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Supplementary Figure from Combinatorial Treatment with PARP-1 Inhibitors and Cisplatin Attenuates Cervical Cancer Growth through Fos-Driven Changes in Gene Expression

Cervical cancer continues to be a significant cause of cancer-related deaths in women. The most common treatment for cervical cancer involves the use of the drug cisplatin in conjunction with other therapeutics. However, the development of cisplatin resistance in patients can hinder the efficacy of these treatments, so alternatives are needed. In this study, we found that PARP inhibitors (PARPi) could attenuate the growth of cells representing cervical adenocarcinoma and cervical squamous cell carcinoma. Moreover, a combination of PARPi with cisplatin increased cisplatin-mediated cytotoxicity in cervical cancer cells. This was accompanied by a dramatic alteration of the transcriptome. The FOS gene, which encodes the transcription factor Fos, was one of the most highly upregulated genes in the dual treatment condition, leading to increased Fos protein levels, greater Fos binding to chromatin, and the subsequent induction of Fos target genes. Increased expression of Fos was sufficient to hinder cervical cancer growth, as shown by ectopic expression of Fos in cervical cancer cells. Conversely, Fos knockdown enhanced cell growth. Collectively, these results indicate that by inducing FOS expression, PARPi treatment in combination with cisplatin leads to inhibition of cervical cancer proliferation, likely through a Fos-specific gene expression program. Implications: Our observations, which link the gene regulatory effects of PARPi + cisplatin to the growth inhibitory effects of FOS expression in cervical cancer cells, strengthen the rationale for using PARPi with cisplatin as a therapy for cervical cancer.

To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC).A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes.A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79).Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P

PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

A new series of nanocomposite polymer electrolytes (NCPEs) was prepared using poly(vinylidene fluoride–co–hexafluoro propylene) P(VdF-HFP) as polymer, magnesium triflate (MgTr) as salt and nano-sized barium titanate (BaTiO3) (3 was revealed through X-ray diffraction (XRD) analysis. From AC impedance spectroscopy, maximum conductivity of 4.11 × 10−4 Scm−1 was attained for the addition of 6 wt% of nano BaTiO3 to the P(VdF-HFP)/MgTr matrix. Dielectric studies were found to be in accordance with the ionic conductivity studies. For the most highly conducting sample, a greater number of mountain valley pattern was observed from Atomic Force Microscopy (AFM) analysis. Thermal stability of the sample, P(VdF-HFP)/MgTr/BaTiO3 (6 wt%) (which possessed maximum ionic conductivity) was observed through TG/differential thermal analysis studies. All these results suggested that these materials are favorable and find application in practical electrochemical devices.

Deep learning is a subfield of machine learning that has gained significant popularity in recent years due to its ability to achieve state-of-the-art results in a variety of applications, ranging from computer vision and natural language processing to robotics and gaming. It is based on artificial neural networks, which are designed to mimic the structure and function of the human brain. In this book, we provide a comprehensive overview of deep learning, including its definition, history, key characteristics, limitations, and applications. Chapter 1, we delve into the fundamentals of deep learning, including its definition, historical overview, and the differences between deep learning and machine learning. Additionally, we introduce Bayesian learning concepts, which are an important aspect of deep learning. We also cover the concept of decision surfaces and how they can be used to visualize and interpret the results of deep learning algorithms. Chapter 2 focuses on linear classifiers, including linear discriminant analysis, logistic regression, and the perceptron algorithm. We also cover linear machines with hinge loss, which is a popular optimization technique used in deep learning. Chapter 3 discusses various types of optimization techniques, including gradient descent and batch optimization. We provide an overview of each optimization method, as well as their variants, and explain how they work. Chapter 4, we introduce neural networks, including the structure of neural networks, how they work, and the key components of neural networks. We then delve into the multilayer perceptron, which is one of the most commonly used neural network architectures, and the back propagation learning algorithm, which is used to train neural networks. Keywords: Machine learning, Artificial neural networks, Computer vision, Natural language processing, Robotics, Gaming, State-of-the-art results, Human brain, Comprehensive overview, Bayesian learning, Decision surfaces, Linear classifiers, Linear discriminant analysis, Logistic regression, Perceptron algorithm, Linear machines, Hinge loss, Optimization techniques, Gradient descent, Batch optimization, Neural networks, Multilayer perceptron, Back propagation learning algorithm, Key components, Training neural networks

The ancient art of storytelling is flavoured with numerous myths. Literature reflects this in various forms of writing. One can find numerous myths in association with religion and culture. Primitive men worshipped nature, as it seemed to be superior to human power. They looked at the environment in awe. And myths prevailed on nature in the ancient era. Later on, men raised questions against these myths based on scientific arguments. They found that these myths were laid to preserve nature. Humans need a healthy environment to live a healthy life. Thus it is mandatory for them to safeguard it. With time humans started disregarding these myths saying that science is more important. Thus the reverence towards nature is also neglected which leads to disrespect and carelessness towards the environment. The present paper focuses on the myths prevalent in Southern India with particular reference to Tamil literature and also points out the mythical reason behind preserving nature. It explores how the human race failed to safeguard nature by neglecting the ancient myths. It attempts to prove that science is there to restore the environment and not to degrade.

Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P.05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P.0001.The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Hand hygiene is a significant component involved in preventing transmission of health care associated infections including COVID-19. Compliance to hand hygiene among the health care workers (HCWs) requires evaluation and timely feedback. "You can't improve what you can't measure" is a famous saying and this multicentric study was designed to measure hand hygiene compliance and have birds eye view on hand hygiene compliance in COVID Intensive care units (ICUs) and wards across India.A prospective multicentric observational study was conducted for a period of 6 months in 92 health care facility across India which included varied type of public and private hospitals. Hand hygiene audit was conducted in COVID ICU and COVID non-ICU wards in all these facilities by their HCWs using the IBHAR mobile application based on WHO's hand hygiene audit tool. Hand hygiene total adherence rate (HHTAR) and hand hygiene complete adherence rate (HHCAR) were analyzed and compared between 2 locations. Adherence rates were analyzed based on the zones, institute type, profession and for each WHO moments.A total of 1,61,056 hand hygiene opportunities were documented and adherence rates were recorded higher in COVID wards (HHTAR-61.4%; HHCAR-28.8%) than COVID ICUs (HHTAR-57.8%; HHCAR-25.6%). Overall, the adherence rates were observed higher in COVID wards (HHTAR- 68.1%; HHCAR-38.3%) of private hospitals, COVID wards of the west zone (HHTAR- 70.2%; HHCAR-36.8%), cleaning staffs of the COVID ward scores better compliance than all other professions in COVID ICUs and COVID wards. HHTAR was found to be the higher in moment 3 (After body fluid exposure-76.3%) followed by moment 4 (after touching patient-73.7%) done in COVID wards compared to moments done in ICUs.This study highlights the practice of hand hygiene in COVID care locations across India. Effective strategies need to be implemented in COVID ICUs across the facilities to improve the compliance.

Cervical cancer continues to be a significant cause of cancer-related deaths in women. The most common treatment for cervical cancer involves the use of the drug cisplatin in conjunction with other therapeutics. However, the development of cisplatin resistance in patients can hinder the efficacy of these treatments, so alternatives are needed. In this study, we found that PARP inhibitors (PARPi) could attenuate the growth of cells representing cervical adenocarcinoma and cervical squamous cell carcinoma. Moreover, a combination of PARPi with cisplatin increased cisplatin-mediated cytotoxicity in cervical cancer cells. This was accompanied by a dramatic alteration of the transcriptome. The FOS gene, which encodes the transcription factor Fos, was one of the most highly upregulated genes in the dual treatment condition, leading to increased Fos protein levels, greater Fos binding to chromatin, and the subsequent induction of Fos target genes. Increased expression of Fos was sufficient to hinder cervical cancer growth, as shown by ectopic expression of Fos in cervical cancer cells. Conversely, Fos knockdown enhanced cell growth. Collectively, these results indicate that by inducing FOS expression, PARPi treatment in combination with cisplatin leads to inhibition of cervical cancer proliferation, likely through a Fos-specific gene expression program.Our observations, which link the gene regulatory effects of PARPi + cisplatin to the growth inhibitory effects of FOS expression in cervical cancer cells, strengthen the rationale for using PARPi with cisplatin as a therapy for cervical cancer.

Background: There is an increased proportion of non-endometrioid histologies in Lynch syndrome-associated compared to sporadic endometrial cancer; however, screening recommendations do not differ between type I and type II cancers. Objective: Our objective was to examine the frequency of Lynch syndrome identified in type I and type II endometrial cancers and their associated characteristics. Methods: We reviewed patients with type I and type II endometrial cancer who were screened for Lynch Syndrome or referred for genetic testing according to an age and family history-based screening protocol. All patients were seen and treated at a large academic institution affiliated with a county safety-net hospital. Clinical, pathologic, immunohistochemistry, and germline genetic testing results were obtained as well as the choice of genetic screening approach, personal and family history, and compliance with testing were assessed. Results: 234 women with type I and 29 patients with type II endometrial cancer were identified. Lynch syndrome was diagnosed in a total of eight (3.4%) type I endometrial cancer patients, all identified after age-based tumor screening. In type II endometrial cancer group, three (10.3%) patients had Lynch syndrome. One was referred for testing after abnormal immunohistochemistry screening under age 60. The other two were >60 years old and identified after abnormal immunohistochemistry screening performed on physician’s request. Conclusion: Age-based screening may not diagnose Lynch Syndrome in women with type II endometrial cancers. Our findings underscore the need for a universal screening approach in patients with type II endometrial cancers, even in a low-resource population.

IntroductionStage IVA cervical cancer is an uncommon diagnosis. The course of the disease and the complications of treatment are not well characterized. The goal of this study was to report treatment outcomes of patients with stage IVA cervical cancer.MethodsA single institution retrospective review was carried out of all patients treated for stage IVA cervical cancer from January 2008 to July 2017. Patients were clinically staged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria for cervical cancer. Inclusion criteria were patients with stage IVA cervical cancer of any histologic subtype, including patients with evidence of para-aortic lymph node involvement, treated at the institution during this time period. Overall survival and progression free survival were calculated using the Kaplan–Meyer method. Comparisons between survival were done using the Cox proportional hazards regression model and the log rank test.ResultsWe identified 25 patients with stage IVA cervical cancer. Mean age at diagnosis was 54 years (range 27–77). Squamous cell carcinoma was the histologic diagnosis in 24 of 25 patients (96%), with 1 case of small cell carcinoma (4%). 21 patients completed a full course of radiation. The median overall survival for patients who completed their treatment was 60 months (range 3–136), with a 2 year overall survival of 63%. The median progression free survival was 27 months (range 0–125), with a 2 year progression free survival of 40%. 11 of 25 patients (44%) developed fistulas during the course of their disease, and 55% of these were complex fistulas. 19 of 25 (76%) patients had a percutaneous nephrostomy for either hydronephrosis or diversion of vesicovaginal fistula. 111 unplanned admissions occurred among the 25 patients, and infections of the urinary tract was implicated in 46 (41%) of these. The cohort had a total of 92 emergency department visits, with pain control (36%) and medication refills (15%) being the most common presentations.DiscussionPatients with stage IVA cervical cancer may have substantial long term survival, although the sequelae of disease and treatment is associated with significant morbidity. Symptoms of fistula, percutaneous nephrostomy complications, and chronic pain present unique issues that require extensive supportive care.

OBJECTIVE. In this article, we provide an updated review on the role of imaging in initial staging, treatment monitoring, and follow-up of cervical cancer with a focus on the role of MRI and FDG PET/CT. In addition, the 2018 International Federation of Gynecology and Obstetrics staging system and its implication on management of cervical cancer are explored. CONCLUSION. Imaging plays a major role in treatment planning and as a prognostic indicator in patients with cervical cancer. MRI and PET/CT have complementary roles: MRI is essential for the local staging of the primary tumor, and PET/CT is the most useful modality for detecting regional nodal and distant metastases.

Characterize prevalence of intimate partner violence (IPV) among breast and cervical survivors receiving care in an urban safety-net healthcare system; Examine the relationship between IPV and clinical characteristics, receipt of cancer treatment, and guideline-recommended survivorship care. From 2010 to 2017, breast and cervical cancer survivors were identified and recruited from a large, integrated, safety-net hospital system. Electronic health records (EHR; to measure survivorship care), cancer registry (to measure clinical characteristics), and patient telephone surveys (to measure IPV) were triangulated among 312 survivors. Bivariate and multivariable models assessed the relationship between victimization and clinical characteristics, cancer treatment, and guideline-recommended survivorship care. Among the 312 participants, 54% identified as IPV+. Among breast cancer, IPV+ cancer participants were twice more likely to develop estrogen receptor negative ER- and/or progesterone receptor negative PR- tumor receptors compared with IPV- cancer participants (AOR = 2.31; 95% CI, 1.20, 4.44). IPV+ breast cancer participants were less likely to have surgery and less likely to have hormone therapy as a first course of treatment compared with IPV- participants. There was no relationship between IPV and adherence to guideline-recommended cancer survivorship care. This study expands our current knowledge on how victimization, and specifically IPV, impact health among specialty care. Future research should determine the feasibility of implementing Trauma-Informed Care in oncology practices to better optimize care. At integrated hospital systems, IPV+ cancer participants should utilize social workers, within their oncology clinics, to connect to victim services.

OBJECTIVE. The purpose of this study is to evaluate the prognostic value of quantitative metabolic parameters from pretreatment PET/CT scans of patients with squamous cell cervical cancer. MATERIALS AND METHODS. This retrospective study included 120 patients with biopsy-proven squamous cell carcinoma of the cervix who underwent FDG PET/CT for initial tumor staging. The primary tumor maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), tumor glycolytic activity, metabolic tumor volume (MTV), and metabolic intratumoral heterogeneity index (calculated as the AUC for the cumulative standardized uptake value [SUV]-volume histogram [CSH] index) were obtained. Information on patient demographic characteristics and tumor staging were collected. Median follow-up was 27.5 months. Overall survival (OS) and progression-free survival (PFS) were calculated using a multivariate Cox proportional hazards regression model and log-rank (Mantel-Cox) test to generate Kaplan-Meier survival plots. RESULTS. The mean (± SD) age of the patients was 54.4 ± 13.1 years. Twenty-two patients had stage I disease; 58, stage II; 23, stage III; and 17, stage IV. Thirty-three patients died, 82 were living, and five were lost to follow-up and were censored; 29 patients had disease progression. The median survival was 74.9 months (95% CI, 63.6-86.9 months). A higher MTV was significantly associated with reduced OS in multivariate analysis (hazard ratio, 1.085; 95% CI, 1.036-1.136; p = 0.0005). A higher AUC-CSH index (denoting lower tumor heterogeneity) was significantly associated with increased OS (hazard ratio, 0.662; 95% CI, 0.448-0.979; p = 0.04) and PFS (hazard ratio, 0.683; 95% CI, 0.471-0.991; p = 0.045) in multivariate analysis. Kaplan-Meier survival analysis using the median value for MTV (61 mL) significantly predicted OS (p = 0.0009). CONCLUSION. Tumor heterogeneity on pretreatment PET/CT is associated with OS and PFS in patients with cervical cancer. MTV is significantly associated with OS.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1–4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy., Graphical Abstract, Developing a successful vaccine against dengue has been challenging. Arun Sankaradoss and colleagues developed a genotype-specific DNA DENV vaccine candidate that elicits robust dengue immune responses. The low cost and thermostability of DNA vaccines should allow countries to implement large-scale vaccination programs, which could greatly reduce dengue cases.

Heart Disease(HD) is one of the most serious health issue that attacks people age from 65 and older and has symptoms are palpitations, loss of conscious, abnormal heart beats and it also can attack younger people who has going through lots of stress, over weight and chest pain and so on. Diagnosing heart disease manually is less efficient and mostly not accurate. Machine Learning (ML) helps efficiently in early prediction of Heart Attack. In this paper we have used LSTM (Long Short Term Memory) a Deep Learning Technique to diagonise heart attack. Diagnosing is complicated as it is important task, it needs to be executed accurately and efficiently. This system helps in prediction of HD which used the supervised learning that has low computation.

Defects in translation lead to changes in the expression of proteins that can serve as drivers of cancer formation. Here, we show that cytosolic NAD(+) synthesis plays an essential role in ovarian cancer by regulating translation and maintaining protein homeostasis. Expression of NMNAT-2, a cytosolic NAD(+) synthase, is highly upregulated in ovarian cancers. NMNAT-2 supports the catalytic activity of the mono(ADP-ribosyl) transferase (MART) PARP-16, which mono(ADP-ribosyl)ates (MARylates) ribosomal proteins. Depletion of NMNAT-2 or PARP-16 leads to inhibition of MARylation, increased polysome association and enhanced translation of specific mRNAs, aggregation of their translated protein products, and reduced growth of ovarian cancer cells. Furthermore, MARylation of the ribosomal proteins, such as RPL24 and RPS6, inhibits polysome assembly by stabilizing eIF6 binding to ribosomes. Collectively, our results demonstrate that ribosome MARylation promotes protein homeostasis in cancers by fine-tuning the levels of protein synthesis and preventing toxic protein aggregation.

Screening for Lynch syndrome (LS) is routinely performed in patients with endometrial carcinoma. Currently, no screening recommendations exist for LS in precancerous lesions. The study goal was to determine the incidence of abnormal protein expression in endometrioid intraepithelial neoplasia/atypical hyperplasia (EIN/AH). We analyzed mismatch repair (MMR) protein expression by immunohistochemistry in EIN/AH concurrent with MMR-deficient endometrial carcinomas, and in endometrial biopsy/curettage specimens with EIN/AH from an unselected group of patients. Of 63 patients with MMR-deficient endometrial carcinoma, 34 demonstrated loss of MLH1/PMS2 expression; 1 showed loss of PMS2 alone; 12 showed loss of MSH2/MSH6, and 15 had loss of MSH6 alone. Genetic testing identified deleterious mutations in 14 cases (LS). 15 tumors demonstrated MLH1 promoter hypermethylation. Abnormal MMR expression in EIN/AH and adjacent carcinoma was concordant in 100% of LS cases and 71% of MLH1 promoter hypermethylation cases. Of 118 patients from the unselected group with EIN/AH, 4 (3%) cases demonstrated absent expression of one or more MMR proteins. Of these, 2 patients were later confirmed to have deleterious mutations in subsequent specimens with endometrial carcinoma. The prevalence of abnormal MMR expression in EIN/AH adjacent to carcinoma and in the unselected group of patients with EIN/AH is similar to the reported prevalence of LS in endometrial carcinoma. Identifying patients at high risk for LS through abnormal MMR expression in EIN/AH provides the benefit of early surveillance, treatment and timely diagnosis for the patient and affected family members.

Objective. Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, serous cystadenomas, and serous borderline tumors. Our previous study with clinicopathological approach showed that the majority ovarian epithelial inclusions are derived from the fallopian tubal epithelia rather than from ovarian surface epithelia. This study was designed to gain further insight into the cellular origin of ovarian low-grade serous carcinomas by differential gene expression profiling studies. Methods. Gene expression profiles were studied in 43 samples including 11 ovarian low-grade serous carcinomas, 7 serous borderline tumors, 6 serous cystadenomas, 6 ovarian epithelial inclusions, 7 fallopian tubal epithelia, and 6 ovarian surface epithelia. Comprehensive analyses with hierarchical clustering, Rank-sum analysis and Pearson correlation tests were performed. Final validation was done on selected genes and corresponding proteins. Results. The gene expression profiles distinguished ovarian low-grade serous carcinomas from ovarian surface epithelia, but not from fallopian tubal epithelia cells. Hierarchical clustering analysis showed ovarian serous tumors and ovarian epithelial inclusions were clustered closely in a branch, but separated from ovarian surface epithelia. The results were further validated by selected proteins of OVGP1, WT-1, and FOM3, which were highly expressed in the samples of the fallopian tube, ovarian epithelial inclusions, and ovarian serous tumors, but not in ovarian surface epithelia. The reverse was true for the protein expression patterns of ARX and FNC1. Conclusions. This study provides evidence in a molecular level that ovarian low-grade serous carcinomas likely originate from the fallopian tube rather than from ovarian surface epithelia. Similar gene expression profiles among fallopian tube, ovarian epithelial inclusions, and serous tumors further support that ovarian low-grade serous carcinomas develop in a stepwise fashion. Such findings may have a significant implication for “ovarian” cancer-prevention strategies.

Chikungunya fever (CHIKF) is an arbovirus disease caused by chikungunya virus (CHIKV), an alphavirus of Togaviridae family. Transmission follows a human-mosquito-human cycle starting with a mosquito bite. Subsequently, symptoms develop after 2–6 days of incubation, including high fever and severe arthralgia. The disease is self-limiting and usually resolve within 2 weeks. However, chronic disease can last up to several years with persistent polyarthralgia. Overlapping symptoms and common vector with dengue and malaria present many challenges for diagnosis and treatment of this disease. CHIKF was reported in India in 1963 for the first time. After a period of quiescence lasting up to 32 years, CHIKV re-emerged in India in 2005. Currently, every part of the country has become endemic for the disease with outbreaks resulting in huge economic and productivity losses. Several mutations have been identified in circulating strains of the virus resulting in better adaptations or increased fitness in the vector(s), effective transmission, and disease severity. CHIKV evolution has been a significant driver of epidemics in India, hence, the need to focus on proper surveillance, and implementation of prevention and control measure in the country. Presently, there are no licensed vaccines or antivirals available; however, India has initiated several efforts in this direction including traditional medicines. In this review, we present the current status of CHIKF in India.

Introduction: Vulvovaginal Candidiasis (VVC) is one of the commonest vaginal infections caused by Candida spp. affecting women of reproductive age group. Though Candida spp. is of endogenous origin several host related and behavioural factors can contribute to the development of infection. Candida albicans is the commonest spp. responsible for infection. However, an increasing emergence of Non-albicans Candida (NAC) has led to the development of recurrent infections, treatment failure and complications. Aim: To characterise Candida spp. isolated from clinically suspected cases of VVC. Materials and Methods: It was an observational prospective study done during the period of May 2017 to Oct 2018. A total of 150 vaginal isolates from samples of vaginal discharge were included in the study. Candida spp identification was done by various methods like gram stain, germ tube test, culture on Sabouraud Dextrose Agar (SDA), Dalmau culture on corn meal agar, colour differentiation on CHROMagar (Chromogenic agar) and sugar assimilation tests. Statistical Package for Social Science (SPSS) was used for statistical analysis. Results: Women of age group 26-35 years were most commonly affected population. Candida albicans (49.3%) and NAC (50.7%) both were present in almost equal number. The commonest isolate found was Candida albicans (49.3%) followed by Candida glabrata (29.3%) and Candida tropicalis (21.4%). Conclusion: Highest infection rate (54%) was seen in the women of age group 26-35 years. Candida albicans being the commonest spp. As NAC are emerging rapidly, speciation will play a vital role in appropriate selection of antifungal agents for the treatment of fungal infections prior to the initiation of therapy.

The endometrium is unique as an accessible anatomic location that can be repeatedly biopsied and where diagnostic biopsies do not extirpate neoplastic lesions. We exploited these features to retrospectively characterize serial genomic alterations along the precancer/cancer continuum in individual women. Cases were selected based on (1) endometrial cancer diagnosis/hysterectomy and (2) preceding serial endometrial biopsies including for some patients an early biopsy before a precancer histologic diagnosis. A comprehensive panel was designed for endometrial cancer genes. Formalin‐fixed, paraffin‐embedded specimens for each cancer, preceding biopsies, and matched germline samples were subjected to barcoded high‐throughput sequencing to identify mutations and track their origin and allelic frequency progression. In total, 92 samples from 21 patients were analyzed, providing an opportunity for new insights into early endometrial cancer progression. Definitive invasive endometrial cancers exhibited expected mutational spectra, and canonical driver mutations were detectable in preceding biopsies. Notably, ≥1 cancer mutations were detected prior to the histopathologic diagnosis of an endometrial precancer in the majority of patients. In 18/21 cases, ≥1 mutations were confirmed by abnormal protein levels or subcellular localization by immunohistochemistry, confirming genomic data and providing unique views of histologic correlates. In 19 control endometria, mutation counts were lower, with a lack of canonical endometrial cancer hotspot mutations. Our study documents the existence of endometrial lesions that are histologically indistinct but are bona fide endometrial cancer precursors. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Objective Invasive pattern of endocervical adenocarcinomas (EACs) is known to influence lymph node metastasis and cancer recurrence. In this study we describe the prognostic significance of necrotic tumor debris (NTD) and tumor nuclear grade on recurrence risk stratification of early-stage cervical adenocarcinoma. Methods Patients who underwent surgery from 2007 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB2 EAC, for whom pathology was available for review were included in this study. Clinico-pathologic variables and clinical recurrence risk stratification (low, intermediate, or high risk) were correlated to intraluminal NTD and tumor nuclear grade (N3). Results Among 50 patients meeting inclusion criteria, all were managed surgically and clinically risk stratified as low (n=33), intermediate (n=13), and high risk (n=4). Twenty-three patients (46%) were NTD-N3 negative and 27 (54%) were NTD-N3 positive. NTD-N3 was significantly associated with higher stage, tumor grade, larger tumor size, positive lymphovascular space invasion, and recurrence of disease (P=0.025). Patients with stage IB1 EAC who were stratified as intermediate or high-risk for recurrence were positive for NTD-N3. Lack of NTD-N3 had 100% negative predictive value for disease recurrence. Conclusions NTD-N3, a novel pathologic finding, may be used to further stratify overall recurrence risk, and may play a role in individualization of patient care in early-stage EAC.

PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose protein substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e.g. growth, migration). Global gene expression analyses in ovarian cancer cells subjected to PARP-7 depletion indicate biological roles for PARP-7 in cell-cell adhesion and gene regulation. To identify the MARylated substrates of PARP-7 in ovarian cancer cells, we developed an NAD+ analog-sensitive approach, which we coupled with mass spectrometry to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including cell-cell adhesion and cytoskeletal proteins. Specifically, we found that PARP-7 MARylates α-tubulin to promote microtubule instability, which may regulate ovarian cancer cell growth and motility. In sum, we identified an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes., eLife digest Cancer is a complex illness where changes inside healthy cells causes them to grow and reproduce rapidly. Specialized proteins called enzymes – which regulate chemical reactions in the cell – often help cancer develop and spread through the body. One such enzyme called PARP-7 labels other proteins by attaching a chemical group which changes their behavior. However, it was unknown which proteins PARP-7 modifies and how this tag alters the actions of these proteins. To investigate this, Parsons, Challa, Gibson et al. developed a method to find and identify the proteins labelled by PARP-7 in ovarian cancer cells taken from patients and cultured in the laboratory. This revealed that PARP-7 labels hundreds of different proteins, including adhesion proteins which affect the connections between cells and cytoskeletal proteins which regulate a cell’s shape and how it moves. One of the cytoskeletal proteins modified by PARP-7 is α-tubulin, which joins together with other tubulins to form long, tube-like structures known as microtubules. Parsons et al. found that when α-tubulin is labelled by PARP-7, it creates unstable microtubules that alter how the cancer cells grow and move. They discovered that depleting PARP-7 or mutating the sites where it modifies α-tubulin increased the stability of microtubules and slowed the growth of ovarian cancer cells. Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. A new drug which suppresses the activity of PARP-7 has recently been developed, and this drug could potentially be used to treat ovarian cancer patients with high levels of PARP-7. Clinical trials are ongoing to see how this drug affects the behavior of cancer cells in patients.

Vulvar squamous cell carcinoma (VSCC) pathogenesis is traditionally defined by the presence or absence of human papillomavirus (HPV), but the definition of these groups and their molecular characteristics remains ambiguous across studies. Here, we present a retrospective cohort analysis of 36 patients with invasive VSCC where HPV status was determined using RNA in situ hybridization (ISH) and polymerase chain reaction (PCR). Clinical annotation, p16 immunohistochemistry (IHC), programmed death ligand-1 (PD-L1) IHC, HPV16 circular E7 RNA (circE7) detection, and RNA-sequencing (RNA-seq) of the cases was performed. A combination of ISH and PCR identified 20 cases (55.6%) as HPV-positive. HPV-status did not impact overall survival (HR: 1.36, 95% CI: 0.307 to 6.037, p=0.6857) or progression-free survival (HR: 1.12, 95% CI: 0.388 to 3.22, p=0.8367), and no significant clinical differences were found between the groups. PD-L1 expression did not correlate with HPV status, but increased expression of PD-L1 correlated with worse overall survival. Transcriptomic analyses (n=23) revealed distinct groups, defined by HPV status, with multiple differentially expressed genes previously implicated in HPV-induced cancers. HPV-positive tumors showed higher global expression of endogenous circular RNAs (circRNAs), including several circRNAs that have previously been implicated in the pathogenesis of other cancers.

Objectives: Pelvic exenteration (PE) is an uncommon radical procedure associated with high perioperative morbidity due to the nature and extent of surgery. Due to surgical innovation and perioperative care advances, postoperative outcomes may have improved for PE. The purpose of this study is to evaluate rates of 30-day postoperative complications (POC) and risk factors associated with POC following PE for gynecologic malignancies. Methods: Data was obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. All patients who underwent PE for a gynecologic cancer from 2012-2018 were identified using appropriate CPT, ICD-9 and ICD-10 codes. Comparative analyses were performed and stratified by admission status to evaluate demographics, preoperative and intraoperative variables, and surgical outcomes. Statistical tests were performed with R Studio v.1.1.456. Results: Between 2012-2018, 473 patients who had undergone a PE for a gynecologic malignancy were identified. The median age at time of surgery was 59 years (range, 22-90 years) and median body mass index (BMI) was 26.1 kg/m2 (range, 15.5-65.7 kg/m2). The median operative time was 385 minutes (range, 55-1090 minutes). At the time of their PE, 21.2% of patients underwent a concurrent myocutaneous flap and 12.3% a urinary conduit. The median length of hospital stay was 10 days (range, 0-114 days). At time of discharge, 79.2% were discharged home, 20.4% were transferred to an acute care or rehab facility, and 0.4% expired. The overall POC rate was 75.9%, but when urinary tract infections and blood transfusions were excluded, the POC rate was 37.6%. The 30-day readmission rate was 20.3% and re-operation rate was 10.4%. Lower preoperative albumin and hematocrit values, longer operative times, higher American Society of Anesthesiology (ASA) class, concurrent flap, and urinary conduit procedures were associated with higher POC rates (Table 1). When adjusting for these factors on multivariate analysis, preoperative albumin levels, and longer operative times remained independent risk factors for higher POC rates. Download : Download high-res image (123KB) Download : Download full-size image Conclusions: There remains a high rate of 30-day POC following PE; although a significant proportion of the POC are driven by the development of urinary tract infections and administration of blood transfusions. The contemporary mortality rate appears to be lower than previously reported historical rates. Preoperative albumin levels and longer operative times may be modifiable risk factors that can reduce POC rates.

Objectives: Large bowel resections (LBR) are occasionally required to achieve optimal resection during cytoreductive surgery for ovarian cancer. Stoma creation (SC) has been proposed as a protective measure to reduce the incidence and potential consequences of an anastomotic leak after LBR; however there is conflicting data on whether this does indeed reduce rates of leak. The objectives of this study were to evaluate the rate of SC at time of LBR during ovarian cytoreductive surgery (OCS), and to determine whether SC reduces the rates of sepsis and reoperation. Methods: Women who underwent LBR at time of OCS from 2013 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database using corresponding CPT, ICD-9, and ICD-10 codes. SC was determined based on CPT codes. Comparative analyses were then stratified by SC to evaluate demographics, preoperative and intraoperative variables, and surgical outcomes. Statistical tests were performed with R Studio v.1.1.456. Results: A total of 8,750 women who underwent OCS were identified, and 1,603 (18.3%) of these women underwent a concurrent LBR. Among the women who had a LBR, 1,418 (88.5%) had one bowel resection and 185 (11.5%) had multiple bowel resections performed. At the time of LBR, 1,003 (62.6%) had a primary anastomosis without SC, 272 (17.0%) had a colostomy, and 190 (11.8%) had an ileostomy. SC data was not available for 138 (8.6%) women, and these women were excluded from analysis. Preoperatively, women with SC tended to be of older age, and have a higher body mass index (BMI), higher American Society of Anesthesiology (ASA) class, higher White blood cell count, and lower albumin level. Women who had multiple bowel resections were more likely to have SC at time of OCS (17.3% vs. 8.4%, p Download : Download high-res image (120KB) Download : Download full-size image Conclusions: Over a quarter of women who had a concurrent LBR at time of OCS underwent SC. These women tended to be older with higher BMI and ASA class. Although the specific indications for SC are not captured in the NSQIP database, SC was associated with higher rates surgical site infection, organ space infection, sepsis, and hospital readmission during the 30-day postoperative period.

Objectives: Pelvic exenteration (PE) is an aggressive, radical procedure associated with high rates of postoperative complications (POC). Although PE was first described for the palliation of gynecologic malignancies, this has been adopted for the management of colorectal and genitourinary cancers. The objective of this study is to evaluate the perioperative risk factors and 30-day surgical outcomes following PE for gynecologic and non-gynecologic cancers. Methods: Data was obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. All women who underwent PE from 2012-2018 were identified using appropriate CPT codes and gender. Comparative analyses were performed and stratified by admission status to evaluate demographics, preoperative and intraoperative variables, and surgical outcomes. Statistical tests were performed with R Studio v.1.1.456. Results: A total of 2,069 women who had undergone a PE were identified from 2012-2018. Of these, 73 were performed for an unknown indication and 109 were for a nonmalignant indication, and these were excluded. The remaining 1,887 were used for our analysis: 473 (25.1%) had a PE for a gynecologic cancer, 973 (51.6%) for a genitourinary cancer, 427 (22.6%) for a colorectal cancer, and 14 (0.74%) for an unspecified cancer. PE performed for gynecologic malignancy were associated with longer operative times (median 385 vs 350 minutes, p Download : Download high-res image (107KB) Download : Download full-size image Conclusions: PE performed for gynecologic malignancies are associated with higher morbidity compared to PE done for non-gynecologic cancers. Flaps are performed more often during PE for gynecologic cancers, which may contribute to the increased morbidity seen in these patients following PE. Data on prior radiation therapy which is not available through the NSQIP database, could be evaluated in future studies.

Objectives: Granulosa cell tumors are characterized by indolent growth and late recurrence; treatment of recurrent disease is not standardized. We sought to evaluate the outcomes of patients who underwent secondary and tertiary cytoreductive surgery as part of treatment for recurrent granulosa cell tumor. Methods: A retrospective review was conducted of women diagnosed with primary or recurrent granulosa cell tumors at an urban university system between 2010 and 2019. Data collected included demographic, clinicopathologic, and treatment factors. Endpoints of treatment outcome was progression free survival. Statistical analyses were preformed using the Kaplan-Meier method, the log-rank test, and Fisher's exact test. Results: 75 patients diagnosed with primary or recurrent granulosa cell tumor were identified. After excluding cases with inadequate follow-up and juvenile granulosa cell tumor, 69 patients were analyzed. The average age at diagnosis was 48.3 years (21.2-86.0). 82.6% of patients had stage I disease; the remainder had stage II (8.7%) or stage III (8.7%) disease. 15 of 69 patients (21.7%) were treated for recurrent disease. The average time to recurrence was 6.27 years (range 1.05-20.71). There was a significant correlation between optimal resection or staging (including omentectomy and peritoneal biopsies) and recurrence (OR 0.171, 95% CI 0.0553-0.560, p=0.0076). Fertility preservation was not associated with recurrence (p=0.08). 71% of women with recurrent disease underwent secondary cytoreduction. Secondary CRS was associated with a significantly higher progression free survival compared to medical management alone at time of recurrence (median 2.3 vs 1.6 yrs, p=-0.01). 10 women were subsequently treated for a second recurrence; 50% were treated with cytoreductive surgery. No PFS benefit was seen with surgical management compared to medical management for the second recurrence (p=0.31). Seven women were then treated for a third recurrence or progression and six women for a fourth. PFS after treatment for second, third, or fourth recurrence or progression was longer among patients whose treatment included surgery compared to those who did not (median 1.708 vs 0.997 years), although this difference was not statistically significant. Conclusions: Complete staging for granulosa cell tumors was associated with decreased risk of recurrence. Secondary CRS at first recurrence is associated with a significantly higher progression free survival.

Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8+ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P=0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PD-L1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P=0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8+ tumor-infiltrating lymphocyte density (CPS: P=0.028; TPS: P=0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR]=4.253 vs. 0.235, P=0.025; TPS: HR=4.98 vs. 0.2; P=0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR=6.15 vs. 0.16, P=0.045; TPS: HR=3.78 vs. 0.26, P=0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PD-L1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.

Background Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. Methods Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. Results One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. Conclusions HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Background Recent advances suggest the fallopian tube as the main anatomic site for high-grade ovarian or pelvic serous carcinoma (O/PSC). Human fallopian tube is mainly lined by two cell types, secretory and ciliated cells. Large number of studies on the biologic role of tubal secretory cells in O/PSC have been performed in the last decade. However, the role of tubal ciliated cells in relation to the development of O/PSC has rarely been explored. The purpose of this study was to determine if change of the tubal ciliated cells shows difference in age and location and to examine their association with serous neoplasia. Methods Three groups (low-risk or benign control, high-risk, and O/PSC) of patients were age matched. The age data was stratified by 10-year intervals ranging from age 20 to older than 80. Ciliated cells from both tubal fimbria and ampulla segments were counted by microscopy and by tubulin immunohistochemical staining. The data was analyzed by standard contingency table, Poisson distribution methods, nonparametric Mann–Whitney U-tests and Spearman correlation analysis after age justification. Results The study revealed that the absolute number of tubal ciliated cells decreased significantly with age within each group. A reduction in ciliated cells within the fallopian tube remained a significant risk factor for serous neoplasia after age adjustment. A dramatic decrease of tubal ciliated cells in both tubal segments was identified in patients with high-risk and with O/PSC compared to those in the low-risk (benign control) group (p

Highlights • The majority of respondents evaluate lymph nodes via sentinel lymph node mapping for grade 1–2 endometrial cancer. • Only 50% of respondents perform intraoperative sentinel lymph node mapping for grade 3 endometrial cancer. • 90% of respondents give chemotherapy-based adjuvant treatment for advanced endometrial cancer. • 75% of respondents combine radiation therapy with chemotherapy in stage III endometrial cancer., The use of sentinel lymph node (SLN) mapping over full lymphadenectomy for endometrioid endometrial cancer (EC) has had varying uptake. Adjuvant therapy for advanced stage EC is also a debated topic globally. Two recent randomized controlled trials have attempted to clarify which treatment approach should be recommended. Our aims were to identify common practice patterns in the intraoperative lymph node evaluation as well as the practice patterns in the treatment of advanced stage (stage III-IV) endometrioid EC among gynecologic oncologists. A 16-question survey was distributed via email to all Society of Gynecologic Oncology members. Study data were collected anonymously and managed using REDCap electronic data tools. Respondents were asked questions regarding demographics, assessing nodal status, and choice of adjuvant treatment for each stage. Descriptive statistics, student’s t-tests, and chi-squared analyses were performed. A total of 1531 surveys were distributed and 187 (12%) members responded. The majority (70%) of respondents identified nodal metastases by performing SLN mapping prior to nodal evaluation in grade 1–2 disease, however only half perform SLN mapping in grade 3 EC. Adjuvant chemotherapy was recommended by 90% of practitioners for advanced EC. However, external beam radiation or brachytherapy was combined with chemotherapy in 74% of stage III EC and 35% of stage IV EC. While 90% of practitioners recommend chemotherapy-based adjuvant treatment for women with stage IIIA–IVA endometrioid EC, decreasing local recurrence appears to be a factor in treatment planning as radiation combined with chemotherapy is used in 63% of cases.

Highlights: • Use of MIS for the treatment of early-stage ovarian cancer appears to be common. • Gynecologic oncologists show interest in performing advanced laparoscopic procedures. • Neoadjuvant chemotherapy may play role in determining use of MIS for ovarian cancer. • Barriers to MIS for ovary cancer were concern for occult disease and lack of evidence., Retrospective studies suggest that minimally-invasive surgery may be safe and effective for the treatment of early-stage ovarian cancer as well as interval cytoreduction after neoadjuvant chemotherapy. Adoption rates and attitudes towards its use remain largely unknown. We aimed to determine the current use of minimally-invasive surgery for the treatment of ovarian cancer and identify perceived barriers towards further adoption of this method. Electronic survey was administered to physician members of the Society of Gynecologic Oncology. Chi-square analysis was used to determine if any correlation existed between variables and the current use of minimally invasive surgery in general practice and, specifically, for the treatment of ovarian cancer. There was a survey response rate of 15.1%. Sixty-five percent of respondents practiced in an academic setting, and 32.1% of respondents had completed fellowship training within the past 5 years. Ninety percent of respondents were performing >50% of their current procedures using minimally invasive surgery. Over seventy percent of respondents said that they performed minimally invasive surgery for primary staging and interval cytoreductive surgery for the treatment of ovarian cancer. Concern for residual disease and lack of scientific validation were the most frequently cited barriers to the implementation of minimally invasive surgery for the treatment of ovarian cancer. A majority of respondents have adopted the use of MIS for the management of early stage ovarian cancer. Advances in imaging to detect occult tumor deposits and a randomized trial to study and promote the use of minimally invasive surgery in ovarian cancer is warranted.

We previously showed, in a pilot study with publicly available data, that T cell receptor (TCR) repertoires from tumor infiltrating lymphocytes (TILs) could be distinguished from adjacent healthy tissue repertoires by the presence of TCRs bearing specific, biophysicochemical motifs in their antigen binding regions. We hypothesized that such motifs might allow development of a novel approach to cancer detection. The motifs were cancer specific and achieved high classification accuracy: we found distinct motifs for breast versus colorectal cancer-associated repertoires, and the colorectal cancer motif achieved 93% accuracy, while the breast cancer motif achieved 94% accuracy. In the current study, we sought to determine whether such motifs exist for ovarian cancer, a cancer type for which detection methods are urgently needed. We made two significant advances over the prior work. First, the prior study used patient-matched TILs and healthy repertoires, collecting healthy tissue adjacent to the tumors. The current study collected TILs from patients with high-grade serous ovarian carcinoma (HGSOC) and healthy ovary repertoires from cancer-free women undergoing hysterectomy/salpingo-oophorectomy for benign disease. Thus, the classification task is distinguishing women with cancer from women without cancer. Second, in the prior study, classification accuracy was measured by patient-hold-out cross-validation on the training data. In the current study, classification accuracy was additionally assessed on an independent cohort not used during model development to establish the generalizability of the motif to unseen data. Classification accuracy was 95% by patient-hold-out cross-validation on the training set and 80% when the model was applied to the blinded test set. The results on the blinded test set demonstrate a biophysicochemical TCR motif found overwhelmingly in women with HGSOC but rarely in women with healthy ovaries, strengthening the proposal that cancer detection approaches might benefit from incorporation of TCR motif-based biomarkers. Furthermore, these results call for studies on large cohorts to establish higher classification accuracies, as well as for studies in other cancer types.

Subsequent to serosurveys 1 and 2 for COVID-19 carried out in three wards of Mumbai in July and August 2020, Municipal Corporation of Greater Mumbai conducted serosurvey 3 in March 2021. This was to identify the extent of exposure by testing specific IgG antibodies against COVID-19.A cross-sectional study was conducted to find the prevalence of seropositivity in Mumbai, which included 10,197 samples belonging to patients visiting public dispensaries (slum population, 6006) and private (nonslum population, 4191) laboratories of Aapli Chikitsa network for blood investigations for non-COVID illnesses. The ward-wise number of unlinked anonymous samples from 24 wards was predecided by using probability proportionate sampling. The samples were collected using quota sampling technique as per predecided sample for each ward. These samples collected from nonimmunized individuals were tested for IgG antibodies at the Molecular Biology Laboratory of Kasturba Hospital for Infectious Diseases by chemiluminescence assay (CLIA) method.The overall seropositivity was found to be 36.3% (41.6% in slum and 28.59% in nonslum population). It was more in city wards (38.28%) followed by western suburb (36.47%) and then eastern suburb wards (34.86%), matching with the proportion of cases in these wards during the study period. There was no significant difference in seropositivity among males and females and in different age groups.Seropositivity is higher in slum areas than nonslum areas. It has reduced in slum areas and increased in nonslum areas as compared to findings of serosurveys 1 and 2. This explains the detection of a greater number of cases from nonslum areas in the second wave. The average seropositivity of 36.3% justifies the necessity of immunization on a wider scale in the city. Periodic serosurveys are required at fixed intervals to monitor the trend of infection and level of herd immunity.

Background Metastatic and recurrent cervical cancer is rarely a curable disease. Systemic chemotherapy is typically recommended for treatment based on clinical trials in the first-line or second-line setting. Rare patients who progress through 2 salvage regimens will have the performance status, medical ability, and desire to continue cytotoxic therapy. For these patients, there are no data to provide effective counseling regarding expected response rates (RRs) and toxicities. We sought to review our experience with this patient population. Methods A single institution review was performed of all patients treated for cervical cancer between January 1, 2000 and June 30, 2013. Eligible patients were those who received at least 3 unique salvage chemotherapy regimens following primary surgery or radiation. RRs, survival statistics and toxicities were evaluated. Results Twenty-three of 710 (3.2%) patients treated for cervical cancer met eligibility criteria. Nineteen received 2 or more cycles of a third-line regimen and were assessed for response and progression-free survival. The remainder were included in analysis of overall survival and toxicity. The RR to third-line chemotherapy was 10% (1 complete, 1 partial). An additional 27% achieved stable disease. In total, 57% suffered a grade 3 or 4 toxicity. The progression-free survival from the beginning of third-line therapy was 3.8 months, and the overall survival was 7.4 months. Conclusions Patients eligible to receive third-line chemotherapy for metastatic and recurrent cervical cancer can expect minimal benefit at the cost of significant toxicity. Quality of life considerations should be of paramount importance when counseling regarding the risks and benefits of further cytotoxic therapy.

BACKGROUND Adjuvant therapy choice for women with FIGO stage III endometrial carcinoma (EC) is controversial. We investigate the comparative benefit of adjuvant chemotherapy (CT) alone, radiation therapy alone (RT) or in combination (chemotherapy and radiation therapy [CRT]) with respect to recurrence-free survival (RFS) and overall survival (OS) in women with pelvis-limited (PL) EC (stage IIIA, IIIB, and IIIC1). MATERIALS AND METHODS A multi-institutional database of 270 surgically staged women with PLEC was analyzed. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. RESULTS Median RFS and OS were 112 and 130 months, respectively, for the full cohort. Adjuvant treatment was CT in 21%, RT in 27%, and CRT in 47%. Age, year of treatment, grade, histology, and adjuvant treatment were significantly associated with RFS and OS on univariate analysis. PLEC patients receiving CT alone fared worse in terms of RFS (P=0.07 relative to RT and