bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pore and fracture pressures prediction — A new geomechanic approach in deepwater salt overthrusts: Case histories from the Gulf of Mexico
Authors: Shaker Selim S. 
Published: July 2024

Along this active exploration belt, applying the conventional effective stress methods and algorithms, wherein the maximum stress ([Formula: see text]) is vertical and can be attained from the subsurface overburden (OB), would lead to unintended and unrealistic results. In the frontier active thrust belt of the Gulf of Mexico, the unique geomechanical setting of [Formula: see text] as the lateral salt creep and the minimum stress ([Formula: see text]) as the OB greatly impact the formation geopressure framework. The buoyancy of thick salt produces two different pressure gradients (PGs) above and below the salt. Moreover, the inclusion of rafted sediments in the salt and the plowing rubble zone at the salt base substantially affects the pore and fracture pressures (PP-FP) profiles. These proceeding geologic settings are the foundation for the conceptual framework. Building an alternative predrilling prediction numerical model based on these anomalous geomechanical settings and the lack of adequate seismic velocity is a challenge. All the available direct measured or pertained PP-FP data from the key wells are collected and tabulated. Prediction models are established by correlating the populated database and generating the empirical algorithm for each data gather. A substantial discrepancy occurs between above and below the salt sections where high PG in the sediment above the salt and slow PG development below the salt. There is considerable regressive pressure (average 2 ppg) in PP-FP subsalt sections. The PP within the salt is contingent on the presence of sediment inclusions, and a substantial FP drop in the rubble zone leads to the extensive loss of mud circulation. The trend lines of each data gather led to generating two depth-dependent equations for the PP-FP above and within the salt and two others for the subsalt. The prediction models are validated against a blind data set. Before drilling, this model establishes the PP-FP versus the sediment subsea depth in an abnormal geomechanical setting and the lack of coherent vertical seismic velocity for PP-FP predictions.
The role of neurocognitive testing in the assessment of fitness to stand trial
Authors: Burns Alistair , Series Hugh 
Published: July 2024

SUMMARYThis article reviews some of the various shorter cognitive tests that are available. They vary in complexity, time taken to administer them and what specific neurocognitive domains they assess. They range from screening tests such as the Mini-Cog to more detailed measures such as the Montreal Cognitive Assessment or the Mini-Mental State Examination. The Addenbrooke's Cognitive Examination is more comprehensive and covers attention, memory, verbal fluency, language and visuo-spatial function. The article suggests areas of cognition that may be related to the six competencies assessed in the determination of fitness to plead and to stand trial.
Possible Mediation of the Association Between Education Attainment and Breast Cancer in a Hispanic Female Population Experiencing Historical Changes in Social Determinants of Health
Authors: Rosario-Rosado Rosa Virgen , Nazario Cruz M. , Mansilla-Rivera Imar , Ramírez Farah A. , da Luz-Sant'Ana Istoni , Nie Jing , Hernández-Santiago Johan , Freudenheim Jo L. 
Published: July 2024

PURPOSE While higher educational level (HEL) is associated with generally better health status, and educational attainment is a well-known social determinant of health, HEL has been associated with an increased breast cancer risk (BCR). Likely this paradox is the result of other mediating factors correlated with education such as parity. In Puerto Rico, there have been important changes in reproductive breast cancer risk factorsin particular, the fertility rate has dropped markedly in the last decades. We explored the possible mediation of parity and other risk factors on the association between education attainment and BCR among Caribbean Hispanic women with considerable variation in education. METHOD The Atabey study was a population-based case-control study (315 cases and 348 controls) in the San Juan Puerto Rico metropolitan area. Unconditional logistic regression models were used to assess the association between education (>12 yrs. vs. ≤12 yrs. as reference) and BCR adjusting independently for age and each of the following: BMI, benign breast disease, family history of breast cancer, age at menarche, age at first birth, age at last birth, number of births, breastfeeding, menopausal status, and age at menopause. Mediation analysis was used to explore if including parity (0, 1, ≥2) in the model changes the association between education attainment and BCR. RESULTS A little more than half of both cases (67.62%) and controls (56.03%) had completed more than high school. The association between education level and BCR remained statistically significant after adjusting by age and each risk factor separately (e.g. OR adjusted by age alone: 1.84 [95% CI: 1.33, 2.56] OR adjusted by age and age at first birth: 1.50 [95% CI: 1.03, 2.19]OR adjusted by age and parity: 1.56 [95% CI: 1.10, 2.21]). Parity appears to mediate this association (e.g., OR graduate studies vs <12 yrs. as reference: 3.74 [95% CI: 2.02, 6.94] direct effect: 1.31 [95% CI: 1.13, 1.51] indirect effect: 1.04 [95% CI: 0.99, 1.11]. CONCLUSION These findings suggest that parity could mediate the association between education and BCR. Further analyses are needed to understand the causal web behind the association between education and breast cancer among Caribbean Hispanic women. Acknowledgement: CDMRP Grant W81XWH-07-1-0329 BCRP HBCU/MI Partnership Training Award and NIAID award number 2U54MD007587.
Prognostic Value of Routine Blood Markers in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Baek David , Hameier Allison , Wetzel Ashley , Outschoorn Ubaldo , Llerena Pablo , Luginbuhl Adam , Myers Ronald , Nunes Kathryn , Curry Joseph , Bar-Ad Voichita , Wang Chun , Barbirou Mouadh , Yang Hushan 
Published: July 2024

PURPOSE The levels of inflammatory blood markers, such as neutrophils, platelets, monocytes, and lymphocytes, can be informative for several cancer prognoses. However, the changes in other blood markers may be additional sources of prognostic information for cancer recurrence and survival. In this study, we aim to investigate the predictive value of non-inflammatory blood markers in HNSCC outcomes. METHOD In a retrospective cohort study, 522 primary HNSCC patients diagnosed between July 2010 and March 2023 were included. Clinicopathological characteristics and blood marker levels were collected and separated by their respective clinical cutoffs. Their associations with locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were evaluated using Cox proportional hazards regression with univariate and multivariate analyses. RESULTS The median follow-up was 34 months. The univariate analysis showed that hemoglobin (HR=0.56, 0.52, 0.32; p<0.004), MCHC (HR=0.51, 0.56, 0.38; p<0.014), and RDW (HR=1.93, 1.83, 2.14; p<0.0006) were each significantly associated with LRR, DFS, and OR. Meanwhile, albumin was significantly associated with DFS only (HR=0.49; 95% CI: 0.26-0.94; p=0.03). In multivariate analysis, BMI (HR=0.80; 95% CI: 0.67-0.96; p=0.01) and lymph vascular invasion (LVI) (HR=8.25; 95% CI: 1.68-40.5; p=0.009) were each significantly associated with OS. Among the routinely tested blood markers, RDW was shown to be an independent predictor of LRR (HR=3.54; 95% CI: 1.02-12.3; p=0.047) and OS (HR=11.2; 95% CI: 1.15-109.9; p=0.038). CONCLUSION Non-inflammatory blood markers can be potential informative markers on locoregional recurrence and overall survival in HNSCC patients.
Saliva IL6 Upregulation As a Potential Indicator of Tobacco-Smoke Associated OSCC and Disease Progression and the Association of Saliva RELA(p65) Upregulation With OSCC Local Invasion in Non-Smokers
Authors: Vageli Dimitra , Doukas Panagiotis , Judson Banjamin 
Published: July 2024

PURPOSE Head and neck cancer (HNC) is a devastating disease associated with tobacco smoking. Tobacco smoke-related mRNA phenotypes in HNC were previously documented in vivo and may be differentially expressed in the saliva of smokers with oral squamous cell carcinoma (OSCC) compared with non-smokers or healthy volunteers (HC) and potentially related to tumor progression. METHODS We collected saliva from 30 individuals, including 16 OSCC patients [8 with local metastases (meta+). 8 without metastases (meta-)] and 14 HC of an equal ratio of former smokers and non-smokers and determined the mRNA levels of eleven tobacco and HNC-related genes by qPCR. Immunohistochemical analysis was performed in tissue sections from tumors and matched lymph nodes. RESULTS Saliva IL6 and RELA(p65) mRNAs were overexpressed in OSCC vs. HC ( >2-fold change, P <0.05, by t-test), particularly IL6 in smokers (OSCC smokers vs. HC smokers >10-fold change, P <0.05OSCC smokers vs.OSCC non-smokers >17-fold change P < 0.05). IL6 and NF-κB immunopositivity was significantly higher in meta(+) vs. meta(-) OSCC, especially IL6 in smokers. Saliva Rela(p65) significantly overexpressed in never-smokers with OSCC vs. HC (>4-fold change, P <0.04 AUC: 73-76%, Sensitivity 62-62.5%, by by ROC curve analysis) and significantly correlated with NF-κB nuclear positivity in OSCC, particularly in meta (+) (r >0.84, P <0.02, by Pearson). CONCLUSION Our pilot study indicates saliva IL6 mRNA upregulation for further clinical testing as a potential biomarker of former smokers for oral cancer and disease progression. Our data also suggests the association of saliva RELA(p65) mRNA upregulation with OSCC local invasion in non-smokers. Such a test is paramount to the provision of effective preventive care via early detection of locally invasive OSCC, as well as risk stratification in smokers and their monitoring.
A Collaborative Partnership Between the Palliative Care Association of Uganda and the Uganda Cancer Institute to Strengthening Cancer Control, Survivorship, and Outcomes Through Research
Authors: Irumba Lisa Christine , Mwesige Benjamin , Zalwango Joyce , Kabagambe Cynthia , Niyonzima Nixon , Mwesiga Mark Donald , Downing Julia , Orem Jackson 
Published: July 2024

PURPOSE Cancer remains a global health challenge with profound implications on individuals, families, and healthcare systems. The changing face of cancer care needs a holistic strategy that goes beyond conventional treatment modalities. Uganda's healthcare system is facing an increasing number of cancer cases, which highlights the need for creative solutions to enhance cancer outcomes, survivability, and control. UCI and PCAU host Uganda Conferences on Cancer and Palliative Care in partnership with the Ministry of Health. These bring together individuals and stakeholders involved in cancer and palliative care to share their research, and experiences of good practice and as such promote collaboration and networking in clinical practice, research, and training. METHODS Every 2 years, the conference brings together experts in the fields of cancer and palliative care, medical professionals, students, legislators, distinguished scholars, corporate partners, donors, and members of the public. Their structure includes plenary sessions, workshops, parallel presentations, special interest side events, poster presentations, and exhibitions. The theme is selected by the scientific committee who reflect on cancer and palliative care issues affecting the country at that time. During their delivery, there are research presentations, capacity building in oncology and palliative care, community engagement, sharing of compelling stories by survivors, and advocacy through involving other line ministries and policymakers. RESULTS 4 biennial conferences have been hosted, in 2017 when the Uganda Cancer Institute celebrated 50 years of existence 451 delegates from 17 countries, in 2019 350 delegates from 8 countries, in 2021 online during the COVID-19 pandemic 350 delegates on Zoom and others on Uganda Broadcasting Television, and in 2023 450 delegates from 13 countries attended. Conference proceedings and lessons have been published in ecancer and ehospice. CONCLUSION This collaborative initiative represents a novel approach to cancer care in Uganda through the exchange of ideas, experiences, and expertise among people with diverse backgrounds. Throughout the conferences, there is always a sense of optimism, resilience, and pledges to the ongoing development of cancer and palliative care services in Uganda.
Travel Time to Cancer Care is Associated With Inferior Survival for Lymphoma Patients in Malawi
Authors: Harrington Meagan , Chirwa Amon , Kasonkanji Edwards , Simwinga Lusayo , Mumba Noel , Chikasema Maria , Kumwenda Phareda , Painschab Matthew , Fedoriw Yuri 
Published: July 2024

PURPOSE Kamuzu Central Hospital (KCH) in Lilongwe, Malawi serves a population of 10 million from the country’s Central and Northern regions. However, KCH is one of just 2 centers in the country providing care to cancer patients, leaving the majority of the population with the burden of travelling long distances for diagnosis and treatment. Spatial barriers to care, particularly in relation to travel time to clinic, are not well defined in adults with hematologic malignancies in Malawi and may contribute to disparities in diagnosis and treatment outcomes. Therefore, it is important to understand patient travel patterns to help inform policy and clinical interventions. METHODS We describe a prospective lymphoma cohort in Malawi, enrolling patients from June 2013 to present day. In total, we included 748 patients in this analysis, enrolled from June 2013 to June 2023. Data collected upon enrollment includes diagnosis, demographics, and laboratory results. Location of residence was mapped using QGIS with further descriptive and survivorship analyses, including demographic and clinical characteristics, conducted in R. AccessMod 5 was used to produce models of travel times to KCH, using speeds from previous literature. RESULTS Estimated travel time to clinic varied significantly based on district of residence (range: 62-763 minutes), with 80% of patients coming from districts adjacent to Lilongwe city. Patients from Lilongwe district had the shortest estimated travel time at 62 minutes, and made up 47% of the study cohort. Overall survival varied significantly by district (p=0.05), and patients with longer estimated travel times to KCH tended to have lower rates of overall survival after 5 years (17% vs 26% p=0.06). We saw no significant relationship between travel time and HIV status or diagnosis. CONCLUSION Cancer care in Malawi is centralized, leading to barriers to accessing care. Travel time to clinic is negatively associated with survival outcomes, emphasizing the importance of policies supporting transport initiatives, such as reimbursement, to assist those who live further away to reach KCH.
Two Novel Precursors of HIV-1 Proteases Inhibitors as a Novel Anticancer Treatment on Multiple Myeloma and Chronic Lymphocytic Leukemia Cell Lines
Authors: Sichetti Marzia , Giglio Eugenia , Giuseffi Martina , Mecca Marisabel 
Published: July 2024

PURPOSE As of today, the central role of mitochondrial metabolism associated with tumorigenesis and progression of malignancies has been deeply investigated. Moreover, oxidative phosphorylation inhibition shows that aerobic glycolysis alone is not sufficient to sustain cancer cell survival. In this study, we used Agilent Seahorse XF-Pro Analyzer to investigate the effect of two different HIV-1 protease inhibitor precursor, by interrogating mitochondrial respiration and glycolysis of live cells in real time. METHODS The Agilent Seahorse XF-Pro Analyzer is a fully integrated 96-wells instrument that measures in real time, directly into the cell culture plate, the flux of oxygen (oxygen consumption rate, OCR) and protons (extracellular acidification rate, ECAR) of respectively mitochondrial respiration and glycolysis. The Seahorse ATP rate assay kit is used a fluorescent biosensor cartridge, able to measure pH and oxygen levels in the medium. Data were expressed as a percentage of OCR or ECAR change comparing metabolic rate after compound exposure to a pre-exposure baseline. Two multiple myeloma cell lines (MM1S and RPMI-8226) and a chronic lymphocytic leukemia cell line (HG3) were treated for 24h with HIV-1 protease inhibitor precursor of Darunavir (RDD-19 and RDD-142). Peripheral blood mononuclear cells (PBMCs) isolated from healthy donators were used as control. RESULTS In the experimental protocol used, we observed that the mitochondrial respiration rates markedly decrease in response to RDD-19 and RDD-142 in all cell lines. In particular, in HG3 (chronic lymphocytic leukemia) cells the effect of RDD-142 compared to RDD-19 and DMSO (negative control) is extremely significant. Interestingly, the mitochondrial ATP production decreases in parallel with the slightly increase of glycolytic rate suggesting a compensatory effect in cellular survival. CONCLUSION The Warburg effect postulated that the increase of glycolysis rate drives malignant transformation. However, the importance of mitochondrial respiration contribution and subsequent energy production still have a fundamental role in tumor growth. Our data confirms this argument and suggests that respiration-deficient cancer cells have a severely compromised ability for tumor progression. In particular, our finding shed light on further investigation of RDD-19 and RDD-142 as promising anticancer candidates on leukemia and myeloma cells.
Association of Glycogen Synthase Kinase 3A (GSK3A) Gene and Prognosis in Breast Cancer Patients: Exploring GSK3α Ligands Using Molecular Docking
Authors: Walter Neha , Dora Sanchit , Kaur Jasmeet 
Published: July 2024

PURPOSE Despite recent advances in early detection and advanced therapeutic regimens, about 30% breast cancer patients have recurring metastatic cancer. Thus, there is a need to find novel prevention and/or treatment targets in breast cancer patients. Glycogen Synthase Kinase-3 (GSK3) phosphorylates diverse substrates, is catalytically active in resting cells and is a substrate of oncogenic kinase, Akt. GSK3 exists in two highly homologous forms in mammals - GSK3α and GSK3β. Here, we evaluated prognostic and predictive role of GSK3A in breast cancer patients and explored potential GSK3α ligands. METHODS GSK3A gene expression was compared in normal and tumor breast tissues using TNM plot ( https://tnmplot.com/analysis/ ). Kaplan-Meier plotter ( https://kmplot.com/analysis/ ) was used to correlate GSK3A mRNA expression with survival in breast cancer patients, using all probe sets for a 240 months follow-up threshold and median expression. ROC plotter ( https://www.rocplot.com ) was used to analyze the predictive role of GSK3A gene in breast cancer patients receiving endocrine, anti-HER2 and chemo-therapy. The data from TNM plot, KM- and ROC-Plotter was downloaded and analyzed using Graphpad PRISM 8. Logrank P, 95% confidence intervals and Hazard ratio (HR) were calculated and P value of < 0.05 was considered to be statistically significant. Five ligand libraries from Selleckchem chemical database were docked with GSK3α protein using PyRx Vina Wizard for virtual screening. Ligands with favorable binding energies were validated for pharmacokinetic and ADMET properties using ProTox Online ( https://tox-new.charite.de/protox_II/ ). RESULTS Breast tumor tissue had significantly higher expression of GSK3A gene compared to adjacent normal tissue. GSK3A mRNA lower expression was significantly correlated to poorer relapse-free survival (RFS) in all breast cancer patients. ROC analysis showed that GSK3A gene expression was significantly associated with pathological and RFS response to endocrine and anti-HER2 therapy, and chemotherapy. Molecular docking predicted several ligands with strong binding affinity for GSK3α. Shortlisted drugs based on their docking scores were analyzed for Lipinski’s rule violation, BBB Permeance, GI absorption, LD50 (mg/kg), carcinogenicity, mutagenicity, immunotoxicity, cytotoxicity and toxicity class. CONCLUSION GSK3A is a potential prognostic and predictive marker in breast cancer patients. (+/-)-Synephrine, 2-dehydro-3-deoxy-L-fuconate, LTURM34 and 603288-22-8 (LY2090314) are strong GSK3α ligands with potential for cancer treatment.
Biocompatibility of a Novel Prebiotic Vaginal Gel for Treating the Underlying Conditions of Vaginal Dysbiosis and Inflammation That Facilitate Cervical Cancer Formation and Progression
Authors: Richorova Raina N. , Lewis Julie , Clifton G. Dennis , Ellington Joanna 
Published: July 2024

PURPOSE PreBioGyn (a user-directed, intravaginal prebiotic gel) aims to reduce the risk of cervical cancer formation and progression associated with vaginal dysbiosis and inflammation. Studies were done to compare in vitro biocompatibility for PreBioGyn versus available vaginal pH-correcting buffer-gels (RepHresh and Trimosan) with regards to vaginal epithelial cell integrity, beneficial lactobacilli colonization, and cytokine production. METHODS Gel biocompatibility was tested with two beneficial Lactobacillus species (L. crispatus and L. jensenii) in a validated 3D human vaginal epithelial model (VEC). Gels mixed with bacterial suspensions were applied to the model for 24h. Bacterial colonization was assessed by colony forming units (CFU) firmly associated with the VEC. Bacterial-gel suspensions at time 0 and tissue lysates at the 24h-time point were seeded on Brucella agar and colonies were counted after 2-4 days. Tissue toxicity was assessed by lactate dehydrogenase release with positive (Triton X-100) and negative (medium only) controls. Medium from the submucosal tissue compartment was analyzed after 24h colonization for: 1) IL-1α, IL-1β and IL-1RA as markers of toxicity and inflammatory activation, and 2) IL-8 as innate immunity effector of inflammation. The VEC tissues were also cocultured with HeLa cells to mimic cervical cancer environments. ANOVA with multiple comparisons tests was performed on biological duplicates from at least 3 experiments for each condition with significance at P< 0.05. RESULTS PreBioGyn demonstrated no VEC toxicity, whereas currently available buffer-gels caused epithelial cytotoxicity. PreBioGyn did not change beneficial lactobacillus survival and growth prior to or during epithelial coculture. In contrast, Trimosan was bactericidal and both Trimosan and RepHresh reduced lactobacillus colonization. None of the gels increased extracellular IL-1α and IL-1β levels, while PreBioGyn reduced IL-8 levels in the presence of HeLa cells without harming VEC, suggesting anti-inflammatory properties. CONCLUSION Overall, impaired vaginal immune barrier function was suggested with the currently available pH-buffer gels due to toxicity to VEC and beneficial lactobacilli. In contrast, the prebiotic PreBioGyn gel supported the vaginal ecosystem function similarly to that observed with homeostatic media co-culture, lending support to this approach for preventing dysbiosis and inflammation to facilitate reduced cervical cancer risk.