Mailing human papillomavirus self-sampling kits to women under-screened for cervical cancer improved detection in cervical cancer screening in a general population study in Japan.

BACKGROUND: One cause of the increase in cervical cancer rates in Japan is the long-term stagnation in the cervical cancer screening consultation rate. Therefore, improving the screening consultation rate is of urgent concern to reduce cervical cancer incidence. Self-collected human papilloma virus (HPV) tests have been successfully adopted in several countries, such as the Netherlands and Australia, as a measure of individuals who have not undergone cervical cancer screening in national programs. This study aimed to verify whether self-collected HPV tests presented an effective countermeasure for individuals who had not undergone the recommended cervical cancer screenings. METHODS: This study was conducted from December 2020 to September 2022 in Muroran City, Japan. The primary evaluated endpoint was the percentage of citizens who underwent cervical cancer screening at a hospital with positive self-collected HPV test results. The secondary endpoint was the percentage of included participants who were diagnosed with cervical intraepithelial neoplasia (CIN) or higher among those who visited a hospital and underwent cervical cancer screening. RESULTS: The included study participants were 7,653 individuals aged 20-50 years with no record of previous cervical cancer examination in the past 5 years. We mailed these participants information on self-administered HPV tests as an alternative screening procedure and sent the kit to 1,674 women who requested the test. Among them, 953 returned the kit. Among the 89 HPV-positive individuals (positive rate, 9.3%), 71 (79.8%) visited the designated hospital for an examination. A closer examination revealed that 13 women (18.3% of hospital visits) had a CIN finding of CIN2 or higher, among whom one each had cervical cancer and vulvar cancer, eight presented with CIN3, and three presented with CIN2; two cases of invasive gynecologic cancer were also identified. CONCLUSIONS: We conclude that the self-collected HPV tests showed a certain efficacy as a measure of individuals who had not undergone the recommended cervical cancer screening. We devised ways to have the unexamined patients undergo HPV testing and ensure that HPV-positive individuals visited the hospital. Despite a few limitations, our findings suggest the effectiveness of this public health intervention.

Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.

Pathological classification of desmoplastic reaction is prognostic factor in cervical adenocarcinoma.

Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

OBJECTIVE: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. METHODS: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. RESULTS: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. CONCLUSION: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

Impacts of iron oxide and titanium dioxide nanoparticles on biogas production: Hydrogen sulfide mitigation, process stability, and prospective challenges.

Anaerobic digestion for biogas production is one of the most used technology for bioenergy. However, the adoption of nanoparticles still needs further studies. Therefore, this study was designed to examine the effect of metal oxide nanoparticles (MONPs) at four different concentrations in two different combinations, 20 (R1) and 100 (R2) mg/L for Fe2O3, 100 (R3) and 500 (R4) mg/L for TiO2, and a mixture of Fe2O3 and TiO2 at rates of 20, 500 (R5) and 100, and 500 (R6), on hydrogen sulfide (H2S) mitigation, biogas, and methane (CH4) yield during the anaerobic digestion of cattle manure (CM) using an anaerobic batch system. The results showed that H2S production was 2.13, 2.38, 2.37, 2.51, 2.64, and 2.17 times lower than that of the control (R0), respectively, when the CM was treated by the aforementioned MONPs. Additionally, biogas and CH4 production were 1.09 and 1.105, 1.15 and 1.191, 1.07 and 1.097, 1.17 and 1.213, 1.10 and 1.133, and 1.13 and 1.15 times higher than those of R0 when R1, R2, R3, R4, R5, and R6 were supplemented with MONPs, respectively. The highest specific production of biogas and CH4 was 336.25 and 192.31 mL/gVS, respectively, which was achieved by R4 supplemented with 500 mg/L TiO2 NPs, while the corresponding values in the case of R0 were 286.38 and 158.55 mL/gVS.

Efficacy of liquid-based genetic diagnosis of endometrial cancer.

Although liquid-based cytology (LBC) has increased the sensitivity of cytological diagnosis of endometrial cancer (EC) compared with conventional smear cytology, the sensitivity of LBC for the detection of EC is between 70% and 96% and remains unsatisfactory. In the present study, we compared the efficacy of LBC with liquid-based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including PTEN, PIK3CA, CTNNB1, KRAS, and TP53 in 48 LBC subjects who underwent endometrial screening. Consequently, LBC classified 15 samples as "positive or suspicious for malignancy" and the 15 were later confirmed as EC. However, LBC failed to identify five cases who were diagnosed as EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10 subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS variants in four, and three TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20). Although five EC were negative for malignancy by LBC and three were negative for pathogenic mutations by LBGDx, the combination of LBC and LBGDx would successfully diagnose all 20 EC. These data suggested that LBGDx is a useful strategy to improve the sensitivity of screening of EC by LBC.

Valorizing waste iron powder in biogas production: Hydrogen sulfide control and process performances.

Biogas is composed of different gases including hydrogen sulfide (H2S), which is a hazardous gas that damages pipes and generators in anaerobic digestion system. The objective of this study was to control H2S by waste iron powder produced by laser cutting machine in a steel and iron industry. Waste iron powder was mixed with dairy manure at a concentration between 2.0 and 20.0 g/L in batch experiments, while the concentration was varied between 1.0 and 4.0 g/L in bench experiment. In batch experiment, a reduction of up to 93% of H2S was observed at waste iron powder of 2.0 g/L (T1), while the reduction was of more than 99% at waste iron powder beyond 8.0 g/L (T4 âˆ¼ T6). The total sulfide concentration (ST) increased together with waste iron powder concentration and was fitted with a quadratic equation with a maximum ST of 208.0 mg/L at waste iron powder of 20.2 g/L. Waste iron powder did not have significant effect on methane yield in batch and bench experiments. However, hydrolysis rate constant was increased by almost 100%, while the lag-phase period was reduced to half in test digesters compared to that in control digester. In bench experiment, H2S concentration was reduced by 89% at 2.0 g/L, while 50% at 1.0 g/L. Therefore, waste iron powder was effectively removed H2S and did not affect negatively anaerobic digestion process.

Rap1GAP inhibits tumor progression in endometrial cancer.

OBJECTIVE: Endometrioid adenocarcinoma (EAC) is a common endometrial cancer with recent dramatic increases in incidence. Previous findings indicate that Rap1GAP acts as a tumor suppressor inhibiting Ras superfamily protein Rap1 in multiple aggressive carcinomas; however, Rap1GAP expression in EAC has not been investigated. In this study, the tumor suppressing activity of Rap1GAP in EAC was explored. METHODS: EAC cell lines were used to examine Rap1GAP levels by real-time RT-PCR and western blotting and the effects of Rap1GAP on cancer cell invasion and migration. Rap1GAP expression was analyzed by immunohistochemical staining for Rap1GAP, E-cadherin in surgically resected tumors of 114 EAC patients scored according to EAC differentiation grade. Prognostic variables such as age, stage, grade, tumor size, and immunostaining for Rap1GAP, E-cadherin were evaluated using Cox regression multivariate analysis. RESULTS: Low Rap1GAP expression was detected in poorly differentiated EAC cells. Rap1GAP deficiency significantly accelerated while Rap1 deficiency decreased cancer cell migration and invasion. Patients with higher Rap1GAP, E-cadherin, and especially combined Rap1GAP/E-cadherin levels had better overall survival than EAC patients with no or weak expression. In addition, Rap1GAP expression was an independent prognostic factor in EAC. CONCLUSIONS: Inhibition of Rap1GAP expression increases EAC cell migration and invasion through upregulation of Rap1. Low expression of Rap1GAP correlates with poor EAC differentiation. Our findings suggest that Rap1GAP is an important tumor suppressor with high prognostic value in EAC.

Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized, open-label, 3-arm parallel comparative, exploratory study.

This study investigated the safety and efficacy of the sodium-glucose co-transporter-2 (SGLT2) inhibitor luseogliflozin with differing carbohydrate intakes in Japanese individuals with type 2 diabetes (T2D). Participants were randomly assigned to 3 carbohydrate-adjusted meals for 14 days (days 1-14; a high carbohydrate [HC; 55% total energy carbohydrate] and high glycaemic index [HGI] meal; an HC [55% total energy carbohydrate] and low glycaemic index [LGI] meal; or a low carbohydrate [LC; 40% total energy carbohydrate] and HGI meal). All participants received luseogliflozin for the last 7 days (days 8-14), continuous glucose monitoring (CGM) before and after luseogliflozin treatment (days 5-8 and days 12-15) and blood tests on days 1, 8 and 15. Luseogliflozin significantly decreased the area under the curve and mean of CGM values in all 3 groups similarly. Fasting plasma glucose, insulin and glucagon were similar at all time points. Ketone bodies on day 15 were significantly higher in the LC-HGI group compared with the HC-HGI and HC-LGI groups. In conclusion, luseogliflozin has similar efficacy and safety in Japanese people with T2D when meals contain 40% to 55% total energy carbohydrate, but a strict LC diet on this class of drug should be avoided to prevent SGLT2 inhibitor-associated diabetic ketoacidosis.

High-solids anaerobic mono-digestion of riverbank grass under thermophilic conditions.

The purpose of this study was to investigate the potential of high-solids anaerobic mono-digestion of riverbank grass under thermophilic conditions, focusing on the effects of the strength and the amount of inoculum. Ensiled grass was inoculated with three different inocula; inoculum from liquid anaerobic digester (LI), inoculum from dry anaerobic digester (DI), and mixture of LI and DI (MI), at feedstock-to-inoculum ratio (FIR) of 1, 2 and 4. The ensiling process of riverbank grass reduced moisture content (p>0.05), while the hemicellulose content was significantly increased from 30.88% to 35.15% (p<0.05), on dry matter basis. The highest methane production was at an FIR of 2 with MI (167L/kg VSadded), which was significantly higher (p<0.05) than with DI, but not significant compared to LI (p>0.05). At an FIR of 4, digesters inoculated with LI and DI failed to produce methane, whereas 135LCH4/kg VSadded was obtained with MI. The kinetic studies showed that at an FIR of 1 with LI and MI, the inoculum had less of effects on the hydrolysis rate constant (0.269day-1 and 0.245day-1) and methane production (135 versus 149L/kg VSadded); rather, it affected the lag phase. In a thermophilic HS-AD of riverbank grass, the mixture of inoculum with low and high total solids content (TS) helps increase the TS of inoculum and digestion process. An FIR of 2 was deducted to be the limit for a better startup time and higher volumetric productivity of methane.

Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial.

AIMS/HYPOTHESIS: Investigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated. METHODS: The experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30-75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m(2) or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by (13)C-acetate breath test involving measurement of (13)CO2 in breath samples collected before and after ingestion of rice steamed with (13)C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment. RESULTS: FR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC-15-240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, FR 1.94 ± 0.22 mmol/l, MR 1.68 ± 0.18 mmol/l, RF 2.77 ± 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 ± 0.21 mmol/l, MR 0.83 ± 0.16 mmol/l, RF 1.18 ± 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC-15-240 min-GLP-1: type 2 diabetes, FR 7,123.4 ± 376.3 pmol/l × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 ± 7.2 min, MR 82.3 ± 6.4 min, RF 29.8 ± 3.9 min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 ± 5.5 min, MR 74.4 ± 7.6 min, RF 32.4 ± 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC-15-120 min-glucose: type 2 diabetes, r = -0.746, p < 0.05; healthy, r = -0.433, p < 0.05) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, r = -0.578, p < 0.05; healthy, r = -0.526, p < 0.05), as well as with increasing GLP-1 (AUC-15-120 min-GLP-1: type 2 diabetes, r = 0.437, p < 0.05; healthy, r = 0.300, p = 0.107) and glucagon (AUC-15-120 min-glucagon: type 2 diabetes, r = 0.399, p < 0.05; healthy, r = 0.471, p < 0.05). The measured outcomes were comparable between the two randomised groups. CONCLUSIONS/INTERPRETATION: Meal sequence can play a role in postprandial glucose control through both delayed gastric emptying and enhanced incretin secretion. Our findings provide clues for medical nutrition therapy to better prevent and manage type 2 diabetes. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000017434. FUNDING: Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation.

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following paclitaxel and carboplatin in patients with gynecologic cancers: A randomized, multicenter, phase-II trial.

AIM: Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's quality of life, leading to poor compliance with further treatments. Previous studies have provided minimal data about carboplatin-based regimens. Female sex is a known risk factor for CINV. The purpose of this study was to evaluate palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by carboplatin plus paclitaxel combination therapy (TC regimen) in patients with gynecologic cancers. MATERIAL AND METHODS: Patients were recruited for this phase-II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX. RESULTS: During the overall period, complete response (CR) was observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was already present (P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in the 1-day DEX arm tended to be lower than in the 3-day DEX arm. CONCLUSION: Combination therapy of palonosetron and 1-day DEX was effective for subjects undergoing a TC regimen for gynecologic cancers. However, the possibility of reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could not be refuted and requires further investigation.

Effects of handling parameters on hydrogen sulfide emission from stored dairy manure.

Hydrogen sulfide (H2S) emission from liquid manure in the process preceding field application is an important issue in fertigation systems. Given that H2S poses a significant health risk, it is important to determine the effects of different handling parameters on H2S emissions to prevent health risks to farmers. In this study, the effects of total solids (TS; 3, 5, 7, 9, and 11%) and mixing speed (100, 200, 300, and 400 rpm), duration (5, 15, 30, and 60 min), and frequency (one, two, three, and four times a day) on H2S emissions from two different dairy manures were investigated. The results indicate that the quantity of sulfur-containing substrate intake determines the potential of dairy manure to emit H2S because manure from cows fed with concentrate-based feed generates higher amounts of H2S than manure from cows fed with forage-based feed. The H2S concentration increased with TS concentration and reached a maximum of 1133 ppm at a TS of 9%; thereafter, it decreased with further increases in TS concentration. H2S emission increased with mixing speed with a peak concentration of 3996 ppm at 400 rpm. A similar trend was observed for mixing duration. However, there were no significant differences between the amounts H2S emitted at different frequencies of mixing (P > 0.05). The results indicate that mixing speed, duration, and TS are the major determinants of the quantity of H2S emitted from dairy manure. Therefore, to prevent health risks associated with H2S emission from dairy manure, it is recommended that the mixing speed and duration should be kept as low as possible, while a TS concentration of above 9% should be applied during the fertigation of dairy manure.

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells. METHODS: Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in ES2 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records. RESULTS: BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. qRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel. CONCLUSIONS: BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer.

Prediction of the therapeutic effect of dienogest in ovarian endometrial cysts using the apparent diffusion coefficient.

The purpose of this study was to investigate whether apparent diffusion coefficient (ADC) mean values can be used for predicting the treatment response in ovarian endometrial cyst patients with dienogest (DNG) administration. Eighteen patients received DNG (2 mg/day, orally) for 60 days, among whom 26 ovarian endometrial cysts were retrospectively identified. Mean ADC values of individual ovarian endometrial cysts were obtained by ADC maps inside the tumor. There was a significant correlation between ADC values and reduction ratio. When calculating the mean ADC values for three groups; more than 50%, 50-25% and less than 25%, ADC values significantly increased with increasing reduction ratio; 2.05 × 10(-3)mm(2)/s, 1.28 × 10(-3)mm(2)/s and 0.94 × 10(-3)mm(2)/s, respectively (p = 0.0180). Multiple regression analysis by reduction ratio (%), ADC mean values (× 10(-3)mm(2)/s), tumor longest diameter (cm) and CA125 (U/ml) revealed that tumor reduction ratio by DNG administration could be predicted by the following equation; R = 19.3 + 24.0x - 0.4y + 0.1z (R: Reduction ratio, x: ADC mean, y: Longest diameter, z: CA125). In conclusion, the ADC mean value is useful for the prediction of the treatment response in ovarian endometrial cyst patients with DNG administration.

Batch anaerobic co-digestion of cow manure and waste milk in two-stage process for hydrogen and methane productions.

Anaerobic co-digestion of cow manure (CM) and waste milk (WM), produced by sick cows during treatment with antibiotics, was evaluated in two-stage process under thermophilic condition (55 °C) to determine the effect of WM addition on hydrogen (H2) and methane (CH4) production potentials, volatile solids (VS) removal, and energy recovery. Six CM to WM VS ratios of 100:0, 90:10, 70:30, 50:50, 30:70, and 10:90 were examined using 1-L batch digesters. The WM VS ratio of 30 % was found to be the minimum limit for significant increases in specific H2 and CH4 yields, and VS removal as compared to digestion of manure alone (P < 0.05). The highest specific H2 and CH4 yields, VS removal and energy yield were 38.2 mL/g VS, 627.6 mL/g VS, 78.4 % and 25,459.8 kJ/kg VS, respectively, in CM:WM 30:70. Lag phases to H2 and CH4 productions were observed in CM-WM mixtures, increased with increasing the amount of WM in the feedstock and were greater than 72 h in CM:WM 50:50 and 30:70. The digestion system failed in CM:WM 10:90. The results suggest that CM:WM 30:70 was optimum, however, due to limited amount of WM usually generated and long lag phase at this ratio which may make the process uneconomical, CM:WM 70:30 is recommended in practice.

Analysis of Treatment Response With Proteins Related to Tumor Immunity in Postoperative Irradiated Cervical Cancer Patients.

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

Prediction of Mismatch Repair Status in Endometrial Cancer from Histological Slide Images Using Various Deep Learning-Based Algorithms.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

The survival of cefazolin-resistant bacteria in mesophilic co-digestion of dairy manure and waste milk.

The use of cefazolin to treat mastitic cows leads to cefazolin residues in milk and manure. This is responsible for the high occurrence of cefazolin resistant bacteria (CRB) in waste and the environment. Anaerobic digestion is considered to have the potential to reduce antibiotic-resistant bacteria present in waste that results from concentrated animal feeding operations. Thus, the objective of this study was to investigate the survival of CRB and the digester performance in mesophilic co-digestion of dairy manure and waste milk. The experiment was carried out using three digester compositions: 100% slurry (slurry), 50% slurry + 50% manure (manure mixture) and 50% slurry + 45% manure + 5% waste milk (milk mixture) in batch digesters of 1 l with a working volume of 800 ml in triplicate at 37°C for 34 days. The daily biogas production in each digester, and methane (CH4) and carbon dioxide compositions in the gas were determined. The population densities of total culturable bacteria (TCB) and CRB were determined by plate counts on agar media at day 0, 10, 20 and 34 of digestion. Milk mixture produced the highest (P < 0.05) daily and cumulative total and CH4 gas. The maximum percentage reductions of TCB and CRB in manure and milk mixture was observed at day 20, the values being 96.2%, 96.0% and 99.8% and 99.8% respectively. Final volatile fatty acids (VFA) and pH values of the digesters confirmed the digester stability. Based on the findings, mesophilic anaerobic digestion can be considered a potent method to avoid the dissemination of CRB in nature.