Search results for: therapeutic radionuclides
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1477

Search results for: therapeutic radionuclides

997 Systems Contextual Integrated Model for Clinical Psychology and Social Work

Authors: Raymond C. Hawkins II, Catherine A. Hawkins

Abstract:

The System Contextual Integrated Model (SCIM), developed as a trans-theoretical framework for selecting measures for psychotherapy process and outcome, is reformulated for behavioral health applications. The SCIM “healing cycle” is an allostatic hedonic affective-cognitive right-hemisphere–left-hemisphere coordinated process involving positive alliesthesia that mitigates traumatic pain and generates psychological flexibility. The SCIM “trauma cycle” is an allostatic overload alliesthesia opponent process with long-lasting pathology sequelae. The social ecological context moderates the “healing cycle” and the “trauma cycle.” Repeated evocation of the “healing cycle” in a therapeutic relationship can gradually relieve trauma sequelae. The SCIM is applied to pain, obese binge eating, and substance use disorders.

Keywords: allostasis, alliesthesia, opponent process, behavioral health, assessment

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996 Integrated Management System Applied in Dismantling and Waste Management of the Primary Cooling System from the VVR-S Nuclear Reactor Magurele, Bucharest

Authors: Radu Deju, Carmen Mustata

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The VVR-S nuclear research reactor owned by Horia Hubulei National Institute of Physics and Nuclear Engineering (IFIN-HH) was designed for research and radioisotope production, being permanently shut-down in 2002, after 40 years of operation. All amount of the nuclear spent fuel S-36 and EK-10 type was returned to Russian Federation (first in 2009 and last in 2012), and the radioactive waste resulted from the reprocessing of it will remain permanently in the Russian Federation. The decommissioning strategy chosen is immediate dismantling. At this moment, the radionuclides with half-life shorter than 1 year have a minor contribution to the contamination of materials and equipment used in reactor department. The decommissioning of the reactor has started in 2010 and is planned to be finalized in 2020, being the first nuclear research reactor that has started the decommissioning project from the South-East of Europe. The management system applied in the decommissioning of the VVR-S research reactor integrates all common elements of management: nuclear safety, occupational health and safety, environment, quality- compliance with the requirements for decommissioning activities, physical protection and economic elements. This paper presents the application of integrated management system in decommissioning of systems, structures, equipment and components (SSEC) from pumps room, including the management of the resulted radioactive waste. The primary cooling system of this type of reactor includes circulation pumps, heat exchangers, degasser, filter ion exchangers, piping connection, drainage system and radioactive leaks. All the decommissioning activities of primary circuit were performed in stage 2 (year 2014), and they were developed and recorded according to the applicable documents, within the requirements of the Regulatory Body Licenses. In the presentation there will be emphasized how the integrated management system provisions are applied in the dismantling of the primary cooling system, for elaboration, approval, application of necessary documentation, records keeping before, during and after the dismantling activities. Radiation protection and economics are the key factors for the selection of the proper technology. Dedicated and advanced technologies were chosen to perform specific tasks. Safety aspects have been taken into consideration. Resource constraints have also been an important issue considered in defining the decommissioning strategy. Important aspects like radiological monitoring of the personnel and areas, decontamination, waste management and final characterization of the released site are demonstrated and documented.

Keywords: decommissioning, integrated management system, nuclear reactor, waste management

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995 Arisarum Vulgare: Bridging Tradition and Science through Phytochemical Characterization and Exploring Therapeutic Potential via in vitro and in vivo Biological Activities

Authors: Boudjelal Amel

Abstract:

Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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994 Termination of the Brachial Artery in the Arm and Its Clinical Significance

Authors: Ramya Rathan, Miral N. F. Salama

Abstract:

The variations in the arteries have been drawing attention of anatomists for a long time because of their clinical significance. The brachial artery is the principal artery of the arm which is the continuation of the axillary artery from the lower border of the Teres Major. It terminates into the radial and ulnar arteries below the elbow joint at the neck radius. The present study aims at exploring the clinical significance of the high termination of the brachial artery. During the routine cadaveric dissection of the arm, for the undergraduate students of medicine at our university, we observed a high bifurcation of the radial and the ulnar artery at the midshaft of the humerus. The median nerve was seen passing between these two junctions. Further, the course and the relations of this artery were studied. The accurate knowledge regarding these kinds of variation in the blood vessels is mandatory for planning of designing. General physicians, surgeons and radiologists should keep in mind the variations in the branching pattern of the arteries in their daily medical, diagnostic and therapeutic procedures to avoid complications in diagnostic and surgical procedures.

Keywords: brachial artery, high termination, radial artery, ulnar artery

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993 The Potential of Hydrophobically Modified Chitosan Cryogels to Be Used as Drug Delivery Systems

Authors: Courtney Evans, Yuto Morimitsu, Tsubasa Hisadome, Futo Inomoto, Masahiro Yoshida, Takayuki Takei

Abstract:

Hydrogels are useful biomaterials due to their highly biocompatible nature and their ability to absorb large quantities of liquid and mimic soft tissue. They are often used as therapeutic drug delivery systems. However, it is sometimes difficult to sustain controlled release when using hydrophobic medicines, as hydrogels are frequently hydrophilic. As such, this research shows the success of chitosan hydrogels modified through hydrophobic interaction. This was done through the imide bonding of the alkyl groups in fatty aldehydes and the amino groups in chitosan, followed by reductive animation. The resulting cryogels could be optimized for strength as well as sorption and desorption (of a hydrophobic dye used to mimic hydrophobic medicine) by varying the alkyl chain length and the substitution degree of the fatty aldehyde. Optimized cryogels showed potential as biomedical materials, particularly as drug delivery systems.

Keywords: biomedical materials, chitosan, drug carriers, hydrophobic modification

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992 miR-200c as a Biomarker for 5-FU Chemosensitivity in Colorectal Cancer

Authors: Rezvan Najafi, Korosh Heydari, Massoud Saidijam

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5-FU is a chemotherapeutic agent that has been used in colorectal cancer (CRC) treatment. However, it is usually associated with the acquired resistance, which decreases the therapeutic effects of 5-FU. miR-200c is involved in chemotherapeutic drug resistance, but its mechanism is not fully understood. In this study, the effect of inhibition of miR-200c in sensitivity of HCT-116 CRC cells to 5-FU was evaluated. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was evaluated using quantitative real- time PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were analyzed by western blotting. Annexin V and propidium iodide staining assay were applied for apoptosis detection. The caspase-3 activation was evaluated by an enzymatic assay. The results showed LNA-anti-miR-200c inhibited the expression of PTEN and E-cadherin protein, apoptosis and activation of caspase 3 compared with control cells. In conclusion, these results suggest that miR-200c as a prognostic marker can overcome to 5-FU chemoresistance in CRC.

Keywords: colorectal cancer, miR-200c, 5-FU resistance, E-cadherin, PTEN

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991 Identification of the Alkaloids of the Belladone (Atropa belladonna L.) and Evaluation of Their Inhibitory Effects Against Some Microbial Strains

Authors: Ait Slimane-Ait Kaki Sabrina, Foudi Lamia

Abstract:

The present work consists of the study of the bio-ecology and the therapeutic effects of the belladone (Atropa belladonna L.). It is a medicinal plant of the Solanacées family, herbaceous, robust 0.5 up to 1.50 m high. The phytochemical analysis of leaves revealed alkaloids, tannins, catechin, coumarins, mucilages, saponins, starch, and reducing compounds. The experimental study concerns the extraction and characterization of belladonna alkaloids. Analysis of the purified extract by staining tests confirmed the presence of tropane alkaloids. The dosage chromatography revealed the presence of components that have been identified atropine, scopolamine and hyoscyamine. Evaluation of antimicrobial and antifungal alkaloids from the methanol extract and aqueous extract of belladonna on pathogenic germs showed a positive bactericidal against strains of Escherichia coli and Staphylococcus aureus. Our preliminary results allow us an overall assessment of the medicinal value of Atropa belladonna.

Keywords: belladone, alkaloid, antibacterial activity, antifungal activity

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990 Multiple Approaches for Ultrasonic Cavitation Monitoring of Oxygen-Loaded Nanodroplets

Authors: Simone Galati, Adriano Troia

Abstract:

Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: cavitation, drug delivery, nanodroplets, ultra-sound

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989 Green Synthesis (Using Environment Friendly Bacteria) of Silver-Nanoparticles and Their Application as Drug Delivery Agents

Authors: Sutapa Mondal Roy, Suban K. Sahoo

Abstract:

The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.

Keywords: silver nanoparticles, ciprofloxacin, density functional theory, drug delivery

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988 Management of the Asthma Crisis in the Unit of Intensive Care of the General Hospital of Reference of Kinshasa

Authors: Eddy K. Mukadi

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The aim of this study was to provide contributing elements to improve the management of the asthma crisis in the intensive care unit of the General Reference Hospital of Kinshasa. This was a descriptive study of all patients in the intensive care unit presenting with the asthma attack during the period from February 5, 2013 to February 5, 2014. The main data were obtained from consultation registry and medical records. A total of 35 patients, 21 of whom were male (majority) compared to 14 female. Average age of patients was 46.48 plus or minus 16.98 with extremes ranging from 21-75 years. The clinic was dominated by dyspnea in 100% of cases, followed by rales with 91.4% of cases. In spite of the control of the crisis obtained after the treatment with B2 mimetic by inhalation was introduced A 91.5%; 88% corticosteroids; 80% oxygen, the therapeutic principle recommended for the management of asthma attacks was not respected in the majority of cases. This is why we suggest that improving the quality of care to be administered to patients will yield more adequate results.

Keywords: asthma crisis, intensive care, general hospital, Kinshasa

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987 Effects of Pulsed Electromagnetic and Static Magnetic Fields on Musculoskeletal Low Back Pain: A Systematic Review Approach

Authors: Mohammad Javaherian, Siamak Bashardoust Tajali, Monavvar Hadizadeh

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Objective: This systematic review study was conducted to evaluate the effects of Pulsed Electromagnetic (PEMF) and Static Magnetic Fields (SMG) on pain relief and functional improvement in patients with musculoskeletal Low Back Pain (LBP). Methods: Seven electronic databases were searched by two researchers independently to identify the published Randomized Controlled Trials (RCTs) on the efficacy of pulsed electromagnetic, static magnetic, and therapeutic nuclear magnetic fields. The identified databases for systematic search were Ovid Medline®, Ovid Cochrane RCTs and Reviews, PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE from 1968 to February 2016. The relevant keywords were selected by Mesh. After initial search and finding relevant manuscripts, all references in selected studies were searched to identify second hand possible manuscripts. The published RCTs in English would be included to the study if they reported changes on pain and/or functional disability following application of magnetic fields on chronic musculoskeletal low back pain. All studies with surgical patients, patients with pelvic pain, and combination of other treatment techniques such as acupuncture or diathermy were excluded. The identified studies were critically appraised and the data were extracted independently by two raters (M.J and S.B.T). Probable disagreements were resolved through discussion between raters. Results: In total, 1505 abstracts were found following the initial electronic search. The abstracts were reviewed to identify potentially relevant manuscripts. Seventeen possibly appropriate studies were retrieved in full-text of which 48 were excluded after reviewing their full-texts. Ten selected articles were categorized into three subgroups: PEMF (6 articles), SMF (3 articles), and therapeutic nuclear magnetic fields (tNMF) (1 article). Since one study evaluated tNMF, we had to exclude it. In the PEMF group, one study of acute LBP did not show significant positive results and the majority of the other five studies on Chronic Low Back Pain (CLBP) indicated its efficacy on pain relief and functional improvement, but one study with the lowest sessions (6 sessions during 2 weeks) did not report a significant difference between treatment and control groups. In the SMF subgroup, two articles reported near significant pain reduction without any functional improvement although more studies are needed. Conclusion: The PEMFs with a strength of 5 to 150 G or 0.1 to 0.3 G and a frequency of 5 to 64 Hz or sweep 7 to 7KHz can be considered as an effective modality in pain relief and functional improvement in patients with chronic low back pain, but there is not enough evidence to confirm their effectiveness in acute low back pain. To achieve the appropriate effectiveness, it is suggested to perform this treatment modality 20 minutes per day for at least 9 sessions. SMFs have not been reported to be substantially effective in decreasing pain or improving the function in chronic low back pain. More studies are necessary to achieve more reliable results.

Keywords: pulsed electromagnetic field, static magnetic field, magnetotherapy, low back pain

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986 Therapeutic Role of Polygonum bistorta and Zingiber roseum by in vivo and in vitro Study

Authors: Deepak Kumar Mittal, Alok Kumar Jena, Deepmala Joshi

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The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the aqueous extract of the roots of Polygonum bistorta (PB) (200 mg/kg) and Zingiber roseum (ZR) (250 mg/kg) in rats treated with carbon tetrachloride (0.15 ml/kg, i.p.). Extract of PB and ZR at the tested doses restored the levels of liver homogenate enzymes, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymes, significantly. The activities of MTT assay significantly recovered the damage and supported the biochemical observations. This study suggests that Zingiber roseum has a higher protective effect on liver, compared to Polygonum bistorta, against carbon tetrachloride-induced hepatotoxicity and possesses antioxidant activities. Also, extracts exhibited moderate anticancer activity towards cell viability at higher concentration.

Keywords: Polygonum bistorta, Zingiber roseum, hepatoprotective effect, carbon tetrachloride, anti-cancerous

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985 Remote Electroacupuncture Analgesia at Contralateral LI4 Acupoint in Complete Freund's Adjuvant-Induced Inflammatory Hindpaw Pain

Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

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There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

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984 Mathematical Modeling of Avascular Tumor Growth and Invasion

Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

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983 Transforming Personal Healthcare through Patient Engagement: An In-Depth Analysis of Tools and Methods for the Digital Age

Authors: Emily Hickmann, Peggy Richter, Maren Kaehlig, Hannes Schlieter

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Patient engagement is a cornerstone of high-quality care and essential for patients with chronic diseases to achieve improved health outcomes. Through digital transformation, possibilities to engage patients in their personal healthcare have multiplied. However, the exploitation of this potential is still lagging. To support the transmission of patient engagement theory into practice, this paper’s objective is to give a state-of-the-art overview of patient engagement tools and methods. A systematic literature review was conducted. Overall, 56 tools and methods were extracted and synthesized according to the four attributes of patient engagement, i.e., personalization, access, commitment, and therapeutic alliance. The results are discussed in terms of their potential to be implemented in digital health solutions under consideration of the “computers are social actors” (CASA) paradigm. It is concluded that digital health can catalyze patient engagement in practice, and a broad future research agenda is formulated.

Keywords: chronic diseases, digitalization, patient-centeredness, patient empowerment, patient engagement

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982 Identifying Network Subgraph-Associated Essential Genes in Molecular Networks

Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

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Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: biological molecular networks, essential genes, graph theory, network subgraphs

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981 Rumination in Borderline Personality Disorder: A Meta-Analytic Review

Authors: Mara J. Richman, Zsolt Unoka, Robert Dudas, Zsolt Demetrovics

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Borderline personality disorder (BPD) is characterized by deficits in emotion regulation and effective liability. Of this domain, ruminative behaviors have been considered a core feature of emotion dysregulation difficulties. Taking this into consideration, a meta-analysis was performed to assess how BPD symptoms correlate with rumination, while also considering clinical moderator variables such as comorbidity, GAF score, and type of BPD symptom and demographic moderator variables such as age, gender, and education level. Analysis of correlation across rumination domains for the entire sample revealed a medium overall correlation. When assessing types of rumination, the largest correlation was among pain rumination followed by anger, depressive, and anxious rumination. Furthermore, affective instability had the strongest correlation with increased rumination, followed by unstable relationships, identity disturbance, and self-harm/ impulsivity, respectively. Demographic variables showed no significance. Clinical implications are considered and further therapeutic interventions are discussed in the context of rumination.

Keywords: borderline personality disorder, meta-analysis, rumination, symptoms

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980 Traditional Chinese Medicine Treatment for Coronary Heart Disease: a Meta-Analysis

Authors: Yuxi Wang, Xuan Gao

Abstract:

Traditional Chinese medicine has been used in the treatment of coronary heart disease (CHD) for centuries, and in recent years, the research data on the efficacy of traditional Chinese medicine through clinical trials has gradually increased to explore its real efficacy and internal pharmacology. However, due to the complexity of traditional Chinese medicine prescriptions, the efficacy of each component is difficult to clarify, and pharmacological research is challenging. This study aims to systematically review and clarify the clinical efficacy of traditional Chinese medicine in the treatment of coronary heart disease through a meta-analysis. Based on PubMed, CNKI database, Wanfang data, and other databases, eleven randomized controlled trials and 1091 CHD subjects were included. Two researchers conducted a systematic review of the papers and conducted a meta-analysis supporting the positive therapeutic effect of traditional Chinese medicine in the treatment of CHD.

Keywords: coronary heart disease, Chinese medicine, treatment, meta-analysis

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979 Hospital Wastewater Treatment by Ultrafiltration Membrane System

Authors: Selin Top, Raul Marcos, M. Sinan Bilgili

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Although there have been several studies related to collection, temporary storage, handling and disposal of solid wastes generated by hospitals, there are only a few studies related to liquid wastes generated by hospitals or hospital wastewaters. There is an important amount of water consumptions in hospitals. While minimum domestic water consumption per person is 100 L/day, water consumption per bed in hospitals is generally ranged between 400-1200 L. This high amount of consumption causes high amount of wastewater. The quantity of wastewater produced in a hospital depends on different factors: bed numbers, hospital age, accessibility to water, general services present inside the structure (kitchen, laundry, laboratory, diagnosis, radiology, and air conditioning), number and type of wards and units, institution management policies and awareness in managing the structure in safeguarding the environment, climate and cultural and geographic factors. In our country, characterization of hospital wastewaters conducted by classical parameters in a very few studies. However, as mentioned above, this type of wastewaters may contain different compounds than domestic wastewaters. Hospital Wastewater (HWW) is wastewater generated from all activities of the hospital, medical and non medical. Nowadays, hospitals are considered as one of the biggest sources of wastewater along with urban sources, agricultural effluents and industrial sources. As a health-care waste, hospital wastewater has the same quality as municipal wastewater, but may also potentially contain various hazardous components due to using disinfectants, pharmaceuticals, radionuclides and solvents making not suitable the connection of hospital wastewater to the municipal sewage network. These characteristics may represent a serious health hazard and children, adults and animals all have the potential to come into contact with this water. Therefore, the treatment of hospital wastewater is an important current interest point to focus on. This paper aims to approach on the investigation of hospital wastewater treatment by membrane systems. This study aim is to determined hospital wastewater’s characterization and also evaluates the efficiency of hospital wastewater treatment by high pressure filtration systems such as ultrafiltration (UF). Hospital wastewater samples were taken directly from sewage system from Şişli Etfal Training and Research Hospital, located in the district of Şişli, in the European part of Istanbul. The hospital is a 784 bed tertiary care center with a daily outpatient department of 3850 patients. Ultrafiltration membrane is used as an experimental treatment and the influence of the pressure exerted on the membranes was examined, ranging from 1 to 3 bar. The permeate flux across the membrane was observed to define the flooding membrane points. The global COD and BOD5 removal efficiencies were 54% and 75% respectively for ultrafiltration, all the SST removal efficiencies were above 90% and a successful removal of the pathological bacteria measured was achieved.

Keywords: hospital wastewater, membrane, ultrafiltration, treatment

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978 Benefits of Therapeutic Climbing on Multiple Components of Attention in Attention Deficit Hyperactivity Disorder Children

Authors: Elaheh Hosseini, Otmar Bock, Monika Thomas

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The purpose of the present study was to determine the effect of climbing therapy on the components of attention of children with attention-deficit hyperactivity disorder (ADHD). Forty children with ADHD were assigned to either an intervention group or a control group. The exercise group participated in a climbing therapy program for ten weeks, whereas no intervention was administered to the control group. All two groups were then assessed with the same battery of attention tests used in our earlier study. We found that compared to the ‘intervention’ group, performance was higher in the ‘control’ group on tests of sustained, divided and distributed attention, on all four tests. The intervention group showed a significant improvement in components of attention after ten weeks. From this we conclude that climbing therapy can improve the attention of children with ADHD and can be considered as a promising intervention and a standalone treatment for children with ADHD.

Keywords: ADHD, climbing therapy, distributed attention, divided attention, selective attention, sustained attention

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977 Genetic Polymorphisms of the Human Organic Cation Transporter 2 gene, SLC22A2, in the Zulu population

Authors: N. Hoosain, S. Nene, B. Pearce, C. Jacobs, M. Du Plessis, M. Benjeddou

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Organic Cation Transporters play a vital role in the absorption, tissue distribution and elimination of various substrates. Numerous studies have suggested that variations in non-synonymous single nucleotide polymorphisms (SNPs) of SLC22A2 could influence an individual’s response to various treatments, including clinically important drugs. This study is the first to determine the baseline frequency distribution for twenty SNPs of SLC22A2in the Zulu population. DNA was collected from 101 unrelated “healthy” Zulu participants. Genotypes of all samples were determined using a multiplex PCR and SNaPshot assay followed by the generation of the haplotype structure. This is the first time that the baseline frequency distribution of SNPs is reported for the Zulu population. Data from this study could be used in in vitro and in vivo pharmacogenetic and pharmacokinetic studies to evaluate the potential role the studied SNPs play in the therapeutic efficacy of clinically important drugs.

Keywords: SLC22A2 gene, SNaPshot assay, PCR, Zulu population

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976 Intervention To Prevent Infections And Reinfections With Intestinal Parasites In People Living With Human Immunodeficiency Virus In Some Parts Of Eastern Cape, South Africa

Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

Abstract:

Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

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975 Vital Pulp Therapy: A Paradigm Shift in Treating Irreversible Pulpitis

Authors: Fadwa Chtioui

Abstract:

Vital Pulp Therapy (VPT) is nowadays challenging the deep-rooted dogma of root canal treatment, being the only therapeutic option for permanent teeth diagnosed with irreversible pulpitis or carious pulp exposure. Histologic and clinical research has shown that compromised dental pulp can be treated without the full removal or excavation of all healthy pulp, and the outcome of the partial or full pulpotomy followed by a Tricalcium-Silicate-based dressing seems to show promising results in maintaining pulp vitality and preserving affected teeth in the long term. By reviewing recent advances in the techniques of VPT and their clinical effectiveness and safety in permanent teeth with irreversible Pulpitis, this work provides a new understanding of pulp pathophysiology and defense mechanisms and will reform dental practitioners' decision-making in treating irreversible pulpits from root canal therapy to vital pulp therapy by taking advantage of the biological effects of Tricalcium Silicate materials.

Keywords: irreversible pulpitis, vital pulp therapy, pulpotomy, Tricalcium Silicate

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974 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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973 Improved Approach to the Treatment of Resistant Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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972 Biomedical Countermeasures to Category a Biological Agents

Authors: Laura Cochrane

Abstract:

The United States Centers for Disease Control and Prevention has established three categories of biological agents based on their ease of spread and the severity of the disease they cause. Category A biological agents are the highest priority because of their high degree of morbidity and mortality, ease of dissemination, the potential to cause social disruption and panic, special requirements for public health preparedness, and past use as a biological weapon. Despite the threat of Category A biological agents, opportunities for medical intervention exist. This work summarizes public information, consolidated and reviewed across the situational usefulness and disease awareness to offer discussion to three specific Category A agents: anthrax (Bacillus anthracis), botulism (Clostridium botulinum toxin), and smallpox (variola major), and provides an overview on the management of medical countermeasures available to treat these three (3) different types of pathogens. The medical countermeasures are discussed in the setting of pre-exposure prophylaxis, post-exposure prophylaxis, and therapeutic treatments to provide a framework for requirements in public health preparedness.

Keywords: anthrax, botulism, smallpox, medical countermeasures

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971 Alpha-Theta a Non-Invasive Treatment for the Self-Exploration of Individuals with Conversion Disorder in Pakistani Society

Authors: Muhammad Tahir Khalily

Abstract:

Aim: The purpose of the present study was to examine the effectiveness of alpha-theta brainwave Neuro feedback treatment for the internal self-exploration of individuals with conversion disorder. Method: A Purposive sample technique was used and data collected from Kalsoom International Hospital Islamabad and Al-Malik Medical Center Rawalpindi. 123 participants were examined, Male child = 5, female child = 6, male adult = 64, female adult = 48. This study retrospectively examined the symptomatic changes in clients with a range of psychiatric disorders particularly 13 (Male = 3, Female = 10) conversion disorder clients who have received Neuro feedback treatment. Results: Our results indicated a significant improvement (P < .001) in the amelioration of our clients’ symptoms which have enabled them to bring their emotional memories into conscious awareness for the peaceful resolution without self-detachment. Conclusion: Majority of the clients improved their psychiatric symptoms including the symptoms of conversion disorder and was discharged from therapy with the accomplishment of therapeutic goals.

Keywords: EEG, neurofeedback, conversion, therapy

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970 First-Principles Modeling of Nanoparticle Magnetization, Chaining, and Motion

Authors: Pierce Radecki, Pulkit Malik, Bharath Ramaswamy, Ben Shapiro

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The ability to effectively design and test magnetic nanoparticles for controlled movement has been an elusive goal in the design of these particles. Magnetic nanoparticles of various characteristics have been created for use towards therapeutic effects, however the challenge of designing for controlled movement remains unmet. A step towards design in this aspect is a first principles model that captures and predicts the behaviors of particles in a magnetic field. The model is governed by four forces acting on the particles, the magnetic gradient, the dipole-dipole forces, the steric forces, and the viscous drag force. The particles are multi-core or single core, and incorporate a preferred magnetization axis. Particles exhibit behaviors, such as chaining, in simulations that are similar to those witnessed through experimentation. Currently, experimental results are being compared to the modeling results for verification of the model, through the analysis of chaining behaviors. This modeling system will be used in designing magnetic nanoparticles for specific chaining and movement behaviors.

Keywords: controlled movement, modeling, magnetic nanoparticles, nanoparticle design

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969 Biochemical Changes in the Liver of Mice after Exposure to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

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968 Comprehensive Analysis of RNA m5C Regulator ALYREF as a Suppressive Factor of Anti-tumor Immune and a Potential Tumor Prognostic Marker in Pan-Cancer

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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