its quantification in plasma becomes a prerequisite. The present article aims to report a validated highly sensitive and specific double sandwich biotin-avidin enzyme linked immunosorbent assay (BA-ELISA) in order to provide a bio-analytical method for its pharmacokinetic (PK) study.
Results: The concentration of rLj-RGD3 in rat plasma was measured at a picogram level by the developed BA-ELISA method, which used two different mouse anti-rLj-RGD3 monoclonal antibodies as capture antibody and detection antibody, respectively, directed at different epitopes. The method was validated to be highly specific (no interference with the detection from blank plasma), precise (within day and between day RSD <10%) and accurate (94%-104%). The absolute recovery was as high as 94%-105%. The calibration curve showed good linearity ranging from 50 to 1600 pg/mL with regression equation of Y = 0.0011X + 0.0328 (r2 = 0.9981), the LOQ was found to be as low as 50 pg/mL. The above validated assay was successfully employed for the assessment of PK disposition of rLj-RGD3 in rats. After i.v. and s.c. dosing 30 µg/kg the rLj-RGD3 plasma concentration declined biexponentially with time, which could be best fitted by the two-compartment model. The drug PK behavior could be characterized by rapid elimination, extensive metabolism and low s.c. bioavailability.
Conclusions: The BA-ELISA method reported here was proved to completely meet requirements for PK study of rLj-RGD3, a toxin protein with effective pharmacological dose at µg/kg BW level.
Incidence and predictors of febrile neutropenia in patients with metastatic castrate- resistant prostate cancer receiving docetaxel
Authors: Peltekian Sophie , Sajwani Shellyza , Wang Xiang , Kanji Salmaan
Published: November 2022

Purpose
The incidence of febrile neutropenia (FN) in adults with castrate-resistant metastatic prostate cancer (mCRPC) receiving docetaxel in real-world settings since the expanded role of hormonal treatments has not been well studied. The study objective is to determine the incidence of FN and neutropenia among adults with mCRPC receiving docetaxel. Secondary objectives are to quantify outcomes of patients who develop FN and to identify predictors for FN in this population.
Methods
A single-centre retrospective cohort study was conducted which included adults with mCRPC receiving docetaxel at the Ottawa Hospital over a 5-year period. Charts were reviewed to collect clinical data to determine the incidence of FN. A multiple logistic regression was used to identify predictors of FN.
Results
In patients receiving docetaxel for mCRPC, the incidence of FN and neutropenia was 34/137 (25%) and 45/137 (33%), respectively. Among 34 patients who developed FN, 94% required hospitalization for FN for a mean of 5 days (+/- 2.8) and 6% died. Following FN, 53% required at least 1 treatment delay, 71% had at least 1 dose reduction and 18% received secondary prophylaxis with WBC Growth-Factors. Age category [OR 2.025, 95% CI 1.13–3.627] and presence of multiple comorbidities [OR 1.466, 95% CI 1.01–2.258] increased the risk of FN.
Conclusion
The incidence of FN and neutropenia in the clinical setting in patients receiving docetaxel for mCRPC is higher than previously reported and high enough to consider primary prophylaxis in high-risk groups. Age and multiple comorbidities were identified as risk factors.
Orientation controls tribological performance of 3D-printed model thermoplastics
Authors: Mahmood Samsul , Guo Emily , Sterling Amanda J. , Schulze Kyle D.
Published: November 2022

Additive manufacturing is rapidly growing in popularity due to its capability to produce parts with customized mechanical properties. Recent studies show that mechanical properties can be altered in a controlled manner by adjusting the relationship between build orientation and the applied loading from the service. In this work, the effect of build orientation on the tribological properties of 3D printed PLA – Polylactic acid and ABS- Acrylonitrile butadiene styrene is investigated. PLA and ABS samples are printed using material extrusion with three different build orientations. Tribological results show that variation in build direction relative to the sliding direction leads to anisotropic wear properties. The best wear properties are achieved when the layers are oriented orthogonally to the sliding direction. The coefficient of friction remains mostly unaffected by the build orientation. PLA samples demonstrate significantly better tribological properties compared to ABS. Varying the sliding speed between the interacting surfaces also affects the wear properties of both PLA and ABS. The results suggest that optimizing the build orientation with respect to service loading can improve the wear performance of additively manufactured thermoplastics. This presents an additional paradigm when designing additively manufactured parts potentially for functionally graded materials.
A new interval constructed belief rule base with rule reliability
Authors: Cheng Xiaoyu , Han Peng , He Wei , Zhou Guohui
Published: November 2022

Combination rule explosion problem of belief rule base (BRB) is a difficult problem to solve in complex systems and has attracted wide attention at present. Aiming at the problem of combination rule explosion in belief rule base, a new interval constructed belief rule base with rule reliability (IBRB-r) is proposed. On the basis of BRB, IBRB-r innovatively introduced rule reliability and established the belief table in the form of interval. This approach can not only clearly indicate the contribution degree of each rule to the model but also solve the problem of combination rule explosion. Therefore, IBRB-r is more suitable for complex system modeling. In the case study section, the structural safety assessment of liquid launch vehicle is introduced to conduct a concrete example analysis. The experimental results show that the proposed model is effective and accurate.
Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment
Authors: Qiao Meng , Zhou Fei , Liu Xinyu , Jiang Tao , Wang Haowei , Li Xuefei , Zhao Chao , Cheng Lei , Chen Xiaoxia , Ren Shengxiang , Wang Zaiqi , Zhou Caicun
Published: November 2022

Background
KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, the response to immunotherapy is heterogeneous owing to the distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor response to PD-1 blockade whereas the mechanism remains undetermined.
Methods
We explored the specific characteristics of tumor microenvironment (TME) in KL tumors using syngeneic KRASG12DLKB1−/−(KL) and KRASG12DTP53−/− (KP) lung cancer mouse models. The impact of focal adhesion kinase (FAK) inhibitor on KL lung tumors was investigated in vitro and in vivo through evaluation of both KL cell lines and KL lung cancer mouse models.
Results
We identified KL tumors as “immune-cold” tumors with excessive extracellular matrix (ECM) collagen deposition that formed a physical barrier to block the infiltration of CD8+T cells. Mechanistically, abundant activated cancer-associated fibroblasts (CAFs) resulted from FAK activation contributed to the formation of the unique TME of KL tumors. FAK inhibition with a small molecular inhibitor could remodel the TME by inhibiting CAFs activation, decreasing collagen deposition and further facilitating the infiltration of anti-tumor immune cells, including CD8+ T cells, DC cells and M1-like macrophages into tumors, hence, converting “immune-cold” KL tumors into “immune-hot” tumors. The combined FAK inhibitor and PD-1 blockade therapy synergistically retarded primary and metastatic tumor growth of KL tumors.
Conclusions
Our study identified FAK as a promising intervention target for KL tumors and provided basis for the combination of FAK inhibitor with PD-1 blockade in the management of KL lung cancers.
Species Composition, Structure and Regeneration Status of Woody Plants and Anthropogenic Disturbances in Zijje Maryam Church Forest, Ethiopia
Authors: Mekonnen Amare Bitew , Wassie Wubetie Adinew , Ayalew Habtemaryam , Gebreegziabher Berhane Gebreslassie
Published: November 2022

Our current study was conducted in Zijje Maryam Church forest, Ethiopia, to explore woody species composition, structure, regeneration status, and anthropogenic disturbances inside the sacred groves. The aforementioned information for adequate conservation and management of the church forest is not well documented. Fifteen main quadrats each having an area of 625m2(25m×25m) were used for vegetation and disturbance data collection. Determination of the sampled quadrants was based on the principle that minimum quadrats give the smallest possible area in which all species occurring in the church forest are present. All woody species with diameter at breast height (DBH) ≥ 2.5cm within the quadrat were identified, counted, and their height and DBH data were recorded. The criterion to start at DBH) ≥ 2.5cm was to exclude seedlings having DBH < 2.5 cm and height ≤ 0.6m. Sapling and seedling data were collected using 45 saplings and 45 seedling quadrat that measured 4 m2 and 1m2, respectively. Vegetation data analysis and ANOVA were used for statistical comparison. A total of 48 woody plant species belonging to 46 genera and 36 families were identified. Fabaceae was the dominant family containing 5 species followed by Rosaceae with 3 species. Total basal area of the church forest was 83.03m2 ha− 1. The density of seedlings, saplings, and matured woody species stem ha− 1 were 15555, 3833, and 865, respectively. Talking these densities, regeneration status of the forest was good. The Shannon diversity and evenness of woody plant species in the forest was high; 3.29 and 0.85, respectively. Juniperus procera 27.67 (9.22%) and Olea europaea were species with the highest IVI. Nearly, 22% of areas of the forest get disturbed and higher anthropogenic disturbances occurred near the edge of the forest. Gathering, clearing, and grazing are the major human disturbances that stakeholders need to tackle for conservation. Zijje Maryam church forest has heterogeneous species composition with varied seedlings and saplings. Therefore, local conservation policies recommended not only protect large forests, but also the small and valuable forests service to the needs of local people.
Molecular Characterization of Measles Viruses in Central African Republic, 2012-2016
Authors: Dote Joël , Tricou Vianney , Gnikpingo Laure Kaye , Pagonendji Marilou , Charpentier Emilie , Hübschen Judith M. , GOUANDJIKA Ionela
Published: November 2022

Despite being preventable through vaccination, measles is still one of the most important causes of morbidity and mortality in young children in Africa. In 2015, several African countries, including the Central African Republic, began implementing national measles elimination programs. However, measles remains a public health problem in Africa, particularly in the Central African Republic. A retrospective study was conducted at the Institut Pasteur de Bangui, using blood samples (n = 255) and oral swabs (n = 7) collected between January 2012 and December 2016 from measles IgM positive cases to attempt genotyping of circulating measles virus strains. Overall, 50 samples were positive by RT-PCR, and 40 sequences of acceptable quality were obtained. The phylogenetic analysis showed that 38 strains belonged to genotype B3 suggesting that the genotype B3 was endemic in the CAR during the study period. No genotype B2 sequences were detected, suggesting that this genotype is no longer present in the CAR.
Sustainable Strategies for Indian coal sector: An Econometric Analysis Approach
Authors: Mishra Animesh , Das Niladri , Mishra Brajesh
Published: November 2022

The thermal power generation based on coal has been identified as the second-largest polluting industry, owing to greenhouse gas emissions caused by coal combustion. The pollution caused by the industry is not limited to generation but is manifested all through product usage. Though the colossal emphasis is being given to replacing coal-based power generation with renewable resources, we proved that Indian power generation would depend on coal for more than fifty percent of its demand in the near future. We employed a mix of linear cointegration, non-linear cointegration, and ARIMA followed by the VECM model to forecast the use of coal based on the Indian industrial index and the extent of electricity generated through coal combustion required to fulfill the demand. As pollution and carbon emissions manifest the coal usage cycle, policy implications and recommendations are drafted to mitigate the consequences, greening the coal usage cycle and coal supply chain.