Search

Background: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. Methods: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. Results: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). Conclusion: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results. [ABSTRACT FROM AUTHOR]

Background and Aims: Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1–rs11543848 and HER2–rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1–rs11543848 and HER2–rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: A total of 314 women including 164 breast cancer patients and 150 age and gender‐matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra‐ARMS‐PCR for genotyping and gel electrophoresis. Results: Our results indicated that HER1–rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258–5.6756, p = 0.0833). Similarly, the HER2–rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876–6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. Conclusion: In conclusion, HER1–rs11543848 and HER2–rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. Methods: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. Results: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). Conclusion: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1–rs11543848 and HER2–rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1–rs11543848 and HER2–rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods A total of 314 women including 164 breast cancer patients and 150 age and gender‐matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra‐ARMS‐PCR for genotyping and gel electrophoresis. Results Our results indicated that HER1–rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258–5.6756, p = 0.0833). Similarly, the HER2–rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876–6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p

Background: Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods: Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results: The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57–3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33–17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27–11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02–1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57–1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61–1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30–2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10–2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42–1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42–105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions: Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.

Aims Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we aim to establish whether tramadol, fentanyl, or codeine affects Nav1.5 current. Methods and results Using whole-cell patch-clamp methodology, we studied the effects of tramadol, fentanyl, and codeine on currents of human Nav1.5 channels stably expressed in HEK293 cells and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. In fully available Nav1.5 channels (holding potential −120 mV), tramadol exhibited inhibitory effects on Nav1.5 current in a concentration-dependent manner with an IC50 of 378.5 ± 33.2 µ m. In addition, tramadol caused a hyperpolarizing shift of voltage-gated (in)activation and a delay in recovery from inactivation. These blocking effects occurred at lower concentrations in partially inactivated Nav1.5 channels: during partial fast inactivation (close-to-physiological holding potential −90 mV), IC50 of Nav1.5 block was 4.5 ± 1.1 μ m , while it was 16 ± 4.8 μ m during partial slow inactivation. The tramadol-induced changes on Nav1.5 properties were reflected by a reduction in AP upstroke velocity in a frequency-dependent manner. Fentanyl and codeine had no effect on Nav1.5 current, even when tested at lethal concentrations. Conclusion Tramadol reduces Nav1.5 currents, in particular, at close-to-physiological membrane potentials. Fentanyl and codeine have no effects on Nav1.5 current. [ABSTRACT FROM AUTHOR]

Copyright of Fly Ash Comprehensive Utilization is the property of Hebei Fly Ash Comprehensive Utilization Magazine Co., Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background The personal, environmental, and behavioral risk factors that play an important role in the spread of SARS-CoV-2 are still largely unclear. At the same time, there is limited evidence on the effectiveness of specific countermeasures for SARS-CoV-2. As a first approach to these questions, we use data from the Cologne Corona Surveillance (CoCoS) study, a large cross-sectional study conducted in Cologne, Germany, in June 2021. Methods This study was conducted in Cologne, Germany. Six thousand randomly selected Cologne residents who were 18 years of age or older were invited to participate in this study. Participant information was obtained via an online survey. Previous SARS-CoV-2 infections were recorded using self-reports. Sociodemographic and environmental information such as age, sex, living situation were collected. Potential SARS-CoV-2 risk behaviors were captured (workplace situation, adherence to hygiene regulations, and regular use of public transportation). Adherence to hygiene regulations was surveyed by determining the compliance with the ‘AHA’-rules (German acronym that stands for keeping a distance of 1.5 m from fellow citizens, hand disinfection, and wearing a face mask). Binary logistic regression analysis was used to identify risk factors for SARS-CoV-2 infection. Results A sample of 2,433 study participants provided information. Comparison of the sample with the general population showed representativeness for most sociodemographic characteristics with a preference for higher level of education in the study sample. Younger age, as well as living with minor children (under 18 years) in the same household were associated with a higher number of self-reported SARS-CoV-2 infections. Adherence to hygiene regulations was associated with fewer self-reported SARS-CoV-2 infections in adults. Gender, size of living space per person, workplace situation (work from home versus working with contact to colleagues/customers), and regular use of public transportation showed no significant association with self-reported SARS-CoV-2 infections in multivariable analysis. Conclusion The presented results provide initial indications of which sociodemographic and behavioral factors may be associated with SARS-CoV-2 infection. However, the fact that these factors were recorded without exact dates and could have changed accordingly during the pandemic or after infection limits the strength of the results. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Background: Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods: Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results: The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57-3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33-17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27-11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02-1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57-1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61-1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30-2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10-2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42-1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42-105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions: Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. Results: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (p < 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Conclusion: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa population. Methods: A case-control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for alleles and genotypes distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator. Results: Multiple parameters such as random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.001), HDL (p < 0.001), BMI (p < 0.001) and hypertension (p = 0.018) exhibited strong association with DR as compared to DM and HC. Our results displayed that the VEGF-rs833061 and RAGE- rs2070600 exhibited significant association (p < 0.05) with an increased DR risk, when compared with T2DM. In contrast, ALR2 didn't display association with DR (p > 0.05) when compared with T2DM, but showed association (p < 0.05) when compared with HC. Conclusion: Statistically significant association was observed in VEGF-rs833061 and RAGE-rs2070600 with DR in type 2 diabetic patients. While, ALR2- rs759853 didn't exhibit significant association with DR. This is the first study to report the association of candidate genes (ALR2, VEGF and RAGE) with DR in type 2 diabetes of Khyber Pakhtunkhwa population. More similar research studies are recommended with larger data sets in other ethnicities both national and international. [ABSTRACT FROM AUTHOR]

This paper uses TVP-VAR dynamic spillover method and spectral clustering algorithms to explore the impact of the Israel–Hamas war on the risk contagion in global financial and commodity markets. The war markedly intensified the overall risk spillover, with short-term impacts surpassing long-term effects. The static risk spillover and dynamic spillovers characteristics exhibited marked changes, but the directional risk spillovers in the time domain and the net risk level for each asset reacted differently. There was a significant shift in the global market's community divisions and net spillover patterns networks, which changed the way risk spreads between the global financial market. • The linkage among global financial and commodity market is examined. • The time–frequency domain dynamic spillover before and during the Israel–Hamas war is evaluated through TVP-VAR. • The community division changes of risk contagion are identified through spectral clustering algorithms. • The Israel–Hamas war has rendered significant impacts on financial and commodity market. [ABSTRACT FROM AUTHOR]

Aim: To assess the risk of sudden cardiac arrest (SCA) associated with the use of carbamazepine (CBZ) and establish the possible underlying cellular electrophysiological mechanisms.Methods: The SCA risk association with CBZ was studied in general population cohorts using a case–control design (n = 5,473 SCA cases, 21,866 non-SCA controls). Effects of 1–100 µM CBZ on action potentials (APs) and individual membrane currents were determined in isolated rabbit and human cardiomyocytes using the patch clamp technique.Results: CBZ use was associated with increased risk of SCA compared with no use (adjusted odds ratio 1.90 [95% confidence interval: 1.12–3.24]). CBZ reduced the AP upstroke velocity of rabbit and human cardiomyocytes, without prominent changes in other AP parameters. The reduction occurred at ≥30 µM and was frequency-dependent with a more pronounced reduction at high stimulus frequencies. The cardiac sodium current (INa) was reduced at ≥30 μM; this was accompanied by a hyperpolarizing shift in the voltage-dependency of inactivation. The recovery from inactivation was slower, which is consistent with the more pronounced AP upstroke velocity reduction at high stimulus frequencies. The main cardiac K+ and Ca2+ currents were unaffected, except reduction of L-type Ca2+ current by 100 µM CBZ.Conclusion: CBZ use is associated with an increased risk of SCA in the general population. At concentrations of 30 µM and above, CBZ reduces AP upstroke velocity and INa in cardiomyocytes. Since the concentration of 30 µM is well within the therapeutic range (20–40 µM), we conclude that CBZ increases the risk of SCA by a reduction of the cardiac INa.

A complex project, which has been recognized as a complex system with intricate interactions among organizations, is inevitably plagued with diverse risks and has fuzzy risk boundaries. Risk systems emerging from organizations and their interactions cannot be accounted for by traditional risk management theory. Research concerning risk response strategies that focus on these areas is urgently required. Through literature review and case analysis, 78 complex project organization-associated risks were identified. Three rounds of brainstorming meetings were used to collect risk association data from nine professional senior engineers participating in the construction process for complex projects within the last decade. The data were processed to model the complex network of complex project risk association. Targeted immunization and improved acquaintance immunization were applied to risk network of specific complex projects to empirically analyze changes in network density, helping to determine the optimal immunization strategy, including identification of critical risks and prevention of abnormal risk-associated transmission. Results demonstrated the feasibility and superiority of the model and the applicability of the response strategies developed. This research develops, for the first time, a list of complex project risks as well as a risk association complex-network model that is applicable to engineering practice, thus providing theoretical support for risk management in complex projects and an understanding of risk response strategies for decision makers. [ABSTRACT FROM AUTHOR]

Abstract Background Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. Methods In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. Results Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P

Background: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region., Methods: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR., Results: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352)., Conclusion: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. Methods: In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. Results: Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P < .001) and sporadic MTC (OR 0.53; 95% CI 0.36‐0.78; P = .001). An increased risk association was identified for NAT2Y94Y SNP (OR 1.62, 95% CI 1.17‐2.25, P = .004) and CDKN2A3′UTR SNP (OR 1.89, 95% CI 1.19‐2.98, P = .006) with sporadic MTC and RET S904S with hereditary MTC (OR 2.82, 95% CI 1.64‐4.86, P < .001). Meta‐analysis of RET SNPs including our cohort identified increased risk association of all four RET SNPs with MTC. Conclusion: In this largest SNP risk association study for MTC and the only risk association study of the 13 most commonly studied MTC associated SNPs in a single cohort of this rare cancer, a significant protective risk association of CDKN1ASer31Arg SNP with MTC was shown for the first time. Meta‐analysis identified significant risk association of all four RET SNPs, not observed in previous meta‐analysis. [ABSTRACT FROM AUTHOR]

Graphene is a nanomaterial with many promising and innovative applications, yet early studies indicate that graphene may pose risks to humans and the environment. According to ideas of responsible research and innovation, all relevant actors should strive to reduce risks related to technological innovations. Through semi-structured interviews, we investigated the idea of graphene as a risk (or not) held by two types of key actors: graphene researchers and innovation advisors at universities, where the latter are facilitating the movement of graphene from the laboratory to the marketplace. The most common idea found is that graphene is not a risk due to, e.g., low toxicity, low amounts produced/used, and its similarity to harmless materials (being “just carbon”). However, some researchers and advisors also say that graphene is a risk, e.g., under certain conditions or due to a lack of risk-related information. We explain the co-existence of these seemingly contradictory ideas through (1) the semantic ambiguity of the word risk and (2) a risk/no-risk rhetoric, where risks are mentioned rhetorically only to be disregarded as manageable or negligible. We suggest that some of the ideas held by the researchers and innovation advisors constitute a challenge to responsible research and innovation regarding graphene. At the same time, we acknowledge the dilemma that the discourse of responsible innovation creates for the actors: denying graphene risks makes them irresponsible due to a lack of risk awareness, while affirming graphene risks makes them irresponsible due to their everyday engagement in graphene development. We therefore recommend more research into what researchers and innovation advisors should do in practice in order to qualify as responsible. [ABSTRACT FROM AUTHOR]

Aims: Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we aim to establish whether tramadol, fentanyl, or codeine affects Nav1.5 current., Methods and Results: Using whole-cell patch-clamp methodology, we studied the effects of tramadol, fentanyl, and codeine on currents of human Nav1.5 channels stably expressed in HEK293 cells and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. In fully available Nav1.5 channels (holding potential -120 mV), tramadol exhibited inhibitory effects on Nav1.5 current in a concentration-dependent manner with an IC50 of 378.5 ± 33.2 µm. In addition, tramadol caused a hyperpolarizing shift of voltage-gated (in)activation and a delay in recovery from inactivation. These blocking effects occurred at lower concentrations in partially inactivated Nav1.5 channels: during partial fast inactivation (close-to-physiological holding potential -90 mV), IC50 of Nav1.5 block was 4.5 ± 1.1 μm, while it was 16 ± 4.8 μm during partial slow inactivation. The tramadol-induced changes on Nav1.5 properties were reflected by a reduction in AP upstroke velocity in a frequency-dependent manner. Fentanyl and codeine had no effect on Nav1.5 current, even when tested at lethal concentrations., Conclusion: Tramadol reduces Nav1.5 currents, in particular, at close-to-physiological membrane potentials. Fentanyl and codeine have no effects on Nav1.5 current., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The current study aims to investigate whether MDM2-SNP309 and p53R72P polymorphisms were associated with the risk of bladder cancer in Mongolian populations. These polymorphisms were evaluated in 79 controls and 63 bladder cancer cases using a PCR-restriction fragment length polymorphism assay, followed by analysis using multivariate logistic regression model and the Kaplan-Meier model to determine the odds ratio (OR) and age at onset of bladder cancer, respectively. The results revealed that the homozygous (G/G) genotype of MDM2-SNP309 increased the risk of bladder cancer compared to the wild-type (T/T) genotype [OR=1.629; 95% confidence interval (CI)=0.622-4.266] among Mongolians. On the other hand, the homozygous (P/P) genotype of p53R72P tended to protect the population from bladder cancer compared with the wild-type (R/R) genotype (OR=0.445; 95% CI=0.1727-2.147). It also showed that G/G genotype of MDM2-SNP309 increased the risk of bladder cancer when combined with the R/R genotype of p53R72P (OR=3.355; 95% CI=0.3914-28.766). Stratification by smoking and history of chronic urinary tract diseases tended towards increasing the risk association of the G/G (OR=2.3704; 95% CI=0.4308-3.044) and T/G genotypes (OR=5; 95% CI=0.8442-30.4088) of MDM2-SNP309 with bladder cancer, respectively. The protective role of P/P of p53R72P remained following stratification. MDM2-SNP309 and p53R72P were not involved in early age onset of bladder cancer in Mongolian patients. Taken together, MDM2-SNP309 and p53R72P had no significant association with bladder cancer in Mongolian patients. The two SNPs were also not able to predict early age at onset of bladder cancer. [ABSTRACT FROM AUTHOR]

Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log10-transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log10-unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. [ABSTRACT FROM AUTHOR]

Background Galectins are a family of carbohydrate binding proteins that regulate several cellular functions such as growth, migration, adhesion and apoptosis. Methods We investigated the expression of galectin (gal)-1 and galectin (gal)-3 in patients with oral squamous cell carcinoma (OSCC) and observed their effects on growth and survival of OSCC cell lines. Results OSCC patients expressed significantly higher levels of gal-1 and gal-3 in circulation (p < 0.0001) and at the tumour sites (p < 0.01) as compared to controls. Patients with higher tumour load showed significantly higher expression of both galectins than those with lower tumour load. In ROC analysis, serum levels of gal-1 and gal-3 at cut-off values of 4.875 and 0.871 ng/ml respectively, discriminated between healthy subjects and patients with more than 80% sensitivity and specificity. Similarly, logistic regression analysis revealed about 3-times higher risk of OSCC in subjects over expressing these proteins. Further, exogenous gal-1 and gal-3 significantly increased survival, proliferation and angiogenesis in OSCC cell lines. Conclusions Serum levels of gal-1 and gal-3 may serve as plausible markers for oral squamous cell carcinoma and may be useful in screening population at a higher risk. [ABSTRACT FROM AUTHOR]

Aim: To assess the risk of sudden cardiac arrest (SCA) associated with the use of carbamazepine (CBZ) and establish the possible underlying cellular electrophysiological mechanisms. Methods: The SCA risk association with CBZ was studied in general population cohorts using a case-control design ( n = 5,473 SCA cases, 21,866 non-SCA controls). Effects of 1-100 µM CBZ on action potentials (APs) and individual membrane currents were determined in isolated rabbit and human cardiomyocytes using the patch clamp technique. Results: CBZ use was associated with increased risk of SCA compared with no use (adjusted odds ratio 1.90 [95% confidence interval: 1.12-3.24]). CBZ reduced the AP upstroke velocity of rabbit and human cardiomyocytes, without prominent changes in other AP parameters. The reduction occurred at ≥30 µM and was frequency-dependent with a more pronounced reduction at high stimulus frequencies. The cardiac sodium current (I Na ) was reduced at ≥30 μM; this was accompanied by a hyperpolarizing shift in the voltage-dependency of inactivation. The recovery from inactivation was slower, which is consistent with the more pronounced AP upstroke velocity reduction at high stimulus frequencies. The main cardiac K + and Ca 2+ currents were unaffected, except reduction of L-type Ca 2+ current by 100 µM CBZ. Conclusion: CBZ use is associated with an increased risk of SCA in the general population. At concentrations of 30 µM and above, CBZ reduces AP upstroke velocity and I Na in cardiomyocytes. Since the concentration of 30 µM is well within the therapeutic range (20-40 µM), we conclude that CBZ increases the risk of SCA by a reduction of the cardiac I Na ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jia, Eroglu, Wilders, Verkerk and Tan.)

Abstract: Objectives: : To investigate the association between IL1B polymorphisms and risk of gastric cancer in a Chinese population, seven SNPs in the IL1B gene were selected for this study. Methods: : A multiplex genotyping method, which is based on adapter ligation and allele-specific amplification, was established to type seven SNPs on the IL1B gene simultaneously. One hundred and forty-one non-cancer outpatients and 97 patients with gastric cancer were genotyped, and the relation between IL1B polymorphisms and gastric cancer was statistically analyzed. Results: : The seven SNPs were successfully typed and the results were consistent with those obtained by both Sanger''s sequencing and PCR-RFLP. Handling with statistical analysis, we observed significantly different genotype frequencies of 0794C>T (χ 2 =6.11, P =0.05), 1274C>T (χ 2 =6.86, P =0.03) and 2143T>C (χ 2 =6.86, P=0.03) between patients and controls. Conclusion: : ALM-ASA is a potential method for multiplex SNP typing with a low consumption of genomic DNA. SNPs 0794C>T, 1274C>T, and 2143T>C are associated with gastric cancer. [Copyright &y& Elsevier]

Objective: To analyze the association between subject characteristics and degree of destructive periodontal disease in a randomly selected sample of 50/55-year-old individuals. Methods: A randomized and geographically stratified (urban/rural districts) subject sample composed of dentate 50-year-old ( n = 190) and 55-year-old individuals ( n = 359) from the county of Värmland, Sweden were examined. Data were collected through full mouth clinical and radiographic examinations and by the use of questionnaires. Based on the cumulative distribution of the individuals with respect to mean probing attachment loss (PAL), subgroups of subjects with the lowest (L20%) and highest (H20%) experience of PAL were identified. Similar classifications were made for never-smokers and current smokers. Correlation analyses and forward stepwise logistic regression models were performed. Results: The subgroup with the most extensive PAL loss (H20%) included a significantly higher proportion of (i) males (60 vs 33%), (ii) subjects with low educational level (65 vs 41%), (iii) smokers (49 vs 15%), and had (iv) less favorable lifestyle characteristics than the subgroup with minimal experience of PAL loss (L20%). The same pattern of differences was observed when the analysis was restricted to never-smokers, with the addition of a significantly lower proportion of subjects living in urban areas (40 vs 69%) in the H20% compared to the L20% subgroup. The stepwise logistic regression analysis revealed that number of teeth and smoking habits were significant factors in the identification of individuals in the L20% subgroup. For the H20% subgroup, number of teeth, gender, number of cigarettes/day and lifestyle index were significant explanatory variables. Conclusion: Number of remaining teeth and smoking habits were identified as the main discriminating factors for classification of subjects with regard to degree of destructive periodontal disease. [ABSTRACT FROM AUTHOR]

Little information is available on the occurrence and genetic variability of the diarrhoea-causing enteric protozoan parasite Giardia duodenalis in indigenous communities in Brazil. This cross-sectional epidemiological survey describes the frequency, genotypes, and risk associations for this pathogen in Tapirapé people (Brazilian Amazon) at four sampling campaigns during 2008–2009. Microscopy was used as a screening test, and molecular (PCR and Sanger sequencing) assays targeting the small subunit ribosomal RNA, the glutamate dehydrogenase, the beta-giardin, and the triosephosphate isomerase genes as confirmatory/genotyping methods. Associations between G. duodenalis and sociodemographic and clinical variables were investigated using Chi-squared test and univariable/multivariable logistic regression models. Overall, 574 individuals belonging to six tribes participated in the study, with G. duodenalis prevalence rates varying from 13.5–21.7%. The infection was positively linked to younger age and tribe. Infected children <15 years old reported more frequent gastrointestinal symptoms compared to adults. Assemblage B accounted for three out of four G. duodenalis infections and showed a high genetic diversity. No association between assemblage and age or occurrence of diarrhoea was demonstrated. These data indicate that the most likely source of infection was anthropic and that different pathways (e.g., drinking water) may be involved in the transmission of the parasite. [ABSTRACT FROM AUTHOR]

• Risk ontology modeling enables risk knowledge sharing and reasoning. • Studying logistics financial risk is based on risk-related perspective. • Apriori mines the associated risks and derives the corresponding association rules. • Jena reasoning machine is more flexible and suitable for ontology model reasoning. Previous research on logistics financial risk pre-warning and pre-control focuses on the linear causal relationship between risk and risk events. In fact, risk events in logistics financial field are often caused by multiple risk factors, which are directly or indirectly related to these risk factors. Therefore, it is helpful for the healthy development of logistics finance to find out the related risks of each logistics financial risk event and screen and control them one by one. This paper proposes OntoLFR (Logistics Financial Risk Ontology), and constructs the logistics financial risk ontology model to adapt to the variability, complexity and relevance of risk in early warning and pre-control. Then, based on the risk source association inference rules obtained by knowledge association analysis, Apriori algorithm is adopted to conduct association analysis on the risk hidden danger database, and the acquired association rules are reintroduced into the knowledge ontology database of risk event source to realize self-learning and self-correction of the knowledge ontology database. Taking the risk event (RW_risk) of the financing enterprise to escape, the feasibility of using the logistics financial risk ontology model for risk-related reasoning and analysis is verified. [ABSTRACT FROM AUTHOR]

Background: The chemopreventive activities of cruciferous vegetables were recognized in the early 1990s, followed by a growth of evidence in various cancer models, including breast cancer. To our knowledge, no studies have examined whether consumption of cruciferous vegetables has changed accordingly, and what impact, if any, on breast cancer risk may have resulted. Objective: The time trend in cruciferous vegetable intake was investigated between 1982 and 1998, and its associations with breast cancer risk were examined. Methods: In a hospital-based case-control study in 1491 patients with breast cancer and 1482 controls, loess curves were constructed to describe the relation between median consumption of cruciferous vegetables and year of admission. ORs and 95% CIs were calculated with unconditional logistic regression, adjusting for age, year of admission, family income, body mass index, cigarette smoking, age at menarche, parity, age at first birth, family history of breast cancer, hormone replacement therapy, and total meat intake. Results: Consumption patterns differed between cases and controls. A slow but steady increase in cruciferous vegetable intake was observed in the cases, although among controls, cruciferous vegetable consumption increased from 1982 to 1987, reached a plateau during 1988-1992, and then declined from 1993 to 1998. Accordingly, although an overall inverse association with breast cancer risk was observed for cruciferous vegetable intake (highest compared with lowest quartile-OR: 0.68; 95% CI: 0.55, 0.86; P -trend = 0.0006), the inverse association tended to be more pronounced within more recent-year strata, with an OR of 0.52 (95% CI: 0.33, 0.83) for 1993-1998 compared with an OR of 0.89 (95% CI: 0.64, 1.23) for 1982-1987. Conclusions: The consumption of cruciferous vegetables increased during the past 2 decades, showing different trends in cases and controls. The subtle but sustained increase in cruciferous vegetable intake reported by the cases could influence association studies with breast cancer risk.