bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival outcomes for metastatic castration sensitive prostate cancer: Real world data from a Danish cohort 2016-2022.
Authors: Zedan Ahmed H. , Hansen Torben , Timm Signe
Published: June 2024

e17088

Background: Metastatic castration sensitive prostate cancer (mCSPC) has the worst prognosis in the whole disease spectrum of prostate cancers. However, the therapeutic armamentarium has dramatically evolved during the last decade leading to a marked improvement in survival outcomes for this population. The main aim of this study is to investigate the impact of treatment options for mCSPC derived from real world data (RWD). Methods: This is a single retrospective observational study performed at Department of Oncology, Vejle Hospital, Denmark. Eligible patients (men aged ≥18 years) had newly diagnosed, histologically confirmed mCSPC, and were treated with androgen deprivation therapy (ADT) plus either docetaxel (DOC) or novel androgen receptor axis-targeted agents (ARATA) such as abiraterone (ABI) or enzalutamide (ENZ). Endpoints included overall survival (OS), both Radiological- and Biochemical progression free survival (rPFS and bPFS) and time to next treatment (TTNT). Subgroup analysis was done for those whose inclusion criteria were matching to those in the randomized controlled trails (RCTs); both CHAARTED and LATITUDE. Results: In total, 259 patients diagnosed with mCSPC from January 2016 until January 2022 have been included in the study. Patients treated with DOC were 224 (87%), while ABI and ENZ were used in 32 (12%), and 3 (1%) patients, respectively. Data analysis was done after a median follow-up of 39.9 months (range 11.4-85.1). Median OS, rPFS and bPFS were not reached during the follow-up period, while median TTNT was 26.7 months (95% CI 23.8-31.2). For the above defined subgroup (233 patients) median TTNT was 26.2 months (95% CI 23.2-29.7). Conclusions: Observations from this study emphasizes the remarkable benefits for treatment intensification for mCSPC population, and inclusion of RWD resulted in outcomes comparable with RCTs.
Chemoresistance in high grade serous ovarian cancer molecular subtypes and the role of NRF2.
Authors: Toma Helen , Al-Odat Omar S. , Hamad Layla , Joshi Hansa , Kelly Rebeca , Katz Chelsea , Shojaei Hadi , Li Yahui , Mitra Ramkrishna , Bendjilali Nasrine , Spitz Francis R. , Chu Christina , Krill Lauren , Pandey Manoj , Wang Yemin , Warshal David Philip , Hamad Samera
Published: June 2024

e17574

Background: Epithelial ovarian cancer accounts for 90% of ovarian cancer diagnoses, 70% of which are high grade serous subtype (HGSOC). The HGSOC is the most aggressive type of Ovarian Cancer with limited therapeutic options. Studies have shown that several molecular subtypes of HGSOC exist such as immunoreactive, differentiated, proliferative, and mesenchymal, which further complicate the effort of finding therapies for this deadly cancer. Nuclear erythroid-related factor-2 (NRF2) is a transcription factor that is found to be frequently activated in ovarian cancer. NRF2 normally protects cells from oxidative damage by regulating more than 500 genes in human body. Hyperactivation of NRF2 in cancer is found to protect cancer cells from oxidative damage, and thus, promotes tumor growth and metastases. NRF2 is also known as an anti-inflammatory pathway and a master regulator of immune cells differentiation, distribution, and infiltration. Patients with high-NRF2 tumors tend to have significantly lower survival than patients with Low-NRF2 tumors. In this study, we investigate the role of NRF2 in HGSOC subtype evolution and responses to chemotherapies. Methods: Two human HGSOC cell lines, OVCAR8 and PEO1 were used to identify and quantify the NRF2 protein level with its down-stream targets. We also quantified differentiation markers such as Vimentin, P63, PD-L1, that are associated with HGSOC subtypes, using western blotting. These human cell lines were also tested for Carboplatin and Paclitaxel half maximal inhibitory concentration (IC50) using MTT assay. RNA-seq data of human HGSOC from The Cancer Genome Atlas (TCGA) was analyzed to compare our in vitro studies with human tumors. Results: The human OVCAR8 cell line had a 50-fold higher expression of NRF2 and 12-fold higher expression of vimentin when compared to the PEO1 cell line. When treated with Carboplatin, the IC50 for OVCAR8 was 112 ± 3.6 µM vs 67.5 ± 5µM for PEO1. For Paclitaxel, the IC50s for the two cell lines were 5 ± 0.4nM and 4 ± 0.15nM, respectively. Finally, RNA sequencing data from the TCGA showed that the NRF2 activation score in mesenchymal subtype was significantly increased compared to the immunoreactive subtype (p=0.004). Conclusions: Our data show that expression of NRF2 is significantly higher in the mesenchymal (the most chemo-resistant and aggressive) subtype, while the subtypes with lower NRF2 tend to be more responsive to chemotherapies. These findings imply that targeting NRF2 in these subtypes could improve responses to chemotherapies and enhance tumor prognosis in patients with HGSOC.
Demographic factors influencing hysterectomy approaches (with vs. without removal of tubes and/or ovaries): An NCDB review.
Authors: Au Kristine , Voth Caitlyn , Keirns Darby , Silberstein Peter T.
Published: June 2024

e17578

Background: Endometrial cancer is the most common cancer of the female reproductive organs in the United States, and surgery involving the removal of the uterus, cervix, and ovaries (total hysterectomy) is the most common treatment. However, some women may have their uterus removed with sparing of the ovaries, resulting in the prevention of menopause but an increased incidence of cancer recurrence. Given the pivotal role of surgical outcomes, it is important to examine the variations in treatment approaches – specifically, the choice between total hysterectomy with and without removal of the tubes and/or ovaries – across different demographic groups. Methods: Patients with endometrial cancer were selected from the National Cancer Database (NCDB) and 19,147 patients were identified between 2004 and 2020. We compared the demographic variables of patients who had a total hysterectomy with and without removal of tubes and ovaries. Descriptive statistics, multivariate, and chi-square analyses on SPSS version 28 was used for all analyses; P < 0.05 was considered significant. Results: Black patients with endometrial cancer were 26% less likely to have a total hysterectomy with the removal of tubes and/or ovaries compared to white patients. Conversely, no significant difference was observed in the choice of surgical approach between Hispanic and non-Hispanic patients. A median household income of $74,063 were 97% less likely to have a total hysterectomy with removal of tubes and/ovaries compared to patients with a median household income of less than $46,277. Patients with insurance, including private, Medicaid, Medicare, or other government insurance did not have a significantly different surgical approach than those without insurance. Furthermore, patients living in more educated areas (where <5% of adults lacked a high school degree) were 29% more likely to receive a total hysterectomy with removal of tubes and/or ovaries compared to less educated areas (where >15.3% of adults lacked a high school degree). Conclusions: This study highlights significant determinants that influence the decision to remove the tubes and/or ovaries during a total hysterectomy for endometrial cancer, with emphasis on race, education, and income. Significant implications with removal of ovaries and/or tubes include changes in a woman’s hormonal balance, infertility, and increased risk of further diseases. Understanding and recognizing these determinants within the context of endometrial cancer treatment can contribute to improved patient outcomes, a reduced risk of ovarian cancer and associated complications, and an improvement in overall quality of life. By acknowledging the versatile nature of this decision, healthcare providers can better individualize treatment plans, ultimately striving for favorable long-term health and well-being outcomes for their patients.
Magnetic resonance texture analysis for predicting histologic tumor type in endometrial cancer.
Authors: Lee Seung-Mi , Lee Hyun-Jung , Lee Juhun
Published: June 2024

e17580

Background: The aim of the present study was to assess the feasibility of texture analysis and histogram on magnetic resonance image for predicting histologic type in patients with endometrial cancer. Methods: A total of 85 patients who underwent surgery and had pathologically confirmed endometrial cancer were included in this study. We investigated the parameters for normalized perfusion map including perfusion ratio and integrated density, defined as the product of area and mean gray value from the normalized perfusion mapping on gadolinum-enhanced T1-weigted pelvic MRI. Apparent Diffusion Coefficient map and texture analysis by gray-level co-occurrence matrix in endometrial cancer, including angular second moment, contrast, correlation, entropy and inverse difference moment. MR parameters were correlated with pathologic feature including tumor type, FIGO staging, tumor invasion and lymph node metastasis. Results: The normalize perfusion map analysis revealed noteworthy distinctions between type 1 and type 2 endometrial cancer. Specifically, we observed significant differences in tumor area (p = 0.014), perfusion ratio (p = 0.001), perimeter (p = 0.002), integrated density (p = 0.042), median (p = 0.001), and roundness (p = 0.018). Entropy form the texture analysis demonstrated associations with integrated density and linear correlation, with notable differences observed between type 1 (R2 = 0.363) and type 2 (R2 = 0.471) endometrial cancer subtypes, displaying statistical significance (p = 0.010). Conclusions: In conclusion, parameters obtained by texture analysis and perfusion map could be useful for predicting the histological type of endometrial cancer.
Demographic factors of malignant endometrioid adenofibroma: An NCDB study.
Authors: Ramos Brianna Eillen , Khatib Rawaan , Tandon Nikhita , Sadighian Assal , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e17592

Background: Malignant endometrioid adenofibroma (MEA) is a rare subtype of ovarian carcinoma characterized by squamous metaplasia and frequently linked with endometriosis and colorectal cancer. This fibrous tumor with cystic spaces is primarily diagnosed in postmenopausal females who present with abnormal vaginal bleeding. The current recommended treatment option is a laparoscopic resection; however, a hysterectomy may be indicated in more serious cases. Analyzing the trends of MEA may provide significant insights into its epidemiology. An analysis of the National Cancer Database (NCDB) was conducted to identify the demographic factors of patients diagnosed with MEA. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included 193 patients with a histologically-confirmed diagnosis of CA (ICD-O-3 code 8381). Demographic factors (age, sex, race, Hispanic status, insurance status, facility type, distance from facility, and Charlson-Deyo score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: 193 patients diagnosed with MEA were recorded in the database from 2004 to 2019, with a strong declining annual incidence rate (R²=0.7833). Women were much more likely to be diagnosed (99.5%) than men (0.5%), where the average age at diagnosis was 61.40 years (SD= 12.89, Range =30-90). The primary site of diagnosis was the endometrium (54%). Most patients were noted to be non-Hispanic (85%) and White (86%), privately insured (59%), and lived in metropolitan areas with a population greater than 1 million (54%). The majority also had a Charlson-Deyo comorbidity score of 0 (78%). In regard to treatment, patients were seen relatively equally at the comprehensive community cancer program (42%) and academic/research program (32%). 93% of patients received surgery as their primary treatment, 20% received chemotherapy, and 20% received radiation. Conclusions: To the best of our knowledge, this is the first NCDB analysis on malignant endometrioid adenofibroma and thus serves to address prior gaps in the topic’s research. Results were similar to descriptions in earlier case reports, where MEA is notably more common in females who identify as non-Hispanic and White, with a primary site diagnosis at the endometrium. This is the first time the socioeconomic factors of MEA patients have been described in the literature: patients are more likely to live in metropolitan areas, be privately insured, and be treated at similar rates at both academic/research and comprehensive community cancer programs. Further studies are essential in promoting the knowledge of this topic, specifically how demographic/socioeconomic factors influence the diagnosis and treatment options of patients with MEA.
Vaginal lacerations during laparoscopic hysterectomy for endometrial cancer and local recurrence risk.
Authors: Nicolais Olivia , Cummings Mackenzie , Edelson Mitchell , Moukarzel Lea , Cardillo Nicholas , Burton Elizabeth , Buchanan Tommy , Shahin Mark S.
Published: June 2024

e17596

Background: Laparoscopic surgery offers equivalent oncologic outcomes as compared to open surgery, while causing lesser morbidity and resulting in a faster recovery. However, vaginal extraction of specimens may cause vaginal or perineal lacerations (VL). To date, no studies have specifically reported the impact of vaginal laceration on local recurrence after surgical treatment for endometrial cancer. The objective of this study is to assess local recurrence rates compared between cases with or without vaginal lacerations (NL). Methods: We identified all patients with endometrial cancer who underwent laparoscopic surgical management between 2014 and 2018. We assessed the rate of local recurrence between patients in VL and NL cohorts. The study included all histologic subtypes and stages. Patients with benign final pathology, cases of synchronous primaries or cases that required laparotomy for extraction were excluded. Results: Among the 540 endometrial cancer MIS cases, 338 were evaluable. There were 40 cases of vaginal laceration during specimen extraction. There was no significant difference in age, race, presence of LVSI, stage, grade, histology or use of vaginal brachytherapy between cohorts. Cases with vaginal lacerations were significantly associated with a higher median BMI of 33.6kg/m2 (range 18.9-66) in the VL group as compared to 32.3kg/m2 (range 19.1-66) in the NL group (p=0.03). Uterine size was greater in the laceration group (VL) with a median of 150.5 g (49 - 462g) versus 110g (33 – 573g) in the NL cohort (p <0.01). The VL cohort was more likely to have received adjuvant treatment. Specifically external beam radiation therapy (EBRT) was administered 20% in the VL group versus 8.4% in the NL group (p = 0.02) and chemotherapy was used in 27.5% of the VL group versus 9.7% in the NL group (p < 0.01). In early stage disease, more cases had non-endometrioid histology in the VL group (23% versus 11.5%, p=0.043) and had increased incidence of chemotherapy and radiation use as well (EBRT 5.6% vs 23% and chemotherapy 6.7% versus 23%, both with p= <0.01). There were no cases of isolated vaginal recurrence (0/40) in the VL group as compared to an incidence of 2% (7/298) in the NL group with a relative risk of 0.48 (CI: 0.03-8.36, p=0.62). There were 4 cases of pelvic recurrence (4/40) in the VL group and 2 cases in the NL group (2/298) with a relative risk of 2.13 (CI: 0.46-9.89, p=0.34). Conclusions: In endometrial cancer cases, we did not observe a significantly increased risk of vaginal or pelvic recurrence after a vaginal laceration at the time of specimen removal. This could be attributed to the higher rate of non-endometrioid histology in early stage disease, which resulted in higher rates of adjuvant chemotherapy or radiation treatment.
Developing machine learning–based prognostic models for gestational choriocarcinoma: Insights into treatment efficacy and patient survival.
Authors: Alshwayyat Mustafa , Alshwayyat Sakhr Abdulsalam , Kamal Haya , Alshwayyat Tala Abdulsalam , Alenezy Abdalwahab
Published: June 2024

e17607

Background: Gestational Choriocarcinoma (GCC) is a highly aggressive tumor derived from syncytiotrophoblasts. There is currently controversy surrounding the initiation of chemotherapy for patients with GCC. We aimed to investigate the influence of chemotherapy on survival rates and develop machine-learning-based prognostic models for GCC patients to improve treatment decisions and personalized medicine. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results database (2000–2020). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or with other concurrent malignancies, and unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. We also investigated the role of multiple therapeutic options using Kaplan-Meier survival analysis. Results: This study included 732 patients, of whom 283 received chemotherapy, 116 underwent surgery alone, and 333 underwent both surgery and chemotherapy. Most patients (54.5%) were aged 30 years or older, with a median age of 32 years. The largest racial group was white, comprising 66.4% of cases, followed by black (16.7 %). Furthermore, most cases were localized (n=262), and only 13% presented with stage IV disease and 44.3% with metastasis. Survival analysis showed no significant differences in survival between the treatment modalities. Multivariate Cox regression analysis identified older age, unmarried status, and AJCC stage II as significant prognostic factors. The random forest classifier (RFC) and K-Nearest Neighbors (KNN) were the most accurate ML models, with the AJCC stage, race, and SEER stage as key factors. Performance metrics for all ML algorithms are summarized in the Table. Conclusions: Our study provides a novel and practical tool for GCC prognosis and management. Although our tool offers a valuable resource for personalized clinical decisions, further research is needed to better understand the role of chemotherapy in GCC treatment and its impact on patient outcomes. [Table: see text]
Zanzalintinib (XL092) plus nivolumab in non-clear cell renal cell carcinoma: The randomized phase 3 STELLAR-304 study.
Authors: Pal Sumanta Kumar , Powles Thomas , Kanesvaran Ravindran , Liu Mohan , Wang Zhong , Bhatt Aarohi , Patel Pritesh , Suárez Cristina
Published: June 2024

TPS4611

Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogenous group of rare, histologic subtypes with limited treatment options. There have been few dedicated randomized controlled studies in nccRCC, and novel treatment options supported by data from robust clinical trials are needed. Sunitinib, a tyrosine kinase inhibitor (TKI), is a commonly used therapy for nccRCC based on clinical benefit demonstrated in phase 2 trials. To date, no treatment has shown a significant overall survival (OS) improvement over sunitinib in any nccRCC subtype. Monotherapy with immune checkpoint inhibitors (ICIs) has shown only modest response rates, but TKI-ICI combinations have shown promising clinical activity in single-arm phase 2 trials. Zanzalintinib is a novel, multi-targeted TKI of VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER) which are involved in tumor angiogenesis, metastasis, and immunosuppression. Zanzalintinib has shown antitumor and immunomodulatory activity in animal models when used alone or in combination with ICIs (Hsu et al. Mol Cancer Ther. 2023). In the phase 1 STELLAR-001 study, single-agent zanzalintinib showed promising antitumor activity (38% objective response rate [ORR] and 88% disease control rate) and a manageable safety profile in patients with heavily pretreated advanced clear-cell RCC (Pal et al. IKCS NA 2023. Abs 1). STELLAR-304 was designed to assess the efficacy and safety of zanzalintinib + nivolumab versus sunitinib in previously untreated advanced nccRCC. Methods: STELLAR-304 (NCT05678673) is a phase 3, global, randomized, open-label study enrolling patients ≥18 years of age with unresectable/advanced/metastatic nccRCC. Patients must have measurable disease per RECIST v1.1, a Karnofsky performance status of ≥70%, and papillary, unclassified, or translocation-associated histology (sarcomatoid features are allowed). Patients with chromophobe, renal medullary carcinoma, or pure collecting duct histology are excluded. Prior systemic anticancer therapy for advanced/metastatic nccRCC is not allowed; however, one prior systemic adjuvant therapy, including ICI (but excluding sunitinib), is permitted for completely resected RCC if recurrence occurred ≥6 months after the last adjuvant therapy dose. Patients (N=291) are randomized 2:1 to receive treatment with zanzalintinib + nivolumab, or sunitinib alone. The dual primary endpoints are progression-free survival and ORR per RECIST v1.1 by blinded independent radiology committee. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in Europe, North and South America, and the Asia-Pacific region. Clinical trial information: NCT05678673 .
SOGUG-NEOWIN: A phase 2, open-label, multi-centre, multi-national interventional trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab (CET) as neoadjuvant treatment in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations.
Authors: Hussain Syed A. , Loriot Yohann , de Velasco Guillermo , Necchi Andrea
Published: June 2024

TPS4623

Background: The standard treatment for nonmetastatic MIBC is neoadjuvant cisplatin-based therapy followed by radical cystectomy (RC). However, many patients are ineligible for cisplatin. Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for metastatic urothelial cancer (mUC), including for cisplatin-ineligible patients. Based on these results, ICIs are being explored as neoadjuvant treatment in resectable UC with preliminary data suggesting antitumour activity. ERDA is a Fibroblast Growth Factor Receptor (FGFR) inhibitor, which has shown efficacy in advanced UC with select FGFR2/3 mutations/fusions. ERDA plus cetrelimab demonstrated clinically meaningful activity in patients with newly diagnosed FGFR-altered mUC in the phase 2 NORSE trial. We hypothesize that ERDA plus cetrelimab will improve the pathological complete response (pCR) rate in patients with FGFR+ MIBC who are candidates for RC and are ineligible for or refuse neoadjuvant cisplatin-based therapy. Methods: SOGUG-NEOWIN is a prospective, non-comparative, open label, multicentre, international trial to assess the efficacy of 9 or 12 weeks of neoadjuvant ERDA (cohort 1) or the combination of cetrelimab and ERDA (cohort 2) in patients with MIBC (cT2-Ta N0/1 M0) and FGFR alterations. Key eligibility criteria include ECOG PS 0-1; pure or predominant UC histology; decline or ineligible for cisplatin-based chemotherapy as defined by one of the following criteria: impaired renal function (GFR < 60 mL/min), ≥ grade 2 hearing loss, or ≥ grade 2 peripheral neuropathy; patients are considered fit for cystectomy; no prior FGFR-targeted or anti-PD-(L)1 therapy; no prior systemic therapy, radiation or surgery (except TURBT or biopsies) for bladder cancer; prior BCG was allowed if completed ≥ 6 weeks before initiation of study treatment; no current retinopathy. A total of 45 patients will be allocated to each cohort by a centralized system. Co-primary endpoints are pCR rate and percentage of pathological downstaging response (<ypT2). Secondary endpoints include event-free survival, overall survival, overall response rate, safety, tolerability, and delay to surgery. Biomarkers of response and resistance will be assessed using baseline archival tissues, blood and urine. Quality of life (QoL) will be assessed using FACT-Bl and EQ-5D-5L. Tumour response assessment via PET-MRI will be performed in a subset of patients. The trial is approved in 4 countries. The first patient was included on 31-Jan-2024. This trial would be the first to systematically address whether ERDA ± cetrelimab improves pCR in patients with FGFR-positive MIBC. (EudraCT 2022-002586-15). Clinical trial information: 2022-002586-15.
Safety and immunological effects of ablative radiotherapy followed by pembrolizumab in patients with advanced adrenocortical carcinoma.
Authors: Raj Nitya Prabhakar , Crane Christopher H. , Ziv Etay , Gopalan Anuradha , Chou Joanne F. , Capanu Marinela , Reidy Diane Lauren , Hajj Carla
Published: June 2024

TPS4630

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with poor prognosis. While pembrolizumab is a NCCN recommended treatment, our prior study showed no benefit in patients with liver metastases (NCT02673333).1 Preclinical evidence suggests combining liver-directed radiation therapy (RT) with pembrolizumab might enhance anti-tumor immunity.2 Our current study will assess the safety and describe preliminary efficacy data for ablative RT to symptomatic liver metastases followed by treatment with pembrolizumab in patients with advanced ACC. Methods: This is a single-center pilot study. Main inclusion criteria include: adult patients with metastatic ACC with symptomatic liver metastases, presence of extrahepatic metastases, ECOG 0-1. Ablative RT in 5 or 10 once daily fractions will be delivered over 1 to 2 weeks; pembrolizumab treatment (200mg Q3W) will begin one week after RT completion. The primary objective is to evaluate the safety of treatment with ablative RT followed by pembrolizumab. The study will include a 6 patient safety lead-in, with 10 to 12 patients enrolled in total. The secondary endpoint, efficacy, is defined as the objective response (partial and complete response) according to RECIST v1.1, in the hepatic and extrahepatic disease. Correlative objectives include evaluation of the innate and adaptive immune response during treatment through analysis of pre- and on-treatment blood and tumor tissue samples, circulating tumor (ct) DNA analyses, and PD-L1 and next-generation sequencing testing in pre-treatment tumor tissue samples to evaluate for biomarkers of response and resistance. This trial began enrollment in 9/27/2023, with 3 patients enrolled to date. References: 1Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RKG, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020;38(1):71-80. 2Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021;27(1):152-64. Clinical trial information: NCT06066333 .
A phase 1 safety and feasibility study of intratumoral placement of bicalutamide implants combined with radiotherapy for localized prostate cancer.
Authors: Citrin Deborah E. , Turkbey Baris , Patel Krishnan , Harmon Stephanie A , Pinto Peter A , Wood Brad , Gurram Sandeep , Ning Holly , Nathan Debbie-Ann , Desai Pujan K , Rairkar Maithili , Choyke Peter , Munster Pamela N. , Mileti Cassidy
Published: June 2024

TPS5126

Background: Systemic androgen deprivation therapy (ADT) is an integral part of therapy for unfavorable intermediate or high-risk prostate cancer treated with radiation therapy (RT). However, systemic anti-androgens are associated with considerable cardiovascular, metabolic, and sexual side effects leading to omission and contraindication in many men. We tested the feasibility of replacing systemic ADT with targeted local delivery of an anti-androgen agent (bicalutamide, Biolen Implant). The Biolen implant consists of a medical grade silicone polymer mixed with 6.3mg bicalutamide into a solid rod-shaped scaffold approximately 0.95 x 15 mm in size. Pre-clinical studies have demonstrated that a silicone/bicalutamide implant is a feasible method for durable localized delivery of an anti-androgen into the prostate. Results for the preclinical studies were presented at the AACR Symposium in April 2023 (Poster # 5261). Methods: Trial Design: This study (CP-002, NCT04943536) is a prospective, single-center, single-arm feasibility study to assess the safety, feasibility and PK profile for Biolen for the localized delivery of bicalutamide into the prostate when delivered with radiotherapy. Up to 20 participants with intermediate to high risk localized prostate cancer who are planned to receive RT and are candidates for systemic ADT will be enrolled. Study participants will have placement of the drug eluting Biolen (bicalutamide) implants. Participants will receive standard of care radiation 9 weeks after implant and will be followed through 2 years post radiation. Patients will undergo plasma collection after Biolen implant at Day 1, 3, Week 1, 2, 4 and seminal fluid collection at 4-7 and 8 weeks for assessment of bicalutamide levels. An MRI will be performed at 6 and 24 months after completion of radiation. Key Eligibility: Patients must have at least 1 MRI detected, biopsy proven localized prostate cancer lesion in whom prostate radiation and ADT is appropriate therapy (such as Intermediate Risk localized prostate cancer). Patients diagnosed as one of the following: a) NCCN intermediate risk prostate cancer, b) NCCN high risk prostate cancer due to Gleason Grade 4 or 5 AND refuses to receive systemic ADT, c) NCCN high risk prostate cancer due to PSA > 20 AND refuses to receive systemic ADT. Trial Status: The study is ongoing at the NCI and 9 patients have been enrolled to date. Clinical trial information: NCT04943536 .
Gonadal Failure in a Male With 3-M Syndrome
Authors: Aldhoon-Hainerova Irena , Baranowski Elizabeth , Kinning Esther , Dias Renuka P
Published: June 2024

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.
Xiqu 2.0
Authors: Ferrari Rossella
Published: June 2024

Xiqu 2.0 designates an experimental approach to adapting and updating the classical theaters of the Sinophone region (xiqu) and a form of expanded Chinese opera in digital times. It highlights strategies of versioning and serialization of classical texts and tropes in (post-)modern performance environments and foregrounds media and textual interactivity, networking, and participatory contexts of production, reception, and circulation—including the production, reception, and circulation of cultural memory in the contemporary Sinosphere. The stage practice of Hong Kong–based multi-genre artist Danny Yung of Zuni Icosahedron and his long-term work with Tang Xianzu's Peony Pavilion (1598) illustrate the multiple dimensions of xiqu 2.0. Representative productions include the digital Kun opera Sigmund Freud in Search of Chinese Matter and Mind (2002, 2016) and the series The Interrupted Dream, launched in 2018. The latter links Tang's oneiric imaginary to the postcolonial critique of orientalism through references to seventeenth-century chinoiserie at the court of Louis XIV. Updated for livestreaming during the COVID-19 pandemic, the series served as a virtual channel of mediated memory across the digital Sinosphere in the aftermath of the 2019–20 Hong Kong protests and as a commentary on ancien and modern regimes, past and present revolutions, old and new Chinese dreams.
MAPEAMENTO DE CRITÉRIOS COMPETITIVOS E ANÁLISE DE POSICIONAMENTO ESTRATÉGICO
Authors: Silva Keren Karolyne Nóbrega , Silva Yuri Laio Teixeira Veras , Andrade Pablo Ramom Matias de
Published: June 2024

A indústria estética no Brasil possui um grande potencial, apresentando um amplo crescimento mesmo nos momentos de dificuldade econômica. Mesmo com projeções positivas, esse setor ainda é carente em direcionamento estratégico, sendo um dos obstáculos mais frequentes. Desse modo, este estudo tem como objetivo “mapear os principais critérios competitivos para organizações de pequeno porte no setor estético”. Para isso, uma empresa atuante no setor foi considerada como objeto de estudo de caso, buscando proceder com uma avaliação em face do seu comportamento estratégico e posicionamento. Durante o processo de diagnóstico e coleta de dados, foram realizadas entrevistas, seguidas de pesquisas de mercado em formato remoto. Assim, os resultados alcançados permitiram identificar os principais critérios competitivo para o objeto em estudo, assim como realizar uma análise detalhada sobre a situação atual da organização e seu posicionamento estratégico no mercado, demonstrando pontos a serem melhorados.
Time to sense biofield (Prana) experiences between hands: A preliminary single blinded randomized placebo controlled trial
Authors: Vijayakumar Vinu , Nagaraja Jois Srikanth , Mallikarjuna Majgi Sumanth , Prasad Krishnamurthy Nagendra , Nanjunda swamy Roopa
Published: June 2024

Aims There is minimal research on the duration of biofield experiences. This preliminary study used the experiential learning practice of Master Choa Kok Sui's hands sensitisation to determine the duration to experience biofield sensations in between hands and to find the relationship between learning style preferences and biofield sensations. Methods This randomized placebo controlled, single blinded trial included 88 male and female pre-service teachers, aged 22.8±1.2 years. Participants completed a ruler drop test for reaction time, and Six Letter Cancellation test for measuring attention, learning style questionnaire for preferred method of learning, before randomization. The experimental (hands facing each other as introduced by Master Choa Kok Sui) and sham (hands facing opposite) groups practiced hands sensitisation. A semi-structured questionnaire was provided to gather information about biofield sensations and the time it took to experience these sensations between the hands. Results All (N=44) the participants in the experimental group and 13 participants in the sham group reported experiencing biofield sensations. A significant difference was noticed in experiencing magnetic (X2 = 38.247, p ≤ .001), physical sensations of energy (X2 = 12.02, p ≤ .001) and pain (X2 = 62.259, p ≤ .001) among the experimental and sham group . In the experimental group, the average time taken to first experience magnetic sensation, other biofield sensations and temperature variation was 34.84±12.97seconds, 40.28±20.96 seconds and 42.50±19.79 seconds, respectively. Minimum time taken to first experience biofield sensation was 5 seconds and lasted up to study duration of 120 seconds. There was no correlation found between reaction time, sustained attention, and the time needed to experience biofield sensations. Conclusions This study highlights importance of Master Choa Kok Sui hand sensitization in controlled setting revealing differences in experiences of various biofield sensations, showing valuable time-related insights and variability of sensation based on preferred learning.
The gap that Matilda will bridge: a look at the Colombian case
Authors: Rivera-Lozada Isabel Cristina , Gómez-Sánchez Andrés Mauricio , Rivera-Lozada Oriana
Published: June 2024

Objective To determine gender gaps in Emeritus researchers in Colombia. Methods Oaxaca-Blinder-Kitakagwa decomposition model, correcting the sample selection bias with the inclusion of Mills’ inverse ratio (Heckman’s Lambda) through an ordered probit model. Data: Information available in the ScienTI Platform – Colombia during the period 2015-2021. Results The results show that the gender gap between female and male researchers is 5.8%. To achieve Emeritus status, one must be over 65 years old, and the possibility of achieving Emeritus status is 5.1% higher for female researchers than for their male counterparts. These differences can be explained by the time constraints that female researchers face in being productive, as they spend more time than male researchers on caregiving responsibilities, either due to motherhood or the care of other dependent family members. Conclusions The results obtained allow us to affirm that there is a gender gap in scientific research in Colombia in the Emeritus research category in the calls for proposals for the period 2015-2021. Moreover, the existing gap cannot be explained by factors associated with attributes of education and academic productivity that are part of the regulatory requirements, insofar as not being explained by them, it evidences the existence of discrimination against women researchers to access the highest research category.
Fathers' experiences, views and perspectives of childbirth attendance: A qualitative evidence synthesis protocol
Authors: AlAmri Nazia , Panda Sunita , Smith Valerie
Published: June 2024

Background The involvement of husbands and male partners in childbirth no longer ceases at conception and pregnancy, rather fathers wish to be more involved in supporting their partners during childbirth. This aligns with the World Health Organization's (WHO) call for promoting male participation in childbirth, emphasising the benefits of support and the positive impact attending childbirth has for husbands/partners, and their maternal partner. This knowledge has led to global initiatives promoting "humanised" birth and a family-approach. To gain in-depth insight and understanding of childbirth attendance from the perspectives of fathers, a qualitative evidence synthesis is proposed. Methods To explore fathers' experiences, views, and perspectives of childbirth attendance. All studies that used qualitative methodologies to explore the phenomenon of interest will be included. MEDLINE, CINAHL, PsycINFO, MIDIRS, Web of Science, and Google Scholar will be systematically searched from their dates of inception to present, supplemented by a search for grey literature and a search of the reference list of included studies. Peer Review of Electronic Search Strategies (PRESS) will be used to ensure the comprehensiveness of the search strategy. Methodological quality assessment of included studies, using The Critical Appraisal Skills Programme assessment tool, and will be extracted from the included studies by two reviewers independently using a standard data extraction form. Thomas and Harden’s three-stage approach will be used to thematically synthesise the data: coding of data, developing descriptive themes, and generation of analytical themes. The Grading of Recommendations Assessment, Development, and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual confidence in the synthesised findings Comprehensive insight and understanding of fathers’ perspectives of childbirth attendance will be ascertained PROSPERO Registration No CRD42023470902
The Beneficial Effects of Aerobic Exercise on Human Systems and Organs: A Literature Review
Authors: Koman Anna Maria , Chamera-Cyrek Katarzyna , Pliszka Marzena , Janik Izabela , Gadżała Katarzyna , Palacz Karolina Alicja , Kułak Klaudia Brygida , Sztybór Izabela
Published: June 2024

Introduction: Engaging in regular aerobic exercise can have a tremendous impact on one's physical and mental well-being. Despite the known benefits, a significant number of adults worldwide continue to lead sedentary lifestyles. Aerobic exercise, in particular, has been shown to improve lipid profiles, reducing the risk of cardiovascular diseases and mortality rates. Additionally, it promotes healthy metabolism, hormonal balance, and mental well-being, all of which contribute to overall health and quality of life. This is especially crucial for cancer patients undergoing treatment.
Aim of the Study: The primary objective of this study is to conduct a comprehensive analysis of the physiological and psychological benefits of aerobic exercise on the human body.
Description of the State of Knowledge: Moderate and regular aerobic exercise has been shown to have a beneficial effect on both physical and mental health. The importance of improving physical performance, overall body fitness, endurance, strength, balance, and mobility cannot be overstated, as it has a proven therapeutic and preventive effect against various diseases.
Materials and methods: An unsystematic scientific literature review was conducted using specific keywords such as earobic exercise, lipid profile, cardiovascular system, cardiovascular disease, diabetes. The review was carried out on PubMed, analyzing a total of 70 sources published until 2023.
Conclusions: Exercise has beneficial effects on all organ systems and is a non-pharmacological form of treatment for cardiovascular, musculoskeletal, metabolic and nervous system diseases. They have the benefits of reducing stress, lowering blood pressure, stimulating osteogenesis, and having a beneficial effect on body shape and self-perception. Exercise can be considered an effective treatment for established diseases or the alleviation of their symptoms.
The effects of sugar addiction on health and the importance of exercise
Authors: Kwaśniak Ksenia , Magierska Agata , Foryś Angelika , Miłek Magdalena , Banach Mariola , Ślusarczyk Monika , Stawska Weronika , Niemczyk Anna , Kmiotek Weronika , Kotowicz Zuzanna
Published: June 2024

Introduction and purpose: Sugar is the primary energy substrate for the brain. Consuming sweet products releases dopamine, which activates the reward system. In this aspect, excessive consumption of sugar is similar to drug use and leads to many health risks. The aim of the study is to systematize information on sugar addiction, highlight the need for preventive measures and create treatment algorithms covering areas such as psychotherapy, pharmacotherapy and the positive impact of physical activity.
Materials and metods: A literature search was conducted using the medical databases PubMed and Google Scholar. Articles were retrieved in English, employing the key words: “sugar addiction”, “sweet taste”, „sugar diabetes” and „sugar sport” in appropriate configurations. The analysis encompassed data from 34 scientific references published between 2007 and 2024.
Conclusions: Many factors contribute to sugar addiction. It is a self-perpetuating cycle, as obese and sugar addicts need more sugar to feel satisfied. At the same time, sugar negatively affects body weight, behavior, mood, cardiovascular, nervous, digestive systems. Which is why steps should be taken to increase public understanding and awareness of the mechanism of sugar addiction and its risks.
Guyon’s Canal Syndrome and its’ impact on everyday life and sport - literature review
Authors: Czajka Andrzej , Szymański Bartłomiej , Rosiak Krzysztof , Reguła Kacper , Waloch Kamil , Wojtania Joanna , Piaszczyński Szymon , Uszok Zofia , Płeska Kacper , Łepik Michał
Published: June 2024

Guyon’s Canal Syndrome is a rare clinical condition resulting from ulnar nerve injury in the distal portion of the nerve, situated in a narrow anatomical corridor at the wrist. It is an example of neuropathy caused by pressure applied on a nerve. The pressure can be caused by various factors, which will be discussed in the following section of the review. The ulnar nerve is a mixed nerve, meaning that it provides motor and sensory innervation to the digits. This property of the nerve results in a variety of symptoms (motor and sensory) that occur during the injury.
The nerve originates from the central rami of the C8 and T1 nerve roots, which form the lower trunk of the brachial plexus. The lower trunk next divides into an anterior and posterior division, with the fibres of the ulnar nerve in the anterior division becoming the medial cord. The nerve leaves the brachial plexus as a terminal branch of the medial cord and lies from the axilla into the medial part of the anterior compartment of the upper arm, where it is located posteriomedial relative to the brachial artery. It then inserts onto the medial epicondyle of the distal humerus and enters the cubital tunnel. It then runs along the medial side of the forearm, lying superficially and being covered mostly by fascia and skin. It subsequently enters Guyon’s canal, a fibro-osseous tunnel formed between two bones: the pisiform and the hamate bone (the hook hamate exactly). The ulnar nerve in Guyon’s canal is laterally bordered by the ulnar artery. Finally, within the canal, the ulnar nerve divides into superficial and deep branches.
Guyon's canal syndrome is a condition that results from the injury of the ulnar nerve at a specific point. The syndromes associated with this injury are characterised by the loss of function of a portion of the nerve, which can be used to differentiate between injuries that are proximal or distal to the nerve.
A LUTA ANTIRRACISTA DE ABDIAS NASCIMENTO A PARTIR DO JORNAL QUILOMBO (1948-1950):
Authors: Carvalho Joselene
Published: June 2024

Este texto tem como objetivo destacar reflexões acerca da luta antirracista do movimento negro brasileiro, tendo a figura de Abdias Nascimento como um importante expoente. A principal fonte deste artigo é o jornal “Quilombo” que circulou nacionalmente e internacionalmente entre os anos de 1948 e 1950. Dessa forma, discutimos como Abdias Nascimento, diretor do jornal, desenvolveu uma teoria de ação social denominada como “Quilombismo” que se relacionava com a ideia do panafricanismo em que valorizava a história e a cultura africana. Além disso, a educação foi vista como um dos elementos cruciais para o combate ao racismo na sociedade brasileira pelo movimento negro. Portanto, discutimos como esse tema aparece nas dez edições do jornal, de modo a compreendermos que conquistas atuais como a lei 10639/03 são resultado de reivindicações e luta do movimento negro brasileiro.