bluuebunny/crossref_metadata_2025 huggingface dataset:
Atlas of Regulated Target Genes of Transcription Factors (ART-TF) in Human ES Cells
Authors: Sharov Alexei , Nakatake Yuhki , Wang Weidong
Published: January 2022

BackgroundTranscription factors (TFs) play central roles in maintaining “stemness” of ES cells and their differentiation into several hundreds of adult cell types. Their regulatory competence is routinely assessed by detecting target genes to which they bind. However, these data do not indicate which target genes are activated, repressed, or not affected by the change of TF abundance. There is a lack of large-scale studies that compare the genome binding of TFs with the expression change of target genes after manipulation of each TF.ResultsIn this paper we associated human TFs with their target genes by two criteria: binding to genes, evaluated from published ChIP-seq data (n = 1891); and change of target gene expression shortly after induction of each TF in human ES cells. Lists of direction- and strength-specific regulated target genes are generated for 319 TFs with expected proportion of false positives ≤0.30, including 64 new TFs not present in four existing databases of target genes. Our lists of direction-specific targets for 182 TFs are larger that in the TRRUST database. In average, 32.8% of genes that respond ≥2 fold to the induction of TFs are regulated targets. Regulated target genes indicate that the majority of TFs are either strong activators or strong repressors, whereas sets of genes that responded ≥2 fold to the induction of TFs did not show strong asymmetry in the direction of expression change. The majority of human TFs (80.2%) regulated their target genes primarily via binding to enhancers. Repression of target genes is more often mediated by promoter-binding than activation of target genes. Enhancer-36 promoter loops are more abundant among strong activator and repressor TFs.ConclusionsWe developed an Atlas of Regulated Targets of TFs (ART-TF) in human ES cells by combining data on TF binding with data on gene expression change after manipulation of individual TFs. Sets of regulated gene targets were identified with a controlled rate of false positives. This approach contributes to the understanding of biological functions of TFs and organization of gene regulatory networks. This atlas should be a valuable resource for ES cell-based regenerative medicine studies.
Genetic Programming for Prediction of Heat Stress Hazard in Underground Coal Mine Environment
Authors: Mishra Devi Prasad , Roy Siddhartha , Bhattacharjee Ram Madhab , Agrawal Hemant
Published: January 2022

Working against nature and uncertain environment makes underground mining a hazardous profession. Every year hundreds of miners lose their valuable lives due to mine hazards. Increasing demand for coal necessitates the extraction of coal at a higher rate. As a result, easily minable shallow coal deposits are depleting speedily, and in near future, deep seated deposits will be left for mining by underground methods. With rising depth and deployment of high-capacity machines, increasing heat stress becomes a major hazard in underground mine environment posing threat to the miners’ health, productivity and safety. Ignoring the effect of heat stress may lead to dangerous circumstances, even result in death. To avoid such unwanted event, it has become imperative to predict the heat stress to reduce its adverse impact in underground coal mines. Therefore, in this study a detailed field survey is conducted to collect the environmental data of three underground coal mines. Genetic programming (GP) is done to develop relation between the environmental parameters and heat stress, by taking the mine survey data as input. The good correlation coefficient (R=0.9816) is obtained between the GP predicted heat stress and actually measured heat stress, which indicates that GP can be effectively used to predict the heat stress in underground mines. A sensitivity analysis (SA) is done to determine the effect of input parameters on heat stress. The SA results reveled that all six input parameters have considerable effect on the heat stress, however, dry-bulb temperature has the highest effect (0.98) on heat stress.
Screening for Various Haemoglobinopathies to Observe Prevalence and Patterns in Population of District Datia (M.P.), India
Authors: Mishra Nalini , Rajasubramaniam S. , Balakrishna S.L. , Kumawat Archana , Gaur Rajesh , Sharma Amita , Gupta Rajesh , Das Aparup
Published: January 2022

Purpose: Haemoglobinopathies are the most common inherited disorder of Red Blood Cells across globe and one of the major public health problems in many regions of India. Variation in ethnic and regional prevalence is observed. The prevalence and pattern of haemoglobinopathies in Datia region has not been reported limiting the knowledge of diseases profile in this region. Present work showed the broad view of various haemoglobinopathies in the local area and population at risk. Efforts were made to identify prevalence of Sickle cell anaemia, β-thalassemia major and G-6-P-D deficiency among patients attending various OPDs of District Hospital, Datia, Madhya Pradesh, India. Methods: All anaemia patients referred by Govt. hospitals/facilities (Datia District hospital) exhibiting anaemia were screened for various haemoglobinopathies. A total of 605 cases exhibiting anemia received from September 2017 to March 2020 at the Model Rural Health Research Unit (MRHRU), Datia, M.P. were tested for different haemoglobinopathies. Samples were received from District Hospital Datia. The samples were tested by solubility and cellulose acetate electrophoresis and HPLC and G6PD deficiency.Results: A total 605 patients were screened for haemoglobinopathies from District Hospital, Datia. It was found that 13 cases (2.14%) were of β thalassemia trait and other rare variants followed by 4 cases (0.66%)of sickle cell trait. A total of 3 cases (0.5%) of β thalassemia major was observed in total samples of 605.Conclusion: Very low prevalence rate of Sickle cell anaemia and thalassemia was observed. Large scale screening in the region is required for identifying the true burden.
Surface Modification of PAN/PVA Nanofibers by Atmospheric Pressure Air Dielectric Barrier Discharge Plasma for Glucose Oxidase Immobilization
Authors: Jahanfar Mehdi , Anaghizi Saeed Javadi , Asadi Sepideh , Ghomi Hamid
Published: January 2022

Polymeric nanoﬁber readies an appropriate circumstance for enzyme immobilization for assortment of utilizations. In this examination, we’ve got made up polyvinyl alcohol /polyacrylonitrile (PVA/PAN) nanoﬁbers utilizing electrospinning. After fabrication of nanoﬁbers, the impact of atmospheric pressure air dielectric barrier discharge plasma (DBD) on PVA/PAN nanoﬁbers were investigated in various times. Among them, 6min treat by air DBD plasma had the most signiﬁcant impact on glucose oxidase (GOx) immobilization. Attenuated total reﬂectance-Fourier transform infrared (ATR-FTIR) spectrographic analysis and hydrophilic capacity and contact angle results uncovered that if there should arise an occurrence of DBD plasma modiﬁed nanoﬁbers, the carboxyl bounds on a superficial level are expanded. The scanning electron microscopy (SEM) pictures indicated that, after GOx immobilization, the modiﬁed nanoﬁbers with plasma has held its nanoﬁber structure. At last, we examined reusability and storage stability of GOx immobilized on plasma modiﬁed and unmodiﬁed nanoﬁbers. The results were additional satisfactory for modiﬁed nanoﬁbers with relevance to unmodiﬁed ones.
Immunoinformatics Approaches for Developing Multi-Epitope Subunit Vaccines to Combat Acinetobacter Baumannii
Authors: Pan Pinhua , Zhu Fei , Ma Shiyang , Rao Mingjun , Zhang Peipei , Peng Wenzhong , Cui Yanhui , Yang Hang , Tan Caixia , Chen Jie
Published: January 2022

Acinetobacter baumannii, a Gram-negative opportunistic pathogen that widely exists in the environment, causes numerous nosocomial infection cases in the ICU. As the agent of pneumonia, septicemia, and meningitis, A. baumannii is usually multidrug-resistant and has a high mortality rate. In this study, we aimed to develop a vaccine for Acinetobacter baumannii through in silico prediction. With the help of immunoinformatic methods, which have proven to be effective and convenient, our team managed to develop multiepitope subunit vaccines for A. baumannii. Three proteins closely associated with the immunologic process were selected and computed. Finally, 9 cytotoxic T-lymphocyte (CTL) epitopes, 10 helper T-lymphocyte (HTL) epitopes, and 11 linear B cell (LBL) epitopes were selected to construct 2 vaccines. LT-IIb was selected as an adjuvant and attached to the vaccine N-terminus. All subunits are linked by suitable linkers. According to examinations, both MEV is antigenic and stable without poisonousness or allergenicity. Molecular docking revealed steady and solid binding ability between MEV and Toll-like receptors (TLRs) and the major histocompatibility complex (MHC). Finally, MEV codons were optimized into a plasmid for in silico cloning, which is pet-28a+ from E. coli K-12 in this research. Although this vaccine performed well in immune stimulation, further experiments are expected to guarantee its safety and immunogenic profile.
Drivers of the Second Wave and clinical characteristics of COVID-19 cases in Uganda: A Retrospective Study of Confirmed SARS-CoV-2 cases, March-June, 2021
Authors: Walekhwa Abel Wilson , Nakazibwe Brenda , Nantongo Mary , Wafula Solomon Tsebeni , Bulafu Douglas , Ayugi Brenda , Nankabirwa Caroline , Nsereko Godfrey , Nalweyiso Martha Dorcas , Tindyebwa Tonny , Mayega Roy William , Ekiri Abel Bulamu , Bagenda Danstan , Musenero Monica , Mugisha Lawrence
Published: January 2022

BackgroundThe COVID-19 continued to pose several public health, social, economic challenges and the drivers for the occurrence of different COVID-19 waves remains undocumented in Uganda. We conducted a cross-sectional population-based survey among recovered COVID-19 cases to establish the drivers of SAR-CoV-2 infections. We performed a retrospective study and interviewed 1120 recovered COVID-19 cases from 10 selected districts in Uganda. We further conducted 38 Key Informant Interviews of members of the COVID-19 District Taskforce and 19 in-depth interviews among COVID-19 survivors from March to June, 2021. Results Out of the 1120 recovered COVID-19 cases interviewed, 62% were aged 39 years and below and 51.5% females with 90.9% under home based care management. Cases were more prevalent in business (25.9%), students (17.2%), farmers (17.1%) and health workers (12.4%) and 79.9% developed COVID-19 symptoms mainly cough, flu, and fever. Being asymptomatic was found to be associated with not seeking healthcare (APR 2, P <0.001). The mortality rate was 3.7% mostly among the elderly (6.3%) and 31.3% aged 40 years and above had comorbidities of high blood pressure, diabetes and asthma. High blood pressure and diabetes were significantly associated with low survival rate (P <0.001) among the COVID-19 cases. ConclusionsOur study identified several drivers under the broad categories of demographic, patient, health facilities and services, social and economic factors that attributed to emergence and sustenance of COVID-19 second wave from March to June, 2021. Specifically, being female, young, asymptomatic, under Home Based Care Management, social gatherings, school going, not vaccinated were among the major drivers of the second wave. We strongly recommend that the Ministry of Health together with National Taskforce for COVID-19 Response to reconsider some aspects of Home-Based Care Management to only established institutions and organizations with potential and facilities to monitor cases in addition to training and monitoring all those involved in supporting the Home Based Care Management.
DQN Based Mobile Edge Computing for Smart Internet of Vehicle
Authors: Zhang Lianhong , Zhou Wenqi , Xia Junjuan , Gao Chongzhi , Zhu Fusheng
Published: January 2022

In this paper, we investigate a multiuser mobile edge computing (MEC)-aided smart internet of vehicle (IoV) network, where one edge server can help accomplish the intensive computational tasks from the vehicular users. For the MEC networks, most of existing works mainly focus on minimizing the system latency to guarantee the user's quality of service (QoS) through designing some offloading strategies, which however fail to consider the pricing from the server and hence fail to take into account the the budget constraint from the users. To address this issue, we jointly incorporate the budget constraint into the system design of the MEC based IoV networks, and then propose a joint deep reinforcement learning (DRL) approach combined with the convex optimization algorithm. Specifically, a deep Q-network (DQN) is firstly used to make the offloading decision, and then the Lagrange multiplier method is employed to allocate the computational capability of the server to multiple users. Simulations are finally presented to demonstrate that the proposed schemes outperforms the conventional ones. In particular, the proposed scheme can effective reduce the system latency up to 56% compared to the conventional schemes.
Successful mRNA COVID-19 vaccination in a patient with a history of severe polyethylene glycol anaphylaxis
Authors: Li Daniel Hanzhang , Lee Erika , Song Christine
Published: January 2022

Background:The mechanism of action behind anaphylactic reactions to the mRNA COVID-19 vaccines remains unknown, but the excipient polyethylene glycol, PEG-2000, has been implicated. Initial recommendations were made for excipient testing with PEG-3350 to help risk stratify individuals and identify an etiology. Here we present a case of a patient with a history of polyethylene glycol anaphylaxis and positive skin testing to PEG-3350, who successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only premedication. Case presentation:A 56-year-old man was referred to our clinic for assessment of his eligibility in receiving the COVID-19 vaccine given a history of anaphylaxis to PEG. He had two anaphylactic episodes: one in 2018 to methylprednisolone acetate intra-articular injection and one to oral PEG-3350 in 2020. Confirmatory skin prick testing was done in our clinic to PEG-3350 that was positive at 35mm with appropriate positive and negative controls. Despite this he wanted to receive the PEG-containing mRNA COVID-19 vaccines and was counselled on the risks and benefits. He successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only pre-treatment with Cetirizine 20mg daily and Montelukast 10mg daily for 5 days. Conclusions: In conclusion, our case demonstrates that a patient with a confirmed polyethylene glycol anaphylaxis could safely receive both doses of the COVID-19 mRNA vaccines in a single step with pre-treatment. We hope that our case will further support the limited role in skin testing to PEG in the assessment of COVID-19 mRNA vaccine allergy and highlight the need for further research to elucidate the mechanism of action behind these allergic reactions.
Effectiveness of a transdiagnostic universal prevention program on anxiety in junior high school students after school closure due to the COVID-19 pandemic
Authors: Kishida Kohei , Hida Noriko , Matsubara Kohei , Oguni Mayuko , Ishikawa Shin-ichi
Published: January 2022

School closures due to the coronavirus disease 2019 (COVID-19) pandemic have worsened mental health problems for children and adolescents worldwide. We aimed to examine the effectiveness of a transdiagnostic universal prevention program for the mental health of junior high school students after a nationwide school closure during the COVID-19 outbreak in Japan. A total of 117 junior high school students were included in the analysis. We used the Unified Universal Prevention Program for Diverse Disorders (Up2-D2) program; the Up2-D2 comprises cognitive-behavioral and positive psychological interventions provided over twelve 45-minute sessions. The program was originally implemented between June and July 2020, immediately after pandemic-related school closures had ended in Japan. The program assessments were based on students’ responses to a questionnaire incorporating five scales to measure indicators of internalizing and externalizing problems. Assessments were carried out before, immediately after, two-month, and six-month after implementing the program using student-reported questionnaires. Mixed models for the whole sample showed small anxiety improvement effects immediately post-intervention and two-month, and six-month assessments (g = -0.25, g = -0.44, and g = -0.30, respectively). The anxiety reducing effects were even greater for the higher-anxiety group at the post-, 2-month, and 6-month assessments (g = -1.48; g = -1.59; g = -1.06, respectively). These results indicate that the transdiagnostic universal prevention intervention effectively reduced anxiety for junior high students returning to school following school closures related to the COVID-19 pandemic in Japan.
Comparative Analysis of Complete Chloroplast Genomes of Eight Ficus Species and Insights Into Phylogenetic Relationships of Ficus
Authors: Xia Xi , Peng Jingyu , Yang Lin , Zhao Xueli , Duan Anan , Wang Dawei
Published: January 2022

Background
The genus Ficus is an evergreen plant, the most numerous species in the family Moraceae, and often used as food and pharmacy source. The phylogenetic relationships of the genus Ficus have been debated for many years.
Results
In this study, the eight Ficus species (Ficus altissima, F. auriculata, F. benjamina, F. curtipes, F. heteromorpha, F. lyrata, F. microcarpa, and F. virens) complete chloroplast(cp) genomes were successfully sequenced and phylogenetic analyses with other Ficus species. The result showed that the eight Ficus cp genomes ranged from 160,333 bp (F. heteromorpha) to 160,772 bp (F. curtipes), with a typical quadripartite structure. It was found that the eight Ficus cp genomes had similar genome structures, containing 127 unique genes. The cp genomes of eight Ficus species contained 89–104 SSR loci, which were dominated by mono-nucleotides repeats. Moreover, we identified eight hypervariable regions eight hypervariable regions (trnS-GCU_trnG-UCC, trnT-GGU_psbD, trnV-UAC_trnM-CAU, clpP_psbB, ndhF_trnL-UAG, trnL-UAG_ccsA, ndhD_psaC and ycf1). Phylogenetic analysis showed that three subgen. (Sycomorus, Ficus. Pharmacosycea) of Ficus as monophyletic, but Urostigma is no-monophyletic.
Conclusions
In our study, we have successfully assembled and analysed the cp genomes of eight Ficus species. The results give useful data for further studies on molecular identification, phylogeny, species identification and population genetics of speciation in the Ficus.
Pseudorabies Virus Infection Induces Endoplasmic Reticulum Stress Through the PERK and IRE1 Pathways of Unfolded Protein Response in Suspension-cultured BHK-21 Cells
Authors: Chen Li , Ni Minshu , Ahmed Waqas , Xu Yue , Bao Xi , Zhuang Tenghan , Feng Lei , Guo Meijin
Published: January 2022

Pseudorabies virus (PRV) is a pathogen of swine resulting in devastating disease. Some viral infections can cause endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to restore ER homeostasis. However, the mechanism of how PRV induces ER stress and UPR activation remains unclear. Here, levels of proteins or transcriptional factors of three UPR pathways were examined in suspension-cultured BHK-21 cells to investigate PRV-induced ER stress. Results showed that PRV triggered ER stress and UPR of the host cells with the upregulated expression of glucose-related protein 78 kD and 94 kD (GRP78 and GRP94). The protein kinase RNA-like ER kinase (PERK) pathway was activated to upregulate ATF4, CHOP, and GADD34 expression. Additionally, the inositol requiring kinase 1 (IRE1) pathway was triggered by splicing of X box-binding protein 1 (XBP1) mRNA and the enhanced expression of p58IPK and EDEM1. Furthermore, our data demonstrated that PRV took advantage of ER stress to accelerate its replication with the activation of the PERK and IRE1 pathways in suspension-cultured BHK-21 cells, and the glycoprotein B played a crucial role in ER stress.
Nicotine Addiction and Psychological Stress: a Case-control Study Among the Unemployed North Indians
Authors: Mishra Anurag , Kumar Rishabh , Mishra Satya Narayan , Vijayaraghavalu Sivakumar , Kumar Munish
Published: January 2022

Background: In India, nicotine addiction causes a huge socio-economic burden, mortality, and morbidity. Chronic intake develops a variety of symptoms and life-long medical complications. The study aims to examine the nicotine-induced effects on cellular oxidative stress and psychological stress and its correlations with homocysteine (Hcy) concentration in nicotine-addicted respondents. Methods & Results: Nicotine-induced psychological stress was assessed through perceived stress scales (PSS) and coping self-efficacy (CSE) scales and oxidative stress was estimated through the markers- Malondialdehyde (MDA), superoxide dismutase (SOD), and Catalase. We found significantly higher (p=0.0001) perceived stress (PS) with diminished CSE in addicted respondents whereas low PS with significantly increased (p=0.0001) CSE were observed in non-addicted. In erythrocytes (RBCs), MDA content was found significantly increased (p=0.0006) in the nicotine-addicted group that may cause oxidative damage. SOD activity was significantly decreased (p=0.0001) in the addicted group. Similarly, plasma Catalase activity was also decreased (p=0.02). Nicotine intake influences Hcy concentration, by 55%, 27.5%, and 7.5% in addicted respondents categorized as moderate, intermediate, and severe Hcy categories. Conclusions: The minimal short-term nicotine consumption has the antioxidant role that promotes positive stimulus on memory and triggers executive functions but the same gets impaired and mitigated on chronic exposure. Chronic nicotine consumption induces oxidative stress and perceived psychological stress as well as influences the Homocysteine concentration in the addicted individuals. Higher oxidative stress impairs cellular defensive mechanisms and causes the risk for severe damage to cells and tissues.
Diet Communication on the Early Silk Road in Ancient China: Multi-Analytical Analysis of Food Remains From the Changle Cemetery
Authors: Ren Meng , Wang Renfang , Yang Yimin
Published: January 2022

Characterization of ancient food remains could reflect how people exploited biological resources and interact with different cultures in the past. In this study, Fourier Transform Infrared Spectroscopy (FTIR), starch grain, phytolith, stable isotope analysis and proteomics were adopted to characterize the composition of the food remains including three cereal foodstuffs, some meat strips and a kebab discovered at the Changle Cemetery (202 BC-AD 220), Ningxia, China, a key area on the Silk Road. The results show that the cereal foods were baked cakes, primarily made from foxtail millet (Setaria italica). One cake was simply made of millet grains, the others were more elaborately comprised of millet flour with the addition of barley flour and meat from cattle (Bos taurus) and chicken (Gallus gallus). These findings indicate that grinding and baking technologies, which were considered as the culinary tradition in western Eurasia, had been at latest adopted by the inhabitants in the Ningxia area at that time. The large-scale migration to Ningxia and the opening of the Silk Road during the Han Dynasty gave rise to diet communication and assimilation in this border area. Moreover, the meat strips were identified as dried beef, and the kebab was likely to be made from sheep/goat meat, wherein the latter is the earliest scientific evidence of mutton kebab in ancient China up to our knowledge. The analytical strategy could be widely applied in characterizing ancient visible food remains in order to better understand their preparation methods.
“medicines Is All That I Can Sometimes Offer Them”: Challenges of Providing Primary Diabetes Care to Persons With Disabilities
Authors: Gopichandran Vijayaprasad , Thiagesan Rajeswaran , Soundari Hilaria
Published: January 2022

Background: Persons with disabilities have a higher risk for and poorer outcomes of type 2 diabetes. Primary health care providers face several challenges in providing primary diabetes care for them. This study was conducted to explore the challenges faced by primary health care providers in delivering primary diabetes services to persons with disabilities. Methods: We performed a qualitative research study by conducting in-depth interviews among 13 primary health care providers including medical officers, staff nurses, community health workers and a physiotherapist. We adopted a grounded theory approach to data collection and analysis. Results: Primary health care providers often could only prescribe medications to persons with diabetes by proxy due to poor accessibility of the facilities. They felt that these patients also had poor compliance to treatment. They felt that the lack of standard guidelines for diet and exercise for persons with disabilities prevented them from giving them appropriate advice on the same and even if they did, persons with disabilities would find it very difficult to adopt dietary changes and physical activity as they were dependent on others for even their daily activities. They also felt that they couldn’t perform annual screening tests due to lack of accessibility to higher facilities. Some primary care providers did local innovations such as formation of peer support groups, utilization of resources of other programs to reach out to persons with disabilities and innovative physical activity techniques to care for persons with disabilities. They recommended that there is a need for specific guidelines for management of diabetes among persons with disabilities, treatment of chronic diseases among persons with disabilities must be incentivized and there must be intersectoral coordination between social welfare department and health department to achieve the goal of care for persons with disabilities.Conclusions: Primary health care providers faced substantial challenges in providing primary diabetes care for persons with disabilities. There is a need for an effective public health policy to address these challenges.
Toward a long-term atmospheric CO2 inversion for elucidating natural carbon fluxes: technical notes of NISMON-CO2 v2021.1
Authors: Niwa Yosuke , Ishijima Kentaro , Ito Akihiko , Iida Yosuke
Published: January 2022

Global estimates of carbon dioxide (CO 2 ) fluxes at the earth’s surface are imperative to understanding carbon cycle mechanisms and making reliable predictions about the global warming. Furthermore, they can provide valuable science-based information for use in reducing human-induced CO 2 emissions. Inverse analysis is a prominent method for quantitatively estimating spatiotemporal variations in CO 2 fluxes; however, this technique involves a certain degree of uncertainty and requires technical refinement, especially to improve the horizontal resolution so that local fluxes can be compared with other estimates made at the regional or national level. In this study, a newly developed set of inversion schemes was incorporated into a state-of-the-art inverse analysis system named NISMON-CO 2 . The introduced schemes involve grid conversion, observational weighting, and anisotropic prior error covariance, the details of which are described in this paper. In addition, pseudo-observation experiments were performed to investigate the effect of the new schemes, as well as to assess the reliability of NISMON-CO 2 for long-term analysis with practical inhomogeneous observations. The experiment results demonstrate the utility of the grid conversion scheme for high-resolution flux estimates (1° × 1°), and significant improvements were achieved through the observational weighting and anisotropic prior error covariance. Furthermore, the estimated seasonal and interannual variations in regional CO 2 fluxes were confirmed to be reliable, although there is some possible bias in terms of global land–ocean partitioning. These results are useful for interpreting flux variations that result from inverse analysis by NISMON-CO 2 ver. 2021.1 using real observations.
Growth-Promoting Effects of Press Water from the Mechanical Drying of Douglas-Fir Wood Chips on Lignocellulolytic Fungi
Authors: Reppke Manfred J. , Gerstner Rebecca , Windeisen-Holzhauser Elisabeth , Richter Klaus , Benz J. Philipp
Published: January 2022

Background:The mechanical drying of wood chips is an innovative method that improves the heating value of sawmill by-products in an energy-efficient continuous process. The liquid that comes out of the wood chips as press water (PW), however, contains a variety of undissolved as well as dissolved organic substances. The disposal of the PW as wastewater would generate additional costs due to its high organic load, offsetting the benefits in energy costs associated with the enhanced heating value of the wood chips. Our research explored if the organic load in PW could be utilized to boost the growth of cellulolytic filamentous fungi. Hence, using the industrially relevant Ascomycete Trichoderma reesei RUT-C30 as well as several Basidiomycete wood-rotting fungi, we examined the potential of press water obtained from Douglas-fir wood chips to be used in growth and enzyme production media. Results: The addition of PW supernatant to liquid cultures of T. reesei RUT-C30 resulted in a significant enhancement of the endoglucanase and endoxylanase activities with a substantially shortened lag-phase. Supplementation with PW allowed to replace several mineral ions (Fe2+, Mn2+, Zn2+, Ca2+, Mg2+, K+) from the liquid media without negative effects on the enzymatic activities. Concentrations of PW above 50% showed no adverse effects regarding the achievable endoglucanase activity but affected the endoxylanase activity to some extent. Exploring the growth-enhancing potential of several individual PW components after chemical analysis revealed that the observed lag-phase reduction of T. reesei RUT-C30 was not caused by the dissolved sugars and ions, nor the wood solids in the PW, suggesting that other, so far non-identified, compounds are responsible. However, also the growth rate of several basidiomycetes was significantly enhanced by the supplementation of PW to the agar medium. Moreover, their cultivation in liquid cultures reduced the turbidity of the PW substantially.Conclusions: PW was identified as a suitable media supplement for lignocellulolytic fungi, including the cellulase and xylanase producer T. reesei RUT-C30 and several wood-degrading basidiomycetes. The possibility to replace several minerals, trace elements and an equal volume of fresh water in liquid media with PW and the ability of fungal mycelia to filter out the suspended solids is a promising way to combine biological wastewater treatment with value-adding biotechnological applications.
Functional Connectivity Correlates of Reduced Goal-directed Behaviors in Behavioural Variant Frontotemporal Dementia
Authors: Godefroy Valérie , Batrancourt Bénédicte , Charron Sylvain , Bouzigues Arabella , Bendetowicz David , Carle Guilhem , Rametti-Lacroux Armelle , Bombois Stéphanie , Cognat Emmanuel , Migliaccio Raffaella , Levy Richard
Published: January 2022

INTRODUCTION: We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD).METHODS: We recorded the behavior of 20 bvFTD patients and 16 healthy controls (HC) in a close-to-real-life situation including a free phase (FP – in which actions were self-initiated) and a guided phase (GP – in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP+GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of connectivity measures (local low-frequency signal power and distant seed-based functional connectivity) and explored their relationship with extracted apathy dimensions. RESULTS: Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of selfinitiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. DISCUSSION: Through a new dimensional approach of apathy, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. This contributes to better understand the role of functional networks in the production of goal-directed behaviors.
Everolimus-induced Hyperpermeability of Endothelial Cells Causes Lung Injury
Authors: Chen Xiaolin , Chen Jianhui , Liu Shuihong , Li Xianfan
Published: January 2022

Background: The mammalian target of rapamycin (mTOR) inhibitors, everolimus (but not dactolisib), is frequently associated with lung injury in clinical therapies. However, the underlying mechanisms remain unclear. Endothelial cell barrier dysfunction plays a major role in the pathogenesis of the lung injury. This study hypothesizes that everolimus increases pulmonary endothelial permeability, which leads to lung injury.Methods：We tested the effects of everolimus and dactolisib on human pulmonary microvascular endothelial cell (HPMEC) permeability by measuring transendothelial electrical resistance (TEER) and the passage of horseradish peroxidase-albumin (Pa）. F-actin remodeling visualized using immunofluorescent imaging and its related key enzymes were measured by western blotting. Then, we established a mouse model using intraperitoneal injections of everolimus and dactolisib, and the total protein in bronchoalveolar lavage fluid (BALF) and the accumulation of Evans blue dye in lungs were used to examine the lung vascular permeability. The protective effects of myosin light chain (MLC) related pathway inhibitors on everolimus-induced hyperpermeability was observed.Results: Everolimus increased HPMEC permeability, which was confirmed by decreased TEER and an increased transendothelial BSA flux, which was associated with MLC phosphorylation and F-actin stress fiber formation. In contrast, dactolisib did not have effect on the permeability of HPMECs. In addition, inhibition, or knockdown of PKCα or MLC kinase attenuated everolimus-induced hyperpermeability and MLC phosphorylation in HPMECs. Furthermore, everolimus induced an increasing concentration of intracellular calcium Ca2+ leakage in HPMECs and this was normalized with ryanodine pretreatment. Additionally, ryanodine decreased everolimus-induced phosphorylation of PKCα and MLC, and barrier disruption in HPMECs. Consistent with in vitro data, everolimus treatment caused a visible lung-vascular barrier dysfunction, including an increase in protein in BALF and lung capillary-endothelial permeability, which was significantly attenuated by pretreatment with an inhibitor of PKCα, MLCK, and ryanodine. Conclusions: This study shows that everolimus induced pulmonary endothelial hyper-permeability, at least partly, in an MLC phosphorylation-mediated EC contraction which is influenced in a Ca2+-dependent manner and can lead to lung injury.
New 1,1-diarylethylene FOXM1 inhibitors potently reduce intracellular FOXM1 and suppress high-grade serous ovarian carcinoma cell viability
Authors: Liu Cassie , Muñoz-Trujillo Catalina , Kim Sung Hoon , Katzenellenbogen John A. , Katzenellenbogen Benita S. , Karpf Adam R.
Published: January 2022

As an oncogenic transcription factor highly upregulated in numerous cancer types and responsible for promoting multiple hallmarks of the disease, Forkhead Box M1 (FOXM1) is a promising target for treatment against high-grade ovarian serous carcinoma (HGSC), a lethal and aggressive cancer that overexpresses FOXM1 and its transcriptional pathway. Several FOXM1 inhibitors have been established, but none have advanced to clinical trials. In this study, we report that our recently developed 1,1-diarylethylene FOXM1 inhibitors (NB compounds) potently and selectively inhibit HGSC cell viability, more so than a panel of other reported FOXM1 inhibitors. The NB compounds decreased FOXM1 expression through proteasomal degradation, which resulted in decreased expression of its downstream target cyclin B1 (CCNB1), without affecting other FOX family members. Moreover, the NB compounds exhibited robust anti-cancer effects by promoting apoptosis, suppressing colony formation more potently than other FOXM1 inhibitors, and synergizing with carboplatin to inhibit the viability of HGSC cells. Our data demonstrate that the NB compounds are promising FOXM1 inhibitors that may serve as a novel therapeutic strategy for HGSC and other cancers whose aggressive cancer biology is driven by FOXM1 and its oncogenic transcriptional pathway.
Normal coronary myocardial infarction due to COVID-19: A case series
Authors: Kazemi Erfan ,   Mehran Gheshlaghi1, Mansoursamaei Ali , Homatash Saba , Sheibani Hossein
Published: January 2022

Background: The prevalence of cardiovascular complications in COVID-19 infection varied in different studies. One of these complications is myocardial infarction. A disturbance of the blood supply can lead to myocardial infarction by clot formation in the arteries. However, no evidence of significant coronary stenosis has been found in more than 50% of patients with COVID-19 and ST elevation.Case Presentation: 38 and 49 years old men (patients 1,2) were admitted to our hospital with the complaint of typical chest pain and COVID-19 symptoms. The real-Time Polymerase Chain Reaction (RT-PCR) test confirmed COVID-19 in both. Patient 1 represented inferior posterior ST-Elevation Myocardial Infarction (STEMI) in his electrocardiogram (ECG). Also, patient 2 has ST-elevation in high lateral and septal leads (I, AVL, V1, V2) and ST-segment depression in AVR and inferior leads (III, AVF). Their troponin was positive. The vital signs were normal in both of them. Patient 2 just had a history of aortic valve replacement (AVR) 5 years ago. However, Patient 1 had no medical history. Transthoracic Echocardiography (TTE) data demonstrated some disturbances in patient 1 Severe hypokinesia of Inferior, Posterior, Lateral, and Septal walls. However, TTE data were unremarkable for patient 2. We prescribed recommended medications for them. Therefore, their ECG changes were corrected, and his condition improved. In addition, Coronary angiography was done that demonstrated patent and normal coronary arteries in both of them.Conclusion: COVID-19 infection can cause normal coronary arteries myocardial infarction with probable two mechanisms prolonged vasospasm or intraluminal coronary thrombogenesis.
Students’ Academic Performance Prediction Model Using Machine Learning
Authors: Sudais Muhammad , Safwan Muhammad , Khalid Maryam Aisha , Ahmed Shaheer
Published: January 2022

Providing quality education to students is the main objective of higher education institutions. The need of identifying students with weak performances has been a rising problem and most teachers have relied on calculating the average of exam grades. The main objective of our project is to predict and identify the students who might fail in semester examinations. This would prove helpful for teachers in providing additional assistance to such students. The data which was analyzed consisted of students’ transcript data that included their CGPA and grades in all courses which were taken from a university. The machine learning algorithms which were used in this research include; Naïve Bayes classifier, Neural Network, Support Vector Machine, and Decision Tree classifier. A comparative analysis has been performed on the obtained accuracy results of the algorithms used. This research shows that machine learning proves useful in predictions, but there is a lot more work to be done using this technology.
Genomic analyses identify marker molecules and processes in metastatic breast cancer tissues
Authors: Wang Xiuying , Wang Mengyao , Gu Hanming , Liu James
Published: January 2022

Breast cancer metastasis is the major reason for deaths from breast cancer. Identification of breast cancer metastasis is of great importance for the management and prediction of cancer progression. However, the key genes and signaling pathways remain unclear in metastatic breast cancers. Our objective is to find the key molecules and signaling pathways by analyzing the RNA-sequence data. The GSE189411 was constructed by the Illumina NovaSeq 6000 (Mus musculus). The KEGG and GO analyses showed the cytokine−cytokine receptor interaction and human papillomavirus infection are the two major processes during the liver metastasis of breast cancer cells. Moreover, we discovered ten key relevant molecules including ITGB2, FCGR3A, CD86, CD80, FOXP3, SYK, CCR5, VCAM1, RAC2, ICAM1. Our study may provide novel insights for the early diagnosis of breast cancer metastasis.
Learning Interpretable Diagnostic Features of Tumor by Multi-task Adversarial Training of Convolutional Networks: Improved Generalization
Authors: Graziani Mara , Otalora Sebastian , Marchand-Maillet Stéphane , Müller Henning , Andrearczyk Vincent
Published: January 2022

Adopting Convolutional Neural Networks (CNNs) in the daily routine of primary diagnosis requires not only near-perfect precision, but also a sufficient degree of generalization to data acquisition shifts and transparency. Existing CNN models act as black boxes, not ensuring to the physicians that important diagnostic features are used by the model.
Building on top of successfully existing techniques such as multi-task learning, domain adversarial training and concept-based interpretability, this paper addresses the challenge of introducing diagnostic factors in the training objectives.
Here we show that our architecture, by learning end-to-end an uncertainty-based weighting combination of multi-task and adversarial losses, is encouraged to focus on pathology features such as density and pleomorphism of nuclei, e.g. variations in size and appearance, while discarding misleading features such as staining differences.
Our results on breast lymph node tissue show significantly improved generalization in the detection of tumorous tissue, with best average AUC 0.89 (0.01) against the baseline AUC 0.86 (0.005).
By applying the interpretability technique of linearly probing intermediate representations, we also demonstrate that interpretable pathology features such as nuclei density are learned by the proposed CNN architecture, confirming the increased transparency of this model.
This result is a starting point towards building interpretable multi-task architectures that are robust to data heterogeneity.
Our code is available at https://bit.ly/356yQ2u.
Predicting the potential for zoonotic transmission and host associations for novel viruses
Authors: Pandit Pranav , Anthony Simon , Goldstein Tracey , Olival Kevin , Doyle Megan , Gardner Nicole , Bird Brian , Smith Woutrina , Wolking David , Gilardi Kristen , Monagin Corina , Kelly Terra , Uhart Marcela , Epstein Jonathan , Machalaba Catherine , Rostal Melinda , Dawson Patrick , Hagan Emily , Sullivan Ava , Li Hongying , Chmura Aleksei , Latinne Alice , Lange Christian , O'Rourke Tammie , Olson Sarah , Keatts Lucy , Mendoza A. Patricia , Perez Alberto , de Paula Catia Dejuste , Zimmerman Dawn , Valitutto Marc , LeBreton Matthew , McIver David , Islam Ariful , Duong Veasna , Mouiche Moctar , Shi Zheng-Li , Mulembakani Prime , Kumakamba Charles , Ali Mohamed , Kebede Nigatu , Tamoufe Ubald , Bel-Nono Samuel , Camara Alpha , Pamungkas Joko , Coulibaly Julien Kalpy , Abu-Basha Ehab , Kamau Joseph , Silithammavong Soubanh , Desmond James , Hughes Tom , Shiilegdamba Enkhtuvshin , Aung Ohnmar , Karmacharya Dibesh , Nziza Julius , Ndiaye Daouda , Gbakima Aiah , Sijali Zikankuba , Wacharapluesadee Supaporn , Robles Erika Alandia , Ssebide Benard , Suzán Gerardo , Aguirre Luis , Solorio Monica , Dhole Tapan , Hitchens Peta , Joly Damien , Saylors Karen , Fine Amanda , Murray Suzan , Karesh William , Daszak Peter , Mazet Jonna , Consortium PREDICT , Johnson Christine
Published: January 2022

Host-virus associations have co-evolved under ecological and evolutionary selection pressures that shape cross-species transmission and spillover to humans. Observed virus-host associations provide relevant context for newly discovered wildlife viruses to assess knowledge gaps in host range and estimate pathways for potential human infection. Using models to predict virus-host networks, we predicted the likelihood of humans as host for 513 newly discovered viruses detected by large scale wildlife surveillance at high-risk animal-human interfaces in Africa, Asia, and Latin America. Predictions indicated that novel coronaviruses are likely to infect a greater number of host species than viruses from other families. Our models further characterize novel viruses through prioritization scores and directly inform surveillance targets to identify host ranges for newly discovered viruses.
The Potential to use Variations in Tree-Ring Geometric Center to Estimate Past Wind Speed Change
Authors: Fang Keyan , He Maosheng , Bai Maowei , Dong Zhipeng , Linderholm Hans W. , Azorin-Molina Cesar , Guo Zhengtang
Published: January 2022

Tree radial growth is characterized by not only the annual ring-width increment but also shifts in the tree-ring geometric center (TRGC) if subjected to asymmetric external forcing, such as prevailing winds. Previous dendrochronological studies have used the asymmetric growth derived from tree-ring widths to reconstruct wind speed changes. Here we propose a novel method use quantitative TRGC measurements to estimate wind speed. We investigated TRGC shifts in northeast China, where the prevailing westerly winds are strong and persistent. We found that the TRGC showed significant correlations (r = 0.64, p < 0.01) with wind speed in May-September. The higher tree geometry sensitivity to wind speed obtained with the new method compared to previous ones, suggests the possibility of reconstructing historical wind change and variability in prevailing winds using TRGC. In addition, by correcting tree-ring radius according to their TRGC shifts, the basal area increment (BAI) was calculated. Our new BAI estimation provided stronger correlations with climate than both the standard tree-ring width chronology and a traditional BAI estimation. We suggest that future dendrochronological studies should consider TRGC shifts to increase the accuracy in climate reconstructions.
Compositional correlation analysis of gene expression time series
Authors: DİKBAŞ Fatih
Published: January 2022

Accurate determination of temporal dependencies among gene expression patterns is crucial in the assessment of functions of genes. The gene expression series generally show a periodic behavior with nonlinear curved patterns. This paper presents the determination of temporally associated budding yeast gene expression series by using compositional correlation method. The results show that the method is capable of determining real direct or inverse linear, nonlinear and monotonic relationships between all gene pairs. Pearson’s correlation values between some of the gene pairs have shown negative or very weak relationships (r ≈ 0) even though they were found to be strongly associated. Inversely, a high positive r value was obtained even though the genes are inversely related as determined by the compositional correlation approach. Comparisons with Pearson’s correlation, Spearman’s correlation, distance correlation and the simulated annealing genetic algorithm maximal information coefficient (SGMIC) have shown that the presented compositional correlation method detects important associations which were not found by the compared methods. Supplementary materials containing the code of the used software together with some extended figures and tables are available online.