bluuebunny/crossref_metadata_2025 huggingface dataset:
Extinction and stationary distribution of a novel SIRS epidemic model with general incidence rate and Ornstein–Uhlenbeck process
Authors: Cao Hong , Liu Xiaohu , Nie Linfei
Published: July 2024

We propose, in this paper, a novel stochastic SIRS epidemic model to characterize the effect of uncertainty on the distribution of infectious disease, where the general incidence rate and Ornstein–Uhlenbeck process are also introduced to describe the complexity of disease transmission. First, the existence and uniqueness of the global nonnegative solution of our model is obtained, which is the basis for the discussion of the dynamical behavior of the model. And then, we derive a sufficient condition for exponential extinction of infectious diseases. Furthermore, through constructing a Lyapunov function and using Fatou’s lemma, we obtain a sufficient criterion for the existence and ergodicity of a stationary distribution, which implies the persistence of the disease. In addition, the specific form of the density function of the model near the quasiendemic equilibrium is proposed by solving the corresponding Fokker–Planck equation and using some relevant algebraic equation theory. Finally, we explain the above theoretical results through some numerical simulations.
The surgical interval between robot-assisted SEEG and epilepsy resection surgery is an influencing factor of SSI
Authors: Xie Xiaolian , Yao Hongwu , Zhao Hulin , Liu Bowei , Bai Yanling , Li Huan , Liu Yunxi , Du Mingmei
Published: July 2024

Background

In recent years, the development of robotic neurosurgery has brought many benefits to patients, but there are few studies on the occurrence of surgical site infection (SSI) after robot-assisted stereoelectroencephalography (SEEG). The purpose of this study was to collect relevant data from robot-assisted SEEG over the past ten years and to analyze the influencing factors and economic burden of surgical site infection.

Methods

Basic and surgical information was collected for all patients who underwent robot-assisted SEEG from January 2014 to December 2023. Logistic regression was used to analyze the factors influencing SSI according to different subgroups (radiofrequency thermocoagulation or epilepsy resection surgery).

Results

A total of 242 subjects were included in this study. The risk of SSI in the epilepsy resection surgery group (18.1%) was 3.5 times greater than that in the radiofrequency thermocoagulation group (5.1%) (OR 3.49, 95% CI 1.39 to 9.05); this difference was statistically significant. SSI rates in the epilepsy resection surgery group were associated with shorter surgical intervals (≤ 9 days) and higher BMI (≥ 23 kg/m2) (6.1 and 5.2 times greater than those in the control group, respectively). Hypertension and admission to the intensive care unit (ICU) were risk factors for SSI in the radiofrequency thermocoagulation group. Patients with SSIs had $21,231 more total hospital costs, a 7-day longer hospital stay, and an 8-day longer postoperative hospital stay than patients without SSI.

Conclusions

The incidence of SSI in patients undergoing epilepsy resection after stereoelectroencephalography was higher than that in patients undergoing radiofrequency thermocoagulation. For patients undergoing epilepsy resection surgery, prolonging the interval between stereoelectroencephalography and epilepsy resection surgery can reduce the risk of SSI; At the same time, for patients receiving radiofrequency thermocoagulation treatment, it is not recommended to enter the ICU for short-term observation if the condition permits.
Voltage-gated sodium channels in cancers
Authors: Liu Hengrui , Weng Jieling , Huang Christopher L.-H. , Jackson Antony P.
Published: July 2024

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from “non-excitable” tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory β-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising.
The relationships between teachers’ evaluation of children’s academic readiness and children’s later outcomes
Authors: Kim Jiye
Published: July 2024

Kindergarten is emphasized as a critical first entry into the education system, as politicians and pundits believe kindergartners’ success can lead to later academic achievement. Therefore, a comprehensive understanding of kindergarten school readiness data should consider how it is measured and how that affects learning. Using the Early Childhood Longitudinal Studies—Kindergarten (ECLS-K) cohort 2010–2011 data, the author examined the relationship between teacher reports about children’s academic readiness at kindergarten entrance and their later outcomes in reading, math, and science through fifth grade. This study used a latent basis growth model with time-invariant predictors to analyze the relationship's trajectory. Overall, findings determined that teachers’ perceptions of children’s Approaches to Learning, mathematical thinking, and science significantly impacted later achievements in math and science direct assessments throughout elementary education. This research discussed the practice and policy implications on teachers’ perceptions of school readiness and its impact on later academic outcomes.
Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes
Authors: Taha Mohamed , Tartor Yasmine H. , Elaziz Rana M Abd , Elsohaby Ibrahim
Published: July 2024

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.

There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.
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

This 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.
Breast Cancer Pharmacogenetics in Botswana
Authors: Nthontho Keneuoe Cecilia , Paganotti Maria , Ndlovu Andrew Khulekani
Published: July 2024

PURPOSE

Breast cancer is one of the utmost neoplastic diseases, with a high mortality globally and especially in sub-Saharan Africa, where, despite a relatively low incidence, mortality is high. In Botswana, breast cancer represents almost 20% of all cancers and accounts for more than 10% of cancer-associated deaths among women. Moreover, the median age of women presenting with breast cancer is younger than those of high-income countries and patients are more likely to present with advanced stage disease. In addition, there is limited availability/access to treatments. Breast cancer in Botswana is also associated to a high risk of treatment failure. One possible explanation may be the genomic modulation of drug response. In fact, individual's genomic profile for drug metabolism also influences the therapeutic outcomes and impacts on compliance and toxicity. To explore the possible interplay between pharmacogenetic profile and 5-year overall survival, a University of Botswana team is carrying out a retrospective study on tamoxifen and paclitaxel pharmacogenetics.

METHODS

A cohort of 248 FFPE breast cancer tissues are undergoing DNA extraction and genotyping for single nucleotide polymorphisms (SNPs) in genes encoding for enzymes that metabolize the two drugs. Breast cancer subtype, survival data, treatment duration, toxicity and other clinical characteristics of the patients will be associated to the genetic makeup of the subjects. Cytochrome P450 2D6 (CYP2D6) (tamoxifen) and CYP2C8 (paclitaxel) genes are being analyzed for SNPs associated to an aberrant metabolism of the two drugs.

RESULTS

Preliminary data show a prevalence of the CYP2D6*4 and CYP2C8*2 alleles among patients in Botswana being 3.8% and 10.9%, respectively. From this, it is possible to estimate a 7.0% and a 19.7% of deviant drug metabolizers for tamoxifen and paclitaxel, respectively. Ongoing work on CYP2D6*2, *9, *10, *17, *29, *41 and gene copy number will refine the expected metabolic phenotypes for tamoxifen.

CONCLUSION

We found a non-negligible rate of subjects showing defective drug metabolism. Almost 20% of women are predicted to not being able to metabolize properly the chemotherapeutic paclitaxel. Concerning tamoxifen, more results will follow to complete the analysis, and assign proper metabolic profiles to the patients.
Cancer Care Gap: Examining Cancer Mortality-Incidence Rate Ratio in Sub-Saharan Africa
Authors: Lawa Qudus Olajide , Lawal Ishak , Eigbefoh Joseph , Aigbonoga Daniel Ehis , Lawal Ganiyat
Published: July 2024

PURPOSE

The 2022 global burden of cancer estimate released by the International Agency for Research on Cancer (IARC) showed a huge burden of 20million new cancer cases and 9.7 million cancer deaths, a threat to the achievement of the 2030 Sustainable Development Goals target on Non-Communicable Diseases (NCDs). Africa accounts for only 5.9% of new global cases and 7.8% of cancer mortalities; however, these figures belie the enormous premature death that has made cancer a death sentence in Africa. A five-year survival rate measures cancer survival. However, due to the scarcity of follow-up data in Africa, the Mortality-Incidence Rate Ratio (MIR) which has an inverse relationship with survival has become a useful substitute for making comparisons on a global scale. The study's purpose is to compare the cancer MIR in Africa with other continents and disaggregate MIR in Sub-Saharan Africa across gender and major cancer sites.

METHODS

Data on Age Standardized Incidence Rate (World)-ASIR and Age Standardized Mortality Rate (World)-ASMR for six continents and the top five cancer sites in Africa (Breast, Prostrate, Cervix, Liver, and Colorectal) were extracted from the IARC Global Cancer Observatory (Cancer Today). MIR (calculated as the ratio of ASIR/ASMR) comparisons were done using Microsoft Excel 2021.

RESULTS

The average global cancer MIR is0.47. Africa has an estimated MIR of 0.67, which is more than double those of North America (0.23) and Oceania (0.23), and far above those of Europe (0.38), Latin America and the Caribbean (0.46). The high figure of Asia, 0.54, is well below the African Cancer MIR. Among the top five cancer sites in Sub-Sahara Africa, the liver has the highest MIR (0.95 compared to global MIR of 0.86) followed by the cervix (0.75 compared to global MIR of 0.50), Colorectal (0.73 compared to global MIR 0.44), prostrate (0.60 compare global MIR 0.38) and Breast (0.52 compare global MIR0.25). Disaggregated by gender, cancer MIR is higher in Sub-Saharan Africa for both sexes above the global average (Male 0.72 compared global MIR0.52; Female 0.67 compared global MIR 0.41).

CONCLUSION

The Mortality-Incidence rate ratio in Sub-Sahara Africa is alarmingly high compared to the global figure, reflecting a huge disparity in cancer care outcomes. A concerted effort to bridge the care gap in Sub-Sahara Africa is required to achieve the SDGs' NCD target, which aims to reduce premature death by a third.
Carriage of ELAC2 and RNASEL Genes and Risk Factors in Patients With Prostate Cancer in Burkina Faso
Authors: Zoure Abdou Azaque , Ky Bienvenu Désiré , Traoré Lassina , Zohoncon Théodora M. , Simpore Jacques
Published: July 2024

PURPOSE

Genetic factors are one of the significant contributors to prostate cancer (PCa) development. The objective of the present study was to analyze the carriage of the C650T (Ser217Leu) and G1621A (Ala541Thr) mutations of the ELAC2 gene and carriage of RNASEL R462Q and D541E mutations of RNASEL gene with the risk factors in prostate cancer patients in Burkina Faso.

METHODS

This case-control study. PCR combined with restriction fragment length polymorphism (RFLP) was used to characterize the genotypes of the Ser217Leu and Ala541Thr polymorphisms of the ELAC2 gene. Real-time PCR genotyping of R462Q and D541E variants using the TaqMan® allelic discrimination technique was used. The correlations between the different genotypes and risk factors for prostate cancer were investigated.

RESULTS

There is no association between prostate cancer risk with the Ser217Leu (p = 0.972), Ala541Thr (p = 0.267) and R462Q (OR = 0.60 95% IC, 0.10–3.51 p = 0.686) and D541E (OR = 2.46 95% IC, 0.78–7.80 p = 0.121. Also, the two ELAC2 SNPs did not correlate with clinical stage, prostate-specific antigen (PSA) level at diagnosis, or Gleason score on biopsies. However, we found that 100% of homozygous carriers of the T650 mutation have an A1621 mutation (P≤0.001). Also, there is a statistically significant difference in the distribution of cases according to the PSA rate at diagnosis (p < 0.001). For the Gleason score distribution, only 13.2% of cases have a Gleason score greater than 7. There is a statistically significant difference in the Gleason score distribution of cases (p < 0.001).

CONCLUSION

These variants, considered in isolation or in combination, are not associated with the risk of prostate cancer.
Collaboration With Global Communities for Outreach Into US Immigrant Communities for Liver Cancer Control to Breakdown Languages Barriers
Authors: Zhang Tingting , Hung Tony
Published: July 2024

PURPOSE

Highlight the necessity to collaborate with global cancer communities to outreach into immigrant communities to control liver cancer which showed increased mortality in immigrants from regions with high liver cancer burdens. These communities in US were often comprised of recent immigrants who speak English “less than very well”.

METHODS

We looked into the underlying cause of death data reported by CDC WONDER to assess death caused by liver cancer in race or ethnic groups with high immigrant percentage and with high mortality from liver cancer in their birth countries as reported from GLOBOCAN. We then looked into recent reports from national cancer registries to assess the needs to increase efforts into outreaching these immigrant communities.

RESULTS

Mortality from liver cancer are higher than white (both Hispanic and non-Hispanic) population in the Vietnamese, Japanese, and Korean population in the US, almost on par with the mortality reported in GLOBOCAN in Vietnam, Japan, or Korea. However, there appeared to be lower mortality reported in the Chinese population than the mortalities reported in China. We also observed much lower mortality reported in the black Hispanic or Native American Hispanic population. These data discrepancies might be results of reporting discrepancy that could bias our national investment into resources to address liver cancer control. We need better outreach into these populations.

CONCLUSION

In order to better outreach into immigrant communities impacted by liver cancer, we need to address the language barriers faced by these communities. We have launched a new patient centered program to convert education and supportive literatures for liver cancer control in different languages/dialects by working with other members of the International Liver Cancer Movement.
Effect of Hospital Teaching Status on Mortality and In-Hospital Outcomes in Patients Hospitalized With Acute Leukemia: A National Study
Authors: Miller Lacey , Javaid Saad , Frasier Kelly , Huisman Katie , Vinagolu-Baur Julia , Nidhiry Anna , Li Vivian
Published: July 2024

PURPOSE

Acute leukemia is a complex hematologic malignancy characterized by the uncontrolled proliferation of developing leukocytes. Prior studies have considerably investigated the impact of medical training settings on the outcomes of hospitalized patients. Nevertheless, there remains a paucity of studies exploring the correlation between teaching hospital status and patient outcomes for those admitted with acute leukemia.

METHOD

We used the National Inpatient Sample (NIS) 2017-2020 to identify patients admitted with the primary diagnosis of acute leukemia (including acute myeloid and acute lymphoblastic leukemia.) We stratified the patients into those admitted to teaching hospitals (TH) and nonteaching hospitals (NTH). The primary outcome studied was mortality between the two groups, and the secondary outcomes included length of stay, total cost of hospitalization, and adverse in-hospital outcomes.

RESULTS

A total of 108,495 patients were hospitalized with acute leukemia, of which 9,156 (8.4%) were admitted to NTH and 99,327 (91.5%) were admitted to TH. The mean age of patients was 49.26 ±25.88, p<0.001. Of the admitted patients, 17.9% were <18 years old, and 82.05% were ≥ 18. Males in TH and NTH were 55.68% vs. 54.34%, respectively, and females in TH and NTH were 44.32% vs. 45.66%, respectively, p<0.001. After adjusting for confounding variables, no difference was noted in the odds of mortality between TH and NTH (OR=1.12, 95% CI (0.91-1.36), p=0.263). Those admitted in TH had prolonged length of stay (+7.92 days, 95% CI (6.77-9.08), p<0.001) and increased total cost of hospitalization ($131,854, 95% CI ($105,895-$157,813), p<0.001). Patients in TH also had increased odds of acute kidney injury (OR=1.20, 95% CI (1.03-1.39), p=0.01), fluid and electrolyte disorders (OR= 1.38, 95% CI (1.21-1.59), p<0.001), sepsis (OR=1.42, 95% CI (1.15-1.76), p=0.001), ICU admission (OR=1.28, 95% CI (1.02-1.61), p=0.03), intubation (OR=1.39, 95% CI (1.09-1.78), p=0.007), vasopressor use (OR=1.92, 95%CI(1.13-3.25), p=0.015), febrile neutropenia (OR=1.62, 95% CI (1.37-1.93), p<0.001), and delirium (OR=2.63, 95% CI (1.35-5.10), p=0.004).

CONCLUSION

Our study shows that hospital teaching status is not considered an independent predictor of mortality in hospitalized patients with acute leukemia. However, patients admitted to TH had prolonged lengths of stay and total costs of hospitalization, along with other adverse hospital outcomes. Further prospective studies are needed to validate the findings of our research.
Effectiveness of an Intervention Based on Pain Neuroscience Education Compared to Conventional Treatment in Adults With Cancer Pain: Clinical Trial Protocol
Authors: Ordoñez-Mora Leidy Tatiana , Rosero Dayana , Bozal Rocio Guil , Morales-Osorio Marco Antonio , Avila Valencia Juan Carlos , Agudelo Jimenez Julián Alberto
Published: July 2024

PURPOSE

Pain is the second most frequent symptom reported in patients with cancer, due to its multidimensional characteristics involving cognitive and central sensitization mechanisms that require other intervention strategies. Modern pain neuroscience has improved the understanding of pain, including the role of sensitization in pain intervention processes. In this regard, the use of educational modalities has been recommended. In this sense, neuroscience education (PNE) is an intervention that provides elements of the neurophysiology of pain that are transferred to the patient through examples or metaphors. The objective is to examine the effectiveness of PNE on pain and biopsychosocial variables in comparison with conventional management.

METHODS

A single-blind controlled clinical trial will be carried out (Trial registration number NCT05581784), which requires 82 adults with the presence of oncological pain due to prostate cancer in men and uterine and breast cancer in women in stages III and IV. A baseline evaluation will be generated considering pain and biopsychosocial variables. After that, randomization will be carried out where two groups will work: one corresponding to pain neuroscience education (PNE), where the participants will carry out one weekly session until completing 9 educational sessions each with a duration of 30 minutes; the second group (control) will not receive the educational intervention; and the two groups will have the elements of conventional management estimated by the treating physician. The post-intervention evaluation will be carried out after 10 weeks for both groups. Within the statistical processing, analysis will be considered per protocol and by intention to treat according to the variables evaluated.

RESULTS

This study is in the process of recruiting patients according to the sample inclusion criteria.

CONCLUSION

It is expected that the intervention based on education in pain neuroscience will have greater effectiveness in pain modulation processes compared to patients who did not receive the intervention; it is expected that the educational content generated can be used in patients with these characteristics.