Human papillomavirus (HPV) 52 is one of the prevalent oncogenic HPV genotypes in East Asia. Chinese women have the highest susceptibility to the HPV52 type, but research data on HPV52 genetic variability and its carcinogenicity in China is lacking.E6 and E7 oncogenes. HPV52 sequence alignment, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed by BioEdit software and MEGA X software.The present study aimed to investigate the genetic variability of HPV52 currently circulating among Chinese women by PCR sequencing the entire E6 gene and C751T, A801G in the E7 gene. Due to the dominance of lineage B in our study population, the results could not be used to assess the association of the HPV52 (sub)lineage with the risk of cervical lesions. In addition, no significant trends were observed between the nucleotide substitutions of HPV52 variants and the risk of cervical carcinogenesis.Between 2016 and 2018, the overall HPV infection rate was 21.3%, of which HPV52 was the most prevalent high-risk type (17.2%) in the Taizhou area, China. A total of 339 single HPV52-positive samples were included in this study. We obtained 27 distinct variation patterns of HPV52 with the accession GenBank numbers ON529577-ON529603. Phylogenetic analysis showed that 96.6% of HPV52 variants belonged to lineage B, which seemed to be uniquely defined by G350T, A379G (K93R) in the Our data showed that HPV52 variants were strongly biased towards lineage B. These results confirmed that cervical lesions in the Taizhou area are highly attributable to HPV52, which may be due to the high infection rate of lineage B in the population.The online version contains supplementary material available at 10.1186/s12985-022-01929-5. E6 and E7, which may increase the risk of infection with HPV52 in Chinese women [Cervical cancer caused by persistent infection with high-risk human papillomavirus (HPV) continues to be a global public health problem. According to GLOBOCAN 2018, there are approximately 106,400 new cases and 47,700 deaths related to cervical cancer annually in China, accounting for 18.6% and 15.2% of the global data, respectively , but theE1, E2, E4, E5, E6, and E7), the late regions (L1 and L2) and the long control region (LCR). When HPV infects cervical epithelial cells and integrates into the host genome, the expression of two major E6 and E7 oncoproteins increases uncontrolled, resulting in host cell immortalization, transformation, and carcinogenesis [E6 and E7 genes of HPV52 obtained from exfoliated cervical cells and explored their role in cervical cancer risk among Taizhou women in China.HPV52 genomes are approximately 7.9 kb, and their gene structure includes the early regions . HPV genotyping was performed using the GP5 + /bioGP6 + -PCR/MPG assay (CFDA Certified No. (2017): 3,404,697). This assay can simultaneously classify 27 different HPV types, including 14 high-risk HPV types  and 13 low-risk HPV types . The detailed operation process of HPV genotyping has been described in our previous studies [E6 and E7 genes of HPV52 were 52E6E7_F 5′-ACCCACAACCACTTTTTTTTAT-3’ and 52E6E7_R 5′-TTGCCTCTACTTCAAACCAGCC-3’, which were cited from a recently published article [The primer sequences specific for the  article . PrimersE6 gene nt 102–548 and E7 gene nt 553–852). Subsequently, the PCR amplification products were purified and sequenced on the ABI 3730xl DNA Genetic Analyser at BGI company. To avoid PCR or sequencing errors, all data were confirmed by repeating the PCR and sequencing reactions at least twice.The size of the PCR amplification product was 957 bp , including HQ537732 (A1), HQ537739 (A2), HQ537740 (B1), HQ537743 (B2), MZ374448 (B3), HQ537744 (C1), HQ537746 (C2), HQ537748 (D), and MZ374428 (E) [In this study, the HPV52 reference sequence (GenBank: HQ537732) was used as the standard for alignment and nucleotide site numbering. The variations in the software . One tho4428 (E) , 13.P values were two-sided, and the results were regarded as statistically significant if the P value was 0.05 or less.The association of cervical lesion risk with HPV52 variants was analysed using the chi-square test or Fisher’s exact test. Odds ratios (ORs) and relative 95% confidence intervals (95% CI) were calculated. All statistical analyses were performed using SPSS version 16.0 . Between April 2016 and December 2018, the overall HPV infection rate was 21.3% (3287/15429) in women who were screened for cervical cancer in Taizhou Hospital. Among all HPV-positive women, the infection rate of HPV subtypes is shown in Fig. E6 and E7 genes from HPV52 were obtained. Fourteen (4.1%) sequences were excluded due to the small number of HPV copies. Among 325 HPV52-infected women, 75 (23.1%) had normal and adequate cervices by colposcopy examination; therefore, no further biopsy diagnosis was performed. Sixty-one (18.8%) women refused further colposcopy examination. The remaining 189 (58.1%) underwent colposcopy biopsy for diagnosis, which was further used for risk association analysis, and 67 were diagnosed with normal cervices after biopsy, 53 with CIN1, 45 with CIN2, 24 with CIN3, and no cases of cervical cancer. The characteristics of the study population categorized by HPV52 (sub)lineage are shown in Table In the present study, 339 women  with a single HPV52 infection were selected  of collected HPV52 samples showed nucleotide variations. To visually distinguish the specific nucleotide variations of HPV52 lineage/sublineages, we summarized all of the changes in nucleotide and amino acid sequences in the entire E6 and E7 genes, a total of 35 single nucleotide substitutions were identified, with 17 (48.6%) nonsynonymous substitutions and 11 (31.4%) novel substitutions. The four most prevalent nucleotide substitutions were G350T , A379G (K93R)  in the E6 gene and C751T , A801G  in the E7 gene. These four nucleotide substitutions were specific to HPV52 lineage B, but no significant trends in the severity of cervical lesions were observed. Notably, there were three amino acid changes in the 93rd genetic code of the E6 oncoprotein: K93G, K93Q, and K93R. The corresponding nucleotide changes were A378G, A378C, and A379G, which belong to the B lineage in this study. To the best of our knowledge, the nucleotide substitutions of G108C (E3Q), T191C, G267A (D56N), T292G (I64S), T309C, G317A, T329C, and A347G in the E6 gene and A822G, C834T, and A843G in the E7 gene have not been reported in previous studies. However, these novel nucleotide substitutions were detected in only one or two samples, and thus, no statistical analysis was performed.In the E6-E7 sequences was inferred from 27 obtained HPV52 variants and 9 reference sequences lineage and a higher risk of CIN2 or worse lesions could not be well evaluated. Other (sub)lineages were not included in these analyses due to small numbers of samples. Furthermore, no significant difference in the relative risk for cervical carcinogenesis progression was observed among the nucleotide variations in HPV52 Persistent high-risk HPV infection has been identified as a major risk factor for cervical cancer. In China, the infection rates of high-risk HPV, such as HPV16, 18, 52, and 58, increase with the severity of cervical lesions . The oveE6 and E7 genes was found to be highly associated with the risk of cervical cancer [In this study, HPV52 was the most prevalent HPV type, followed by HPV58, 53, 16, 81, 39, 61, and 18. It is worth noting that the Gardasil 9-valent prophylactic vaccine approved for marketing in China in 2016 mainly targets HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. Therefore, the development of polygenic vaccines containing HPV53, 81, 39, and 61 would be more helpful for Chinese women to prevent HPV infection. Among all HPV types in China, the infection rate of HPV52 was relatively low in the late 1990s but has gradually increased since then , 22. Recl cancer –26. The E6 and E7 genes from HPV52 in the Taizhou area. Most of the HPV52 (96.6%) variants belonged to lineage B, which was consistent with previous reports on HPV52 (sub)lineage distribution in East Asia [We obtained 325 complete sequences of the ast Asia –30. It hast Asia . Given tast Asia . Therefoast Asia . Studiesast Asia , 31. DurE6 gene and C751T (96.6%), A801G (98.8%) in the E7 gene, which were specific to HPV52 lineage B. Of these, K93R was the only nonsynonymous substitution. Notably, in this study, there were three amino acid changes in the 93rd genetic code of the E6 oncoprotein, K93G, K93Q, and K93R, but no significant trends between the nucleotide substitutions of HPV52 variants and the risk for cervical carcinogenesis were observed. Previous studies have shown that K93R was associated with an increased cervical lesion risk in Korean women, but it has no correlation in Chinese women [Compared with the HPV52 reference sequence (GenBank: HQ537732), the four most prevalent nucleotide substitutions were G350T (98.8%), A379G (K93R) (96.3%) in the se women –33. The se women . In addiE6 and E7 genes in the Taizhou area, Southeast China. Our study confirmed that the common HPV52 infection in the Taizhou area of China when compared to other areas around the world is largely due to the high infection rate of lineage B in the population.In summary, this is the first comprehensive study to evaluate the genetic variants and phylogenetics of the HPV52 Additional file 1. Clinical data for HPV52 study in Taizhou area, China.


Raphanus sativus L. var. radculus pers) roots can appear after harvest. The antioxidant system and content of reactive oxygen species (ROS) will affect the blue discoloration. Currently, the reason for the blue discoloration is not yet clear. In order to reveal the mechanism of the blue discoloration of cherry radish, we selected the blue discolored cherry radish as the research object and the white cherry radish as the control. The difference in the antioxidant system between them were compared, including related enzymes and non-enzymatic antioxidants in this system. Meanwhile, the changes in the contents of 4-hydroxyglucobrassicin as a precursor substance and ROS were compared. The results showed that the activities of typical antioxidant enzymes decreased and the cycle of Glutathione peroxidase (GPX) and Ascorbic acid–Glutathione (ASA–GSH) was disturbed, leading to the reduction of antioxidant effect and the failure of timely and effective decomposition of superoxide anions (O2•−) and hydrogen peroxide (H2O2). In addition, the elevated level of O2•− and H2O2 led to the disorder of the antioxidant system, while the 4-hydroxybrassinoside was oxidized under the catalysis of peroxidase (POD) and eventually led to the internal blue discoloration in cherry radish. These results can provide a theoretical basis for solving the blue discoloration problem.Internal blue discoloration in cherry radish ( Raphanus sativus). This physiological phenomenon is related to oxidative stress in radish roots [2O2 or other ROS in the presence of POD, leading to the discoloration [Raphanus sativus L. var. radculus pers) is a type of four-season radish with a bright color which can be used in salad dressings [Radish is a vegetable species of brassica vegetables planted all over the world, and its main edible part of the plant is the thickened main root . Additiosh roots . The 4-hloration ,6,7. Theressings . In our 2O2 and O2•− are the two common forms of ROS, and their levels can be adjusted by the antioxidant systems [ROS is the typical oxidizing substance in plants, which is produced by various metabolic pathways and plays an important role in the physical process ,10. In n systems . An anti systems ,15. The  systems ,17,18,19In order to investigate the mechanism of blue discoloration in the cherry radish, we selected the blue discolored cherry radish and the white cherry radish as the materials of research in this study. Then, we explored the effect of internal blue discoloration on the cherry radish, including color, precursor, ROS and antioxidant system, with the aim of elucidating the possible mechanisms involved. The results would provide a theoretical basis for the inhibition of cherry radish internal bluing during postharvest storage.L*, a*, and b* values . Meanwhile, compared with the white cherry radish, the b* value of blue discoloration in the cherry radish decreased from 6.34 to 3.87 (p < 0.05), which indicated a direct correlation with blue change. The two sets of cherry radishes mentioned previously would be used for subsequent analysis.As illustrated in * values C–E were p < 0.05); 0.070 mg g−1 and 0.062 mg g−1, respectively. Studies have shown that the content of 4-hydroxyglucobrassicin is consumed in the process of discoloration during the storage, apparently [As parently ,20. Comp2O2 and O2•− were selected for evaluating the degree of oxidative stress. As 2•− and H2O2 of cherry radish increased significantly (p < 0.05) after blue discoloration. The O2•− content of blue discolored samples (0.062 μmol/g) was about 10 times that of samples without blue discoloration (0.006 μmol/g). The half-life of O2•− is very short and it does not cause more cellular damage by itself; however, O2•− easily transforms into more toxic forms of ROS [2O2 content of the discolored samples was 0.32 μmol/g, which was twice that of the samples without discoloration (0.17 μmol/g). H2O2 is a by-product of aerobic metabolism, which could be synthesized by both enzymatic and nonenzymatic cellular processes such as photorespiration, redox reaction and electron chain [2O2 is a moderately reactive and long-lived molecule, it plays an important role in various physiological processes, but the overproduction could cause oxidative damages of the cell [2•− and H2O2 were observed in the discolored cherry radish, which indicated the occurrence of oxidative stress. This is consistent with the previous findings of elevated H2O2 and O2•− content in blue discolored radishes [The ROS content is one of the indexes for evaluating the degree of oxidative stress . In our s of ROS . The H2Oon chain . Additiothe cell . In our ation 0.1 μmol/g. y p < 0.0 after blp < 0.05), especially superoxide dismutase (SOD) and catalase (CAT) . The removal of O2•− is transformed into H2O2 by SOD, and then decomposed into H2O and O2 by CAT.The results showed that the activity of the antioxidant enzymes of the blue discolored cherry radish were significantly lower than the uncolored cherry radish (se (CAT) A,B. The O and O2 . The CAT2O2 into H2O, resulting in a partial aggregation of H2O2. The decreased activity of the two enzymes explained the change in ROS content, which was consistent with the results of the H2O2 and O2•− content measurements. In radish roots, SOD can suppress ROS [Both enzymes showed reduced activity in the blue discolored samples. The reduction in CAT activity also reduced the degree of decomposition of Hress ROS . As reporess ROS .2O2 to produce H2O [−1 and the white cherry radish was 432.68 U g−1; the difference in activity was nearly two-fold. With the decrease of GPX activity, H2O2 cannot decompose into water in time and its content increases. Furthermore, GPX use GSH as a cofactor, and hence convert to glutathione disulfide (GSSG) [−1 and 0.12 U g−1, respectively  . Glutathe (GSSG) . The GR ectively B. At thesh roots .p < 0.05). The ASA content was 13.59 mg 100g−1 in the blue discolored cherry radish and 18.24 mg 100 g−1 in the uncolored cherry radish. ASA is the most abundant antioxidant in plants, which is also one of the most powerful compounds for reducing ROS, by the ASA–GSH cycle or directly [−1 and 286.82 μg g−1, respectively. As a reductant of ROS and a substrate for certain peroxidases, GSH plays a vital antioxidant role in plants. A higher content of GSH contributes to relieve drought, salinity, high/low temperatures and heavy metal [−1; it was significantly lower than the enzyme activity in the white cherry radish (10.53 U g−1). DHAR is a key enzyme regulating the oxidation reduction state of ASA, which can promote the reduction of docosahexaenoic acid (DHA) to regenerate ASA, which is used to scavenge free radicals in the body and protect plants from damage [−1 and 0.027 U g−1, respectively   E. APX hag stress .2O2 elimination [2O2 could not be decomposed effectively and its content increased. The activity of DHAR and GR decreased by different degrees, and the ability of DHAR and GR to catalyze the generation of ASA and GSH decreased. Therefore, in the blue discolored cherry radish, the lower ASA and GSH contents and DHAR and GR activities increased ROS production and oxidative stress. This was consistent with the finding that blue discoloration of the radish root was associated with oxidation and reduction systems [Research has also shown that the higher enzyme activities of the ASA–GSH cycle largely contribute to Hmination . In the  systems . Specifi−1) than samples without blue discoloration (2122.31 U g−1). Teranishi et al. reported for the first time that 4-hydroxyglucobrasicin produces blue substances under the catalysis of POD, and Zhang et al. also found that POD acts as an oxidation factor to oxidize precursor substances to blue [POD and PPO are typical oxidoreductases in plants which may cause the undesired change in color of fruits and vegetables during postharvest storage ,35. Ther to blue . Therefo2•− was transformed into H2O2 by SOD, and then decomposed into H2O and O2 by CAT, the GPX cycle and the ASA–GSH cycle. In the GPX cycle, the GSH content, GR and GPX activities in blue discolored cherry radishes were lower than those in the white cherry radish group. The ability of GR to catalyze GSSG to generate GSH and GPX to decompose H2O2 decreased. There was also a phenomenon in the ASA–GSH cycle that the decomposition effect of H2O2 decreased and the activity of related enzymes to catalyze the production of ASA and GSH decreased. In the cycle of ASA–GSH, the enzymes involved in the regulation of blue discoloration were mainly DHAR and APX, but not MDHAR. Although ASA and GSH as reducing substances were thought to delay the discoloration of fruits and vegetables, their content was reduced and the production pathway was inhibited in the blue discolored cherry radish [Researchers have reported that the blue discoloration of the radish root was related to oxidation and reduction systems ,36. By sy radish ,38. The y radish . This waRaphanus sativus L. var. radculus pers) were purchased from a commercial market, Guoxiangsiyi . The 4-hydroxyglucobrassicin was purchased from PhytoPlan . The methanol was purchased from Thermo Fisher Scientific (China) Co., Ltd. . The trifluoroacetic acid (TFA) was purchased from Sigma-Aldrich . The ASA was purchased from Biotopped . Additionally, the ammonium molybdate was purchased from AI Qaeda chemical plant . Other chemicals were obtained from Beijing Chemical Plant .The cherry radishes . Then, they were stored at −80 °C for further analyses, including the precursor content, ROS content, enzymatic activities and non-enzymatic antioxidants content.L* , a* (negative indicates green and positive indicates red), and b* (negative indicates blue and positive indicates yellow).The surface color of cherry radish was measured by a colorimeter CM-700d1 , and parameters were measured three times at three different points on each cherry radish and expressed as v/v) trifluoroacetic acid (TFA) solution (A) and methanol solution (B). The flow rate was 0.8 mL/min in a linear gradient starting from 100% A and reaching 50% A in 20 min. The injection volume of the sample was 20 μL and the determination wavelength was 280 nm, using external standard as quantitative method. The standard curve was linear between 0.05 and 1 mg mL−1.The determination of 4-hydroxyglucobrassicin was carried out by high-performance liquid chromatography (HPLC), and the method was performed as described by Teranishi and Masayasu . Then, t2O2 and O2•− were carried out using commercial kits . For O2•− measurement, samples (1 g) were added to 1 mL extraction solvent, then the mixture was ground in an ice bath and centrifuged at 12,000 rpm for 20 min at 4 °C. Additionally, for H2O2 measurement, samples (0.5 g) were extracted with 1 mL extraction solution in an ice bath, and after grinding the mixture was centrifuged at 8000 rpm for 10 min at 4 °C. The supernatant was used to analyze the contents of O2•− and H2O2 according to the manufacturer’s instructions. The absorbance was measured at 530 nm and 415 nm by UV-1800 spectrophotometer . The results are expressed in μmol g−1.The measurements of H−1.The activities of POD, PPO, SOD, GPX, CAT, APX, MDHAR, DHAR and GR were measured by commercial kits  and a UV-1800 spectrophotometer . Firstly, samples were extracted by extraction solvent (solid–liquid ratio is 1:5), the mixture was ground in an ice bath, and centrifuged at 10,000 rpm for 10 min at 4 °C to obtained the enzyme extract. The next steps were measured according to the manufacturer’s instructions. The results are expressed in U g1 was the volume of the tested sample (mL) and W was the quality of the sample (g).The content of ASA was determined using a molybdenum blue colorimetric method with minor modification . For ASA−1. The standard curve was made by 3.125–100 μg mL−1 GSH.For GSH measurement, the samples were flushed twice by phosphate-buffered solution (PBS), firstly, then the samples were accurately quantified (0.2 g) and extracted with extraction solvent (1 mL). The mixture was centrifuged at 8000 rpm for 10min at 4 °C, and measured by a commercial kit  according to the manufacturer’s instruction. In addition, the absorbance was measured by UV-1800 spectrophotometer  at 412 nm. The results are expressed in μg gt-tests of comparison of means using SPSS Statistic 25 . The value of p < 0.05 represents statistical significance. The different letter above the bars represented significant difference (p < 0.05).All measurements were repeated three biological times, and each value in figures was presented as the mean ± standard error. All the data were analyzed with independent samples Blue discoloration will occur in cherry radishes during post-harvest storage. Compared with the uncolored cherry radish, the blue discolored cherry radish had the higher content of ROS. The higher content of 4-hydroxyglucobrassicin as the precursor was oxidized by the overproduction of ROS due to the disturbance of the antioxidant system under the catalysis of POD, and blue discoloration in cherry radish appeared. This study provides a theoretic basis and experiment foundation for the inhibition of internal blue discoloration of the cherry radish during postharvest storage.


High-density polyethylene (HDPE) materials have many applications in the municipal solid waste (MSW) landfills. HDPE gravity drainage pipes are commonly utilized in MSW landfills because of the polymer’s resistance to harsh chemical conditions. When landfill wastes are freshly filled, the weight acting on the leachate collection pipe increases. The temperature of the leachate collection pipe increases as a result of the heat produced by the decomposition of organic components after waste filling. In this paper, the effects of sequentially applying pressure and elevating temperature on the deformation characteristics (such as deformations and strains) of HDPE pipes are investigated. Measurements of pipe deformations and circumferential strains from model experiments in which 110 mm HDPE pipes were backfilled with sand and subjected to 300 kPa of maximum vertical pressure at temperatures of 20, 60 and 80 °C showed the following results: (1) a classification of pipe behavior relative to the surrounding soil stiffness is advantageous for HDPE pipe design; (2) when temperature increases to 60 °C and 80 °C, the strain distribution around the pipe changes from V-shaped to U-shaped, and the pipe deformation profile changes from elliptical to rectangular; (3) when temperature increases from 20 °C to 60 °C, the vertical and horizontal pipe deflections increase by a factor of 1.08~1.19; (4) when temperature increases from 60 °C to 80 °C, the vertical and horizontal pipe deflections increase by a factor of 1.15~1.31; and (5) the existing analytical method that considers two extreme interfaces can capture the deformations measured in the model test well. In addition, preliminary recommendations for the design of leachate collection pipes are provided based on the analysis of differences in pipe profile versus temperature. High-density polyethylene (HDPE) pipes are an essential component of the leachate collection system of a number of municipal solid waste (MSW) landfills ,5,6,7,8.Existing research quantifies the effect of coarse gravel and backfill construction on landfill leachate collection pipe deformation ,10. KrusRecent studies indicate, however, that municipal solid waste dumps may be far hotter than anticipated a decade ago. Presently, the liner temperature of a conventional municipal solid waste landfill is anticipated to be between 30 and 40 °C, whereas the liner temperature of a municipal solid waste dump may reach 60 to 80 °C . KrushelIn previous studies, strain gauge measurements at ambient temperatures were used to forecast the deformation profiles of buried flexible pipes ,18, whilThis work aims to evaluate the effect of successively applying pressure and elevating temperature on the deformation characteristics of a buried HDPE pipe. Large-scale physical tests were conducted to assess the deformation and circumferential strain of HDPE pipes backfilled with sand at 20 °C, 60 °C and 80 °C and at up to 300 kPa of vertical pressure. The observed pipe deformations and circumferential strains were compared with known analytical solutions and their efficacy was evaluated. In addition, preliminary recommendations for the design of leachate collection pipes are provided based on analyses of differences in pipe profile versus temperature.This study presents the results of tests conducted on specimens using a three-directional mobile loading platform developed by the authors. The platform featured a reaction frame consisting of a self-balancing three-dimensional loading steel structure, two static actuators, an electrohydraulic servo loading control system, and a test tank measuring 1 m in length, 1 m in width, and 0.71 m in height . The standard dimension ratio is defined as the ratio of the pipe’s outer diameter to the pipe’s thickness. The pipes that were examined had an external diameter of 110 mm.Both the SDR 11 and the SDR 26 pipe were put to the test. The SDR 11 pipe had an average wall thickness of 10 mm, and the SDR 26 pipe had an average wall thickness of 4.2 mm. To an accuracy of within 0.01 mm around the pipe’s center, vertical and horizontal diameter changes of the pipes were measured with displacement transducers. The variations of the inner diameter of the pipes during the tests were also obtain by a laser displacement transducer inside the pipe. There were gaps with a width of 5 mm that were covered with foam boards. These gaps existed between the ends of the pipe and the tank walls. Because of this treatment, the HDPE pipes’ axis deformation was not restricted throughout the testing, and backfills were prevented from entering the interior space of the HDPE pipes. In addition to that, this treatment is effective in preventing the HDPE pipes from becoming jammed up against the tank walls.According to GB/T13663.2 , the matThe sand was backfilled with sand pourers to the height of the bottom of the pipe. After the HDPE pipe was put on the existing sand, the sand was backfilled with sand pourers to the designed height of the specimen. Sand pouring is a method through which the density and uniformity of backfill soil can be well-controlled ,23.During the test, strain gauges were utilized so that the HDPE pipe strain could be determined. Before testing, river sand was used to fill the test tank, and then it was allowed to dry before being screened using mesh sizes of 2.36 mm. Sand pourers were used to prepare the specimens. The characteristics of the materials used for backfilling are detailed in Poorly graded and medium-coarse consistency sand was used in this study, as specified by .During the experiments, measurements were taken of the earth pressure distributions in the backfill materials. During the testing, a strain-type micro earth pressure cell with an accuracy of 0.25 percent FS was utilized. The range of the cell was from 6 to 600 kPa. The diameter of the earth pressure cell was 35 mm, while its thickness measured 15 mm. The earth pressure cell had a temperature range of operation that went from −40 °C to 125 °C.The procedure for the tests conducted in this study was designed to simulate the sequential application of pressure and elevated temperature on leachate collection pipes in MSW landfills.3 in this study [With each additional layer of waste that is placed in a landfill, there is a corresponding increase in the amount of pressure exerted on the HDPE pipe that is used for leachate collection. The height of the daily filled waste is assumed to be 5 m , and theis study ,27. As ais study ,8. DurinFollowing completion of the waste filling process, heat generation occurs in landfills as a result of the degradation of organic components. This heat generation correlates to an increase in the temperature of the waste. According to Yeșiller et al. , the temIn this particular piece of research, temperature sensors with an accuracy of 0.2 °C. and a temperature range of −50 °C to 500 °C were utilized so that the temperature of the HDPE pipe could be brought up to the desired level. As can be seen in The details of the tests conducted in this study are outlined in Even though many readings were collected over the course of the test procedure, the ones discussed are limited to those that pertain to the strain and deformation of the pipe walls. Additional information can be found in . MeasureThe circumferential strain of each section after the application of vertical pressure to an HDPE pipe at a temperature of 20 °C is shown below.As shown in The strain profiles that were taken from the pipe walls during this test are displayed on a circular axis in In addition, the strain profiles allowed for the prediction of the shape that the pipe would have once it was distorted. Howard  demonstrAs shown in The design for the currently used landfill leachate collection pipes is primarily based on a widely used calculation method for buried pipe design. This method is known as the Iowa formula ,31,32,33v) is negative, indicating compression. The horizontal deformation (ΔDh) is positive, indicating tension.The long-term mechanical behavior of buried pipe is very important for pipe design , and thev of the HDPE pipe was −0.1983 mm and the ΔDh of the HDPE pipe was 0.1482 mm. After the temperature of the specimen was increased to 60 °C for three days, the ΔDv of the HDPE pipe increased to −0.2357 mm, which was increased by a factor of 1.19, and the ΔDh of the HDPE pipe increased to 0.1750 mm, which was increased by a factor of 1.18. After the temperature of the specimen was increased to 80 °C for three days, the ΔDv of the HDPE pipe increased to −0.2604 mm, which was increased by a factor of 1.31, and the ΔDh of the HDPE pipe increased to 0.1865 mm, which was increased by a factor of 1.26.As shown in The creep measurements of the HDPE pipe in the duration of the test under 50 kPa, 100 kPa, 150 kPa, and 200 kPa vertical pressures are quantified and shown in cE = the elastic modulus of the HDPE pipe at certain temperature (kPa); 20E°C = the elastic modulus of the HDPE pipe at 20 °C (kPa); T = the temperature of the HDPE pipe (°C).Calculations of pipe deflections were performed at temperatures of 20 °C, 60 °C and 80 °C using an analytical approach provided by Zhang et al.  based onθ = 45° were determined by Equation (2):ru = radial deformation of the HDPE pipe (mm); r = radius to the centroid of the pipe (m); cE = the elastic modulus of the HDPE pipe (kPa); cv = Poisson’s ratio of the HDPE pipe; xa and xb are undetermined coefficients depending on the boundary conditions.According to Zhang et al. , the defThe deformations of the pipe that were calculated are depicted in Underground conduits are used for a variety of purposes, including culverts, oil lines, coal slurry lines, subway tunnels, water mains, gas lines, telephone and electrical conduits, sewer lines, drain lines, water mains, gas lines, heat distribution lines, and telephone and electrical conduits ,37,38,39There is a wide range of physical and chemical compositions among soils. In the tests of this paper, poorly-graded sand was used, as shown in The interface of the pipe and soil should lie between the two extreme conditions of perfectly smooth and fully bonded. Considering the two extreme conditions, the deflections of buried HDPE pipes can be predicted within a range by Zhang et al. . ReferriR = 0.055 m and R0 = 0.053 m, respectively; the elastic modulus and Poisson’s ratio of the soil are referred to [cE = 875 MPa and cv = 0.46, respectively. Based on Equation (2), the deflection of the HDPE pipe in different sand and rocks can be determined under a perfectly-smooth pipe-soil interface and a fully-bonded pipe-soil interface, respectively. The calculated results determined under 280 kPa vertical pressure are shown in The following parameters are used in the calculation: The outer and inner radii of the HDPE pipe are erred to ; the elav) of the inner wall, considering both a perfectly-smooth pipe-soil interface and a fully-bonded pipe-soil interface. Comparing the four types of backfill materials, it is found that maximum deflection of the HDPE pipes is the greatest in clay gravel, followed by poorly-graded sand (used in the tests of this paper) and poorly-graded gravel.As shown in (1)The wall thickness and profile of a pipe contribute uniquely to the overall stiffness of the pipe. Despite this, a broad classification of pipe behavior in relation to the stiffness of the soil in the surrounding area is beneficial.(2)The strain distributions around a pipe change from a V-shape to a U-shape as the temperature increases from 20 °C to 60 °C and from 60 °C to 80 °C. The deformation profile of the pipe changes from an ellipse to a rectangle when the strain distributions change from a V shape to a U shape.(3)Even though the deformation profile of a buried HDPE pipe shifts from an ellipse to a rectangle as the ambient temperature rises and the location of the maximum circumferential strain shifts, the current analytical method that considers two extreme interfaces is able to capture the deformation in the model test well.(4)The findings presented in this paper demonstrate that the elevated temperatures prevalent in landfills lead to deformations in HDPE pipes that result in nonelliptical pipe shapes. Therefore, while designing a pipe that collects leachate from a landfill, in addition to taking into consideration the maximum vertical and horizontal deformations, one should also take into consideration the stress and strain to determine whether the pipe is stable.HDPE pipes, which are essential components of landfill leachate collection and drainage systems, can sustain damage when subjected to significant amounts of earth pressure and elevated temperatures during construction and operation phases. With each additional layer of waste added to a landfill, there is a corresponding increase in the amount of pressure exerted on the HDPE pipes used for leachate collection. After completion of the trash filling process, heat generation occurs in landfills as a result of the breakdown of organic components. This heat generation adds to an increase in the temperature of the waste. For this reason, the strain and deformation need to be re-evaluated under conditions in which vertical pressure is applied and temperature increases. The following are the important inferences from this study:


The clinical course of multiple sclerosis (MS) is highly variable among patients, thus creating important challenges for the neurologist to appropriately treat and monitor patient progress. Despite some patients having apparently similar symptom severity at MS disease onset, their prognoses may differ greatly. To this end, we believe that a proactive disposition on the part of the neurologist to identify prognostic “red flags” early in the disease course can lead to much better long-term outcomes for the patient in terms of reduced disability and improved quality of life. Here, we present a prognosis tool in the form of a checklist of clinical, imaging and biomarker parameters which, based on consensus in the literature and on our own clinical experiences, we have established to be associated with poorer or improved clinical outcomes. The neurologist is encouraged to use this tool to identify the presence or absence of specific variables in individual patients at disease onset and thereby implement sufficiently effective treatment strategies that appropriately address the likely prognosis for each patient. Multiple sclerosis is a highly heterogeneous disease of the central nervous system (CNS) that affects over 2.8 million people worldwide . The disWhen seeing a person with relapsing-remitting MS (RRMS) for the first time, the MS neurologist must address a fundamental question: “What is the nature of the disease activity and likely prognosis of the person with MS before me?” As the course of action taken by the neurologist at this point will likely prove pivotal to the long-term outcomes of this patient, the challenge here is for correct decisions to be taken concerning the DMT to be used and the treatment regimen  to be followed so that the best possible result for the patient is achieved. Local prescribing guidelines usually reserve higher efficacy DMTs for patients who have failed first-line treatments or who have ‘high disease activity’ as indicated by clinical (relapses) or imaging [magnetic resonance imaging (MRI) lesion activity] features. However, we propose that a much more proactive approach on the part of the neurologist is needed if patients’ long-term needs are to be fully addressed from the outset and if a level of care is to be provided that is over and above that of simply administering DMTs in order of efficacy as per local guidelines. Herein lies the difficulty for the busy neurologist, who might see hundreds of patients every month, to be fully cognizant of each patient’s treatment needs.We propose that the correct approach to treating persons with MS is according to each person’s prognosis, and not solely on the basis of ‘clinical or imaging features’ at the initial MS diagnosis. A patient with a poor prognosis may not necessarily have ‘highly active disease’ but may exhibit numerous clinical disease characteristics that have been shown to be associated with poor long-term outcomes and indicating the need for a more effective treatment strategy to be implemented. Excellent reviews have been published outlining the scientific basis for the prognostic value of many clinical, imaging, biomarker, and related parameters in MS patients [see e.g .]. In thThe concepts and recommendations presented here by the authors were developed over the course of several meetings held by a panel of experts belonging to the ParadigMS Foundation, a private, non-profit entity whose primary endeavour is to provide educational materials to the MS medical community. Consecutive iterations of the prognosis tool were reviewed and revised until the present version was arrived at.This practical guideline was developed by first considering objectives from the points of view of the neurologist and the patient, and then defining the most relevant and easily measurable parameters that impact on and signify prognosis.The assumption here is that the patient sitting before the neurologist has a confirmed diagnosis of MS according to the Lublin classification . From thAside from the patient’s perspective, we believe that an appropriate starting objective for the neurologist prior to treatment initiation is NEDA (No Evidence of Disease Activity)-3 at 2 years. This is defined as no relapse activity, no new MRI lesions, and no disability progression after two years of treatment. Rotstein et al. (2015)  showed tThe achievement of objectives and justification of the treatment decision are highly dependent on the patient’s initial prognosis. It would be futile to start a patient on a low-efficacy DMT if the initial clinical profile suggests a poor prognosis. To this end, the patient’s initial prognosis needs to be well established.Our prognosis tool consists of parameters categorised into five key areas: Demographic, Clinical, MRI, Biomarkers, and Evoked Potentials (EPs) /Optical Coherence Tomography (OCT). Some of these parameters have binary outcomes (two possible options to choose from), whereas others have ranges over which the prognostic weight can be distributed over several values.https://paradigms.foundation/prognosis/Responses to this section in the prognosis tool can be viewed in Older age has been associated with poorer prognosis in MS. For example, older individuals at onset had more rapid disability worsening –8, were Scoring: Age brackets above and below 40 years indicating progressively poorer and better prognosis, respectively.While the number of females affected by MS is proportionally much greater than that of males (3:1) , studiesFor these reasons, we include the male gender as a risk factor for poorer prognosis.Scoring: Binary outcome – Male/female.Vitamin D is a steroid hormone that is involved in many important physiological functions in humans and has been strongly implicated in MS disease activity and disability progression , 11, 16.Scoring: We suggest that a serum 25(OH)D concentration of <50 nmol/L may indicate a poorer prognostic outcome, while >50 nmol/L is preferred.The smoking of tobacco products has long been associated with an increased risk of MS and of disease progression. Smoking induces a proinflammatory environment that is linked to numerous manifestations of exacerbated outcomes in MS patients. These include greater brain lesion loads on MRI scans –27, as wScoring: Binary response, with ‘Smoker’ indicating a poorer prognosis versus ‘Non-smoker.’Conditions such as cardiovascular diseases , obesityScoring: A good prognosis is indicated by the absence of comorbidities. A poorer prognosis will result from the presence of 1, 2, ≥3 concomitant comorbidities of increasing weight contribution.Responses to this section in the prognosis tool can be viewed in As discussed above, most DMTs target inflammatory activity in MS, which is typically associated with relapsing forms of the disease and is therefore treatable to some extent. In contrast, a patient with PPMS at the initial consultation, or an RRMS patient who shows evidence of transition to SPMS on follow-up visits, is accruing irreversible disability, and at a faster rate , 39. SucScoring: Binary outcome – Relapsing (better prognosis)/Progressive (poorer prognosis).Scalfari et al. 2010)  showed t010  showScoring:Relapse rate:Better prognosis: Weighted values of ≤1 in two years since diagnosis and <1 per yearPoorer prognosis: 1 in previous year and ≥2 per yearInterval between relapses:Better prognosis: weighted values of ≥2 years and >1 yearPoorer prognosis: weighted values of <1 year and <6 monthsRecovery:Better prognosis: fully recoveryPoorer prognosis: incomplete recoveryIn a recent, systematic review of prognosis prediction models for RRMS based on a sample of 30 studies, Brown et al. (2020)  showed tScoring: EDSS score ≤2.0 (better prognosis); EDSS score >2.0 (poorer diagnosis).A 2001 study by Amato and Ponziani  highlighScoring: Binary (Yes/No) response to note the presence or absence of symptom onset involving the brainstem, cerebellar or spinal cord systems at MS diagnosis.A polysymptomatic onset of MS activity has been associated with poorer recovery and greater disability progression with time –61. We cScoring: Binary outcome – Monosymptomatic/Polysymptomatic.th percentile of the control group are considered indicative of cognitive impairment   showed tpairment .Scoring: Better prognosis: No cognitive decline.Poorer prognosis: 1. Mild cognitive decline; 2. Moderate/severe cognitive decline.Responses to this section in the prognosis tool can be viewed in The use of MRI to measure brain lesion activity is a commonly available diagnostic technique forming part of routine clinical practice at most major medical centres. Significant advances in instrument characteristics and protocols over the last 25 years has pushed MRI and other imaging modalities to the forefront of MS diagnosis, follow-up, and research.Numerous studies point to the fact that the number and volume of brain T2 lesions on MRI scan at diagnosis, and their change early in the disease course, are correlated to long-term disability outcomes –73. GiveScoring: Better prognosis: ≤4 T2 lesions.Poorer prognosis: (weighted) 5-9 T2 lesions; ≥10 T2 lesionsIn a recent study by Brownlee et al. (2019) , the preScoring: Binary outcome: Absent (better prognosis); Present (poorer prognosis).T1 hypointense (black holes) lesions are the final MRI measure to be included in the prognosis tool. These lesions have been associated with demyelination, axonal loss, and neurodegeneration, and are therefore considered to be markers of irreversible clinical disability –77. A reScoring: Presence or absence of black holes. Binary answer: Yes/No.Responses to this section in the prognosis tool can be viewed in In a recent review of studies that examined the prognostic value of immunoglobulin G (IgG) oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of MS patients, Magliozzi and Cross (2020)  reportedScoring: IgG OCBs Binary: Absent (better prognosis); Present (poorer prognosis).IgM OCBs: Even poorer prognosis than IgG OCBs when present.th percentile in healthy controls indicated a considerably higher risk of increased EDSS. Likewise, Kuhle et al. (2019)  in the CSF or serum given that this biomarker, although a good indicator of neurodegeneration, is not specific to MS. However, the weight of evidence from numerous studies involving MS patients points to a correlation of high NfL levels with disability progression. For example, Disanto et al. (2017)  showed t. (2019)  reported. (2019) , 85–88. . (2019) , 83, pro. (2019)  and far . (2019)  showed tResponses to this section in the prognosis tool can be viewed in Many studies have shown that OCT can be used to obtain valuable prognostic information about the MS patient. Baseline RNFL thinning is indicative of subclinical axonal damage and early neurodegeneration that can be measured by OCT. Oreja-Guevara et al. (2012)  showed tScoring: Binary outcome: Presence or absence of an RNFL thickness ≤88 μm at baseline.via the use of EPs offer a relatively straightforward means to assess long-term prognosis. Leocani et al. (2006)   showed t. (2006)  describe. (2006) . Keep in. (2006)  and coulScoring: We suggest that ≤1 abnormal EP is associated with a better prognostic outcome, while two or ≥3 abnormal EPs would denote a progressively poorer outcome.We have presented here a prognosis tool which we believe should enable the MS neurologist to optimally profile newly diagnosed MS patients and to consequently define appropriate treatment strategies relevant to each patient’s disease status. DMT indications tend to be based on patients’ current disease status as evidenced by clinical and imaging findings. However, we contend that ‘disease activity’ at MS diagnosis and ‘poorer prognostic signs’ are not one and the same thing. A patient with a poor prognosis may not necessarily have ‘highly active disease’ at diagnosis, but may exhibit, as we have shown here, numerous other disease characteristics requiring a more proactive treatment approach. Such an approach demands a higher degree of vigilance by the neurologist that is guided by the severity of the prognostic factors defined here in the tool, enabling the MS neurologist to provide a level of care superior to that of simply administering DMTs in order of efficacy as per local prescribing guidelines. A key objective of this strategy is to stop or slow-down disability progression early in the disease in order to prevent transition to SPMS. It is well recognised that most currently available DMTs primarily address the peripherally-driven focal inflammatory component of MS typically seen in relapsing forms of the disease, with the expectation being that disability progression can be minimised if this activity can be controlled. The importance, therefore, of a proactive approach on the part of the neurologist to effectively control early focal inflammatory activity is crucial from the outset.The inherent value of this prognosis tool lies in the fact that most, if not all of the parameters we have chosen for the tool can be measured using clinical, biochemical, and imaging procedures/techniques that now form part of standard practice in many parts of the world. Implementing these tests in the newly diagnosed MS patient should orientate the MS neurologist to the patient’s likely prognosis (if left untreated or inadequately treated), and to identify ‘red flags’ in the patient’s profile indicating the need for heightened vigilance and/or a more effective treatment approach.While other authors have addressed in various ways the topic of the prognostic value of individual or grouped clinical and imaging parameters (see e.g , 96–100,Our prognosis tool has some limitations that should be noted. For example, although backed by literature reports and many years of clinical experience on the part of the authors, the tool has not been scientifically validated. Moreover, while the parameters used will orient the neurologist to potentially poor or better prognostic outcomes in specific patients, the presented responses have not been weighted on the basis of their importance to overall prognosis. The validation and weighting aspects of the tool will form the basis of future work to be performed.In summary, this MS prognosis tool brings together a considerable amount of data specific to each MS patient, thereby providing the MS neurologist with a comprehensive overview of each patient’s current and potential disease status in the future. The tool should also facilitate the development of personalised treatment approaches based on individualised prognostic evidence, enabling outcomes for MS patients to be optimised.Development of the tool was led by BW, with input from all other authors at regular meetings. BW wrote the manuscript, with feedback on early versions provided by H-PH and CO-G. All authors contributed to manuscript revision and read and approved the submitted version.Medical writing support for the preparation of this manuscript along with the payment of publishing fees were provided by the ParadigMS Foundation.The creation and communication of educational materials by the ParadigMS Foundation is sponsored by Sanofi, Roche, and Merck.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Determining the high-risk human papillomavirus (HR-HPV) genotypes burden in women with and without cervical cancer afford a direct comparison of their relative distributions. This quest is fundamental to implementing a future population-based cervical cancer prevention strategy in Ghana. We estimated the cervical cancer risk by HPV genotypes, and the HPV vaccine-preventable proportion of cervical cancer diagnosed in Ghana.st October 2014 to 31st May 2015. Cases were women diagnosed with cervical cancer and controls were women without cervical cancer who were seeking care at the two hospitals. Nested multiplex polymerase chain reaction (NM-PCR) was used to detect HPV infection in cervical samples. Logistic regression was used to determine the association between the risk of cervical cancer and identified HPV infection. P ≤0.05 was considered statistically significant.An unmatched case-control study was conducted at the two largest cervical cancer treatment centres in Ghana from 1HPV deoxyribonucleic acid (DNA) data were analysed for 177 women with cervical cancer (cases) and 201 without cancer (controls). Cervical cancer was diagnosed at older ages compared to the age at which controls were recruited . Most women with cervical cancer were more likely to be single with no formal education, unemployed and less likely to live in metropolitan areas compared to women without cervical cancer . HPV DNA was detected in more women with cervical cancer compared to those without cervical cancer (84.8% vs 45.8%). HR-HPV genotypes 16, 18, 45, 35 and 52 were the most common among women with cervical cancer, while 66, 52, 35, 43 and 31 were frequently detected in those without cancer. HPV 66 and 35 were the most dominant non-vaccine genotypes; HPV 66 was more prevalent among women with cervical cancer and HPV 35 in those without cervical cancer. Cervical cancer risk was associated with a positive HPV test (Adjusted OR (AOR): 5.78; 95% CI: 2.92–11.42), infection with any of the HR-HPV genotypes  or multiple HPV infections (AOR: 9.57 95% CI 4.06–22.56).Women with cervical cancer in Ghana have HPV infection with multiple genotypes, including some non-vaccine genotypes, with an estimated cervical cancer risk of about six- to ten-fold in the presence of a positive HPV test. HPV DNA tests and multivalent vaccine targeted at HPV 16, 18, 45 and 35 genotypes will be essential in Ghana’s cervical cancer control programme. Large population-based studies are required in countries where cervical cancer is most prevalent to determine non-vaccine HPV genotypes which should be considered for the next-generation HPV vaccines. Cervical cancer is the second common female cancer in Ghana . HoweverIn the last 20 years, major efforts have been made worldwide to generate epidemiological data on cervical HPV-DNA. HPV prevalence and genotype distribution are discrepant, mainly caused by several factors, including early sexual debut, risky sexual habits and lack of systematic vaccination and screening programmes . In WestThe available HPV vaccines have activity against up to nine HPV types  . The bivCervical cancer prevention through vaccination against HPV and early detection and treatment of cervical cancer is critical in the WHO strategy for the disease elimination . The femA case-control study was conducted from October 2014 to May 2015 among women seeking care at Ghana’s two largest tertiary hospitals.In the absence of a population-based cervical cancer preventive strategy, several health facilities, including Korle Bu Teaching Hospital (KBTH), Accra and Komfo Anokye Teaching Hospital (KATH), Kumasi, provide opportunist screening for cervical cancer in Ghana. Albeit cervical cancer screening in Ghana is limited, government and non-governmental institutions have actively undertaken projects on cervical cancer. Opportunistic screening for cervical cancer at the two tertiary hospitals started in May 2004 through a John Hopkins Programme for International Education in Obstetrics and Gynecology (JHPIEGO) initiative supported by the Ghana Government and Ministry of Health (MOH). They account for the most significant number of women screened per institution and remain relevant in decisions regarding cervical cancer control in Ghana. The Departments of Obstetrics and Gynaecology and Radiation Oncology of these hospitals provide services for up to 600 women with cervical cancers annually https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  15 Dec 202222nd November, 2022Dear Dr Aimagambetova,We thank you for taking the time to carefully read our manuscript and for the valuable comments you have provided, which helped us in improving the revised paper that we are re-submitting. We have made all requested changes, ensured it complies with all the journal requirements.Yours truly,Dr Yvonne NarteyHere is our point-by-point response to the reviewer’s comments: (Reviewer comments in bold)This is an well written article on the topic of HPV in Ghana. The analysis presented in the paper are really interesting. I would leave a minor comment on enriching the discussion. In the last paragraph, you might include two or three sentences on Ghana's existing HPV screening program and how your study findings can improve the existing approach.Response: We have, accordingly, added the following sentence to the last paragraph of the discussion session.“Currently, Ghana do not have a national HPV screening program for cervical cancer. However, there are some public and private health facilities that offer such services. The current study provides useful information on the type of HPV likely to lead to cervical cancer and may help in the triage of women for follow-ups. “ - Page 20, paragraph 1, line 2.Nartey and colleagues present an interesting study on the prevalence of different HPV genotypes among women in Ghana. Studies like this are particularly important in understanding if newer vaccines are needed to treat different strains and the effectiveness of HPV vaccination in other areas. Additional comments are noted below.In line 109, authors state that HPV vaccine effectiveness studies have mainly been conducted among Caucasians. While there is a lack of diversity in research participants in biomedical research, this statement ignores the positive gains made in preventing cervical cancer in multiple countries that has had benefits for people across multiple races. Additionally, this statement seems out of place considering the authors do not mention race and ethnicity throughout the article. The authors should consider either removing this statement are include additional information about how research is needed among different races/ ethnicities and results from this study differ from previous studies conducted among majority Caucasian populations.Response: We have, accordingly, revised the sentence to reflect the reviewer comment. The sentence has been altered to the following: “The available HPV vaccines have activity against up to nine HPV types ”. – Page5, paragraph 2, line 7.It's unclear if the authors are trying to promote the usage of currently available HPV vaccines in Ghana or if they are requesting a new one. It would be helpful if the authors were clearer about this. Especially in lines 470-471 in the conclusion.Response: We have, accordingly, revised the sentence to reflect the reviewer comment. The sentence has been altered to the following: “HPV DNA testing for cervical screening and multivalent vaccine targeted at the most prevalent HPV types will be a valuable contribution to Ghana’s cervical cancer control programme than the currently available licensed vaccine.” – page 20, paragraph 2, line 8.AttachmentResponse to reviewer.docxSubmitted filename: Click here for additional data file. 2 Jan 2023Human papillomavirus genotype distribution among women with and without cervical cancer: Implication for vaccination and screening in Ghana.PONE-D-22-28450R1Dear Dr. Yvonne Nartey,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. 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The CAPS-based genotype of flo4 gene completely correlated to the phenotype of endosperm in two populations. This CAPS marker could be helpful for rice breeders to develop new cultivars harboring floury endosperm of the flo4-303 gene.Rice flour is useful as a substitute for wheat flour, however, to obtain fine flour, millers need special milling facilities, which increase the cost of milling. To reduce the milling cost, we developed a floury mutant line by irradiating gamma-rays to dry seeds of the japonica cultivar ‘Hoshinoyume’. The line was registered as a new cultivar, ‘Hoshinoko’. Genetical analysis of the floury trait was conducted using an F Rice is the staple food in Japan, however, rice consumption per capita is decreasing year by year, which reflects the change in diet habits, that is, various bread, pasta, etc., are taking the place of rice. Rice has traditionally been consumed as cooked rice, however, rice flour is useful as a substitute for wheat flour, and rice flour-based products such as breads, noodles, and cakes are expected to increase the consumption of rice  in 2000. The mutant line was registered as a new cultivar, ‘Hoshinoko’, in Japan in 2012.1 plant in a greenhouse to obtain F2 seeds subjected to genetical analysis. The F2 plants were grown in an experimental field at the Hokkaido Agricultural Research Center, NARO (HARC), in 2007.For genetical analysis for floury trait, ‘Hoshinoko’ was crossed with ‘Corbetti’  in a greenhouse in 2006, followed by growing the F5 generation in experimental fields.To validate the CAPS marker for selection of floury genotype, ‘Hoshinoko’ was crossed with ‘Hatsushizuku’  in 2007, followed by being self-pollinated till Fwaxy locus on floury trait, breeding lines originated from crosses between ‘Hoshinoko’ (waxy locus = Wxb: intermediate amylose content) and ‘Hakucho-mochi’ (waxy locus = wx: glutinous), ‘Yukigasumi’ (waxy locus = Wx1-1: moderately low amylose content), or ‘Kitamizuho’ (waxy locus = Wxa: high amylose content) were grown in the HARC field with their parents, followed by being evaluated for their starch damage in rice flour. The genotypes of the breeding lines are shown in To clarify the existence of effect of t-test.Agronomical traits of ‘Hoshinoko’ and ‘Hoshinoyume’ were evaluated as a yield performance trial for rice breeding lines in the HARC field in 2008. They were grown according to customary methods for rice breeding at HARC with two replications. Differences in mean values of heading date, maturity date, ripening period, culm length, panicle length, panicle number per plant, panicle number per square meter, grain number per panicle, grain yield and 1000-grain weight were subjected to Rice grains were polished with an experimental rice polisher VP-31T . Rice flours were prepared by Pin Mill  or Jet Mill KV-3  under dry conditions. The milling percentage of ‘Hoshinoko’ and ‘Hoshinoyume’ were approx. 75% and 90%, respectively. The lower value of ‘Hoshinoko’ was ascribed to higher yield of broken rice. The apparent amylose content of rice flours was determined using the iodine absorption method with an Auto Analyzer II system . The median diameter of the flour particles was measured with a laser diffraction particle size analyzer LS 13 320 . Damaged starch content was evaluated by a starch damage assay kit . After cutting the grains using a cutter, the endosperm structure of the cross sections was observed with a TM-1000 Miniscope .2 plant, ‘Hoshinoko’ and ‘Hoshinoyume’ were extracted according to the method described by The DNA of each ‘Hoshinoko’/‘Corbetti’ FPCR-based assays were performed using primer sets for simple sequence repeat (SSR) markers developed by the International Rice Genome Sequencing Project . DNA wasflo4 of ‘Hoshinoko’ and ‘Hoshinoyume’ were sequenced as follows: according to the sequence of OsPPDKB gene  in a greenhouse. Total RNA was extracted from flag leaves and panicles collected at 20 days after flowering using TRIzol RNA Isolation Reagents (Invitrogen) according to the manufacturer’s instructions. Single-stranded cDNA was synthesized from 1 μg of total RNA with a High-Capacity RNA-to-cDNA Kit , and PCR amplification was performed with Ex Taq polymerase . Gene expression of Heading date, maturity date, ripening period, calm length, panicle length, and grain number per panicle were not significantly different between the floury mutant ‘Hoshinoko’ and the wild type ‘Hoshinoyume’, wheares ‘Hoshinoko’ showed significantly higher values of panicle number per plant, panicle number per square meter, and significantly lower yield and 1000-grain weight compared to ‘Hoshinoyume’ at 5% or 1% levels respectively .The appearance of grains differed: the grains of ‘Hoshinoko’ appeared opaque like glutinous rice while that of ‘Hoshinoyume’ appeared translucent . The cro2 individual plants derived from a cross between ‘Hoshinoko’ and ‘Corbetti’, according to the appearance of F3 grains, floury, heterozygote, and wild type were observed to be segregated as 32:40:22 ratio, suggesting that floury mutation of ‘Hoshinoko’ is controlled by one gene . Furthermore, it was observed that one of the heterozygote plants produced 155 wild-type and 62 floury-type grains, suggesting that the floury character is inherited as a recessive trait .Among 94 Fflo4 mutation was OsPPDKB, located on chromosome 5 at 19.64 Mbp close to the RM163 marker. Thus, we sequenced the ORFs of OsPPDKB in both cultivars. The obtained sequence data showed a two-bp (CA) insertion in the eighth exon of ‘Hoshinoko’ compared to that of ‘Hoshinoyume’  in Flo4 was available. Primers were designed to contain this restriction site in their amplicon (SexAI were 544 and 310 bp for Flo4, and 856 bp for flo4-303.Based on the obtained sequence data, we developed a CAPS marker to detect individual rice plants harboring amplicon . Fragmen2 plants derived from a cross between ‘Hoshinoko’ and ‘Corbetti’ and those of F5 plants derived from a cross between ‘Hoshinoko’ and ‘Hatsushizuku’ were compared with the phenotypes of their self-pollinated seeds. The genotypes and phenotypes were fully agreed (flo4-303 gene.Genotypes determined by the CAPS marker in Fy agreed , indicatflo4 and waxy loci. Regardless of the waxy genotypes, the starch damage of lines harboring flo4-303 showed lower values compared to those with the Flo4 genotype. The levels of decrease were large in order of Wxa, Wxb, Wx1-1 and wx, which coincides to the levels of amylose content of these waxy genotypes (In this study, we examined the quality of rice grains and flour of floury mutation cultivar, ‘Hoshinoko’, prepared by dry milling method. Because rice flour with finer particle size and lower damaged starch content is suitable for rice bred (flo1–flo16, which are distributed on chromosomes1, 2, 3, 4, 5, 8, 9, 10, and 12. Various genes have been cloned from these floury mutants of which transcription levels were generally quite low, indicating that loss-of-function mutations had occurred. As for flo4, besides flo4-303 identified in this study, flo4-1, flo4-2, and flo4-3 have been reported (flo4-1 gene, the transcription level of OsPPDKB of was quite low in ‘Hoshinoko’ harboring flo4-303, which could be ascribed to the frameshift mutation of OsPPDKB gene (flo4 mutants reported by According to the review paper by DKB gene , indicatflo4-1 and flo4-2 mutants compared to wild type, while flo4-4 mutant. These increase and decrease might be ascribed to the alternation of carbon metabolism caused by mutation of PPDK gene as suggested by Amylose content of ‘Hoshinoko’ was lower than that of ‘Hoshinoyume’ . Kang etflo4-1 and flo4-2 genes, reduction of grain weight was observed in the case of flo4-303 (flo4-303 mutant compared to wild type. Thus, for the extension of rice cultivars harboring a flo4-303, it is required to combine extra high yielding potential with floury traits, as reported by As well as flo4-303 , which cWx genotype on the phenotype of flo4-303. In our study, flo4-303 decreased damage starch content irrespective of the Wx genotype including wx, Wx1-1, Wxb and Wxa (flo4-303 show higher starch damage content, which requires further investigation to confirm it due to limited number of employed lines.Various products are made from rice flour ( and Wxa , though This shows that a series of floury rice cultivars with different amylose contents could be developed, implying the creation of novel demands for rice consumption.flo4-303, we developed a CAPS marker for convenient selection of flo4-303. As the CAPS marker was developed based on the two-bp insertion occurred in the eighth exon of PPDK gene of ‘Hoshinoko’, PCR-based marker also can be utilized. However, due to the small difference of two-bp, the PCR-based marker requires polyacrylamide electrophoresis, whereas CAPS marker can be conducted by using agarose gel. In our program, breeding new floury cultivars with high yield potential is currently underway using the CAPS marker.To accelerate breeding cultivars harboring S. M., T. U., and N. I. designed the study; S. M., H. S., T. I., and N. Y. developed the plant materials, S. M., W. M., and M. K. performed the genetical analysis; H. K. performed RT-PCR analysis; S. M. and T. U. performed floury characteristic analysis; S. M. and T. U. analyzed the data; and S. M. and N. I. wrote the paper.Supplemental Table


Discussions about increasing diversity in economics have ignored the role that associations play in the engagement of underrepresented economists. We continue work on diversity and inclusion in the Northeastern Agriculture and Resource Economics Association (NAREA) and other associations by analyzing membership and meeting attendance to promote diversity in economics. We estimate a vector error correction model (VECM) to identify the determinants of membership and meeting attendance and use member survey data to model membership and meeting attendance behavior. We find inequalities across gender, income, and professional status. Recommendations include locating meetings in accessible cities, increasing networking opportunities, and providing more services supporting underrepresented groups. The term diversity can refer to gender identity, age, race, ethnicity, nationality or national origin, sexual orientation, religion, disability, health condition, physical appearance, marital status, parental status, socioeconomic status, professional status, or personal connections. Due to data availability, we are only able to focus on socioeconomic status, gender, and professional status and to refer to these aspects as diversity in the paper, although we readily admit that other elements of diversity are equally important – if not more – to study at the present in time.The remainder of this paper proceeds as follows: in the next section, “Data and Descriptive Statistics,” we describe the membership and survey data that we have collected from external sources and our own survey. Then, in the following section, “Empirical Methodology and Results,” we use two empirical strategies to identify policies for increasing participation in economics associations and annual meetings. Because our data are non-stationary, we use a vector error correction model (VECM) to analyze time-series data on membership and meeting attendance of three associations over time and to identify the impact of policy on membership and attendance. In addition, we use a Poisson model to estimate individual membership and attendance while controlling for socioeconomic characteristics of members. We consider the role of socioeconomic status, gender, and professional status in the determinants of these models and provide practical recommendations on how NAREA and different types of associations can sustain or increase the diversity of their membership and participation in their meetings. In the “Conclusions” section, we offer with suggestions for how our findings can be used to increase diversity in economics.4 There are other regional associations in this category, which target smaller geographic areas but remain open to all subdisciplines, such as the New York State Economics Association. Field associations target a subdiscipline within economics and have no regional boundaries, such as the Agricultural and Applied Economics Association and Urban Economics Association. Finally, regional-field associations target specific subdisciplines within a regional boundary, such as NAREA and Midwestern Law and Economics Association.Two sources of data are used to investigate the determinants of association membership and meeting attendance. They are a 40-year panel from three large economics associations and survey data from 2,931 members of four associations. We group economic associations into four categories: national, regional, field, and regional-field. The American Economic Association (AEA), founded in 1885, is a national association in the United States . The fou5 These data suggest that average AEA membership increased from over 19,000 in the 1970s to an average of 21,109 between 1986 and 1995. Then between 2006 and 2015 it declined to 17,945  were obtained from ,945 see . Average45 see 6. These cA Dickey-Fuller (DF) test suggests that many of the variables included in our models of AEA, SEA, and WEAI membership and attendance are non-stationary see  and ther7 In each case, members were emailed an invitation to participate in an online survey. Two follow-up emails were sent to each group, resulting in a response rate ranging from 16 to 44 percent . The first part of the survey gathered information on respondent membership benefits, ranking of the reported benefits, information on membership status, and attendance at the association’s annual meeting over time. The second part of the survey gathered demographic information, including employment status, type of employer, field of expertise, educational attainment, gender, and income.Our second set of data includes survey responses from 2,931 participants from four economics associations, including one national, regional, field, and regional-field association (NAREA).cent see . Respons9The top-ranked benefits reported for associations include access to the association journal, the annual meeting, job market opportunities, staying professionally current, and networking see . With thWe use two empirical strategies to identify policies to increase participation in economics associations and annual meetings. First, because our data are non-stationary, we (1) use a vector error correction model (VECM) to analyze time-series data on membership and meeting attendance of three associations over time, and (2) identify the impact of various policies imposed by associations on membership and attendance. Second, we use a Poisson model to estimate individual membership and attendance while controlling for socioeconomic characteristics of members.t (Mt) is given by Pt), lagged membership (Mt-1), meeting attendance (At), the number of new economics PhDs earned in the U.S. (PhDt), national gross domestic product (GDPt), dummies for association policy changes (Policyt), and locational dummies for the annual meeting (Xt).We first estimate the factors that drive membership and meeting attendance over time. We assume that the time-series relationship for membership in time t), lagged meeting attendance (At-1), the number of new economics PhDs earned, national gross domestic product, dummies for association policy changes, and location dummies for the annual meeting.Similarly, the relationship for meeting attendance  is given by m is an integer between 1 and k that defines the lag placement of the VECM term, k is the lag length, and the deltas represent the differenced independent and dependent variables (to make our data stationary). We identify the number of lags to be included using the Johansen integration test . The general VECM model takes the general formion test  and estiion test . Tests fion test . Our finion test  and Johaion test . The lag10 For AEA we identified two policy changes over this time period. First, in 2000 the association began to require at least one paper author be a member of AEA or one of the other affiliated associations (policy 1), and second, in 2009 AEA began to require that users of the online hotel reservation system for the conference were members (policy 2). For SEA we identified one policy change in the registration fee structure: in 2004 the meeting registration fee was higher for non-members. We identified one policy change for WEAI. In 1994 WEA added “International” to its name and began to hold  biennial meetings in the Pacific Rim. It is likely that other policy changes, particularly in the early years of our dataset, also took place. If so, these policy changes are not in the institutional memory of these associations as far as we can discern. AEA has never charged different registration fees for members and non-members and WEAI has always charged a higher rate for non-members.We include at least one policy variable in each of our estimations.11 The short-run results include differenced lags of the controls  and policy and meeting location dummy variables (long-run results only include differences and thus no policy variables).12 The results suggest that locating the annual meeting in New York increases attendance by 1,572 and locating the annual meeting in Washington, DC, increases attendance by 1,800. However, locating the annual meeting in these locations does not translate into increases in membership. The policy to require at least one paper author be a member of AEA (policy 1) is correlated with 1,894 fewer conference registrants and 2,196 fewer members. The requirement that attendees must be members to register in the meeting hotels (policy 2) is correlated with an increase of 2,164 conference registrants, but this policy was not correlated with an increase in membership.We discuss each association’s short-run effects see  and begi13We continue with the estimation of SEA membership and meeting attendance, where the short-run results suggest that locating the annual meeting in New Orleans increases attendance by 133 and locating the annual meeting in Washington, DC, increases attendance by 175. Locating the meeting in Washington, DC, also translates into an increase of approximately 149 new members, but there is no impact on membership when the annual meeting is held in New Orleans. These positive and significant Washington, DC, conference attendance results for both SEA and AEA make sense, since the city has the largest concentration of economists in the country.We conclude with the estimation of WEAI membership and meeting attendance. According to our results, the policy initiated in 1994 to become WEA International had negative impacts on meeting attendance. According to our results, this decision decreased attendance at the annual meeting by 268. This might be because members treat the domestic and international meetings as substitutes, resulting in a decline in meeting attendance. Finally, the results suggest that locating the annual meeting in San Francisco increased membership by 167 members.In sum, these estimations suggest that the findings from some previous less-sophisticated models  continuei’s count of memberships or meetings attended each year (Qi) is a function of price (Pi) that is proxied by an indicator of payment out of pocket, household income (Ii), and a series of socioeconomic characteristics (Si), including the number of years employed, gender, holding a PhD, university employment, and years of membership. The stochastic disturbance term (εi) represents the net impact of all unobservable factors that influence the dependent variable.14While the estimations above can point to policies that can increase membership and annual meeting attendance, these policies do not address diversity, since they are based on association and not individual data. To explore policies that target different socioeconomic groups, we estimate membership and attendance with survey data and the Poisson model given by:Results in Duration and type of employment affects the number of memberships and meetings attended. University employees are members of more associations and attend more meetings than others, all else being equal. However, those who have worked at a university for more than six years, a proxy for the post-tenure period, attend fewer meetings compared to respondents with less than six years at a university (Models 3 and 4). The number of years employed is negative and significantly related to the number of meetings, but has a positive impact on the number of memberships in Model 1. We also identify what we term a tenure effect: faculty who have been employed for more than six years are less likely to attend meetings (Model 4). Together, these results suggest that early-career scholars attend conferences and present their research more often, during what is likely the pre-tenure years and then reduce the number of meetings per year as careers advance, but memberships are still maintained.There are several interesting insights that can be drawn across demographic characteristics. First, household income does not affect the number of memberships economists hold, but it does affect how many meetings per year economists attend. Respondents who self-pay tend to hold more memberships but attend fewer meetings. Given the large expense of travel compared to association membership, it makes intuitive sense that lower household incomes and those who self-pay attend fewer meetings per year. Respondents that hold a PhD do not maintain more memberships, but they do attend more meetings. Another interesting result is that male economists do not appear to hold more memberships than female economists, but males do attend more meetings per year compared to females, suggesting that females face greater barriers for meeting attendance. This implies that there is no gender gap in terms of association memberships, which have little impact on career trajectory (since anyone can pay a membership fee), but a gender gap does exist for meeting attendance, which prevents women from accessing important opportunities for professional development.This study analyzes time-series association data and cross-sectional survey data from a large sample of economic association members to draw conclusions on how NAREA and other associations can increase the diversity of association membership and meeting attendance. Our empirical results allow us to identify several barriers to meeting access. First, income status can be a barrier to meeting attendance. Because cost of travel is closely linked to meeting location and opportunity cost, this is one policy area under the direct control of association leadership. Similar to previous work, we find that meeting locations that are easily accessible and are relatively less costly  translatAlthough AEA has taken measures to reduce membership fees for lower income levels, our results suggest that income is typically not a barrier to becoming a member. Survey data suggest that members do not place much importance on membership dues or meeting registration fees. Yet graduate students or low-income individuals may be more sensitive to membership fees, because they are less likely to have institutional support for travel. Subsidies or grants for student participants, new members, and low-income individuals could help provide better access to association services and help increase the diversity of members.Our survey data also reveal heterogeneity across membership characteristics and perceived benefits: while a majority of association members are academic economists, the national association members tend to have higher incomes and participate in fewer annual meetings and associations. Furthermore, we find that the importance of networking increases as association size decreases. This points to the rationale for economists to maintain multiple memberships, since each association provides different professional development opportunities. NAREA and associations that are relatively small and focused on a region or field would therefore benefit from events that build on this strength, such as cocktail hours, meet-and-greet opportunities, mentoring programs, meeting field trips, and opportunities to participate in governance; networking services should specifically target those who are underrepresented in the profession. Associations can also build upon technological advances to supplement in-person networking opportunities. For example, social media, virtual meeting experiences, or mentoring experiences not directly tied to meeting attendance may be more equitable for those facing barriers to attending meetings and are likely to become more common and more advanced in a post-pandemic world. Of course, the global pandemic may pose different barriers to women and people of color, which needs to be carefully considered. Associations that are large and display other core competencies, such as job market activities and high-quality journals, should improve upon and maintain these services. Reducing bias in job market activities and publishing should be a priority for these associations.Finally, we find important differences across demographic characteristics. We provide evidence that inequalities in meeting attendance do exist for women, lower-income individuals, and non-academic economists. We believe that underrepresented groups not directly analyzed in this paper face even greater barriers. Our time-series analysis of meeting attendance and membership show that association policy changes can influence membership. Furthermore, because our estimations also suggest that female economists attend fewer meetings than males but do not hold fewer memberships, we believe this points to inequalities and additional barriers women may face to attend meetings. To change this, associations should increase their support of women and underrepresented minorities by providing a more inclusive environment at meetings, providing meeting childcare services, providing more professional development opportunities targeting these members, and exploring other policy options with the groups of interest. NAREA has taken a leadership role in these endeavors by creating a committee on diversity and inclusion and starting several new initiatives to attract and elevate diverse members. We suspect these findings can help target their next steps.


Although widely used in industry, organocatalysis has classically been limited to ex vivo application. In addition, the small molecule activation of enzymes has so far been exerted by allosteric control. Recently, we reported that small molecules can act as organocatalysts for the DNA repair enzyme 8‐oxoguanine DNA glycosylase 1 (OGG1). The underlying principle allows for a full control of enzymatic function with potential for alleviating oxidative stress to the genome or as a new strategy in cancer therapy.1Organic molecules that partake in a chemical reaction, increase its rate and exit it chemically unaltered are called organocatalysts.After base excision, bifunctional DNA glycosylases commonly generate an enzymatic intermediate that is called Schiff base Figure .3 In o2The creation of activators of OGG1 required knowledge of the enzyme's biochemistry and structural biology, as well as a fine‐tuning of a catalytic nitrogen base as a new variable in medicinal chemistry. Before, we have developed OGG1 inhibitors3The two types of OGG1 activator molecules stimulated either the intrinsic OGG1 β‐lyase activity, or the OGG1 β, δ‐lyase activity. Although both classes enhanced OGG1 turnover on 8‐oxoG and abasic sites in vitro, in cells this OGG1 activation increased the kinetics of recruitment and repair of oxidized chromatin. However, depending on the type of activity that OGG1 uses to incise the abasic site upon activation, the BER downstream direction and enzymes required for continuation and completion of the repair process change. Although this moment represents a bottleneck in the general repair process, it is also an opportunity to design specific strategies in which we can take advantage of either type of molecule.Using activator molecules that stimulate the β‐lyase activity will not alter the repair pathway excessively, as it will continue to use the original downstream enzymes to complete repair. Moreover, although APE1 receives a greater amount of reaction intermediates as a result of OGG1 β‐lyase stimulation, the enzyme is extremely efficient and abundantly expressed in the cell, which ensures a constant supply of intermediates compatible with the terminal enzymes of BER. Thus, we can imagine a scenario in which OGG1 β‐lyase activators reduce levels of oxidative damage without other downstream implications. These types of molecules would be good candidates to develop drugs with a clinical value for the treatment of oxidative stress–related diseases.On the other hand, molecules that stimulate the β,δ‐lyase activity generate a product that can no longer be processed by APE1 and will require additional biochemical modifications to complete BER. Indeed our in vitro studies demonstrated that the enzyme PNKP1 was essential to process the 3′‐phosphate upon installed β,δ‐lyase activity of OGG1. Further, in the absence of PNKP1, BER progression was interrupted. In turn, the generated lesion was not repaired, leading to the formation of DNA strand breaks. In cells, this artificial dependence of PNKP1 can be exploited using specific inhibitors. Thus, by simultaneously treating cells with TH10785 and PNKP1 inhibitors, the repair process is driven to an endless road where 3′‐phosphate intermediates accumulate in the form of unrepairable DNA strand breaks, which are toxic for the cell. This artificial PNKP1 dependency using activators of OGG1 β,δ‐lyase function connects BER to other DNA repair pathways and could thus be exploited as a strategy to treat cancers with high levels of oxidative stress, or bearing inactivating mutations in other DNA repair enzymes.4The findings outlined in this commentary lay the basis for a new class of biologically active molecules. Increasing enzymatic function in acute disease scenarios or due to occurring mutations is an attractive avenue for the future development of drug candidates. As enzyme‐targeted organocatalysts increase the biochemical reaction rate by a multitude, a limited number of enhanced enzyme copies suffice to, for example, double substrate turnover. This rerouting can either rescue disease burden or overload repair pathways. The strategy stands in sharp contrast to classical inhibition approaches, where a roadblock should almost be complete. Although first of its kind and promising as a technology, additional compound development and applicability in disease settings will be necessary to mature organocatalysts of OGG1 to clinical stages.TH is listed as inventor on US patent no. WO2019166639A1, which covers OGG1 inhibitors. The patent is fully owned by a non‐profit public foundation, the Thomas Helleday Foundation for Medical Research and TH is a member of the foundation board. TH is a shareholder of Oxcia AB, a company that holds a license to WO2019166639A1. All remaining authors declare that they have no competing interests.