bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum harmonic free energies for biomolecules and nanomaterials
Authors: White Alec , Li Chenghan , Chan Garnet Kin-Lic
Published: January 2022

Obtaining the free energy of large molecules from quantum mechanical energy functions is a longstanding challenge. We describe a method that allows us to estimate, at the quantum mechanical level, the harmonic contributions to the thermodynamics of molecular systems of unprecedented size, with modest cost. Using this approach, we compute the vibrational thermodynamics of a series of diamond nanocrystals, and show that the error per atom decreases with system size in the limit of large systems. We further show that we can obtain the vibrational contributions to the binding free energies of prototypical protein-ligand complexes where the exact computation is too expensive to be practical. Our work raises the possibility of routine quantum mechanical estimates of thermodynamic quantities in complex systems.
Nanometric transverse displacement metrology in range of hundreds of micrometers with polarization-encoded metasurface
Authors: Zang Haofeng , Xi Zheng , Zhang Zhiyu , Lu Yonghua , Wang Pei
Published: January 2022

A long range, high precision and compact transverse displacement metrology method is of crucial importance in many research areas. We propose and experimentally demonstrate the first prototype polarization-encoded metasurface for ultrasensitive transverse displacement metrology. The transverse displacement of the metasurface is encoded into the polarization direction of the outgoing light via the Pancharatnam-Berry phase. By measuring the output light polarization direction, the metasurface’s position can be readout directly according to the Malus law. We experimentally demonstrate nanometer displacement resolution with the uncertainty on the order of 100 pm for a large measurement range of 200 µm with the total area of the metasurface being within 900 µm x 900 µm. The measurement range can be extended further using a larger metasurface. Our work largely broadens the existing application areas of metasurface and opens new avenue of applying metasurface in the field of ultrasensitive optical transverse displacement metrology.
Evolution of Surgical Treatment of Metastatic Spine Tumors.
Authors: Sullivan Patricia Zadnik , Niu Tianyi , Abinader Jose Fernandez , Syed Sohail , Sampath Prakash , Telfeian Albert , Fridley Jared , Klinge Petra , Camara Joaquin , Oyelese Adetokunbo , Gokaslan Ziya
Published: January 2022

Purpose
The treatment of cancer has transformed over the past forty years, with medical oncologists, radiation oncologists and surgeons working together to prolong survival times and minimize treatment related morbidity. With each advancement, the risk-benefit scale has been calibrated to provide an accurate assessment of surgical hazard. The goal of this review is to look back at how the role of surgery has evolved with each new medical advance, and to explore the role of surgeons in the future of cancer care.
Methods
A literature review was conducted, highlighting the key papers guiding surgical management of spinal metastatic lesions.
Conclusion
The roles of surgery, medical therapy and radiation have evolved over the past forty years, with new advances requiring complex multidisciplinary care.
Perceived Barriers, Benefits, Facilitators, and Attitudes of Health Professionals Towards Type 2 Diabetes Management in Oujda, Morocco: A Qualitative Focus Group Study
Authors: Dankoly Usman Sani , Vissers Dirk , Mostafa Souad Ben El , Ziyyat Abderrahim , Rompaey Bart Van , Royen Paul Van , Maamri Abdellatif
Published: January 2022

Background: In Morocco, the treatment of type 2 diabetes (T2D) is mainly focused on medication and only 2% of patients are coached towards a healthier lifestyle. In Oujda, Eastern Morocco the prevalence of T2D is 10.2%, and the current trend is alarming, especially for women. Therefore, the aim of this study is to explore healthcare professionals' (HCP) views about the perceived barriers and benefits towards an integrated care approach in primary healthcare centers (PHCCs) to T2D management in Oujda.Methods: A descriptive study using focus groups in 8 PHCCs. This resulted in a sample of 5 doctors and 25 nurses caring for diabetes patients. The transcripts of all conversations were coded to allow for thematic analysis.Results: The participants mentioned different barriers to an integrated approach of DM management:: excessive workload; poor reimbursement policy; lack of staff and equipment; interrupted drug supply; poor working environment; limited referral; gap in the knowledge of general practitioners; health beliefs; poverty; advanced age; gender; the use of psychotropic drugs. An integrated approach could be facilitated by simplified electronic records and referral; uninterrupted free care; staff recruitment; continuous professional development; internships. Benefits: structured care; promotion of care in PHCCs; empowerment of self-management.Conclusion: HCP views reflect the urge to strengthen the management of T2D in PHCCs. There is a need for HCP with expertise in physical activity and nutrition to solve the current gap in the multidisciplinary integrated care approach. The specific local context can contribute to patients' reluctance to change their lifestyles and is a challenge to provide care in an efficient and sustainable manner. More research is needed to see how a patient-centered multidisciplinary approach to T2D management can help motivate patients in Morocco to change to a healthier lifestyle.
Does China’s Fertility Policy Induce Employment Discrimination Against Women? Evidence from a Nationwide Correspondence Experiment
Authors: Li Xun , Wen Dan , Ye Lin , Yu Jiang
Published: January 2022

We apply a two-wave nationwide correspondence experiment to assess the effects of the two-child and three-child policies in China. Using 13,751 observations collected through this experiment, we find that the announcement of the two-child policy led to a 4.9% decrease in total interview callbacks overall, and decreases of 4.3%, 5.7%, and 5.6% for single women, those married with no children, and those married with one child, respectively. The implementation of the three-child policy led to a 10.4% decrease, but only for married women with two children. The discrimination broadly affected all women, whether they disclose marriage and fertility status information or not, as we find their callback rates decreased by 4.5% under the universal two-child policy and 6.6% after the three-child policy.
LRRC15 suppresses SARS-CoV-2 infection and controls collagen production
Authors: Loo Lipin , Waller Matthew , Cole Alexander , Stella Alberto , Moreno Cesar , Denes Christopher , Hamoudi Zina , Chung Felicity , Aggarwal Anupriya , Low Jason , Patel Karishma , Siddiquee Rezwan , Mackay Joel , Turville Stuart , Hesselson Daniel , Neely G.
Published: January 2022

Although ACE2 is the primary receptor for SARS-CoV-2 infection, a systematic assessment of factors controlling SARS-CoV-2 host interactions has not been described. Here we used whole genome CRISPR activation to identify host factors controlling SARS-CoV-2 Spike binding. The top hit was a Toll-like receptor-related cell surface receptor called leucine-rich repeat-containing protein 15 (LRRC15). LRRC15 expression was sufficient to promote SARS-CoV-2 Spike binding where it forms a cell surface complex with LRRC15 but does not support infection. Instead, LRRC15 functioned as a negative receptor suppressing both pseudotyped and live SARS-CoV-2 infection. LRRC15 is expressed in collagen-producing lung myofibroblasts where it can sequester virus and reduce infection in trans. Mechanistically LRRC15 is regulated by TGF-β, where moderate LRRC15 expression drives collagen production but high levels suppress it, revealing a novel lung fibrosis feedback circuit. Overall, LRRC15 is a master regulator of SARS-CoV-2, suppressing infection and controlling collagen production associated with “long-haul” COVID-19.
Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis
Authors: Dang Lei , Zhang Chunbo , Su Biru , Na Ning , Huang Qiuling , Zhou Su , Wu Meng , Ma Wenqing , Wang Man , Cui Pengfei , Li Yan , Wang Shixuan
Published: January 2022

Background: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with ZSYT pills. However, the pharmacological mechanism of action of these pills remains unclear.Methods: The components of ZSYT found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of ZSYT pills. The potential targets of components were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and SwissTargetPrediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, therapeutic target database, and Genetic Association Database. The overlapping genes between the potential targets of ZSYT components and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.Results: Nineteen components in ZSYT pills were detected in the serum of POF mice after oral administration. A total of 695 ZSYT-related targets was screened, and 344 POF-related targets were collected. From the results of ZSYT-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with ZSYT pills. Moreover, the pathway enrichment results suggested that ZSYT pills treat POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.Conclusions: We demonstrated that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis are very likely to be therapeutic mechanism of ZSYT pills in treating POF. Our study suggests that combining the analysis of ZSYT pills components in blood in vivo in the POF models and network pharmacology prediction may offer a tool to characterize the mechanism of ZSYT pills in the POF.
Elimination of [PSI+] Prion and Influence on Yeast Cell Growth
Authors: Versockienė Justina , Jonutytė-Trembo Neda , Novickij Vitalij , Lastauskienė Eglė
Published: January 2022

Background

Prions are proteinaceous infectious particles that act as pathogens and cause the development of lethal neurodegenerative diseases in humans and other animals. Yeast Saccharomyces cerevisiae is a widespread model system in which mechanisms of prion induction and elimination have been identified. New and safe substances and methods are being sought to cure cells of prion proteins. It is particularly important that by treating cells from prions and restoring them from the [PSI+] to the [psi−] form, the primary growth of the cells is restored. One of the main objectives of this study was to determine the growth dynamics of S. cerevisiae cells with different [PSI+] prion variants, cells that have lost [PSI+] prion variants, and cells that never had [PSI+] prion variants.
Results

In this research, we applied GuHCl and combined GuHCl and PEF treatment against [PSI+] prion. We evaluated cells culture growth dynamics – optical density and doubling time and determined that method of [PSI+] prion elimination does not affect cell doubling time. Also, we found that both elimination methods affect the optical density reached by [psi−] cells. However, the cells in which the [PSI+] prion has been eliminated by GuHCl alone are able to reach the same optical density as unaffected [psi−] cells and higher optical density than the affected [psi−] cells by GuHCl alone.
Conclusions

These findings indicate the potential long-term positive effect of [PSI+] prion on cell growth, which persists after [PSI+] removal.
Inhibitory KIR2DL2 Receptor and HHV-8 in Classic or Endemic Kaposi Sarcoma
Authors: Bortolotti Daria , Corazza Monica , Rotola Antonella , Bencivelli Dario , Schiuma Giovanna , Danese Elisabetta , Rizzo Sabrina , Beltrami Silvia , Rizzo Roberta , Borghi Alessandro
Published: January 2022

KIR2DL2, an inhibitory Killer cell Immunoglobulin-like Receptor (KIR), has been shown to predispose to the development of several herpesvirus-associated diseases by inhibiting the efficiency of Natural Killer (NK) cells against virus-infected cells. The aim of this observational study was to assess the prevalence of KIR2DL2 and Human Herpes Virus 8 (HHV8) in patients affected with classical and endemic Kaposi sarcoma (KS), as well as in controls. Blood samples collected from 17 Caucasian, HIV-negative, immunocompetent patients affected with classical KS (c-KS), 12 African, HIV-negative patients with endemic KS (e-KS), 83 healthy subjects and 26 psoriatic patients were processed for genotypization by PCR for two KIR alleles, such as KIR2DL2 and KIR2DL3 and analyzed for HHV-8 presence. The totality of both c-KS and e-KS patients presented HHV-8 infection, whereas HHV8 was found in 26.9% of psoriatic subjects and 19.3% of healthy subjects. KIR2DL2 was found in the 76.5% of c-KS subjects, while the receptor was found in 41.7% of the e-KS group, 34.6% of psoriatic patients and 43.4% of healthy controls (p<0.0001). A significantly higher prevalence of KIR2DL2 in c-KS patients than in all the other subjects was also confirmed comparing age-matched groups. Based on these results, the inhibitory KIR2DL2 genotype appears to be a possible cofactor which increases the risk of developing c-KS in HHV8-positive, immunocompetent subjects, while it seems less relevant in e-KS pathogenesis.
Feature Extraction from MRI ADC Images for Brain Tumor Classification Using Machine Learning Techniques
Authors: Vijithananda Sahan M. , Jayatilake Mohan L. , Hewavithana Badra , Gonçalves Teresa , Rato Luis M. , Weerakoon Bimali S. , Kalupahana Tharindu D. , Silva Anil D. , Dissanayake Karuna D.
Published: January 2022

Background: Diffusion-weighted (DW) imaging is a well-recognized magnetic resonance imaging (MRI) technique that is being routinely used in brain examinations in modern clinical radiology practices. This study focuses on extracting demographic and texture features from MRI Apparent Diffusion Coefficient (ADC) images of human brain tumors, identifying the distribution patterns of each feature and applying Machine Learning (ML) techniques to differentiate malignant from benign brain tumors.Methods: This prospective study was carried out using 1599 labeled MRI brain ADC image slices, 995 malignant, 604 benign from 195 patients who were radiologically diagnosed and histopathologically confirmed as brain tumor patients.The demographics, mean pixel values, skewness, kurtosis, features of Grey Level Co-occurrence Matrix (GLCM), mean, variance, energy, entropy, contrast, homogeneity, correlation, prominence and shade, were extracted from MRI ADC images of each patient.At the feature selection phase, the validity of the extracted features were measured using ANOVA f-test. Then, these features were used as input to several Machine Learning classification algorithms and the respective models were assessed.Results: According to the results of ANOVA f-test feature selection process, two attributes: skewness (3.34) and GLCM homogeneity (3.45) scored the lowest ANOVA f-test scores. Therefore both features were excluded in continuation of the experiment. From the different tested ML algorithms, the Random Forest classifier was chosen to build the final ML model since it presented the highest accuracy. The final model was able to predict malignant and benign neoplasms with an 90.41% accuracy after the hyper parameter tuning process.Conclusion: This study concludes that the above mentioned features (except skewness and GLCM homogeneity) are informative to identify and differentiate malignant from benign brain tumors. Moreover, they enable the development of a high-performance ML model that has the ability to assist in the decision-making steps of brain tumor diagnosis process, prior to attempting invasive diagnostic procedures such as brain biopsies.
Identifying Long-range Synaptic Inputs Using Genetically Encoded Labels and Volume Electron Microscopy
Authors: Ayuso-Jimeno Irene P. , Ronchi Paolo , Wang Tianzi , Gallori Catherine , Gross Cornelius T.
Published: January 2022

Enzymes that facilitate the local deposition of electron dense reaction products have been widely used as labels in electron microscopy (EM). Peroxidases, in particular, can efficiently metabolize 3,3′-diaminobenzidine tetrahydrochloride hydrate (DAB) to produce precipitates with high contrast under EM following heavy metal staining, and can be genetically encoded to facilitate the labeling of specific cell-types or organelles. Nevertheless, the peroxidase/DAB method has so far not been reported to work in combination with 3D volume EM techniques (e.g. Serial blockface electron microscopy, SBEM; Focused ion beam electron microscopy, FIBSEM) because the surfactant treatment needed for efficient reagent penetration disrupts tissue ultrastructure and because these methods require the deposition of large amounts of heavy metals that can obscure DAB precipitates. However, a recently described peroxidase with enhanced enzymatic activity (dAPEX2) appears to successfully deposit EM-visible DAB products in thick tissue without surfactant treatment. Here we demonstrate that multiplexed dAPEX2/DAB tagging is compatible with both FIBSEM and SBEM volume EM approaches and use them to map long-range genetically identified synaptic inputs from the anterior cingulate cortex to the periaqueductal gray in the mouse brain.
Tailoring Pullulanase PulAR from Anoxybacillus sp. AR-29 for Enhanced Catalytic Performance by A Structure-Guided Consensus Approach
Authors: Li Shu-Fang , Xu Shen-Yuan , Wang Ya-Jun , Zheng Yu-Guo
Published: January 2022

Pullulanase is a well-known debranching enzyme that can specially hydrolyze α-1,6-glycosidic linkages in starch and oligosaccharides, however, it suffers from low stability and catalytic efficiency under industrial conditions. In the present study, four sites (A365, V401, H499, and T504) lining the catalytic pocket of Anoxybacillus sp. AR-29 pullulanase PulAR were selected for site-directed mutagenesis (SDM) by using a structure-guided consensus approach. Four beneficial mutants (PulAR-A365V, PulAR-V401C, PulAR-A365/V401C, PulAR-A365V/V401C/T504V, and PulAR-A365V/V401C/T504V/H499A) were created, which showed enhanced thermostability, pH stability, and catalytic efficiency. Among them, the quadruple mutant PulAR-A365V/V401C/T504V/H499A displayed 6.6- and 9.6-fold higher catalytic efficiency toward pullulan at 60 ℃, pH 5.0 and 6.0, respectively. In addition, its thermostabilities at 60 ℃ and 65 ℃ were improved by 2.6- and 3.1-fold, respectively, compared to those of the wild-type (WT). Meanwhile, its pH stabilities at pH 4.5 and 5.0 were 1.6- and 1.8-fold higher than those of WT, respectively. In summary, the catalytic performance of PulAR was significantly enhanced via rational engineering by a structure-guided consensus approach. The resultant quadruple mutant PulAR-A365V/V401C/T504V/H499A demonstrated potential applications in the starch industry.
Young Nursing and Medical Students’ Knowledge and Attitudes Toward Contraceptive Methods
Authors: Juan-Pablo Scarano-Pereira , Alessandro Martinino , Manicone Francesca , Cristina Álvarez-García , Lucía Ortega-Donaire , María-Zoraida Clavijo-Chamorro , M López- Medina Isabel , Carmen Álvarez-Nieto , Sebastián Sanz-Martos
Published: January 2022

Background: Living sexuality fully and without risk to one's health is an international priority. The youth age group has specific characteristics that make it a particularly vulnerable group for adverse consequences such as unwanted pregnancies or sexually transmitted infections. Health professionals are an important group to address this issue; however, to achieve a good result, sufficient knowledge is required to solve all the issues. This study aimed to assess the level of knowledge of young university students studying toward a nursing or medical degree.Methods: A descriptive cross-sectional study of young medical and nursing students was conducted. The Sexuality and Contraceptive Knowledge Instrument scale was used to measure knowledge level. A bivariate analysis was conducted using the Mann–Whitney U test or the Kruskal–Wallis H test, depending on the number of categories of the independent variable. Finally, a multivariate analysis was conducted using a multiple linear regression model, establishing the level of knowledge as the dependent variable and all variables that obtained statistical significance in the bivariate analysis as predictors.Results: Participants had a good level of knowledge, with 77.9% answering 50% of the questions correctly. Before training, 34.15% of the participants did not pass 50% of the questions asked. This percentage decreased to 12.87% after receiving sexuality training during the university degrees. The main training gaps were found for the items on hormonal contraceptive methods. The bivariate analysis showed that female participants had significantly higher knowledge scores, as did those who had used a hormonal contraceptive method during the most recent intercourse or were aware of family planning centers. These variables maintained their significant effect at the multivariate level, obtaining two models with good explanatory power for participants of both university degrees. Conclusion: The general level of knowledge of the healthcare students was high and sufficient after receiving training during the university degree. The main training gap was found for items on hormonal contraceptive methods, which should be emphasized in future training programs.
Molecular Characterization and Transmission Study of the Begomovirus on Hollyhock Plant Causing Leaf Curl Disease for the First Time in Province Punjab, Pakistan
Authors: Azeem Hajra , Perveen Rashida , Tahir Muhammad Nouman , Umar Ummad-ud-din , Ölmez Fatih , Ali Amjad
Published: January 2022

I. Background: Hollyhock (Alcea rosea) is an ornamental plant belonging to the Malvaceae family and has a remarkable aesthetic and medicinal value. Previously in Pakistan, the hollyhock plant was not found to be infected by begomovirus and the plant first time showed the symptoms of typical leaf curling, puckering as well as thickened veins. II. Methods and Results: During the year 2018, symptomatic samples of the hollyhock plants were collected that exhibited characteristic typical leaf curling, puckering as well as thickened veins. DNA was extracted from the samples and the PCR technique was optimized for the detection of begomovirus followed by sequencing. The samples were detected to be infected with begomovirus by using Av/Ac core, Begomo 01/02, and CLCV 01/02 primer showed positive results with 579bp, 2.8kb, and 1.1kb nucleotide respectively. The betasatellite was amplified by using beta01/02 and CLCuMuBF11/R33 showed positive results with 1400bp and 481bp respectively. Sequencing results showed that diseased hollyhock plants were associated with Cotton leaf curl Multan virus-Rajasthan strain along with Cotton leaf curl Multan betasatellite. III. Conclusion: Hollyhock plants infected by begomovirus has been reported for the first time as a possible source of virus inoculum from Pakistan.
Comparative Study of the Effect of Solvents on the Efficacy of Neonicotinoid Insecticides Against Malaria Vector Populations Across Africa
Authors: Tchouakui Magellan , Assatse Tatiane , Mugenzi Leon M. J. , Menze Benjamin D. , Nguiffo-Nguete Daniel , Tchapga Williams , Kayondo Jonathan , Watsenga Francis , Manzambi Emile Zola , Osae Michael , Wondji Charles S.
Published: January 2022

Background New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO. Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations. In this study, we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.MethodsMosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon (Njombe-Penja, Nkolondom, and Mangoum), the Democratic Republic of Congo (Ndjili-Brasserie), Ghana (Obuasi), and Uganda (Mayuge). Using the CDC bottle test, we compared the effect of three different solvents (ethanol, acetone, MERO) on the efficacy of neonicotinoids against Anopheles gambiae s.l. In addition, TaqMan assays were used to genotype key pyrethroid-resistant markers in An. gambiae and to evaluate potential cross-resistance between pyrethroids and clothianidin.ResultsLower mortality were observed when using absolute ethanol or acetone alone as solvent (11.4- 51.9% mortality in Nkolondom, 31.7- 48.2% in Mangoum, 34.6- 56.1% in Mayµge, 39.4- 45.6% in Obuasi, 83.7- 89.3% in Congo and 71.05- 95.9% in Njombe pendja) compared to acetone + MERO for which 100% mortality were observed for all the populations. Synergist assays (PBO, DEM and DEF) revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility. A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors (OR=0.5; P=0.02). However, the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes (OR=2.10; P=0.013). ConclusionsThis study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting to lower mortality, thus possibly overestimating resistance, whereas the MERO consistently showed a greater efficacy of neonicotinoids but it could prevent to detect early resistance development. Therefore, we recommend monitoring the susceptibility using both acetone alone and acetone+MERO (8-10µg/ml for clothianidin) to capture the accurate resistance profile of the mosquito populations.
Effects of the Pathological E200K Mutation on Human Prion Protein: A Computational screening and Molecular Dynamic approach
Authors: Gharemirshamloo Fatemeh Rahimi , Majumder Ranabir , Bamdad Kourosh , Frootan Fateme , Un Cemal
Published: January 2022

The Human Prion protein gene (PRNP) is mapped to short arm of chromosome 20 (20pter-12). Prion disease is associated with mutations in the Prion Protein encoding gene sequence. The mutations that occur in the prion protein could be divided into two types based on their influence on pathogenic potential: 1. Mutations that cause disease. 2. Disease-resistance mutations. Earlier studies found that the mutation G127V in the PRNP increases protein stability, whereas the mutation E200K, which has the highest mutation rate in the Prion protein, causes Creutzfeldt–Jakob disease (CJD) in humans and induces protein aggregation. We used a variety of bioinformatic algorithms, including SIFT, PolyPhen, I-Mutant, PhD-SNP, and SNP&GO, to predict the association of the E200K mutation with Prion disease. MD simulation is performed and graphs for RMSD, RMSF, Rg, DSSP, PCA, porcupine and FEL are generated to confirm and prove the stability of the wild type and mutant protein structures. The protein is analyzed for aggregation, and the results indicates more fluctuations in the protein structure during the simulation by the E200K mutation, however the G127V mutation makes protein structure stable against aggregation during the simulation.
Integrating crop redistribution and improved managements could meet China’s food demand with lower environmental costs
Authors: Wang Zihan , Yin Yulong , Wang Yingcheng , Tian Xingshuai , Ying Hao , Zhang Qingsong , Xue Yanfang , Zhou Feng , Du Mingxi , Ma Lin , Zhang Fusuo , Cui Zhenling
Published: January 2022

Sustainably feeding the growing population in China attracts attention globally. Despite practices success, producing enough food to simultaneously address resource and pollution problems has been infeasible. To assess how to achieve this goal in 2035, we created a pathway that synergistic combining improved managements and cropland redistribution based on 11.1 million farmer surveys and 4,272 georeferenced field observations. Here, we firstly selected the practices of top 10% performers in crop yield and nitrogen (N) efficiency as crop-specific attainable improved managements at the county level. The optimized crop distribution within improved managements was then performed to minimize inputs (N and phosphorus fertilizer, irrigation water) or environmental impacts (reactive N [Nr] loss and greenhouse gas [GHG] emissions). We identified that combing improved managements and cropland redistribution could produce enough food demands in 2035, with 24% more production compared to 2012. It also reduced the inputs and environmental impacts in a range of 19%-35%, mainly sourced from the central and eastern coastal areas by improved productivity and diminished cropland of fruit and vegetables. These findings highlight the necessity for a synergistic combination of measures to sustainably feed the growing population and establish a more realistic and effective policy.
Advanced Glycation End-products Are Associated With Limited Range of Motion of the Shoulder Joint Following Rotator Cuff Tears
Authors: Shinohara Issei , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Yamaura Kohei , Mukohara Shintaro , Yoshikawa Tomoya , Kato Tatsuo , Furukawa Takahiro , Hoshino Yuichi , Matsushita Takehiko , Kuroda Ryosuke
Published: January 2022

Background: Most degenerative rotator cuff tears (RCTs) are associated with a limited range of motion (ROM) of the shoulder joint. Additionally, patients with diabetes mellitus (DM) show a higher frequency of limited ROM. Recently, advanced glycation end products (AGEs) of proteins have been observed to cause tissue fibrosis, primarily through abnormal collagen cross-linking and oxidative stress. In this study, we investigated the effect of AGEs on ROM limitation in the shoulder capsule and its relationship with DM.Methods: 16 patients (8 each in the DM and non-DM groups) who underwent arthroscopic surgery for RCT with limited shoulder ROM were included in this study. AGE-related pathologies in both groups were compared, and the relationship between AGE accumulation and shoulder joint ROM was evaluated. Shoulder capsule tissue was harvested and subjected to histological and in vitro evaluation. Results: The DM group displayed high levels of AGEs and reactive oxygen species (ROS), and reduced cell viability. There was a significant positive correlation between ROS expression, apoptosis, and preoperative hemoglobin A1c. ROS expression, apoptosis, and ROM of the shoulder joint showed a negative correlation. The NADPH oxidase (NOX) expression and collagen III/I ratio were significantly higher in the DM group than in the non-DM group.Conclusions: The DM group showed significant AGE deposition in the shoulder capsule. Additionally, there was a significant association between AGEs and ROM limitation. The oxidative stress induced by AGE deposition, which leads to fibrosis and local inflammation, might contribute to the limited ROM of the shoulder joint.
Impact of Wetland Development and Degradation on the Livelihoods of Wetland-Dependent Communities: A Case Study from the Lower Gangetic Floodplains
Authors: Adhya Tiasa , Banerjee Sayan
Published: January 2022

Wetland ecosystem services exceed those provided by terrestrial ecosystems and their ‘wise use’ has implications for achieving sustainable development goals. Yet we have lost almost 87% of wetlands since pre-industrial times with losses projected to be much higher by 2050 in developing economies, particularly in Asia. Little is known about how this loss impacts people’s dependency at local scales in human-dominated landscapes. We identified 18 ecosystem services of Dankuni wetlands located in the Lower Gangetic Floodplains by analysing oral testimonies of wetland-dependent villagers. The ecosystem services include 12 provisioning services and two each of regulatory, cultural and supporting services. Farming and use of wetland products including molluscs, fuelwood, fodder, fibre and fish was found to subsidize living costs and provide diverse livelihood options to local residents. Encroachment of wetlands by factories and blockage of its riverine connection was reportedly degrading the wetland’s quality and eroding its ecosystem services since the last 20 years and especially since the last three years. In years of excessive and unseasonal rainfall such as during the study year, post-monsoon farming was severely impacted. We portray the human costs of wetland development which will affect vulnerable sections the most, especially landless widows and older residents. Respondents believed that it was possible to rejuvenate the wetland by restoring its riverine connections but stressed that local politicians had vested interests in supporting its degradation. We strongly assert the need to increase government accountability for protection of wetlands amidst a determined pursuit of development at the cost of sustainability.
Probabilistic Cooperative Coded Forwarding for Broadcast Transmissions in Industrial Mobile Edge Communications
Authors: Huang Wenjun , Li Xu , Liang Yanan
Published: January 2022

Mobile edge computing (MEC) has been considered as a key enabler for the industrial internet of things (IIoT) to cope with the ever-increasing communication and computing demands of nodes. In consideration of the limited power and resource of the IIoT nodes, it is necessary to design cost-effective data sharing mechanisms for MEC-enabled wireless industrial communication networks. In this article, we propose the probabilistic cooperative coded forwarding (PCCF) scheme based on network coding (NC) to minimize the required transmission number in both the data source and relay nodes. The data packets are encoded sparsely in a systematic coding framework so that the decoding process at the receivers can be more efficient. The relationship between the forwarding and coding parameters of the proposed scheme and the successful decoding probability are comprehensively analyzed and the approximations are numerically verified. Throughout the analysis, we find the optimal sparsity of network coding vectors and also the existence of minimum transmission numbers.
Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant
Authors: Sato Kei , Suzuki Rigel , Yamasoba Daichi , Kimura Izumi , Wang Lei , Kishimoto Mai , Ito Jumpei , Morioka Yuhei , Nao Naganori , Nasser Hesham , Uriu Keiya , Kosugi Yusuke , Tsuda Masumi , Orba Yasuko , Sasaki Michihito , Shimizu Ryo , Kawabata Ryoko , Yoshimatsu Kumiko , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , Sawa Hirofumi , Ikeda Terumasa , Irie Takashi , Matsuno Keita , Tanaka Shinya , Fukuhara Takasuke
Published: January 2022

The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, is the most urgent concern in the global health in December 2021. Our statistical modelling estimates that Omicron is >3.0-fold and >5.6-fold more transmissible than Delta in South Africa and the UK, respectively. Intriguingly, cell culture experiments show that Omicron is less fusogenic than Delta and ancestral SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into the two subunits, which facilitates cell-cell fusion, Omicron S is faintly cleaved. Further, in hamster model, Omicron shows decreased lung infectivity and is less pathogenic compared to Delta and ancestral SARS-CoV-2. Our data suggest that the efficacy of SARS-CoV-2 S cleavage and viral fusogenicity are closely associated with viral pathogenicity, and Omicron evolved to exhibit increased transmissibility and attenuated pathogenicity.
Regulation of NSCLC Cell Proliferation By MARCH7 Via the NF-κB and Wnt/β-Catenin Signaling Pathways
Authors: Lu Xiaomi , Shao Lili , Qian Ye , Zhong Sixun , Chen Jinhong , Yan Aiting , Zhuang Zhixiang , Zhang Yan
Published: January 2022

The aim of the study was to explore the role of the E3 ubiquitin ligase MARCH7 in the development of non-small-cell lung cancer (NSCLC) and to explore the underlying molecular mechanism.Western blot and immunohistochemistry results showed that the expression of MARCH7 in NSCLC cancer tissues was higher than that in paracancerous tissues. Tissue microarray staining results and clinicopathological parameters of NSCLC patients revealed that MARCH7 expression was closely related to TNM stage, degree of tumor differentiation and lymph node metastasis of NSCLC patients. Furthermore, univariate and multivariate analyses and survival curve analysis showed that high expression of MARCH7 was associated with poor prognosis.In vitro, siRNA was constructed and transfected into A549 cells to inhibit the expression of MARCH7. The CCK-8 assay indicated that the growth rate of tumor cells in the interference group was reduced. The number of colonies and cells in the interference group decreased in the plate clone formation experiment. Flow cytometry showed that G0/G1 phase cells were predominantly increased after blocking endogenous MARCH7 expression, and G0/G1 phase arrest occurred in A549 cells. The reporter gene activity of the NF-κB signaling pathway and Wnt/β-catenin signaling pathway was reduced, as validated by a double luciferase reporter gene assay. Western blot analysis showed that the expression of NF-κB P50, NF-κB P65 and β-catenin was decreased, while the expression of E-cadherin was elevated.In vivo, MARCH7-overexpressing virus was constructed and transfected into A549 cells and then subcutaneously injected into nude mice. It was demonstrated that the tumor volume was significantly larger in the MARCH7 overexpression group than in the control nude mice during the same period. Elevated expression of PCNA and Ki-67 was observed in the tumor mass of the MARCH7 overexpression group, as measured by immunohistochemical analysis, accompanied by enhanced levels of NF-κB P50, NF-κB P65 and β-catenin, as detected by Western blot. These results provide a new idea for the experimental basis for the treatment of NSCLC in the future.
The Impact of Mixed-use Development, Small Businesses, and Walkability on Carbon Emissions in Cool Climate Cities
Authors: Zagow Maged
Published: January 2022

United States (US) cities of cool climate zone such as Chicago and Boston are witnessing a reduction in carbon emissions potentially due to focusing on public transportation, and alternative energy resources. It's difficult to validate or deny optimal practices and regulations due to a lack of reliable data on carbon emissions and urban comparative studies amongst metropolitan areas. Therefore, we have examined at the relationship between land use, walkability, socioeconomics variables and carbon dioxide emissions at the zip code level. The current study compares the carbon footprints of four metro regions in cool climatic zone 5 with a model of all US zip code, to generate a benchmarking predictive model for climate change across all US zip codes. Our research shows that increasing number of businesses within walkable distance in cool climate reduces CO2 emissions. This signifies that enhancing walkability in cities and remodeling of retail, art, entertainment, and recreation facilities in accordance with urban sustainability policies can greatly cut down CO2 emissions.
Comparative Genomics Revealed Genus Specific Encoding of Amino Acids by Tri-Nucleotide SSRs in Human Pathogenic Streptococcus and Staphylococus Bacteria
Authors: Mahfooz Sahil , Narayan Jitendra , Ahmed Ruba Mustafa Elsaid , Hag Amel Bakri Mohammed El , Mohammed Nuha Abdel Rahman Khalil , Kausar Mohd Adnan
Published: January 2022

Pathogenic bacteria use phase variation of surface molecules and other characteristics as a significant adaptation mechanism. Repetitive sequences made up of numerous identical repeat units can be found in many phase variable genes. Here, we investigated the frequency and distribution of long-SSRs in 15 human pathogenic Staphylococcus, Streptococcus, and Enterococcus bacteria. Long-SSRs were found to be distributed differently in the genic and intergenic sequences. In the genic sequences, 61.3 SSRs were discovered on average, while 16.2 SSRs were found in the intergenic regions. Staphylococci exhibited the highest frequency of SSRs, followed by Enterococcus, and Streptococci had the lowest frequency of SSRs. Higher A+T content was found to be the best predictor of long-SSR in these human pathogens. Tetranucleotide repeats predominated in intergenic regions, while trinucleotide repeats predominated in genic regions. In human pathogenic Streptococcus and Staphylococcus bacteria, genus-specific encoding of amino acids by tri-nucleotide SSRs was observed. A genetic relationship between these human pathogenic bacteria was derived based on the presence of SSRs in the housekeeping genes and compared to the phylogeny generated based on the 16S ribosomal RNA gene.
Indigenous Knowledge On Medicinal Plants Practiced At Myagdi District, Nepal
Authors: Poudel Anit
Published: January 2022

Indigenous knowledge on medicinal plants and practices is outdistancing and vulnerable to loss if not properly documented. A survey on medicinal plants and their practices was carried in the Myagdi district. Around 40 tribal people from four different villages were interviewed using a semi-structured questionnaire. Documentation of the indigenous knowledge was done in written form and the pictures of available medicinal plants were taken. The study showed that 93.51% of the respondent has used medicinal plants and 87.20% found them effective in curing several diseases and injuries. They are commonly used to cure diseases like bone fractures, abdominal pain, fever, common cold, dysentery, eye opacity, scabies, worm infection, reproductive problems, mental disorder, and cardiovascular problems. As reported, with access to modern pharmaceuticals, the use of medicinal plants has been less practiced these days. The knowledge on medicinal plants and practices are restricted to older-aged groups of the community (76.32%) reflecting that valuable indigenous knowledge is on the wane. This study portrays the commonly used medicinal plants along with their preparation techniques practiced in the study area.
DNA Methylation and Transcriptomic Features are Preserved Throughout Disease Recurrence and Chemoresistance in High Grade Serous Ovarian Cancers
Authors: Gull Nicole , Jones Michell , Peng Pei-Chen , Coetzee Simon , Silva Tiago , Plummer Jasmine , Reyes Alberto , Davis Brian , Chen Stephanie , Lawrenson Kate , Lester Jenny , Walsh Christine , Rimel Bobbie , Li Andrew , Cass Ilana , Berg Yonatan , Govindavari John Paul , Rutgers Joanna , Berman Benjamin , Karlan Beth , Gayther Simon
Published: January 2022

Background

Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations.
Results

Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P=0.006) in these BRCA1/2 carriers.
Conclusions

These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.
Identification of biomarkers related to metabolically unhealthy obesity in Korean obese adolescents: A cross-sectional study
Authors: Jeong Sarang , Jang Han Byul , Kim Hyo-Jin , Lee Hye-Ja
Published: January 2022

BackgroundObesity is classified as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO). The current study aimed to screen for relationships and different potential metabolic biomarkers involved between MHO and MUO in adolescents.MethodsThe study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences (AbsoluteIDQ™ p180 kit) between adolescents in the MHO group and those in the MUO group. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS in adolescents.ResultsThere were significant differences in the 3 acylcarnitines, 5 amino acids, glutamine/glutamate ratio, 3 biogenic amines, and 2 glycerophospholipids between the obese adolescents in the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO in adolescents. Additionally, several metabolites were inversely correlated with MHO in adolescents of the MUO group.ConclusionsWe observed that histidine, lysine, PCaaC34:1, and several clinical factors in adolescents of the MUO group were reverse correlated with the results in adolescents of the MHO group. In addition, the triglyceride-glucose index was related to MUO in adolescents, compared with the homeostasis model assessment of insulin resistance. Thus, the biomarkers found in this study have a potential to reflect the clinical outcomes of MUO in adolescents. These biomarkers will lead to a better understanding of MetS in obese adolescents.