bluuebunny/crossref_metadata_2025_split huggingface dataset:
BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression
Authors: Tancredi Alessandro , Gusyatiner Olga , Bady Pierre , Buri Michelle , Lomazzi Rémy , Chiesi Davide , Messerer Mahmoud , Hegi Monika 
Published: August 2022

Abstract
Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50% of patients whose glioblastoma exert an unmethylated MGMT promoter.
Occupational Exposure to Pesticides Applied Among Rice Growers in Malaysia
Authors: Wong Hie Ling , Garthwaite David G , Jais An Nurainee , Norman Nurul Najiah , Shobri Nurin Dalila Mohd , Brown Colin D 
Published: August 2022

Abstract
Occupational exposure of rice growers to pesticides can be assessed cost-effectively using mathematical exposure models. This study investigates rice growers’ exposure to pesticides due to the use of knapsack/backpack sprayers, a practice which is widespread in developing countries including Malaysia. Pesticide application information was collected from 23 rice growers during November 2020 – March 2021 using personal interviews and questionnaires. The information was used to predict total daily exposure to individual active substances via dermal and inhalation routes during mixing/loading and application activities using selected exposure models. The estimated exposures were assessed against the agricultural operator exposure levels (AOELs) for single active substances, where any exceedance indicates a potential risk to health. Across the rice growing season, the 23 rice growers had different application practices including total number of active substances applied on single spray days (1–8 compounds), total rice cultivation areas (0.6–3.8 ha), and total number of spraying days (3–13 days). Individuals had estimated average daily exposures to single active substances of 7.7x10− 2 – 1.2 mg kg-bw− 1 day− 1 (7.5x10− 2 – 1.1 and 1.7x10− 3 – 2.2x10− 1 mg kg-bw− 1 day− 1 during application and mixing/loading activities, respectively), where dermal exposure constituted 99.6–99.98% of the total exposure. Overall, 56% of all the applications reported by the 23 growers had exposure estimates that exceeded the AOEL, mainly due to the use of relatively toxic pesticides, products formulated as wettable powders, and growers neglecting to wear gloves whilst handling pesticides. All of these factors can be influenced by provision of training and information on selection of pesticide products and application practices. Study findings can be used to target efforts to minimise pesticide risks to health in developing countries.
Risk assessment of some heavy metals (Cd, Pb, Zn) caused by drilling mud cuttings of the Ahvaz Mansouri oil field
Authors: khalili Peyman , hoodaji Mehran , Nadoushan Mozhgan Ahmadi , chamani Atfeh 
Published: August 2022

Abstract
The most important wastes generated from oil and gas exploration are drilling mud and cuttings. Contamination of these wastes destroys the environment. Therefore, the purpose of the current research was to identify the hazards and health risks of heavy metals (Cd, Pb, Zn) caused by drilling cuttings on the employees and residents of the study area and their reduction using phytoremediation. For this purpose, contaminated drilling cuttings were mixed with non-contaminated soil in proportions of 5, 10, 15%, and after laboratory analysis was utilized to cultivate barley, wheat, oats, and quinoa. After 70 days, plants were harvested and soil samples were analyzed. The concentration of metals (Cd, Pb, Zn) in soil samples was measured with an atomic absorption device and then the Average daily doses, Hazard quotient, Geo-accumulation index, Contamination factor, Pollution load index, Hazard index, and Risk index were computed to determine risk assessment. The highest value of the indices was in the pre-sowing soil samples and in the mixing percentages of 50 and 100% of contaminated soil, which were in a critical state. The geo-accumulation index of these metals was following the guidelines of the American Environmental Protection Agency in the polluted and severe pollution range. Meanwhile, with the plants' cultivation, these amounts were planted suitably in the rhizosphere soil and were at an acceptable level. Only in the sample of 5% contaminated soil and wheat plant, the pollution load index was in the medium range. For the age category of adults compared to children, these indices decreased. The high rate of skin absorption and the risk index through inhalation indicate an increase in the possibility of non-cancerous risk for the drilling workers and the adverse health effects for the residents of the area. The probability of carcinogenicity of the two metals lead and cadmium for adults was much higher than the standard level. The mean comparison of all pollution indices was significantly different between pre and post-sowing samples. Therefore, in oil regions, plant remediation technology can reduce the risks of the presence of heavy metals caused by the drilling mud and cuttings in agricultural lands to an acceptable level for human health.
Provenance investigation of material of Spring and Autumn Period Stone Chimes unearthed in the State of Chu in China
Authors: Li Liuliu , Qin Ying , Guo Jingxian , Huang Yali , Kan Xuhang , Huang Jianxun 
Published: August 2022

Abstract
To investigate the provenance of the Spring and Autumn Period stone chimes unearthed in the State of Chu in China and the relationship of ancient stone chime and Lingbi Qing stone, seven ancient stone chime samples that were collected from the Jiu Liandun tombs, Lei Gudun tombs and Shuangdun tomb were analysed by petrographic microscope and X-ray fluorescence spectrometry. The results from the chime samples were compared with the seven stone samples that were found nearby the ancient sample sites. The results indicate that the raw material of two samples unearthed from the Shuangdun tomb in Anhui province may have come from Lingbi city, the composition of stone chime samples JIdM1-27 and LgdM2:122 were similar to marble sample Xft2 from Suizhou City, and samples JldM2-34 and LgdM2-117 were distinctly different from the contrastive sample such that the provenance of the stone materials was unclear. This research is the first to study the provenance of Chinese ancient stone chime materials, and the results should provide insight into the study of Chinese ancient stone chime and Chu Music.
A novel overlapping community detection algorithm in smart city combining interest topic and local density
Authors: CHEN Yanyan , JIANG Yuanyuan , HOU Pengfei , Li Hui , GONG Rongrong , YANG Juan 
Published: August 2022

Abstract
It is very important to use ontology user portraits to describe the semantic structure interests of users and to study the similarity relations among user portraits for discovering overlapping interest communities in the process of building smart cities. The user interest’s hierarchical characteristics can produce different similarity relationships, forming interest clusters. The current paper proposes an overlapping community identification method based on hierarchical characteristics of user interest and local density is proposed, which can effectively promote the construction of smart cities. Firstly, a user hierarchical interest model based on ontology knowledge base was constructed to determine the users’ multi-granularity topic similarity. Then, a heterogeneous hypergraph was constructed by using multi-granularity topic similarity and user following similarity to describe the interest network. Using the peak mechanism of interest density, the community detection method was applied to identify the communities of interest. The real performance of the algorithm on multiple networks was verified by experiments. Experimental results showed the superiority of the presented algorithm over the classical overlapping community identification approach in terms of precision and recall rate.
Influence of 4-dodecylbenzenesulfonic acid as a surfactant on a graphite-based dielectric in powder mixed electric discharge machining
Authors: Pellegrini Giuseppe , Ravasio Chiara , Rosace Giuseppe , Trovato Valentina 
Published: August 2022

Abstract
A recent trend in micro EDM is the addition of powders into the dielectric. The presence of powders helps to lower the dielectric breakdown voltage and therefore the discharge occurs early. As a result, the discharge energy is better distributed, resulting in a greater number of discharges, each with less energy. The main advantage of using this method is the improvement of both the process performance and surface finishing of the workpiece. A critical aspect of the implementation of this technology is in general the management of the powder. In fact, to obtain advantages during the machining, the powders should be maintained dispersed into the dielectric to avoid their aggregation. This paper aims to study the concentration of the powder and the surfactant in the dielectric fluid on micro EDM drilling performance. Titanium alloy was used as workpiece material, hydrocarbon oil as dielectric, graphite as powder and 4-dodecylbenzenesulfonic acid as surfactant. The performance was evaluated considering the Material Removal Rate, the Tool Wear Ratio and the geometrical characteristics of the holes (overcut and taper rate). Graphite content positively affected both Material Removal Rate and Tool Wear Ratio; a larger spark gap was observed as well. The use of surfactant is required for mix stability but increasing its percentage generally reduces the effects of graphite and increases data dispersion as well.
Reversion of the loss of breast epithelial polarity caused by obesity
Authors: Vidi Pierre-Alexandre , Holmes Julia , Gaber Mohamed , Jenks Monica , Wilson Adam , Loy Tucker , Lepetis Cassandra , Vitolins Mara , Herbert Brittney-Shea , Cook Katherine 
Published: August 2022

Abstract
Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of obesity, and cultured breast acini. Proliferation and disruption of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, epithelial polarity loss was prevented by antioxidants and could be reverted by normalizing culture conditions. This study provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.
Microrobotics a new approach in ocular drug delivery system: a review
Authors: Kakde Ishwar , Dhondge purva , Bansode Deepali 
Published: August 2022

Abstract
The traditional drug delivery system (DDS),which includes needles and pills, somehow doesn't support the desired consistent medication level in the body. The distribution location, tissue barriers, and the type of pharmacological agents used all have a role in the success of therapeutic drug delivery. The human eye is a light sensitive and pressure sensitive organ. The reason for this is due to the eye's complicated structure and physiology, which restricts the effectiveness of some medical operations. The drug delivery medium must be compatible with the drug and bind to it easily. Microrobotics is possible method for minimally invasive targeted therapy which is a wireless manipulation, positioning of drug delivery magnetic millimeter and submillimeter platforms into the eye. Microrobots have shown that they can do microscale activities such as drug delivery, cell manipulation, micro assembly, and bio sensing with minimal human intervention. Much more futuristic devices, such as drug-delivery submarines, are also being researched (Microrobots). Microrobots operated by external magnetic fields are a viable method for delivering minimally invasive medicine (MIM). The article includes Ocular microrobots when posses the potential to revolutionize the treatment of a wide range of disorders affecting the front and posterior regions of the eye, its mechanics using magnet.
Safety and Immunogenicity of SARS-Cov-2 Vaccine MVC-COV1901– Do Elderly Need a Higher Dose?
Authors: Lien Chia-En , Waits Alexander , Chen Jau-Yuan , Cheng Wei-Hong , Yeh Jih-I , Hsieh Szu-Min , Chen Charles , Janssen Robert , Lin Tzou-Yien 
Published: August 2022

Abstract
Older adults are subject to higher COVID-19 infection and mortality rates. Even though vaccination programs prioritize the elderly, they are under-represented in clinical trials. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine has been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age. To further assess safety and immunogenicity of MVC-COV1901 vaccine in participants of 65 years and older, a double-blind, randomized, multi-center study compared high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart. The results have been stratified by the comorbidity status. Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities. Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommended high dose for the elderly.
Comparative effects of dietary methionine and cysteine supplementation on redox status and intestinal integrity in immunologically challenged-weaned pigs
Authors: Koo Bonjin , Choi Janghan , Holanda Debora Muratori , Yang Chengbo , Nyachoti Charles Martin 
Published: August 2022

Abstract
The study aimed to investigate the effects of dietary Met and Cys supplementation in immunologically challenged weaned pigs. Forty weaned piglets (6.5 ± 0.3 kg) were randomly allocated to five treatment groups. The treatment included: (1) sham-challenged control (SCC), (2) challenged control (CC), (3) MET (CC + 0.1% DL-Met), (4) CYS (CC + 0.1% L-Cys), and (5) MET+CYS (CC + 0.1% DL-Met + 0.1% L-Cys). On day 7, all pigs were intramuscularly injected with either Escherichia coli O55:B5 lipopolysaccharides or phosphate-buffered saline. Blood, liver, and jejunum samples were analyzed for immune response and redox status. The CC group had lower (P < 0.05) villus surface area and higher (P < 0.05) flux of 4-kDa fluorescein isothiocyanate dextran (FD4) than the SCC group. A lower (P < 0.05) glutathione (GSH) concentration was observed in the jejunum of pigs in the CC group than those in the SCC group. Dietary Cys supplementation increased (P < 0.05) villus surface area, GSH levels, and reduced (P < 0.05) the flux of FD4 in the jejunum. Dietary Met supplementation enhanced (P < 0.05) hepatic GSH content. Pigs in the MET group had lower serum IL-8 concentration than those in the CC group. There was a Met × Cys interaction (P < 0.05) in serum IL-4 and IL-8 concentrations, and Trolox equivalent antioxidant capacity. Dietary L-Cys supplementation restored intestinal integrity and GSH levels that were damaged by lipopolysaccharides administration. Dietary DL-Met supplementation improved hepatic GSH and reduced systemic inflammatory response, but antagonistic interaction with dietary L-Cys supplementation was observed in the inflammatory response and redox status.
U.S. Medical Organizations and Climate Change Advocacy: A Review of Public Facing Websites
Authors: Bush Thomas , Jensen William A. , Katsumoto Tamiko R. 
Published: August 2022

Abstract
Background
Climate change poses a risk of health catastrophes and must be expeditiously addressed across the health care sector. Physicians are considered trustworthy and are well positioned to discuss climate change with patients. A unified strategy by all U.S. medical societies is essential to effectively mitigate their carbon footprint and address health concerns.
Methods
We conducted a review of the public facing websites of member organizations of the AMA House of Delegates and the AMA, which were scored based on inclusion of content related to climate change in position statements or policies, task forces or committees, patient education materials, practice recommendations and any official society publications. Membership in the Medical Consortium on Climate Change and Health or participation in the organization My Green Doctor were recorded as indicators of a commitment to providing educational resources about mitigation and adaptation to climate change. The availability of a virtual option for annual meetings, as a potential means to reduce the carbon footprint of attendees, was trended from 2021 to 2022.
Results
Fifty out of 111 U.S. medical organizations (45%) had at least one metric with a reference to climate change and sixty-one organizations (55%) had no evidence of such website content. Out of 111 websites, only 20% (N = 22) had position statements or policies pertaining to climate change, 11% (N = 12) had committees or task forces dealing with climate change, 8% (N = 9) provided patient education resources on climate change, 21% (N = 23) included green practice recommendations and 45% (N = 50) had an article in an official society publication addressing climate change. Only 14% (N = 15) were listed as member societies of the Medical Consortium on Climate Change and 2% (N = 2) were participating organizations with My Green Doctor.
Conclusions
Viewed through the lens of medical society websites, there was a wide variation in efforts to address climate change. The high performing organizations can serve as a guide for other societies to help mitigate and adapt to the climate emergency.
Nesfatin-1 stimulates CCL2-dependent monocyte migration and M1 macrophage polarization: implications for rheumatoid arthritis therapy
Authors: Chang Jun-Way , Liu Shan-Chi , Lin Yen-You , He Xiu-Yuan , Wu Yi-Syuan , Su Chen-Ming , Tsai Chun-Hao , Chen Hsien-Te , Fong Yi-Chin , Hu Sung-Lin , Huang Chien-Chung , Tang Chih-Hsin 
Published: August 2022

Abstract
Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and Ccl2 mRNA expression. Nesfatin-1-induced stimulation of CCL2 expression and monocyte migration involved the MEK/ERK, p38 and NF-κB signaling pathways. Notably, nesfatin-1-induced increases in CCL2 expression favored M1 macrophage polarization, which increased the expression of proinflammatory cytokines IL-1β, IL-6 and TNF-α. Finally, nesfatin-1 shRNA ameliorated the severity of inflammatory disease and reduced levels of M1 macrophage expression in CIA mice. Our studies confirms that nesfatin-1 appears to be worth targeting in RA treatment.
Joint effects of prenatal household air pollution exposure from multiple sources on preterm birth - A case-control study with propensity score matching
Authors: Liu Xin-Chen , Strodl Esben , Yang Wei-Kang , Huang Li-Hua , Yin Xiao-Na , Wen Guo-Min , Sun Deng-Li , Xian Dan-Xia , Hu Bing-Jie , Chen Weiqing 
Published: August 2022

Abstract
Prenatal exposure to household air pollution (HAP) has been suggested as a major risk factor for preterm birth (PTB). However, the effects of simultaneous prenatal exposure to multiple HAP sources on PTB have rarely been studied. We therefore conducted a case-control study on 21995 mother-child dyads after propensity score matching (PSM). After PSM, a series of logistic regression analysis on associations of environmental tobacco smoke (ETS), cooking oil fumes (COFs), burning mosquito coil (BMC), indoor burning incense (IBI) and household renovation (HR) with PTB were conducted to evaluate their independent and joint effects on PTB. Compared to mothers without exposure, prenatal exposure to each individual HAP source increased the PTB risk. Moreover, the accumulative effects of prenatal exposure to five sources of HAP on the risk of PTB were observed. Finally, we found synergistic effects between prenatal exposure to COFs and IBI, as well as between BMC and IBI, on PTB on both multiplicative and additive scales. Our results suggest that prenatal exposure to different sources of HAP might increase the risk of PTB and that accumulative effects, as well as synergistic interactions, between different HAP sources on PTB might exist.