Segmenting Skin Biopsy Images with Coarse and Sparse Annotations using U-Net.

The number of melanoma diagnoses has increased dramatically over the past three decades, outpacing almost all other cancers. Nearly 1 in 4 skin biopsies is of melanocytic lesions, highlighting the clinical and public health importance of correct diagnosis. Deep learning image analysis methods may improve and complement current diagnostic and prognostic capabilities. The histologic evaluation of melanocytic lesions, including melanoma and its precursors, involves determining whether the melanocytic population involves the epidermis, dermis, or both. Semantic segmentation of clinically important structures in skin biopsies is a crucial step towards an accurate diagnosis. While training a segmentation model requires ground-truth labels, annotation of large images is a labor-intensive task. This issue becomes especially pronounced in a medical image dataset in which expert annotation is the gold standard. In this paper, we propose a two-stage segmentation pipeline using coarse and sparse annotations on a small region of the whole slide image as the training set. Segmentation results on whole slide images show promising performance for the proposed pipeline.

Comparative evaluation of normal saline, 1/3-2/3, and ringer's lactate infusion on labour outcome, PH, bilirubin, and glucose level of the umbilical cord blood in nulliparous women with labour induction: a randomised clinical trial.

This study aimed to compare the effects of infusion of normal saline, 1/3-2/3, and Ringer's lactate fluids on labour outcome, pH, bilirubin, and glucose level of umbilical cord blood. In this randomised clinical trial, 450 nulliparous women with Bishop score ˂5 and indication of pregnancy termination were randomly divided into three groups to receive normal saline, 1/3-2/3, or Ringer's lactate infusion at a rate of 125 mL/h for hydration, upon starting induction of labour. Results of this study indicated that the incidence of hypoglycaemia (p = .19), hyper bilirubinemia (p = .87) and acidosis (p = .10) was similar in neonates of the three groups. Also, there were no statistically significant differences between the three groups with regard to the duration of labour; glucose, bilirubin and pH level of cord blood; and mode of delivery. It can be concluded that infusion of Ringer's lactate, normal saline or 1/3-2/3 fluid during labour is not associated with different maternal or foetal/neonatal outcomes, and none of the fluids has superiority to the others.Impact statementWhat is already known on this subject? Several studies have been conducted on the association between type and volume of infused fluid on labour duration and neonatal outcomes. However, there has been some controversy.What do the results of this study add? This is the first study that has investigated the association between infusion of Ringer's lactate, normal saline or 1/3-2/3 fluid during labour with labour outcome and pH, bilirubin, and glucose level of the umbilical cord blood and results showed that these fluids have no effect on maternal or foetal/neonatal outcomes and also none of these fluids has superiority to the others.What are the implications of these findings for clinical practice and/or further research? Due to contradictory results of previous studies, further research with greater sample sizes and different fluids type and volumes may be needed to examine the association between infusion of fluids and neonatal and labour outcomes more precisely.

Isonicotinic acid hydrazide (INH) versus extra-amniotic saline infusion (EASI) for cervical ripening at term: a randomised controlled trial.

The purpose of this trial was to compare extra-amniotic saline infusion (EASI) and intravaginal isoniazid (INH) for cervical ripening. This randomised clinical trial included 150 pregnant women who were undergoing induction of labour and who required pre-induction cervical ripening. Patients were randomly assigned to receive EASI or intravaginal INH. Bishop's score at the beginning of the study and before oxytocin infusion was not significantly different between INH and EASI groups. However, the time from first intervention to the beginning of the induction and also to the beginning of the active phase were significantly shorter in EASI group (p value ≤.001). Moreover, INH did not influence the labour process after the beginning of the active phase of labour. In conclusion, INH could be used for cervical ripening especially in the outpatient setting; however, it is a slower ripening agent compared to EASI.Impact StatementWhat is already known on this subject? To date there has been only one study about the safety and effectiveness of isoniazid (INH) in cervical ripening at term pregnancy which has compared INH with misoprostol.What do the results of this study add? The results of this study showed that vaginal INH is an effective agent for cervical ripening at term but in comparison to extra-amniotic saline infusion (EASI) it takes a longer time.What are the implications of these findings for clinical practice and/or further research? INH can be used in outpatient settings for cervical ripening at term pregnancy which makes it convenient for patient and cost effective for both patient and health system. Further studies are needed to discover the clinical efficacy of INH in comparison to other ripening methods and also the best dosage of INH for cervical ripening.

Prediction of Intraperitoneal Adhesions in Repeated Cesarean Section Using Sliding Sign, Striae Gravidarum, and Cesarean Scar.

Background: Intraabdominal adhesions are associated with an increase in complications during cesarean section because of recurrent cesarean sections. This is why the possibility of predicting adhesions is important. In this study, the diagnostic value of depressed scar, severe striae gravidarum, and negative sliding sign, and their combinations were evaluated for predicting intraabdominal adhesions of cesarean candidates. Methods: This prospective descriptive study was performed during 2019-2020 on 123 pregnant women referred to Ayatollah Taleghani university hospital with a gestational age of ≥36 weeks 0 days who were candidates for cesarean section because of a previous cesarean section. In each patient, the presence of a depressed scar, a severe striae gravidarum, the absence of a sliding sign, and the presence and severity of adhesions during the operation were examined. Sensitivity and specificity, and positive and negative predictive values of each of the 3 indicators and their combinations were calculated. Results: The frequency distribution of severe adhesion in these individuals was 16.27%. The highest sensitivity was related to depressed scar and negative sliding sign (65%). The highest specificity was related to the negative sliding sign and its combinations (97%-99%). The highest positive predictive value was related to negative sign sliding and its combinations (81%-92%). The negative predictive values of depressed scar, negative sliding sign, and severe striae gravidarum, and even their combinations were almost the same and approximately between 89% and 93%. Conclusion: To predict the presence of adhesions in a cesarean candidate because of a previous cesarean section, you should first examine the striae gravidarum and scar. In the absence of a depressed scar and severe striae gravidarum, there is a 90% chance of no adhesions. According to this study, if both signs are present, it is recommended to check the sliding sign to obtain a more accurate estimate.

Investigation of microRNA-10b values for the discrimination of metastasis due to melanoma.

BACKGROUND: Melanoma is one of the most invasive cutaneous cancers with characteristics such as rapid progression and distant metastasis. The early diagnosis and staging of melanoma can help better manage the patients. The current study is aimed to assess the values of microRNA-10b (miRNA-10b) in the discrimination of metastatic melanomas. MATERIALS AND METHODS: The current cross-sectional study has been conducted on forty patients diagnosed with melanoma since 2011. Cell culture of melanoma cell lines derived from the cancerous tissue, including WM115, BLM, K1735, WM793, and A375M, was cultured. In order to assess miRNA-10b levels, the real-time polymerase chain reaction was utilized. The absence (n = 20)/presence (n = 20) of metastasis was diagnosed with chest computed tomography or chest X-ray. The values of miRNA-10b for the discrimination of metastasis incidence were assessed. RESULTS: The demographic characteristics, including age and gender of the metastatic and nonmetastatic patients, were similar (P > 0.05). The specimen cultures were positive for miRNA-10b in 14 (35%) of the metastatic cases versus 4 (20%) of the nonmetastatic ones (P = 0.004). The quantitative analysis of miR-2b revealed significantly higher levels in metastatic cases (-1.59 ± 1.13 in metastatic vs. -0.16 ± 0.67 in nonmetastatic cases; P = 0.001). The measured area under the curve for the value of miRNA-10b was 0.923 (P < 0.001; 95% confidence interval: 0.811-1) with sensitivity and specificity of 100% and 94.4%. CONCLUSION: Based on this study, metastatic melanoma was associated with elevated levels of miRNA-10b. This marker had the sensitivity and specificity of 100% and 94.4% for the discrimination of metastatic melanoma from nonmetastatic ones.

Association of HOTAIR gene polymorphisms and haplotypes with uterine leiomyoma susceptibility in southeast of Iran.

Uterine leiomyoma (UL) is the most common benign tumor of the uterus. HOX transcript antisense RNA (HOTAIR) as a lncRNAs is the product of HOXC gene that plays a major role in the invasion and development of different tumors. Several lines of evidence have been suggested the effects of HOTAIR polymorphisms on cancer risk. The aim of the present study was to analyze the effects of HOTAIR polymorphisms (rs12826786, rs920778, rs4759314 and rs1899663) on UL in southeast of Iran. A total of 152 women with UL and 182 age-matched healthy women were selected in the case-control study. The PCR-RFLP and ARMS-PCR methods were used for genotyping. HOTAIR rs920778 polymorphism was associated with a lower risk of UL in dominant [OR, 0.5 (95% CI, 0.3-0.9); P = 0.03], recessive [OR, 0.6 (95% CI, 0.4-0.9; P = 0.016] and allelic models [OR, 0.6(95% CI, 0.5-0.9); P = 0.004]. However, HOTAIR rs12826786 polymorphism was associated with a higher risk of UL in dominant [OR, 2.6 (95% CI, 1.6-4.1); P = 0.0001], recessive [OR, 1.9 (95% CI, 1-3.6); P = 0.04] and allelic models [OR, 1.8 (95% CI, 1.3-2.4); P = 0.0003]. There was no association between HOTAIR rs4759314 and rs1899663 polymorphisms and UL susceptibility. The frequency of CTGA haplotype was lower in UL women; however, the CCGA, TCGA, TTTA, and TTGA haplotypes were more frequent in UL women. Our results indicated that HOTAIR rs12826786 and rs920778 polymorphisms had a significant effect on UL susceptibility. The HOTAIR haplotypes could affect UL susceptibility.

Breast cancer diagnosis: Imaging techniques and biochemical markers.

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer.

Genetic variants in 3'-UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis.

Preeclampsia (PE) as a pregnancy-specific disorder is the major cause of mortality and morbidity of mothers and fetuses. This study attempts to investigate the possible association between the 2572C>A (rs4846049) and 4869C>G (rs1537514) polymorphisms in the 3'- untranslated region of MTHFR gene and the risk of PE. A total of 198 patients diagnosed with PE and 171 unrelated, age matched healthy pregnant women, were recruited for this case-control study. The MTHFR 2572C>A and 4869C>G genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CG genotype of MTHFR 4869C>G was associated with decreased risk of PE, and this genotype was found to be a protective factor for PE susceptibility. There was no significant difference in the genotypes of MTHFR 2572C>A polymorphism between PE patients and control group. The frequency of combined AC/CG genotypes of MTHFR 2572C>A and 4869C>G polymorphisms were less frequent in PE patients and were associated with a lower risk of PE. The C-G and A-G haplotypes of MTHFR 2572C>A and 4869C>G polymorphisms were significantly lower in PE patients. In conclusion, the CG genotype of MTHFR 4869C>G polymorphism was associated with a lower risk of PE. No association was found between MTHFR 2572C>A polymorphism and PE.

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility.

PURPOSE: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. METHODS: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1-2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4-6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC-GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4-8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 - 2], P = 0.01). CONCLUSIONS: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC-GG combined genotype and C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.

Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion.

It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA. Impact statement What is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population. What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population. What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities on the role of TCN2 and TCN2R polymorphisms in the pathogenesis of RSA.

Association between oral lichen planus and Epstein-Barr virus in Iranian patients.

BACKGROUND: Oral lichen planus (OLP) is a common mucocutaneous disease with malignant transformation potential. Several etiologies such as humoral, autoimmunity, and viral infections might play a role, but still there is no definite etiology for this disease. The aim of this study was to investigate the presence of Epstein-Barr virus (EBV) genome in Iranian patients with OLP as compared to people with normal mucosa. MATERIALS AND METHODS: The study was carried out on a case group including 38 tissue specimens of patients with histopathological confirmation of OLP and a control group including 38 samples of healthy mucosa. All samples were examined by nested polymerase chain reaction (PCR) method to determine the DNA of EBV. RESULTS: Twenty-two (57.9%) female samples and 16 (42.1%) male samples with OLP were randomly selected as the case group, and 20 (52.6%) female samples and 18 (47.4%) male samples with healthy mucosa as the control group. There was a statistically significant difference in the percentage of EBV positivity between the case (15.8%) and the control groups (P < 0.05); in the case group, three female samples (13.6%) and three male samples (18.8%) were infected with EBV; the difference between the genders was not statistically significant (P = 0.50). CONCLUSION: Results emphasized that EBV genome was significantly higher among Iranian patients with OLP so antiviral therapy might be helpful.

Estrogen receptor alpha XbaI GG genotype was associated with severe preeclampsia.

PURPOSE: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore, ERα gene could be a possible candidate for preeclampsia (PE) susceptibility. In current study we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. METHODS: A total of 192 pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequencies of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; p = 0.02) and in severe PE compared to normotensive women [OR = 1.8 (1.1-3), p = 0.02] after adjusting for age, ethnicity, and primiparity. CONCLUSIONS: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.

The MDM2 promoter T309G polymorphism was associated with preeclampsia susceptibility.

PURPOSE: Preeclampsia (PE) is a hypertensive disorder of pregnancy in which abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role in its pathophysiology. The aim of the current study was to examine the association between Mouse Double Minute 2 (MDM2) T309G and 40 bp insertion/deletion (I/D) polymorphisms and PE risk. METHODS: A case-control study was conducted on 208 PE women and 164 healthy pregnant women matching age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping. RESULTS: The MDM2 309GG genotype was associated with PE, and this genotype was found to be a risk factor for PE. There was no association between the MDM2 I/D polymorphism and PE. The haplotype-based association analysis revealed no association between MDM2 T309G and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined genotypes were significantly higher in PE women with marginal P values (P = 0.046). CONCLUSIONS: The MDM2 309GG genotype was associated with higher risk of PE. The TT-DD and GG-DD combined genotypes were higher in PE women.

The -2549 insertion/deletion polymorphism of VEGF gene associated with uterine leiomyoma susceptibility in women from Southeastern Iran.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is an important angiogenic factor that regulates angiogenesis and mediates sex steroid-induced cell growth. The present study investigated the association of VEGF gene-2578C/A (rs699947) and -2549 insertion/deletion polymorphisms in the promoter region of VEGF-A gene and uterine leiomyoma susceptibility in Southeast of Iran. MATERIAL AND METHODS: One hundred and fifty five women with uterine leiomyoma and 157 age, BMI, and ethnicity matched healthy women were enrolled in this study. VEGF gene -2578C/A polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the -2549 insertion/dele-tion polymorphism was analyzed by PCR method. RESULTS: The frequency of alleles and genotypes of VEGF-2578C/A polymorphism was not different between women with uterine leiomyoma and the controls; however, a significant association was revealed between II genotype of -2549 insertion/deletion (I/D) polymorphism of VEGF gene and uterine leiomyoma. CONCLUSIONS: The findings showed that VEGF gene -2549 insertion/deletion polymorphism was associated with uterine leiomyoma.

The effects of p21 gene C98A polymorphism on development of uterine leiomyoma in southeast Iranian women.

Uterine leiomyoma (UL) is a monoclonal tumor which arises from uninhibited proliferation of a single myometrial cell; therefore, the imbalance in cell cycle regulation could be a key event in its development. In the present study, we aimed to assess the association of p21 gene polymorphisms and UL. Genomic DNA was extracted from blood samples of 154 women with UL and 197 age-, BMI-, and ethnically matched controls. p21 C98A (rs1801270) and C70T (rs1059234) polymorphism genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The CA genotype of p21 C98A polymorphism was significantly higher in UL women (28 %) compared to the controls (18 %), and the UL risk was 1.8-fold greater in women with CA genotype compared to CC genotype before and after adjusting for age, BMI, and ethnicity (OR, 1.8 [95 % CI, 1.1 to 3]; P = 0.02). There was no association between the AA genotype of p21 C98A polymorphism and UL. Moreover, the frequency of p21 98A allele was significantly higher in the UL women compared to controls (17 vs. 12 %, p = 0.04). The p21 C70T polymorphism did not correlate with UL before and after adjusting for age, BMI, and ethnicity. There was no difference in haplotype frequency of p21 C70T and C98A polymorphisms between UL patients and the controls. CA genotype of p21 C98A polymorphism may be a risk factor for UL susceptibility; however, p21 C70T polymorphism did not associate with UL.

Association of interleukin-1 receptor antagonist VNTR polymorphism and risk of pre-eclampsia in southeast Iranian population.

AIM: Pre-eclampsia (PE) is an obstetric disorder that may result in maternal and neonatal mortality and morbidity. Growing evidence indicates that cytokines, such as interleukins, are involved in the pathogenesis of this complication. Hence the current study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and PE susceptibility in southeast Iranian women. MATERIAL AND METHODS: The IL-Ra VNTR polymorphism was evaluated in 192 PE women and 186 age-matched normotensive pregnant women by the polymerase chain reaction method. RESULTS: The frequency of the A2 allele and the A2A2 genotype of IL-Ra VNTR polymorphism was significantly lower in PE patients compared to controls: therefore, A2 allele may play a protective role in PE development (odds ratio = 0.13 95% CI, [0.04-0.03]; P < 0.0001). In addition, there was no relation between the IL-Ra VNTR polymorphism and severity of the disease. CONCLUSION: The A2 allele of the IL-Ra VNTR polymorphism could be a protective factor for PE susceptibility.

Vascular endothelial growth factor (VEGF)-634G/C polymorphism was associated with severe pre-eclampsia and lower serum VEGF level.

AIM: Vascular endothelial growth factor (VEGF) is an angiogenic factor whose production is increased in pre-eclampsia (PE). Therefore, the present study was conducted aiming at assessing the possible association of VEGF polymorphisms with PE susceptibility in the southeast of Iran. MATERIAL AND METHODS: Overall, 192 PE women and 186 unrelated age-matched normotensive pregnant women were genotyped for the VEGF-2578C/A (rs699947), -1154G/A (rs1570360), and -634G/C (rs2010963) polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism method. Serum VEGF levels were determined by the enzyme-linked immunosorbent assay method. RESULTS: There was no significant difference in VEGF-2578C/A, -1154G/A and -634G/C polymorphisms between PE women and controls. However, the frequency of VEGF-634GC and CC genotypes was significantly higher in women with severe PE compared to mild PE and controls. In addition, serum VEGF levels were significantly lower in PE women. The VEGF-634CC genotype was associated with lower serum VEGF levels compared to the VEGF-634GG genotype. Moreover, serum VEGF levels were significantly lower in individuals with the VEGF-634CC genotype compared to VEGF-634GC genotype only in the control group. The mean serum VEGF levels did not differ significantly between genotypes of VEGF-2587C/A and -1154G/A polymorphisms. CONCLUSION: Our findings suggest that the association of VEGF-634G/C polymorphisms with severe PE and the VEGF-634CC genotype was correlated with lower serum VEGF levels.

The early-onset preeclampsia is associated with MTHFR and FVL polymorphisms.

PURPOSE: The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. METHODS: This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. RESULTS: No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. CONCLUSION: MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.

Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies.

BACKGROUND: The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation of the immune modulatory impact on collagen architecture within the TME remains limited. METHODS: We introduce CollaTIL, a computational pathology method that quantitatively characterizes the immune-collagen relationship within the TME of gynecologic cancers, including high-grade serous ovarian (HGSOC), cervical squamous cell carcinoma (CSCC), and endometrial carcinomas. CollaTIL aims to investigate immune modulatory impact on collagen architecture within the TME, aiming to uncover the interplay between the immune system and tumor progression. RESULTS: We observe that an increased immune infiltrate is associated with chaotic collagen architecture and higher entropy, while immune sparse TME exhibits ordered collagen and lower entropy. Importantly, CollaTIL-associated features that stratify disease risk are linked with gene signatures corresponding to TCA-Cycle in CSCC, and amino acid metabolism, and macrophages in HGSOC. CONCLUSIONS: CollaTIL uncovers a relationship between immune infiltration and collagen structure in the TME of gynecologic cancers. Integrating CollaTIL with genomic analysis offers promising opportunities for future therapeutic strategies and enhanced prognostic assessments in gynecologic oncology.

The role of cells that are part of our immune system in altering the structure of the protein collagen within cancers is not fully understood, particularly within cancers that affect women such as ovarian, cervical and uterine cancers. Here, we developed a computer-based method called CollaTIL to explore how immune cells influence collagen in these tumors and affect their growth. We found that a higher presence of immune cells leads to less organized collagen in the tumor. Conversely, when there are fewer immune cells, the collagen tends to be more structured. Additionally, CollaTIL identifies patterns that predict patient outcomes in these cancers. These findings not only enhance our understanding of tumor biology but also may be useful in helping clinicians to predict which patients are at risk of their disease progressing.

Retraction notice to "The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model" [Cancer Lett. 419 (2018) 30-39].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.