cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Integrating network pharmacology with molecular docking for elucidation of molecular biological mechanisms of Jiedu Qingjin formula for non-small cell lung cancer
Creators: name: Xu, Bowen
name: Dan, Wenchao
name: Wu, Jingyuan
name: Wang, Xinmiao
name: Qin, Xiaoyan
name: Han, Yingying
name: Song, Xiaotong
name: Zhang, Xiaoxiao
name: Li, Jie
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Computational Biology

description: Traditional Chinese medicine is an important part of complementary alternative medicine. Jiedu Qingjin formula (JDQJF) is an effective national invention patent for the treatment of non-small cell lung cancer (NSCLC). We investigated the molecular biological mechanisms based on network pharmacology, molecular docking, and molecular dynamics simulations. Compounds of JDQJF were screened through the TCMSP, ETCM, and literature. Targets were searched by DrugBank and predicted by SwissTargetPrediction. GEO database was applied for screening differentially expressed genes between cancerous tissues and healthy tissues of NSCLC. Subsequently, the protein-protein interaction between JDQJF and NSCLC were obtained by Cytoscape. Visual analyses were carried out to extract candidate genes, then subjected to Metascape for enrichment analyses. Finally, molecular docking was performed by AutoDock, and the best complexes were subjected to molecular dynamics simulation and binding energy calculations by MMPBSA. A total of 273 compounds, 390 targets, 3146 GO terms, and 174 KEGG pathways were obtained. Five potential compounds (quercetin, adenosine, apigenin, heptadecanoic acid, and luteolin) were notably modulated by key targets AKT1, MAPK3, and RAF1. Enrichment results included cell cycle process, growth transduction factor, immune response-activating transduction, and involved PI3K/AKT, MAPK, NF-κB and VEGF pathway. RAF1-quercetin showed the highest binding affinity (-9.1 kcal/mol), revealed stable interactions during the simulation, and the highest estimated relative binding energy of the RAF1-Heptadecanoic was −184.277 kcal/mol. This study suggested that EMT-related, inflammation-related, immune-related, and angiogenesis-related pathways may be associated with JDQJF, and involved in the advancement of NSCLC, which points out the research direction for subsequent utility mechanism validation. Communicated by Ramaswamy H. Sarma
supplemental_material – Supplemental material for Hyperinsulinemia contributes to impaired-glucose-tolerance-induced renal injury via mir-7977/SIRT3 signaling
Creators: name: Gao, Zhongai
name: Wang, Ziyan
name: Zhu, Hong
name: Yuan, Xinxin
name: Sun, Mengdi
name: Wang, Jingyu
name: Zuo, Minxia
name: Cui, Xiao
name: Han, Ying
name: Zhang, Yi
name: Yang, Shaohua
name: Qin, Yongzhang
name: Xu, Jie
name: Yang, Juhong
name: Chang, Baocheng
Publisher: name: SAGE Journals
Year: 2020
Subjects: subject: Cardiology
subject: Endocrinology
subject: Geriatrics and Gerontology
subject: Neurology and Neuromuscular Diseases
subject: FOS: Clinical medicine
subject: Aged Health Care
subject: Pharmacology and Pharmaceutical Sciences not elsewhere classified
subject: Psychology not elsewhere classified
subject: Psychiatry (incl. Psychotherapy)
subject: Respiratory Diseases

description: Supplemental material, supplemental_material for Hyperinsulinemia contributes to impaired-glucose-tolerance-induced renal injury via mir-7977/SIRT3 signaling by Zhongai Gao, Ziyan Wang, Hong Zhu, Xinxin Yuan, Mengdi Sun, Jingyu Wang, Minxia Zuo, Xiao Cui, Ying Han, Yi Zhang, Shaohua Yang, Yongzhang Qin, Jie Xu, Juhong Yang and Baocheng Chang in Therapeutic Advances in Chronic Disease
Feed Substitution for adopting mitigation measures to reduce N2O Emission in Irish Dairy and Cattle Farming
Creators: name: Francisco-Cruz, Carlos Alberto
name: Buckley, Dr. Cathal
name: Breen, Dr. James
Publisher: name: Unknown
Year: 2024
Subjects: subject: Demand and Price Analysis
subject: Environmental Economics and Policy
subject: Feed substitution
subject: Price and Cross-Price Elasticity
subject: Mitigation Measures
subject: N2O Emissions

description: This paper aims to estimate the capacity to substitute concentrate feed for home-produced feed by adopting two specific mitigation strategies to reduce Nitrous Oxide (N2O) emissions in the agriculture sector: (i) Low Emissions Slurry Spreading (LESS) and (ii) applying protected urea instead of CAN fertiliser. A translog cost function is estimated to obtain the price and cross-price elasticities of demand for concentrate and home-produced feed. To achieve our aim, we use the Teagasc National Farm Survey (NFS) from 2014 to 2021, which contains detailed information on agricultural activity. Furthermore, farms are categorised into four groups based on their environmental characteristics to show how environmental conditions influence farmers' decision-making processes. Our results show a marginal change in the purchase of concentrates due to adopting the two mitigation measures analysed, which is reflected in an increase in cross-price elasticity. However, these results are conditioned to the biophysical conditions of the farm soils.
Therapeutic potential of dietary phytochemicals from Drynaria quercifolia to modulate gut microbiome: an in silico approach
Creators: name: Ragavan, Mangala Lakshmi
name: Srinivasan, Hemalatha
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Inorganic Chemistry
subject: FOS: Chemical sciences

description: Drynaria quercifolia is one of the pioneer medicinal plants which exert many beneficial effects on humans. Fatty acids are hydrophobic ligands that act as membrane substrates, metabolic signalling molecules, and metabolic energy sources. It could enhance the mucus production in the intestine which maintain mucosal homeostasis. The inflammatory responses were also regulated by 5-HT receptors. Serotonin 2 A receptors are G-protein coupled receptors targeted by various types of ligands viz. antidepressants, antipsychotics and anti-migraine drugs. The interaction of mucin protein and fatty acid could increase the antimicrobial activity and anti-inflammatory activity of gut microbiome. In this study, dietary phytochemicals were extracted from D. quercifolia and characterized using GC-MS analysis. The result shows presence of 38 various compounds viz. decanoic acid, indole, and dodecanoic acid and etc., Among the all, dodecanoic acid showed good drug likeness and pharmaceutical properties. Target proteins viz. 3IFB (Intestinal fatty acid binding protein) and 7WC4 (5-hydroxytryptamine receptor 2 A) were docked with dodecanoic acid using Auto dock software. The fatty acids produced in the gut could interact with 3IFB and 7WC4 proteins to maintain intestinal integrity and improved gut-brain function respectively. Dodecanoic acid exhibits the highest binding energy with mutated 3IFB (-6.01) than native whereas 7WC4 native protein showed (-7.3 kal/mol) the highest affinity than mutated protein. Structural changes were predicted by using SOPMA and ProSA. Evaluation results indicate that 3IFB was having more stability, good quality, and enhanced affinity than 7WC4. Further, MD simulations were done for 3IFB to check the stability of protein-ligand complex using WebGro platform. The model was investigated by root mean square deviation and fluctuations. Therefore, dodecanoic acids have been considered as a potential agonists and offer opportunities for developing innovative medications for gastrointestinal diseases. Communicated by Ramaswamy H. Sarma
Additional file 1 of Racial differences in length of stay and readmission for asthma in the all of us research program
Creators: name: Correa-Agudelo, Esteban
name: Gautam, Yadu
name: Mendy, Angelico
name: Mersha, Tesfaye B.
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Science Policy

description: Additional file 1: Table S1. STROBE Statement—checklist of items that should be included in reports of observational studies. Table S2. ICD-9/ICD-10 billing codes used to search asthma and comorbidities diagnoses. Table S3. Univariate expected length of stay (LOS) and readmission within 30-days showing median and 95% credible intervals for associations between asthma hospitalizations and significant risk factors (demographics, individual- comorbidities, temporal and place-based). Table S4. Validation performance summary in expected length of stay (LOS) and readmission. We compare ELPD using a Leave-one-group-out (LOGO) scheme in two statistical models (null and adjusted set of covariates). Figure S1. Trace rank plots for chains distribution in the multivariate asthma LOS and readmission models. Intertwined chain lines for intercept parameter mean MCMC chains are exploring parameter space efficiently. A Asthma LOS; B Asthma readmission within 30-days. Figure S2. Pareto smoothed importance sampling (PSIS) for multivariate asthma LOS and readmission models: A Asthma LOS model exhibited about of 21.1% of subject-specific observations over-optimistic inference; B Asthma readmission within 30-days showed about of 6.1% of subject-specific observations over-optimistic inference.
title: Availability and use of medical devices for primary reproductive health care: technological capabilities for cervical cancer screening in Kenya.
Creators: name: Arun, Richard
Publisher: name: The Open University
Year: 2024

description: LMICs face increasing burden of NCDs, requiring primary prevention, screening and early detection. Cervical cancer (CC) is a major Kenyan public health concern. Medical devices (MDs) are key to health systems’ performance, yet there is limited research literature on their availability, especially for primary and preventive services.


This thesis answers the question: To what extent is poor cervical cancer screening (CCS) service performance attributable to availability and utilization of MDs, and how can CCS performance limitations be improved at facility level?


An explanatory sequential mixed methods design included a Phase I quantitative health facilities survey on availability of MDs and readiness indicators for CC prevention. A qualitative Phase II investigated utilization of MDs and internal working processes for provision of CCS services. Analysis was guided by the dynamic capabilities theoretical framework, to understand inter-facility performance variations.


Survey findings showed high levels of readiness to provide CCS services in the public sector, including availability of most essential MDs, but specific tests and consumables were less available and reported screening numbers showed low and variable performance. Readiness, MDs availability and reported screening numbers were all lower in the civil and private sectors.


Qualitative research confirmed low actual public sector CCS services provision despite potential demand in the form of family planning visits. CCS numbers were mainly driven by referrals and sporadic outreaches. Facilities had failed to sense and seize opportunities to increase CCS services, with none purposively transforming working processes towards a “prevention culture”.


Revision of service availability indicators can improve facility-level information on readiness and ‘actual do.’ Prioritisation of cancer prevention requires a shift of working culture in healthcare through organisational culture change at facility level. The dynamic capabilities framework offers a complementary perspective for health system research to better understand how to promote preventive services at health facility level.
Supplemental Material, Appendix_A_-_Data_Sharing_Survey - Cancer Patient Perspectives on Sharing of Medical Records and Mobile Device Data for Research Purposes
Creators: name: Franklin, Elizabeth F
name: Nichols, Helen M
name: House, Linda
name: Buzaglo, Joanne
name: Thiboldeaux, Kim
Publisher: name: SAGE Journals
Year: 2020
Subjects: subject: 111708 Health and Community Services
subject: FOS: Health sciences
subject: Medicine

description: Supplemental Material, Appendix_A_-_Data_Sharing_Survey for Cancer Patient Perspectives on Sharing of Medical Records and Mobile Device Data for Research Purposes by Elizabeth F Franklin, Helen M Nichols, Linda House, Joanne Buzaglo and Kim Thiboldeaux in Journal of Patient Experience
Assessing the inhibitory potential of anti-dengue compounds against Japanese encephalitis virus RNA dependent RNA polymerase: an in silico study
Creators: name: Bajrai, Leena H.
name: Alandijany, Thamir A.
name: Alsaady, Isra
name: El-Daly, Mai M.
name: Tolah, Ahmed M.
name: Khateb, Aiah M.
name: Dubey, Amit
name: Dwivedi, Vivek Dhar
name: Azhar, Esam I.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Neuroscience
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Japanese encephalitis (JE), a neurological infection of severe nature, is caused by the Japanese encephalitis virus (JEV) and is transmitted by the mosquito vector. The polymerase domain of Non-structural 5 (NS5), which is also referred to as RdRp (RNA-dependent RNA polymerase), is considered a potential therapeutic target for JEV. The present study employed molecular dynamics modelling and high-throughput virtual screening to evaluate the possible antiviral activity of anti-dengue drugs against JEV RdRp. Furthermore, a ranking was performed utilising the MM/GBSA analysis to identify the three most promising compounds. Compound ID 57409246 exhibited the highest binding affinity with the protein, as evidenced by its minimum binding free energy of −72.96 kcal/mole. In contrast, the other two compounds had minimum binding free energies of −67.57 and −59.19 kcal/mole, respectively. Upon conducting a 100 nanosecond molecular dynamics simulation to confirm the binding of the chemical complexes, it was observed that the three hits, namely 57409246, 70683874, and 44577154, exhibited a consistent and stable RMSD. Subsequently, the binding strength of the trajectory was confirmed through MM/GBSA analysis. The compounds 70683874 and 57409246 exhibited the lowest binding free energies, which were −97.58 kcal/mol and −96.38 kcal/mol, respectively. The binding free energy (ΔG Bind) values for the native ligand ATP and molecule 44577154 were −65.64 kcal/mol and −69.44 kcal/mol, respectively. Overall, compared to the native ligand ATP, all three compounds exhibited higher binding affinity. The study proposes three anti-dengue molecules as a potential remedy for JE, which can be confirmed through in vitro and in vivo investigations. Communicated by Ramaswamy H. Sarma
Additional file 1 of Longitudinal associations of movement behaviours with body composition and physical fitness from 4 to 9 years of age: structural equation and mediation analysis with compositional data
Creators: name: Migueles, Jairo H.
name: Delisle Nyström, Christine
name: Dumuid, Dorothea
name: Leppänen, Marja H.
name: Henriksson, Pontus
name: Löf, Marie
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: Sociology
subject: FOS: Sociology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health
subject: Cardiology

description: Additional file 1: Table S1. Covariance matrices for the daily time-use in movement behaviours. Table S2. Comparison of baseline demographic characteristics (4 years old) of children included and not included in this study. Fig. S1. Ternary plots for the daily time-use in the movement behaviours at 4 years old in the included children (A) and the dropouts (B). The crosshair marks represent the geometric mean of the awake time behaviours at 4 years old in the (A) included children (i.e., VPA: 10 min/day, MPA: 55 min/day, LPA: 348 min/day, SB: 512 min/day, Sleep: 515 min/day) and (B) 9 years old (i.e., VPA: 8.4 min/day, MPA: 51 min/day, LPA: 272 min/day, SB: 562 min/day, Sleep: 645 min/day). Concentric rings represent the 25, 50 and 75% confidence regions. The difference in the time-use composition of VPA, MPA, LPA, SB, and sleep is not significantly different between the included children and the dropouts (P = 0.628). Fig. S2. Lagged associations of the 24-h movement behaviour composition with body composition and concurrent relationships at 9 years old (n = 196). The model is adjusted for sex and age at baseline and follow up, group allocation, maternal education, and energy intake at baseline and follow up. Gray lines indicate shared covariance. Only statistically significant paths (P < 0.05) are shown. Model fit indices: CFI: 0.99, RMSA: 0.05, SRMR: 0.025. Data presented are standardized coefficients (standard error). Fig. S3. Lagged associations of the 24-h movement behaviour composition with physical fitness and concurrent relationships at 9 years old (n = 196). The model is adjusted for sex and age at baseline and follow up, group allocation, maternal education, and energy intake at baseline and follow up. Gray lines indicate shared covariance. Only statistically significant paths (P < 0.05) are shown. Model fit indices: CFI: 0.99, RMSA: 0.05, SRMR: 0.025. Data presented are standardized coefficients (standard error).
Identification of additional mechanistically important residues in the multidrug transporter styMdtM of Salmonella Typhi
Creators: name: Shaheen, Aqsa
name: Tariq, Anam
name: Ismat, Fouzia
name: Naveed, Hammad
name: De Zorzi, Rita
name: Iqbal, Mazhar
name: Storici, Paola
name: Mirza, Osman
name: Walz, Thomas
name: Rahman, Moazur
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Pharmacology
subject: Evolutionary Biology
subject: Environmental Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified

description: Multidrug efflux is a well-established mechanism of drug resistance in bacterial pathogens like Salmonella Typhi. styMdtM (locus name; STY4874) is a multidrug efflux transporter of the major facilitator superfamily expressed in S. Typhi. Functional assays identified several residues important for its transport activity. Here, we used an AlphaFold model to identify additional residues for analysis by mutagenesis. Mutation of peripheral residue Cys185 had no effect on the structure or function of the transporter. However, substitution of channel-lining residues Tyr29 and Tyr231 completely abolished transport function. Finally, mutation of Gln294, which faces peripheral helices of the transporter, resulted in the loss of transport of some substrates. Crystallization studies yielded diffraction data for the wild-type protein at 4.5 Å resolution and allowed the unit cell parameters to be established as a = b = 64.3 Å, c = 245.4 Å, α = β = γ = 90°, in space group P4. Our studies represent a further stepping stone towards a mechanistic understanding of the clinically important multidrug transporter styMdtM. Communicated by Ramaswamy H. Sarma
Assessing cytotoxic activities, theoretical and in silico molecular docking calculations of phthalocyanines bearing cinnamyloxy-groups
Creators: name: Özten, Özge
name: Kuznetsov, Aleksey E.
name: Gokce, Mustafa
name: Erkan, Sultan
name: Bulut, Emrah
name: Taskin, Omer Suat
name: Kurt, Belma Zengin
name: Yıldız, Mustafa Zahid
name: Sobotta, Lukasz
name: Güzel, Emre
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biochemistry
Medicine
Neuroscience
Pharmacology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Cancer

description: Cancer has been recognized as one of the deadliest diseases in the world in recent years. By chemically tailoring specific properties, anticancer agents can be prepared very effectively for the treatment of various cancer types. In this manner, as anticancer agents, a series of soluble metal-free and metallophthalocyanines carrying cinnamyloxy-groups at peripheral β-positions have been prepared. All synthesized phthalocyanines were characterized by various spectroscopic approaches such as ultraviolet − visible (UV − Vis), Fourier transform infrared (FT-IR), and matrix-assisted laser deionization/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) techniques. These compounds are highly soluble in dimethyl sulfoxide (DMSO) and soluble in common organic solvents. The spectroscopic properties, cytotoxicity, and theoretical calculations of these complexes have been investigated. In cytotoxicity tests, compounds 1, 4, and 7 are the most active against HT-29 cell lines with IC50 values of 36.9 μM, 32.5 μM, and 51.1 μM, respectively. Also, the most and the least cytotoxic compounds against healthy CCD cell line is compounds 5 and 6 with the IC50 value of 13.4 μM and >250 μM, respectively. The PDB ID:4BQG target protein representing the HT-29 cancer cell line and the anti-cancer activities of phthalonitrile and its phthalocyanines were supported by molecular docking studies. Density Functional Theory (DFT) study supported the experimental results, including the spectral data, and implied that the compounds 5-7 are comparable by their characteristics, such as electronic properties, optical properties, electrostatic potentials, reactivity parameters, with the earlier studied compounds 2-4, which were successfully proved to be good candidates for cancer treatment. Communicated by Ramaswamy H. Sarma
Additional file 1 of ProfhEX: AI-based platform for small molecules liability profiling
Creators: name: Lunghini, Filippo
name: Fava, Anna
name: Pisapia, Vincenzo
name: Sacco, Francesco
name: Iaconis, Daniela
name: Beccari, Andrea Rosario
Publisher: name: figshare
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Science Policy

description: Additional file 1: Table S1. Detailed statistics on the selected 46 targets, listing their Uniprot ID, the number of unique molecules, the average pK value (range in brackets), pK standard deviation and for which liabilities the target is relevant for. Table S2. Detailed performance of generated models. The Pearson correlation coefficient (R), the R2 determination coefficient and the Root Mean Squared Error (RMSE), are reported for each type of validation: validation set (external), fivefold cross validation (CV), bootstrap and y-scrambling. Figure S1. PCA loadings plot. Figure S2. PCA explained variance plot. Figure S3. Extended version of Fig. 4-a. Pairwise comparison of the 46 datasets pACTIVTY distributions computed by Kolmogorov–Smirnov statistical test. The color scale has been normalized between 0 and 1: higher values (red) indicate that the given datasets pair show significantly different distributions, as opposite to values closer to 0 (blue). Figure S4. Extended version of Fig. 4-b. Pairwise average Tanimoto similarity among the compounds of the given datasets pair. The color scale has been normalized between 0 and 1: higher values (red) indicate that the given datasets pair show higher chemical similarity, as opposite to values closer to 0 (blue). Table S3. Dataset size, IC50/Ki measurements correlation and performance comparison between Combined, IC50-only and Ki-only models. Figure S5. Plot of R2 performances of Table S3. Figure S6. External validation performance in terms of R2 (a) and RMSE (b) according to different train/test splitting strategies. Stratified bar (grey) is referred to R2ext in table S2. Table S4. ProfhEX benchmarking against already published models. Figure S7. Comparison of ProfhEX performances (in terms of cross-validated RMSE) against the models published in the work Cortes-Ciriano [76]. Figure S8. Comparison of ProfhEX performances (in terms of cross-validated ROC AUC) against the models published in the works of Yao et al. [77] and Mayr et al. [31]. Figure S9. Comparison of ProfhEX performances (in terms of balanced accuracy) against the blind dataset selected from Bosc et al. [35]. Figure S10. Enrichment factor performance on the CDDI database. Plots a) and b) depict the enrichment factor and AUC based on liability group scores; whereas c) and d) depict the enrichment factor and AUC for the individual targets. EF has been computed at 1, 5, 10% cutoffs. Table S5. List of 536 pre-registered, registered and withdrawn drugs taken from Cortellis Drug Discovery Intelligence database.
Novel pyrrolone-fused benzosuberene MK2 inhibitors: synthesis, pharmacophore modelling, molecular docking, and anti-cancer efficacy evaluation in HNSCC cells
Creators: name: Yamini
name: Anand, Prince
name: Bhardwaj, Vijay Kumar
name: Kumar, Ashish
name: Purohit, Rituraj
name: Das, Pralay
name: Padwad, Yogendra
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Head and neck Squamous Cell Carcinoma (HNSCC) is a growing concern worldwide and MAPKAPK2/MK2 (Mitogen-Activated Protein Kinase Activated Protein Kinase 2) is crucially involved in HNSCC progression. Increased disease burden and lacuna of targeted therapies require novel and safe pharmacological inhibitors to suppress the well-explored molecular targets in HNSCC. Here, we used dibromo-substituted benzosuberene synthesized from the mixture of α, β, γ-himachalenes and utilized as a precursor for the synthesis of Pyrrolone-fused benzosuberenes (PfBS) as MK2 inhibitors through aminocarbonylation approach in a single-pot reaction. The devised protocol provides a broad substrate scope, facile recovery, recyclability of Polystyrene-supported palladium (Pd@PS) nanoparticle catalyst, and fewer synthesis steps. In-silico molecular docking, pharmacophore modeling, and ADMET revealed MK2-inhibitory potential and drug-likeliness of PfBS analogues. Surface plasmon resonance (SPR) analysis revealed effective high binding affinity (KD) and kinetics of PfBS analogues with MK2. Additionally, the SPR-mediated in-solution inhibition assay established the MK2-inhibition properties of PfBS analogues through abrogation of MK2-Hsp27 interaction. Further, in-vitro studies validate the findings in HNSCC cells. PfBS analogues exhibited significant anti-proliferative effects on CAL 27 tongue squamous carcinoma cells and were found safe on IEC-6 intestinal epithelial cells. Moreover, immunofluorescence analysis and western-blot assays potentiated, that selected analogues inhibited the inflammatory cytokine TNF-α induced activation of MK2 on cellular and molecular levels in HNSCC cells. In conclusion, this study presents novel MK2-inhibitors and opens the avenue for further pre-clinical and clinical efficacy evaluation of developed PfBS analogues in the treatment of HNSCC. Communicated by Ramaswamy H. Sarma
Appendix5 - Supplemental material for Mid-term results of a stemless ceramic on polyethylene shoulder prosthesis – A prospective multicentre study
Creators: name: RW Jordan
name: CP Kelly
name: G Pap
name: T Joudet
name: RW Nyffeler
name: F Reuther
name: U Irlenbusch
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 110314 Orthopaedics
subject: FOS: Clinical medicine
subject: 110604 Sports Medicine
subject: FOS: Health sciences
subject: 110323 Surgery

description: Supplemental material, Appendix5 for Mid-term results of a stemless ceramic on polyethylene shoulder prosthesis – A prospective multicentre study by RW Jordan, CP Kelly, G Pap, T Joudet, RW Nyffeler, F Reuther and U Irlenbusch in Shoulder & Elbow
Additional file 1 of Needs for mobile and internet-based psychological intervention in patients with self-injury and suicide-related behaviors: a qualitative systematic review
Creators: name: Luo, Meiqi
name: Yue, Yuchuan
name: Du, Na
name: Xiao, Yu
name: Chen, Chunyan
name: Huan, Zongsu
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health

description: Additional file 1. The original search strategy for this study.
Supplemental material for Preferential centrality – A new measure unifying urban activity, attraction and accessibility
Creators: name: Hellervik, Alexander
name: Nilsson, Leonard
name: Andersson, Claes
name: Behnisch, Martin
name: Hecht, Robert
name: Herold, Hendrik
name: Jiang, Bin
Publisher: name: SAGE Journals
Year: 2019
Subjects: Geography
Urban and Regional Planning not elsewhere classified

description: Supplemental Material for Preferential centrality – A new measure unifying urban activity, attraction and accessibility by Alexander Hellervik, Leonard Nilsson and Claes Andersson in EPB: Urban Analytics and City Science
Supplement_6_example_indiv_use – Supplemental material for A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis
Creators: name: Winckel, Ann Van De
name: Gauthier, Lynne
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 110308 Geriatrics and Gerontology
subject: FOS: Clinical medicine
subject: 110904 Neurology and Neuromuscular Diseases
subject: Neuroscience

description: Supplemental material, Supplement_6_example_indiv_use for A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis by Ann Van de Winckel and Lynne Gauthier in Neurorehabilitation and Neural Repair
Unraveling the mechanisms of Cefoxitin resistance in methicillin-resistant Staphylococcus aureus (MRSA): structural and molecular simulation-based insights
Creators: name: Alshabrmi, Fahad M
name: Alatawi, Eid A.
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: Evolutionary Biology
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: Methicillin-resistant Staphylococcus aureus (MRSA) severely affects human health, including the skin glands, nasal cavity, wound infections, bone infections, and pneumonia. Among the most effective MRSA drugs, Cefoxitin also develops resistance due to mutations in the mecA gene. Four mutations at positions E229K, E239R, G246K, and E447K are classified as high-level resistance mutations. However, the resistance mechanism of MRSA towards Cefoxitin caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Cefoxitin. Therefore, our present study was designed to explore the mechanisms of binding interactions between wild-type and mutated PBP2a against Cefoxitin using molecular docking and MD simulations. Subsequently, we identified that the mutant form of PBP2a affects the activity of Cefoxitin. Interestingly, the binding of Cefoxitin with G246K and E239R mutants demonstrates unstable behavior compared to E447K-Cefoxitin and E229K-Cefoxitin. In this study, we propose the resistance mechanism of Cefoxitin at the atomic level. The proposed drug-resistance mechanism will provide valuable guidance for the design of MRSA drugs. This research might provide a new framework for designing new agents against the mutated form of PBP2a. Communicated by Ramaswamy H. Sarma
Additional file 2 of Needs for mobile and internet-based psychological intervention in patients with self-injury and suicide-related behaviors: a qualitative systematic review
Creators: name: Luo, Meiqi
name: Yue, Yuchuan
name: Du, Na
name: Xiao, Yu
name: Chen, Chunyan
name: Huan, Zongsu
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health

description: Additional file 2. The findings, illustrations and credibility assessment of the 16 included articles.
Supplement_8_DIF_and_local_dependency – Supplemental material for A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis
Creators: name: Winckel, Ann Van De
name: Gauthier, Lynne
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 110308 Geriatrics and Gerontology
subject: FOS: Clinical medicine
subject: 110904 Neurology and Neuromuscular Diseases
subject: Neuroscience

description: Supplemental material, Supplement_8_DIF_and_local_dependency for A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis by Ann Van de Winckel and Lynne Gauthier in Neurorehabilitation and Neural Repair
Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives
Creators: name: Akkoc, Senem
name: Sahin, Dicle
name: Muhammed, Muhammed Tilahun
name: Yıldız, Mustafa
name: Ilhan, Ilhan Ozer
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer

description: Cancer is a global public health problem that affects millions each year. Novel anticancer drug candidates are in need to treat various cancers and to overcome the resistance that exists against drugs in use. Benzimidazole derivatives have been reported as anticancer agents. These lead us to synthesize similar benzimidazole derivatives and investigate their anticancer activity. In this study, six new 1,3-dihydro-2H-benzimidazol-2-one-based molecules (2a-f) were synthesized. The structures of these molecules were verified by spectroscopic methods. The antiproliferative activities of molecules 2a-f were screened against a panel of human cancer cell lines, including the liver, colon, lung, and breast. The molecules were also tested towards normal human lung cell line to determine their selectivity. The results demonstrated that compound 2d had the highest cytotoxic effect compared to compounds 2a-c, 2e, and 2f against DLD-1 and MDA-MB-231 cell lines. The binding potential of the relatively active compound, 2d, with three targets was investigated through molecular docking. The stability of target-compound complexes procured from the docking was explored through molecular dynamics (MD) simulation. The docking and MD simulation studies revealed that compound 2d had the highest potential to bind to GALR3 among the targets. Furthermore, the computational pharmacokinetic study demonstrated that the synthesized compounds had drug-like properties. Communicated by Ramaswamy H. Sarma
E-cigarette vaping, chemical composition and lung toxicity
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Electronic cigarettes (e-cigarettes) have gained incredible popularity in the US and world market. Since its first introduction in US commerce in the mid 2000s, sales in the e-cigarette industry increased to $3.5 billion in 2015. The study of the health effects of these products is complicated by the fact there are hundreds (and perhaps thousands) of e-cigarette devices and thousands of e-liquids (liquids used in the e-cigarette devices) available to consumers. New e-cigarettes, such as third generation devices or open-tank systems, have increased the functionality for consumers by allowing any e-liquid to be added to the device and offering variable power settings, which can increase the temperature of the device, as well as the output of aerosol and delivery of nicotine. While third generation e-cigarette devices have gained popularity over prior device generations, it is not well understood how varying device settings and e-liquid formulations may influence chemical exposure and respiratory health effects in comparison to smoking conventional tobacco cigarettes. The purpose of this research is to advance the understanding of the hazardous chemical profile of e-cigarette “smoke” (defined here as a mixture of vapor and aerosol particles) and the implications for respiratory health effects. This research will assess how e-cigarette device and e-liquid (liquid used in e-cigarette devices) parameters influence e-cigarette smoke chemistry, specifically the production of hazardous thermal degradation products and particle size distribution. Inhalation toxicology studies will evaluate how differences in e-cigarette vapor/aerosol characteristics under varying e-cigarette device and e-liquid parameters influence effects in the respiratory tract, which will provide a better understanding of the mechanisms by which e-cigarette smoke may impact the respiratory system in comparison to conventional cigarette smoke.
Additional file 3 of Needs for mobile and internet-based psychological intervention in patients with self-injury and suicide-related behaviors: a qualitative systematic review
Creators: name: Luo, Meiqi
name: Yue, Yuchuan
name: Du, Na
name: Xiao, Yu
name: Chen, Chunyan
name: Huan, Zongsu
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health

description: Additional file 3. One of the themes of qualitative synthesis: Needs in the perception link.
Remediation of Tobacco Toxicants Polluting Low-Income Multiunit Housing
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Tobacco smoke residue is known to pollute homes long after smoking has ceased. Stale tobacco odor is a recognized problem for residents moving into homes formerly occupied by smokers, as well as for landlords and realtors. Tobacco residue, also called thirdhand smoke, contains toxic chemicals and carcinogens. This is expected as tobacco smoke is known to contain many toxic compounds. A concern for many affected people is “How can this tobacco residue be removed or reduced? How risky is this residue?” This research will directly address these questions. We will investigate whether a commercial cleaning can reduce toxic chemicals related to tobacco smoke residue in house dust samples from low income homes. We will measure these samples before and after cleaning. We choose to focus on house dust samples as children are known to be at risk from toxicants in contaminated house dust, and well established methods exist for determining exposure and risks to children. Due to their hand-to-mouth behaviors and short stature, children ingest much more house dust than adults. In addition, resuspension of dust near the floor results in breathing in dust, and an increase in skin contact coupled with a thinner skin relative to adults can lead to significant skin exposures. Therefore, tobacco residue exposures through house dust can pose a risk to children. In terms of cleaning up tobacco residue, little is available to guide cleaning methods and remediation efforts, and no standards exist to help decide if clean-up has been achieved. Indeed, some of the methods described on the internet, such as using ozone generators to remove odors, likely result in secondary formation of toxic products. This study will provide information on the levels of toxic components of thirdhand smoke and the effectiveness of commercially available deep cleaning procedures on reducing thirdhand smoke residue in real home settings. We have already collected these samples from low income homes in San Diego County. We will measure a wide range of toxic chemicals in the dust and calculate risks to children from contaminated house dust both before and after the cleaning was performed. We hypothesize that levels of these pollutants in dust and on surfaces were reduced through the cleaning protocols and that risks to children will be measurably reduced.
Determining a role for long noncoding RNAs in smoke-induced COPD
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Chronic obstructive pulmonary disease (COPD) is a debilitating inflammatory lung disease associated with tobacco smoking and the third leading cause of death worldwide. COPD is made up of a number of clinical features including airway inflammation (chronic bronchitis) in addition to destruction of lung tissue (emphysema). The processes involved in leading to these clinical manifestations are poorly understood. We know that inflammation associated with cigarette smoke (CS) is a contributing factor, however little is known about what drives the chronic inflammation observed in COPD. Current treatments fail to inhibit this chronic inflammation activated by CS exposure. Thus, there is a desperate need for new avenues of investigation aimed at identifying novel regulators of smoke-induced inflammation. We are interested in studying RNA genes and determining their role in controlling inflammation. From RNA-sequencing studies we now know that less than 3% of the human genome codes for protein, yet over 85% is actively transcribed. Why so much RNA is produced and whether it is all biologically relevant remains a fundamental unsolved problem. Long noncoding RNAs (lncRNAs), defined as transcripts greater than 200 nucleotides that do not encode proteins, represent the largest group of genes transcribed from the genome. LncRNAs have emerged as key regulators of biological processes and we have discovered the first case of a lncRNA that functions to regulate inflammation in critical immune cells called macrophages. Specifically, we identified lincRNA-Cox2, as one of the top genes turned on following inflammation, which functions to regulate critical genes within inflammatory pathways. The aim of our research is to better understand the basic mechanisms involved in controlling inflammation within chronic obstructive pulmonary disease. This project is a pilot study to test our hypothesis that lncRNAs function within the immune system to control inflammation. We are taking two approaches to test our hypothesis; one is a high throughput approach to study all lncRNAs and identify those involved in controlling inflammation and the second is a focused approach to study lincRNA-Cox2 in animal models to determine if it is involved in COPD disease progression. Completing this project will accelerate our long-term goal of identifying new targets for therapeutic intervention for COPD.
Additional file 4 of Needs for mobile and internet-based psychological intervention in patients with self-injury and suicide-related behaviors: a qualitative systematic review
Creators: name: Luo, Meiqi
name: Yue, Yuchuan
name: Du, Na
name: Xiao, Yu
name: Chen, Chunyan
name: Huan, Zongsu
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health

description: Additional file 4. One of the themes of qualitative synthesis:Balance safety needs.
Regulation of Endothelial Inflammatory Responses by GPCRs
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Smoking has been well established to affect the ability of blood vessels to function correctly. This creates a sustained disease state throughout the body called vascular inflammation and causes cardiovascular disease. Cardiovascular disease is the leading cause of death in the United States, and impacts over 61 million Americas each year. A properly functioning blood vessel cell has many tightly regulated proteins sending signals to turn on or off other proteins controlling different functions of the cell. Smoking has been shown to disrupt this cell signaling. This proposal examines one such pathway. However, to understand how this is affected by smoking, first, the mechanisms by which this cell signals in healthy conditions must be examined. The goal of this proposal is to understand how activation of a receptor in the blood vessels, specifically the protease-activated receptor-1 (PAR1), leads to vascular inflammation. We have previously shown the protein, p38 MAPK is activated by PAR1 and it is well established p38 MAPK is an important mediator of inflammation. Yet, how PAR1 signals via p38 MAPK to promote vascular pro-inflammatory responses remains poorly understood. The specific objective of this proposal is to elucidate the mechanisms by which p38 MAPK signaling induced by activated PAR1 promotes vascular inflammation. The proposed studies will determine if PAR1 activation of p38 functions through two proteins, MAPKAPK2 (MK2) and heat shock protein 27 (HSP27) to promote inflammatory responses. Both MK2 and HSP27 are shown to be turned on by p38 MAPK and have been shown to influence vascular inflammation. In preliminary studies, I found that both MK2 and HSP27 are turned on through a p38-dependent pathway following stimulation of PAR1 in endothelial (blood vessel specific) cells. The focus of the proposed studies will be to determine how PAR1 stimulated of MK2 and HSP27 regulate vascular inflammation by using both cell and animal models to assess this question. The contribution of this work is expected to be significant and will provide new information regarding a novel signaling pathway in blood vessels that modulates vascular inflammation and new strategies for targeted-drug development to control vascular inflammation. This includes, drug targets for the treatment of smoking-induced disruption of blood vessel signaling pathways mitigating the deleterious effects of sustained vascular inflammation on blood vessel function.