bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-produced aging-associated oncometabolite, methylmalonic acid, promotes cancer-associated fibroblast activation to drive metastatic progression
Authors: Li Zhongchi , Low Vivien , Luga Valbona , Sun Janet , Earlie Ethan , Parang Bobak , Ganesh Kripa Shobana , Cho Sungyun , Endress Jennifer , Schild Tanya , Hu Menying , Lyden David , Jin Wenbing , Guo Chun-Jun , Dephoure Noah , Cantley Lewis , Laughney Ashley , Blenis John 
Published: May 2022

Abstract
The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) that fosters cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite that is also produced by aggressive cancer cells, activates fibroblasts in the TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways in CAFs. EV-associated IL-6 functions as a stroma-tumor messenger that activates the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promote an epithelial-to-mesenchymal transition (EMT) and drug resistance in vitro, and metastatic progression in vivo. Our findings reveal the role of MMA in the activation of CAFs to drive metastatic reprogramming, unveiling multiple potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.
Model-based Surveillance System Design under Practical Constraints with Application to White Nose Syndrome
Authors: Oh Gina , Aravamuthan Srikanth , Ma Ting Fung , Reyes Juan Francisco Mandujano , Ballmann Anne , Hefley Trevor , McGahan Ian , Russell Robin , Walsh Dan , Zhu Jun 
Published: May 2022

Abstract
Infectious diseases are powerful ecological forces structuring ecosystems, causing devastating economic impacts and disrupting society. Successful disease prevention and control require not only awareness of the current disease situation, but also the ability to understand disease dynamics, all of which rely on collection of data at strategically chosen locations during surveillance seasons. In particular, knowledge about the location of the disease front is foundational for deploying disease counter measures to prevent further disease spread and focusing control efforts to reduce disease intensity in affected areas. In this paper, we develop a model-based approach to designing sampling strategies for wildlife disease surveillance at the disease front. Specifically, we use a mechanistic spatio-temporal model based on an underlying partial differential equation to track the disease dynamics and predict the disease prevalence in the future surveillance season. We also devise an optimal surveillance system design at the disease front that takes into account practical constraints of sampling. We evaluate the effectiveness of our proposed design via a simulation study and demonstrate the application of the proposed approach by designing a surveillance strategy for white-nose syndrome in the contiguous US.
Identification of biomarkers for prognosis and immunotherapy in clear cell renal cell carcinoma
Authors: Yu Zuhu , Lu Bin , Gao Hong 
Published: May 2022

Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the dominating subtype of renal cancer with high malignancy and poor prognosis.Objective: To identify novel potential biomarkers for the prognosis and immunotherapy of ccRCC patients.Methods: We screened out differentially expressed genes (DEGs) between ccRCC tissues and adjacent normal tissues with 4 microarray series from GEO database and took function analysis of DEGs with GO and KEGG pathway. We constructed PPI network and identified target genes with prognostic value in ccRCC, performed immunological correlation analysis of the candidate genes to seek potential biomarkers of immunotherapy.Results: In total, 382 DEGs were screened out and 11 genes were found to be associated with prognoses of ccRCC patients. Down-regulation of PCK1, HMGCS2, and up-regulation of RRM2 were significantly correlated with poorer prognoses both in overall survival and disease-free survival in ccRCC. Further immunological correlation analysis showed RRM2 expression was correlated with immune infiltration and immunological checkpoint in ccRCC.Conclusions: We identified PCK1, HMGCS2 and RRM2 as potential markers for the prognosis of ccRCC patients with bioinformatic analyses. RRM2 may plays an important role in the oncogenicity of ccRCC and maybe a potential target for immunotherapy of ccRCC patients.
Capacity development for the Bangladesh Delta Plan from the perspective of delta professionals: A qualitative study
Authors: Kabir Ashraful , Syed Abu , Zevenbergen Chris , Ferdous Jannatul , Pathirana Assela 
Published: May 2022

Abstract
Many deltaic regions around the world are exploring or adopting planning initiatives to address the complex challenges associated with future economic development and climate change. A key feature is their adaptive nature, also coined as adaptive delta management (ADM). ADM refers to the development of strategies and measures that allow us to adapt to change over a long time. The Government of Bangladesh has recently approved the Bangladesh Delta Plan 2100 (BDP2100) – a long-term adaptive strategy for sustainable water resources management. This study aims to explore the future capacity requirements from the perspective of water/delta professionals for implementing BDP2100. This calls for structural and institutional changes, and new skills and competencies to address the specific organisational and individual needs for effective delivery. A capacity development programme as an integral part of BDP2100 is currently under development. Adopting a qualitative approach, 16 key informant interviews were conducted with experts and professionals from the water and water-related sectors in Bangladesh. A thematic analysis approach was used to analyse the data. The participants reflected that an integrated and adaptive system is critical for sustainable delta management; collaboration and coordination between water/delta professionals (e.g., policy planners, consultants, and academics) and delta expert stakeholders with deep local familiarity (e.g., communities, activists, and civil society members) were deemed essential. In addition, a powerful independent institutional body is recommended to provide stewardship and leadership in the implementation process.
Thin-film nanocomposite forward osmosis membrane for water desalination: synthesis, characterization and performance improvement
Authors: Konsowa A. H. , AbdAllah H. Z. , Nosier Shaaban , Eloffy M. G. 
Published: May 2022

Abstract
The major scope of this study is the fabrication and development of a substrate and polyamide rejection layer for an efficient thin-film hydrophilic composite forward osmosis (TFC-FO) membrane. Fabrication of a thin-film nanocomposite forward osmosis membrane employing interfacial polymerization and modification of substrate characteristics using titanium dioxide (TiO2) nanoparticles as additives (TFNC-FO) are studied. Characterizations of the prepared TFC-FO and TFNC-FO membranes were determined. The morphologies of cross-section, upper and bottom surfaces for the TFC-FO and TFNC-FO membranes were studied using scanning electron microscopy (SEM). Energy-dispersive X-ray (EDX) spectroscopy was used to examine the compositions of different elements for both membranes. The hydrophilicity of the prepared TFC-FO and TFNC-FO membranes was investigated using the measurement of the contact angle test. A Fourier Transform Infrared (FT-IR) spectrophotometer was used to observe the existing functional groups of the TFC-FO and TFNC-FO membranes. The thermal stability of the membrane was evaluated via thermogravimetric analysis (TGA). The overall performance of TFC-FO membranes was evaluated with and without adding TiO2 nanoparticles through different parameters, such as membrane flux, initial feed concentration, draw solution concentrations, reverse solute fluxes, membrane permeabilities, and finally, the effect of FO membrane orientations. FO membrane performance was successfully enhanced by adding different concentrations of TiO2 nanoparticles from 0.5 to 1.5 wt%. The findings indicated that an increase in the concentration from 0.5 to 1 wt% leads to a clear increase in both the porosity and hydrophilicity of the nanocomposite substrate and consequently, an increase in the water flux. However, further increasing the concentration of TiO2 nanoparticles to more than 1 wt% affects the membrane performance.
Perillaldehyde Building Block’s Derivatives: Targeted Bioactivities and Molecular Docking
Authors: Chebrouk Farid , Cherfaoui Brahim , Mounir Bouhenna Mustapha , Nebbak Amira , E.C. Ziani Borhane , Dahmoune Farid , Chader Henni , Eddaikra Naouel , Harrat Zoubir , Madani Khodir 
Published: May 2022

Background:Recently, the essential oil (EO) of Ammodaucus leucotrichus has attracted particular attention in hemi-synthesis due to the reactivity of its main monoterpenes.Objective:In vitro cytotoxic and antileishmanial activities of the EO and hemi-synthesized compounds were evaluated, and an in-silico simulation was conducted.Methods:The EO was characterized by GC-MS. Two benzodiazepines (C1, C2), benzimidazole (C3), and Schiff base (C4) were hemi-synthesized by an in situ condensation of its major monoterpenes (perillaldehyde) with different amine derivatives. Synthesized compounds and the EO were evaluated for their cytotoxic activity against laryngeal carcinoma-Hep2 and rhabdomyosarcoma-RD cell lines and for their antileishmanial activity against Leishmania (L) major. Molecular docking was performed to pin the binding interactions of active molecules.Results:A significant cytotoxic effect of benzodiazepines C1 and C2 was noted against Hep2 cells (IC50/C1 = 39.48 ±0.7 μM, IC50/C2 = 48.82±1.33 μM) and RD (IC50/C1 = 15.96±1.99 μM; IC50/C2 = 74.3±2.44 μM), while the EO highly inhibited Hep2 cell lines (IC50/EO = 17.3±0.85 μg/mL). C4 strongly inhibited L. major growth with an IC50 value of 8.00±1.37 Μμ. The docking scores of ligand-C4 on L. major pteridine reductase and L. major methionyl-tRNA synthetase and ligands-(C1, C2) on the human protein kinase and epidermal growth factor kinase presented significant affinity to the receptor active sites (ΔG from -7.7 to -8.8 kcal/mol).Conclusion:The cytotoxic effect of derivatives C1, C2, and EO, as well as the anti-parasitic effect of C4, may suggest them as effective bioactive agents or pharmaceutical probes.
A Review of Salivary Biomarkers in Breast Cancer
Authors: Koopaie Maryam , Fatahzadeh Mahnaz , Kolahdooz Sajad , Mousavi Reza 
Published: May 2022

Objective:This study aimed to review the literature related to salivary biomarkers used to diagnose breast cancer or predict responses to therapy and its prognosis.Methods:Studies were eligible for inclusion if they had compared salivary diagnostics for breast cancer with the gold standard or other biomarkers. Six databases (PubMed, EMBASE, ScienceDirect, Scopus, Web of Science, and Ovid) and Google Scholar search engine searched for pertinent literature using specific search terms: breast cancer, diagnosis, prognosis saliva, and salivary biomarker. Of the 513 studies screened, 110 were selected for inclusion in this review. Different salivary biomarkers were classified and discussed.Results:Our analysis indicated that the sensitivity and specificity of salivary biomarkers, such as cerb- B2 and sialic acid in BC detection are comparable with serum values. Salivary levels of autoantibodies against MUC1, CA 15-3, and adiponectin had a better correlation with breast cancer than serum levels. Assessment of biomarkers, such as HER-2, helps develop a treatment plan and evaluates response to treatment.Conclusion:Our study confirms that salivary biomarkers are becoming increasingly important in breast cancer diagnosis and treatment planning, as well as in predicting therapeutic response and prognosis. Salivary biomarkers such as c-erb-B2 in association with traditional criteria offer the promise of use as a noninvasive screening method for breast cancer. Additional studies are warranted to determine the most sensitive and specific salivary biomarkers for this purpose.
Ethnomedicinal Plant Stephania hernandifolia and its Active Fraction 2-
Chloroethyl Linoleate Inhibits HSV-2 Infection by Blocking Viral Immediate
Early and Early Transcription
Authors: Chattopadhyay Debprasad , Mondal Joy , Patra Chiranjit , Mahapatra Ananya Das , Mandal Keshab Chandra 
Published: May 2022

Aim:
The aim of this study is validation of antiviral activity of Stephania hernandifolia
against HSV-2.

Background:
Ethnomedicinal plant Stephania hernandifolia, traditionally used for the management of
skin, digestive and nerve ailments demonstrated significant anti-HSV-1 activity; similar to Stephania
cepharantha having neuroinflammatory and anti-HSV activities.

Objectives:
Thus, the present study aimed to validate the potential of the most active fraction-2 (F-2)
of S. hernandifolia against HSV-2 in vitro, along with the underlying mode or mechanism of action.

Methods:
The standardized F-2 was characterized by GC-MS, 1H-NMR, Mass and FTIR spectroscopy.
Cytotoxicity (CC50) and antiviral activity (EC50) were evaluated by MTT and Plaque reduction assay.
To determine the mode of action, we have used time-of-addition, virus inactivation, and entry (attachment
and penetration) assays, followed by semiquantitative PCR. Furthermore, the protein expression
levels of immediate early (IE) and early (E) gene products of drug-treated virions were measured
by Western blot.

Results:
The results showed that HSV-2G and ICMR/VU-2012/20, the clinical isolate of HSV-2, were
inhibited by F-2 at EC50 of 20.0 and 20.43 μg/ml respectively, with Selectivity Index (SI) of 12. Timeof-
addition assay showed that F-2 significantly inhibited HSV-2 infection in Vero cells at 4-8 h posttreatment.
The infectivity of the virion was lost within 1h of exposure to F-2 (EC50 and EC99). Furthermore,
semi-Q-PCR and Western blot studies demonstrated significant downregulation of IE and E
gene products. The characterization revealed that 2-chloroethyl linoleate is the lead compound in the
F-2 fraction.

Conclusion:
Thus, our results showed that the bioactive fraction F-2 inhibits both IE and E transcription
of HSV-2.
A Review on Pathophysiological Aspects of Sleep Deprivation
Authors: Agrawal Shelly , Kumar Vishal , Singh Vishesh , Singh Charan , Singh Arti 
Published: May 2022

Abstract:
Sleep deprivation (SD) (also referred as insomnia) is a condition in which individuals fail to
get enough sleep due to excessive yawning, facing difficulty to learn new concepts, experiencing forgetfulness
as well as depressed mood. This could occur due to several possible reasons, including
medications and stress (caused by shift work). Despite the fact that sleep is important for normal physiology,
it currently affects millions of people around the world, especially the US (70 million) and Europe
(45 million). Due to increased work demand nowadays, lots of people are experiencing sleep deprivation
hence, this could be the reason for several car accidents followed by death and morbidity. This
review highlighted the impact of SD on neurotransmitter release and functions, theories (Flip-flop theory,
oxidative stress theory, neuroinflammation theory, neurotransmitter theory, and hormonal theory)
associated with SD pathogenesis; apart from this, it also demonstrates the molecular pathways underlying
SD (PI3K and Akt, NF-κB, Nrf2, and adenosine pathway. However, this study also elaborates on
the SD-induced changes in the level of neurotransmitters, hormonal, and mitochondrial functions.
Along with this, it also covers several molecular aspects associated with SD as well. Through this
study, a link is made between SD and associated causes, which will further help to develop a potential
therapeutic strategy against SD.
Rationalizing the Use of Polyphenol Nano-formulations in the Therapy of
Neurodegenerative Diseases
Authors: Verma Anita Kamra , Kumari Namrata , Daram Nagarjuna , Alam Md. Sabir 
Published: May 2022

Abstract:
Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain
cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of β- synuclein in the neurons are the hallmark of Parkinson’s disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in
AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while LDOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current
treatment for these NDs is limited due to the blood–brain barrier (BBB) that hinders drug targeting
towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that
act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but
their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds
with anti-inflammatory properties to the site of action.
Increased Salivary Cytokines and Nitric Oxide Levels in Behçet’s Disease: Interleukin-32, a Novel Player in Disease Prognosis
Authors: Touil-Boukoffa Chafia , Hadjimi Zohra , Belguendouz Houda , Benchabane Sarah , Ghozali Nour El Houda , Amri Manel , Kocheida Racha , Hakem Djenette , Biad Ahmed , Otmani Fifi , Kemikem Yasmine , Terahi Malika 
Published: May 2022

Background:Oral aphthosis is one of the major manifestations of Behçet’s disease (BD), a chronic, multisystemic vasculitis. BD etio-pathogenicity related to oral health lack.Objective:This study investigated the possible relationships between poor oral hygiene, oral activity, disease severity and saliva’s Interleukin (IL)-32, IL-6, IL-10 and nitric oxide (NO) levels in Behçet’s patients to determine their role in disease prognosis and their potential therapeutic interest.Method:Fifty-six patients with BD (22 orally active; 34 orally inactive) and 31 healthy subjects have been included in our study. Salivary levels of IL-32, IL-6, and IL-10 were measured using ELISA, while NO levels were assessed by modified Griess’s method. Oral health status and disease severity scores were recorded for each participant. Kruskal-Wallis test and Spearman’s test were performed for statistical analyses.Results:We observed that the tested molecules were increased in BD patients compared to healthy controls (p˂0.05). Moreover, only IL-32 levels were associated with oral activity in patients (p˂0.05). Interestingly, the disease severity score was noted to be correlated positively and significantly with both IL-32 saliva levels (p˂0.01) and plaque index (p˂0.05) in BD patients. Furthermore, IL-32 levels were correlated with plaque index (p˂0.0001).Conclusion:Our results suggest that IL-32, IL- 6, IL-10 and NO were increased in saliva during BD. Our study indicated that IL-32 was associated with the genesis of oral ulcers in response to dental plaque. Ultimately, salivary IL-32 may serve as a prognostic biomarker and a possible therapeutic target for managing Behçet’s disease severity.
Design and Fabrication of Gallic Acid Loaded Chitosan Nanoformulation
Authors: Pathak Kalyani , Das Ratna Jyoti , Saikia Riya , Sahariah Jon Jyoti , Pathak Hemanta , Sarma Himangshu , Das Aparoop 
Published: May 2022

Background:
Gallic acid is a natural phenolic compound found in several fruits and me-dicinal plants. It is reported to have several health-promoting effects, including antioxidant, anti-inflammatory, antidiabetic, and antineoplastic properties in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders.

Aims:
The aim of the present work was to study the influence of formulation factors on the physi-cochemical properties of gallic acid-loaded chitosan nanoparticles in order to optimize the formula-tion.

Methods:
Active chitosan nanoparticles could be used to support the modification of gallic acid delivery. The nanoparticles were prepared by the emulsification-solvent evaporation method using sonication. A 3-factor, 2-level BBD (Box-Behnken Design) was applied for exploring and opti-mizing the main effects, quadratic effects, as well as interaction effects of the ingredients of the formulation on the performance of the nanoparticles. The responses like particle size, poly-dispersity index, zeta potential, and encapsulation efficiency were also determined.

Results:
The concentration of gallic acid nanoparticles seems to be the most critical element affect-ing their properties. The concentration of chitosan was increased, which resulted in an increase in particle size. The optimised drug-loaded nanoparticles have a zeta potential of -5.2 mV due to their largely negative surface charge. Although the measured zeta potential was low, the nanoparticle dispersion remained stable, and no significant change in the shape or particle size of the gallic acid-loaded chitosan nanoparticles was seen after two weeks at 4°C. The gallic acid-loaded nanoparticles have a particle size of 230 nm. Gallic acid reduced the particle size after it was added. One probable explanation for this is that the loaded medicine increased the cohesive force of the hydrophobic con-tact, resulting in the size reduction. A formulation was optimised based on the acquired results, and the experimental values were comparable to the expected values. FTIR examination revealed that gallic acid-loaded chitosan nanoparticles displayed both hydrogen bond and ionic interactions, al-lowing for active agent encapsulation and augmentation.

Conclusions:
The overall results indicated that by decreasing the chitosan concentration, drug en-trapment efficiency increased and gallic acid concentration was the main factor influencing particle size, while entrapment efficiency was predominantly affected by the chitosan concentration.