Improved Neural Inductivity of Size-Controlled 3D Human Embryonic Stem Cells Using Magnetic Nanoparticles.

Background: To improve the efficiency of neural development from human embryonic stem cells, human embryoid body (hEB) generation is vital through 3-dimensional formation. However, conventional approaches still have limitations: long-term cultivation and laborious steps for lineage determination. Methods: In this study, we controlled the size of hEBs for ectodermal lineage specification using cell-penetrating magnetic nanoparticles (MNPs), which resulted in reduced time required for initial neural induction. The magnetized cells were applied to concentrated magnetic force for magnet-derived multicellular organization. The uniformly sized hEBs were differentiated in neural induction medium (NIM) and suspended condition. This neurally induced MNP-hEBs were compared with other groups. Results: As a result, the uniformly sized MNP-hEBs in NIM showed significantly improved neural inductivity through morphological analysis and expression of neural markers. Signaling pathways of the accelerated neural induction were detected via expression of representative proteins; Wnt signaling, dopaminergic neuronal pathway, intercellular communications, and mechanotransduction. Consequently, we could shorten the time necessary for early neurogenesis, thereby enhancing the neural induction efficiency. Conclusion: Overall, this study suggests not only the importance of size regulation of hEBs at initial differentiation stage but also the efficacy of MNP-based neural induction method and stimulations for enhanced neural tissue regeneration.

Effects of Interfacial Electron Transport on Field Electron Emission from Carbon Nanotube Paste Emitters.

Field electron emission from carbon nanotubes (CNT) is preceded by the transport of electrons from the cathode metal to emission sites. Specifically, a supporting layer indispensable for adhesion of CNT paste emitters onto the cathode metal would impose a potential barrier, depending on its work function and interfacial electron transport behaviors. In this paper, we investigated the supporting layer of silicon carbide and nickel nanoparticles reacted onto a Kovar alloy (Fe-Ni-Co) cathode substrate, which has been adopted for reliable CNT paste emitters. The X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and electrical conductivity measurements showed that the reaction of silicon carbide and nickel nanoparticles on the Kovar metal strongly depends upon the post-vacuum-annealing conditions and can be classified into two procedures of a diffusion-induced reaction (DIR) and a diffusion-limited reaction (DLR). The prolonged annealing at 750 °C for 5 h before the main annealing of the CNT paste emitters at 800 °C for 5 min led to the DIR that has enhanced the Ni silicide phase and a lower potential barrier for the interfacial electron transport, resulting in increased and weakly temperature-dependent field electron emission from the CNT paste emitters. On the other hand, the DLR with only the main anneal of the CNT paste emitters at 800 °C for 5 min gave rise to a higher potential barrier for the electron transport and so lower and strongly temperature-dependent field electron emission. From the results of the interfacial electron transport for the DIR and DLR mechanisms in the CNT paste emitters, we concluded that the ambient temperature dependency of field electron emission from CNT tips in the moderate range of up to 400 °C, still controversial, is mainly attributed to the supporting layer of the CNT emitter rather than its intrinsic electron emission.

Implementation and evaluation of an end-of-life care education program for oncology nurses working in medical-surgical wards: A quasi-experimental study.

Background: The issue of a good death for cancer patients is becoming more prevalent. Hence, nurses' end-of-life work performance and stress levels in medical-surgical wards can significantly impact the quality of life of cancer patients and their caregivers. This study aimed to develop an end-of-life care education program for nurses taking care of cancer patients in medical-surgical ward and verify the program's preliminary effect. Method: Quasi-experimental research using a one-group pretest-posttest design was carried out for this study. The end-of-life care manual for nurses in general wards were developed through expert validation. Initial in-person and follow-on online self-education sessions were conducted based on the end-of-life care manual. A total of 70 nurses participated in the end-of-life care education program. End-of-life care stress and end-of-life care performance were measured as preliminary program effects. An online survey was conducted before the initial in-person education and after the follow-up online education. Results: The end-of-life care education program effectively improved general ward nurses' end-of-life care performance. This performance was improved in the physical and psychological domains. However, this program did not improve the nurses' performance in end-of-life care in the spiritual domain. Furthermore, it did not effectively reduce the stress on end-of-life care, indicating that improvements should be made. Conclusions: The improvement of effective end-of-life care education programs for nurses caring for cancer patients in general wards is required. Most importantly, efforts at the hospital organization level are necessary to reduce the stress of end-of-life care by improving the working environment. Additionally, it is necessary to conduct preemptive tailored intervention programs for nurses, such as a resilience improvement program.

A potential treatment option for advanced non-small cell lung cancer: Three cases.

OBJECTIVE: Recent progress in targeted therapy and immunotherapy has reduced the mortality of advanced-stage patients with non-small cell lung cancer (NSCLC). However, despite advances in treatment, only some patients are eligible for and benefit from genome-targeted therapy, while few patients are ineligible for genome-driven therapy or have limited treatment options due to performance status, comorbidity, and adverse events or rejection of chemotherapy. CLINICAL FEATURES AND OUTCOMES: We report the cases of three patients with advanced NSCLC who were not available to continue conventional anticancer therapy, who were able to maintain progression-free survival (PFS) or disease-free survival (DFS), and who have shown symptom amelioration after treatment with herbal Medicine. Patients were managed only with herbal medicines according to their disease status and symptoms, without conventional anticancer therapy. Two patients with metastatic NSCLC maintained PFS for 19 and 20 months after the discontinuation of chemotherapy, respectively. A patient with locally advanced NSCLC showed no evidence of recurrence for more than 5 years despite an increase in squamous cell carcinoma antigens. These patients had considerable clinical outcomes to maintain relatively long PFS and DFS. CONCLUSION: This study demonstrates the potential treatment option of herbal medicine in inhibiting tumor progression and prolonging PFS and DFS in patients with advanced NSCLC.

Enhanced osteogenic differentiation of human mesenchymal stem cells using size-controlled graphene oxide flakes.

Recently, it has been revealed that the physical microenvironment can be translated into cellular mechanosensing to direct human mesenchymal stem cell (hMSC) differentiation. Graphene oxide (GO), a major derivative of graphene, has been regarded as a promising material for stem cell lineage specification due to its biocompatibility and unique physical properties to interact with stem cells. Especially, the lateral size of GO flakes is regarded as the key factor regulating cellular response caused by GO. In this work, GO that had been mechanically created and had an average diameter of 0.9, 1.1, and 1.7 m was produced using a ball-mill process. When size-controlled GO flakes were applied to hMSCs, osteogenic differentiation was enhanced by GO with a specific average diameter of 1.7 µm. It was confirmed that osteogenic differentiation was increased due to the enhanced expression of focal adhesion and the development of focal adhesion subordinate signals via extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MEK) pathway. These results suggest that size-controlled GO flakes could be efficient materials for promoting osteogenesis of hMSCs. Results of this study could also improve our understanding of the correlation between hMSCs and cellular responses to GO.

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies.

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.

Therapeutic effects of TM4SF5-targeting chimeric and humanized monoclonal antibodies in hepatocellular and colon cancer models.

The transmembrane 4 L six family member 5 (TM4SF5) is aberrantly expressed in hepatocellular and colorectal cancers, and has been implicated in tumor progression, suggesting that it could serve as a novel therapeutic target. Previously, we screened a murine antibody phage-display library to generate a novel monoclonal antibody, Ab27, that is specific to the extracellular loop 2 of TM4SF5. In this study, we evaluated the effects of chimeric Ab27 using cancer cells expressing endogenous TM4SF5 or stably overexpressing TM4SF5 in vivo and in vitro. Monotherapy with Ab27 significantly decreased tumor growth in liver and colon cancer xenograft models, including a sorafenib-resistant model, and decreased the phosphorylation of focal adhesion kinase (FAK), p27Kip1, and signal transducer and activator of transcription 3 (STAT3). No general Ab27 toxicity was observed in vivo. Combination treatment with Ab27 and sorafenib or doxorubicin exerted higher antitumor activity than monotherapy. In addition, we humanized the Ab27 sequence by the complementarity-determining region (CDR) grafting method. The humanized antibody Ab27-hz9 had reduced immunogenicity but exhibited target recognition and antitumor activity comparable with those of Ab27. Both Ab27 and Ab27-hz9 efficiently targeted tumor cells expressing TM4SF5 in vivo. These observations strongly support the further development of Ab27-hz9 as a novel therapeutic agent against liver and colorectal cancers.

Patient discomfort levels during instrumentation procedure using nickel-titanium files with different kinetic movements.

This study evaluated the perceived vibration, noise and discomfort levels associated with two nickel-titanium file systems with different kinetics; reciprocating motion (REC) using WaveOne Gold and continuous rotation motion (CON) using ProTaper NEXT. Forty roots with two canals from maxillary premolar and molar of 40 patients were included. Root canals were instrumented using each system for each canal. Patients were surveyed about the vibration, noise and discomfort experienced using visual analogue scale, and their preference. The responses were statistically analysed using Wilcoxon Signed-Rank test, Mann-Whitney U test and Spearman's rank correlation test at the 95% of significance level. The vibration, noise and discomfort experienced were significantly greater in REC than CON (P < 0.05). In REC, male subjects reported significantly higher vibration than female (P < 0.05). Majority respondents (72.5%) preferred the CON method. The perceived vibration, noise and discomfort were less apparent from the CON than the REC.

Solvent-Free Mechanochemical Post-Polymerization Modification of Ionic Polymers.

Despite their superior stability and facile handling, ionic polymers have limited solubility in most organic solvents, restricting the range of substrates and reaction conditions to which they can be applied. To overcome this solubility issue, the present study presents a solvent-free mechanochemical reaction. Specifically, a post-polymerization modification of ammonium-functionalized polyether was demonstrated using a solvent-free vibrational ball-milling technique. The formation of imine bonds between the ionic polymer and an aromatic aldehyde led to the complete conversion to imine within 1 h without any bond breakage on the polymer backbone. The viability of this approach for a wide range of aldehydes was also evaluated, highlighting the potential of the mechanochemical post-polymerization modification of polymers that are inaccessible by conventional solution approaches.

Chemical Upcycling of Waste Poly(bisphenol A carbonate) to 1,4,2-Dioxazol-5-ones and One-Pot C-H Amidation.

Chemical upcycling of poly(bisphenol A carbonate) (PC) was achieved in this study with hydroxamic acid nucleophiles, giving rise to synthetically valuable 1,4,2-dioxazol-5-ones and bisphenol A. Using 1,5,7-triazabicyclo[4.4.0]-dec-5-ene (TBD), non-green carbodiimidazole or phosgene carbonylation agents used in conventional dioxazolone synthesis were successfully replaced with PC, and environmentally harmful bisphenol A was simultaneously recovered. Assorted hydroxamic acids exhibited good-to-excellent efficiencies and green chemical features, promising broad synthetic application scope. In addition, a green aryl amide synthesis process was developed, involving one-pot depolymerization from polycarbonate to dioxazolone followed by rhodium-catalyzed C-H amidation, including gram-scale examples with used compact discs.

Enhanced interfacial reaction of silicon carbide fillers onto the metal substrate in carbon nanotube paste for reliable field electron emitters.

Adhesion of carbon nanotube (CNT) onto a cathode substrate is very crucial for field electron emitters that are operating under high electric fields. As a supporting precursor of CNT field emitters, we adopted silicon carbide (SiC) nano-particle fillers with Ni particles and then enhanced interfacial reactions onto Kovar-alloy substrates through the optimized wet pulverization process of SiC aggregates for reliable field electron emitters. As-purchased SiC aggregates were efficiently pulverized from 20 to less than 1 micro-meter in a median value (D50). CNT pastes for field emitters were distinctively formulated by a mixing process of the pulverized SiC aggregates and pre-dispersed CNTs. X-ray photoelectron spectroscopy studies showed that the optimally pulverized SiC-CNT paste-emitter had a stronger Si 2p3/2 signal in the Ni2Si phase than the as-purchased one. The Si 2p3/2 signal would represent interfacial reaction of the SiC nano-particle onto Ni from the CNT paste and the Kovar substrate, forming the supporting layer for CNT emitters. The optimal paste-emitter even in a vacuum-sealed tube exhibited a highly reliable field emission current with a high current density of 100 mA cm-2 for over 50 h along with good reproducibility. The enhanced interfacial reaction of SiC filler onto the metal substrates could lead to highly reliable field electron emitters for vacuum electronic devices.

A potential treatment option for elderly non-Hodgkin lymphoma patients with multiple comorbidities: Two case reports and literature review.

Non-Hodgkin lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy. More than half of the NHL cases occur in patients over 65 years of age. As elderly patients have a poor performance status and multiple comorbidities, the use of standard chemotherapy is often limited, leading to poor clinical outcomes and an increasing need for an alternate therapeutic modalities. A 73-year-old man was diagnosed with extranodal NK/T-cell lymphoma concurrently combined with recurrent gastric adenocarcinoma and metastatic prostate cancer. A 79-year-old woman was diagnosed with T-cell and B-cell dual-phenotype NHL on the right chest wall showing tumor thrombosis and multiple enlarged lymph nodes under chronic emphysema with extensive pleural calcification. Both elderly patients had multiple comorbidities and pathologically confirmed non-Hodgkin lymphoma. Both patients achieved tumor responses following anticancer treatment with Korean medicine (KM), suggesting that the extracts of Angelica gigas Nakai and Geopungtang are potential options for treating NHL in elderly patients with multiple comorbidities. Considering the clinical outcomes of KM treatment in the two elderly patients with NHL and multiple comorbidities, this study generates a research hypothesis for future prospective clinical studies in patients with NHL who are ineligible for conventional anticancer therapy.

Meta-analysis of cytokine and C-reactive protein levels in high-risk psychosis.

OBJECTIVE: Schizophrenia is associated with aberrant blood cytokine and C-reactive protein (CRP) levels. However, less is known about alterations in these markers prior to the onset of psychosis. We performed a meta-analysis of blood cytokines and CRP in subjects at high-risk for psychosis. METHOD: We identified articles by systematic searches of PubMed, PsycINFO, and Web of Science databases, and the reference lists of identified studies. Eight studies met the inclusion criteria, including seven studies of high-risk psychosis versus controls, and four studies of high-risk subjects who converted to a psychotic disorder versus non-converters. RESULTS: Blood IL-6 levels were significantly higher (SMD = 0.31, 95% CI 0.02-0.59, p = 0.04) and blood IL-1ß levels were significantly lower (SMD = -0.66, 95% CI -1.27 to -0.05, p = 0.05) in subjects at high-risk for psychosis versus controls. Between-study heterogeneity was not significant for either IL-1ß or IL-6, and there was no evidence of publication bias. There was a non-significant trend for higher blood IL-12 levels in converters versus non-converters (SMD = 0.86, 95% CI -0.06-1.79, p = 0.07). CONCLUSION: We found limited evidence for blood cytokine and CRP alterations in subjects at high-risk for psychosis. Our findings should be interpreted with caution in light of a small number of studies, cumulative sample size, and heterogeneity of high-risk criteria, but warrant investigation in larger samples. This includes studies of subjects at high-risk of developing psychosis and controls, as well as the potential of inflammation as a predictor of conversion to psychosis. These findings have important potential implications for our understanding of the pathophysiology of schizophrenia.

Selection and Characterization of Monoclonal Antibodies Targeting Middle East Respiratory Syndrome Coronavirus through a Human Synthetic Fab Phage Display Library Panning.

Since its first report in the Middle East in 2012, the Middle East respiratory syndrome-coronavirus (MERS-CoV) has become a global concern due to the high morbidity and mortality of individuals infected with the virus. Although the majority of MERS-CoV cases have been reported in Saudi Arabia, the overall risk in areas outside the Middle East remains significant as inside Saudi Arabia. Additional pandemics of MERS-CoV are expected, and thus novel tools and reagents for therapy and diagnosis are urgently needed. Here, we used phage display to develop novel monoclonal antibodies (mAbs) that target MERS-CoV. A human Fab phage display library was panned against the S2 subunit of the MERS-CoV spike protein (MERS-S2P), yielding three unique Fabs (S2A3, S2A6, and S2D5). The Fabs had moderate apparent affinities (Half maximal effective concentration (EC50 = 123-421 nM) for MERS-S2P, showed no cross-reactivity to spike proteins from other CoVs, and were non-aggregating and thermostable (Tm = 61.5-80.4 °C). Reformatting the Fabs into IgGs (Immunoglobulin Gs) greatly increased their apparent affinities (KD = 0.17-1.2 nM), presumably due to the effects of avidity. These apparent affinities were notably higher than that of a previously reported anti-MERS-CoV S2 reference mAb (KD = 8.7 nM). Furthermore, two of the three mAbs (S2A3 and S2D5) bound only MERS-CoV (Erasmus Medical Center (EMC)) and not other CoVs, reflecting their high binding specificity. However, the mAbs lacked MERS-CoV neutralizing activity. Given their high affinity, specificity, and desirable stabilities, we anticipate that these anti-MERS-CoV mAbs would be suitable reagents for developing antibody-based diagnostics in laboratory or hospital settings for point-of-care testing.

Small Data and Its Visualization for Diabetes Self-Management: Qualitative Study.

BACKGROUND: As digital healthcare expands to include the use of mobile devices, there are opportunities to integrate these technologies into the self-management of chronic disease. Purpose built apps for diabetes self-management are plentiful and vary in functionality; they offer capability for individuals to record, manage, display, and interpret their own data. The optimal incorporation of mobile tablets into diabetes self-care is little explored in research, and guidelines for use are scant. OBJECTIVE: The purpose of this study was to examine an individual's use of mobile devices and apps in the self-management of type 2 diabetes to establish the potential and value of this ubiquitous technology for chronic healthcare. METHODS: In a 9-month intervention, 28 patients at a large multidisciplinary healthcare center were gifted internet connected Apple iPads with preinstalled apps and given digital support to use them. They were invited to take up predefined activities, which included recording their own biometrics, monitoring their diet, and traditional online information seeking. Four online surveys captured the participants' perceptions and health outcomes throughout the study. This article reports on the qualitative analysis of the open-ended responses in all four surveys. RESULTS: Using apps, participants self-curated small data sets that included their blood glucose level, blood pressure, weight, and dietary intake. The dynamic visualizations of the data in the form of charts and diagrams were created using apps and participants were able to interpret the impact of their choices and behaviors from the diagrammatic form of their small personal data sets. Findings are presented in four themes: (1) recording personal data; (2) modelling and visualizing the data; (3) interpreting the data; and (4) empowering and improving health. CONCLUSIONS: The modelling capability of apps using small personal data sets, collected and curated by individuals, and the resultant graphical information that can be displayed on tablet screens proves a valuable asset for diabetes self-care. Informed by their own data, individuals are well-positioned to make changes in their daily lives that will improve their health.

Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies.

BACKGROUND: In order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule. METHODS: The study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis. RESULTS: Prss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro. CONCLUSION: Our study demonstrates that Prss14/ST14 is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration.

Mechanochemical polymerization is a rapidly growing area and a number of polymeric materials can now be obtained through green mechanochemical synthesis. In addition to the general merits of mechanochemistry, such as being solvent-free and resulting in high conversions, we herein explore rate acceleration under ball-milling conditions while the conventional solution-state synthesis suffer from low reactivity. The solvent-free mechanochemical polymerization of trimethylene carbonate using the organocatalysts 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) are examined herein. The polymerizations under ball-milling conditions exhibited significant rate enhancements compared to polymerizations in solution. A number of milling parameters were evaluated for the ball-milling polymerization. Temperature increases due to ball collisions and exothermic energy output did not affect the polymerization rate significantly and the initial mixing speed was important for chain-length control. Liquid-assisted grinding was applied for the synthesis of high molecular weight polymers, but it failed to protect the polymer chain from mechanical degradation.

Effects of non-paretic arm movements during bridge exercises on trunk muscle activity in stroke patients.

[Purpose] The purpose of this study was to determine the effects of non-paretic arm movement during the bridge exercise on trunk muscle activity in stroke patients. [Participants and Methods] In total, 18 stroke patients were recruited. Surface EMG electrodes were attached over the trunk muscles (rectus abdominis, RA; internal oblique, IO; erector spinae, ES), and three kinds of bridge exercises were performed: 1) 'standard' bridge, 2) bridge with unilateral isometric arm flexion, and 3) bridge with unilateral isometric arm horizontal abduction. [Results] According to the activity of the trunk muscles measured during bridge exercises, only the IO and ES showed significantly greater muscle activity during bridges with isometric arm horizontal abduction and flexion than during the standard bridge. Additionally, comparison of the paretic and non-paretic sides showed that muscle activity was higher on the paretic side. [Conclusion] This study showed that, as an exercise to heighten the activity of the trunk muscles in stroke patients, bridge exercises with accompanying non-paretic arm flexion and horizontal abduction were more effective clinically than a standard bridge.

Migration of lead and arsenic from food contact paper into a food simulant and assessment of their consumer exposure safety.

Paper is one of the most commonly used food packaging materials. During the production of packaging paper, it is possible for trace amounts of heavy metals to be incorporated as contaminants. These could migrate into food when packaging paper (food contact paper) is used for cooking, storing and eating. The aim of this study was to determine the migration of lead (Pb) and arsenic (As) from food contact paper into a food simulant and then to assess human safety through the estimated daily intake (EDI) with consumption factor. Migration tests were conducted for 310 samples using 4% acetic acid as a food simulant at 25°C for 10 min and at 95°C for 30 min. Concentrations of Pb and As in a food simulant were quantified by inductively coupled plasma mass spectrometry. LODs for Pb and As were 0.002 and 0.005 µg L-1, respectively. The migration of Pb from food contact paper ranged from not detected (ND) to 17.5 µg L-1 at 25°C for 10 min and from 0.10 to 25.6 µg L-1 at 95°C for 30 min while As ranged from ND to 0.44 µg L-1 at 25°C for 10 min and from ND to 0.87 µg L-1 at 95°C for 30 min. The migration of Pb and As determined in this study confirm that the human exposure was within safe levels based on the EDI of food contact paper compared with the provisional tolerable weekly intake for Pb of 25 µg kg-1 bw and for As of 15 µg kg-1 bw.