bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality Rate of Oncological Patients Undergoing Pancreaticoduodenectomy Procedure in Brazil From 2021 to 2023: A Cross-Sectional Study
Authors: Filipin Von Muhlen Pedro Henrique , Hass Yasmin Ricarte , Lech Gabriele Eckerdt 
Published: July 2024

PURPOSE Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The current standard therapy for pancreatic tumors situated in the head of the pancreas is pancreaticoduodenectomy. However, this surgery is associated with significant postoperative morbidity. Great improvement in pancreatic surgery has led to mortality rates of less than 5% at high-volume centers, and the majority of case series in the literature reported a mortality rate of 8%. The study aims to analyze the mortality rate over three-years among Brazilian regions associated with treatment by pancreaticoduodenectomy in oncological patients. METHODS A cross-sectional study was designed using data collected from DATASUS, a Brazilian Health Ministry database. The study compared and analyzed the number of deaths and the total number of pancreaticoduodenectomies performed on oncological patients among Brazilian macro-regions (North, Northeast, Southeast, South, and Midwest) in the period of 2021 to 2023. Statistical analysis was performed using SPSS software v.18. RESULTS In this three-year, 1,871 pancreaticoduodenectomies were performed on oncological patients in Brazil. The year with the highest number of surgeries was 2021, with 633, and the year with the lowest number was 2022, with 611. Among these cases, 268 patients died during the procedure or in the postoperative period 14.32% of patients. The Southeast region had the highest number of pancreaticoduodenectomies, 979, and the highest number of recorded deaths, 139. However, its mortality rate is the second lowest among the five regions (14.20%). The South region, with the second highest number of surgeries and deaths, had the highest mortality rate, 16.16%. CONCLUSION Brazil had a significantly higher mortality rate than what is presented in the literature. Nevertheless, the number of surgeries performed in the country was significantly low in four of the five regions, but the Southeast region, with a considerable number of pancreaticoduodenectomies, also had a high rate. Two databases, from an American study and a French study, reported that mortality rates were significantly higher in lower-volume services. Another detail is the profile of the populations evaluated. Brazil tends to have a more compromised socioeconomic level.
Nanoparticle's Encapsulation Ability Is More Efficient for Characterization of Invading Breast Cancer Cells Than EMT Markers
Authors: Kontareva Elizaveta , Maksimova Ksenia , Pustovalova Margarita , Leonov Sergey , Merkher Yulia 
Published: July 2024

PURPOSE Metastasis is leading cause of cancer death. The essential step of metastasis is invasion. The actin cytoskeleton plays a pivotal role in invasion and is closely linked to endocytosis process. We previously distinguished highly and lowly invasive breast cancer (BC) cell lines based on their tendency to encapsulate 100-200 nm nanoparticles. Epithelial-to-mesenchymal transition (EMT) primarily initiates invasion, with EMT marker expression often used to gauge tumor invasiveness. The Boyden chamber migration assay serves as the gold standard for assessing tumor invasiveness, measuring cancer cells' migration towards a chemoattractant through subcellular pores. This study aims to characterize BC cell subpopulations, separated by the Boyden chamber, based on nanoparticle encapsulation and EMT marker expression. METHODS The highly invasive (HI) and lowly invasive (LI) BC cell lines (MDA-MB-231 and MCF-7, respectively) were separated into migrated and non-migrated subpopulations by Boyden chambers with 8µm membrane pores for 72 h. To assess encapsulation ability, cells were incubated with 200nm fluorescent carboxylated nanoparticles and nuclei stain for 1 hour, extensively washed with PBS and trypsin, and fixed. The images were captured by fluorescent microscopy, and nanoparticle colocalization with cells was quantified using Pearson`s coefficients. The standard antibody staining protocols were utilized for EMT markers: E-cadherin, N-cadherin, Vimentin and Snail1/2. The fluorescence intensity per image for each marker was normalized, and statistical significance was determined by ANOVA analysis. RESULTS The subpopulations of migrated cells were 32% and 2.2% for HI and LI cell lines, respectively. The significant differences between the expression of EMT markers in subpopulations were observed only in vimentin of HI cells (5% difference) and E-cadherin of LI (11% difference). At the same time, the differences in encapsulation efficiency between separated subpopulations of HI and LI cells were 30 % and 43%, respectively. CONCLUSION The EMT markers were found to be able to differentiate HI and LI cell lines, however they were not effective for distinguishing subpopulations within the same cell line. In contrast, the subpopulations can be clearly differentiated by the efficiency of nanoparticles encapsulation.
Nek2A Prevents Centrosome Clustering and Induces Cell Death in Cancer Cells Via KIF2C Interaction
Authors: Kalkan Batuhan , Ozcan Can , Cicek Enes , Acilan Ceyda 
Published: July 2024

PURPOSE Modern chemotherapeutics frequently suffer from selective targeting of cancer cells. In contrast to normal cells, cancer cells frequently exhibit extra centrosomes, which tend to form multipolar spindles (MPS), triggering cell death. Nevertheless, cancer cells can divide successfully by coalescing their extra centrosomes into two poles. Nek2 is a mitotic kinase regulating several mitotic processes. Our preliminary data showed that Nek2 overexpression unclusters extra centrosomes while its disruption favors centrosome clustering. Thus, revealing the molecular mechanism and targeting Nek2 in cells with extra centrosomes may be an alternative strategy for selective targeting for cancer cells. METHODS IF stainings, cell viability, apoptosis and competition assays were performed to investigate the effect of Nek2 overexpression to induce MPS. To investigate how Nek2 regulates centrosome clustering, we tested known Nek2 targets with relevant function (C-NAP1, Rootlein, Trf1, Hec1, Gas2L1) and assessed their involvement in centrosome clustering by knock out or siRNA mediated silencing. Next, we identified the interactome of Nek2 using TurboID proximity labelling and validated our results with co-IP. RESULTS Cells harboring supernumerary centrosomes were depleted from the population upon Nek2 overexpression. Known Nek2 targets exhibited no effect on centrosome clustering. Furthermore, the effect of Nek2 overexpression on MPS was additive with other known unclustering factors such as HSET, suggesting an independent mechanism. We identified several potential targets of Nek2 using TurboID proximity labelling. NuMA - also previously known to uncluster centrosomes, was significantly enriched in our samples. Interestingly, while NuMA did not co-IP with Nek2, its knockdown reverted the unclustering activity. Another significantly enriched motor protein, Kif2C not only reverted Nek2 activity, but also co-IP'ed with Nek2. Moreover, we identified MAPRE3 a regulator of microtubule dynamics, as interaction partners of both Nek2 and Kif2C. Our data suggests that Nek2 partners with Kif2C and MAPRE3, regulating centrosome clustering. CONCLUSION We assigned a novel function for Nek2 in centrosome clustering. We are currently elucidating the detailed mechanism of action for how target proteins interact with Nek2 regulating its centrosome unclustering activity in cancer cells. Understanding the mechanism will provide new translational approaches for cancer-specific treatment.
Screening Will Always Be Essential. Providers and Staff Discuss the Implementation of Anal Cancer Screening for Persons Living With HIV in Mexico City
Authors: McClellan Sean P. , Unger-Saldaña Karla , Gómez-Zepeda Mario , Gabriela-Hernández Julia , Hernández-Salazar Sonia , Palefksy Joel M. , Potter Michael B. , Salmerón Jorge , Torres-Ibarra Leticia , Koester Kimberly A. 
Published: July 2024

PURPOSE Screening for and treating anal squamous intraepithelial lesions (ASIL) in persons living with HIV (PLWH) prevents anal cancer but has not been widely implemented, especially in low-and-middle income countries. METHODS We conducted semi-structured qualitative interviews with providers and staff affiliated with two clinics from the Mexico City HIV program to understand barriers and facilitators to the implementation of a permanent anal cancer screening program. A limited program for anal cancer was already in place at these clinics as part of an international research collaboration. Interviews in Spanish were conducted in person or by video conference, audio-recorded, transcribed and thematically analyzed using domains from the Consolidated Framework for Implementation Research. RESULTS Between October 2023 and January 2024, we conducted 17 interviews, of which 9 were with nurses or physicians who were part of the existing screening research program and 8 were with referring physicians or administrators. Interviewees agreed that establishing a permanent screening program was necessary given documented high rates of ASIL. The most significant barriers were related to resources required to sustain a program, especially infrastructure for collecting and processing pathology specimens. The clinics’ current participation in a research collaboration was recognized as a facilitator that could help overcome barriers related to procurement of anoscopes and training staff. Some interviewees believed that given resource limitations, screening would have to be scaled up in a stepwise process, requiring the creation of triage strategies to identify and prioritize high risk patients for screening. Barriers related to patient participation included lack of patient knowledge and, particularly among cis-women, stigmatization and logistical challenges to attending appointments. The clinics’ patient-centered culture and existing educational and clinical workflows promoting preventive health were facilitators that could help overcome patient-level barriers. CONCLUSION Staff believed that establishing a permanent anal cancer screening program was necessary and possible but acknowledged that it would require additional external resources. In the next phase of data collection, we will interview PLWH who receive care at the clinics.
Prevalence of Hospitalizations for Malignant Brain Neoplasms in Adults in the Last 5 Years in the Brazilian Territory
Authors: Gonçalves Castelo Ana Carolina , Guidugli Enrico Lázaro , Rahal de Albuquerque Roberta , Paesi Dutra Pedro Henrique , Loureiro Yasmin Marques 
Published: July 2024

PURPOSE The presence of abnormal cells that originate within the brain tissue characterizes malignant neoplasia of the brain, a form of brain tumor. The study aims to analyze hospitalizations for malignant brain neoplasia in adults in the five regions of Brazil from 2019 to 2023, investigating the demographic distribution in terms of regions of the country, year, age group, sex and ethnicity. In addition, seek to evaluate the characteristics of care, including the nature of hospitalizations, length of stay and mortality rates. METHODS A cross-sectional, descriptive, retrospective and quantitative study was carried out on hospitalizations for malignant neoplasia of the brain in adults in the 5 regions of Brazil (North, Northeast, Center-West, South, Southeast) between January 2019 and December 2023. The data used were collected through the Department of Informatics of the “Unified Health System of Brazil” (DATASUS) in the “SUS Hospital Information System” section, gathering those that discussed the age group, sex, ethnicity of the patient, character of care, the rate of hospital stay and the mortality rate. RESULTS The analysis covers the years 2019 to 2023, totaling 75,719 hospitalizations. The region that received the highest number of hospitalizations was the southeast (43.24%), while the north had the lowest number (4.28%). The highest number of cases occurred in 2022 (20.56%), followed by 2019 (19.76%). Urgent hospitalizations represented 76.71% of the total. The most affected age group was 60 to 69 years old (19.88%). Men were more affected than women (52.07%) and white people represented 43.4% of hospitalizations. The average stay was 9.2 days and the mortality rate was 13.60%. CONCLUSION Given the data analyzed, it is possible to draw an epidemiological profile in which non-white men are the population most affected by brain cancer. Furthermore, there is an alarming number of urgent hospitalizations, highlighting the severity of the disease. Therefore, based on the observed profile and other data collected, it is important that measures are developed to mitigate this serious public health problem in Brazil.
Prostate Cancer Observed Survival for Harare, Zimbabwe: Utilizing a Population-Based Cancer Registry Platform
Authors: Mazhindu Tinashe A. , Ndlovu Ntokozo , Borok Margaret Z. , Meki Shingirai , Campbell Thomas B. , Flaig Thomas W. 
Published: July 2024

PURPOSE The population-based cancer observed survival rate is affected by patient, disease and treatment factors. Survival of prostate cancer (PC) patients has improved over the past three decades globally. In low-to-middle-income countries the increasing incidence of cancer risks globally reversing this improvement. Population-based cancer registries can help estimate cancer survival, the emerging trend and guide interventions. This study aimed at determining the PC observed survival in Harare, Zimbabwe and the utility of data available in the registry to assess factors impacting survival. METHODS In a cohort study, 615 prostate cancer patients, were registered in Zimbabwe National Cancer Registry which is a population-based cancer registry between 1 January 2017 and 31 December 2018. Basic demographic, disease-related, and treatment-related data was extracted exclusively from the registry. Vital status was determined through direct patient or family contact telephonically. The Hazard Ratio (HR) for survival was assessed using the log-rank test, and observed survival estimated up to 2-years from date of diagnosis. RESULTS The median age of the patients was 71 years, 99% were ethnic Africans, and 8% had health insurance. Clinical stage 1, stage 2, stage 3, stage 4 and unknown stage was recorded for 2 (0%), 11 (2%), 69 (11%), 155 (25%) and 381 (62%) study participants. Histological diagnosis was recorded for 83% of participants. The 6, 12, 18 and 24-month observed survival rates were 88.5, 77.9. 62.5, and 22.5%, respectively. The 2-year OS rate for stage 1, stage 2, stage 3, stage 4 and unknown stage disease was 100, 90, 40, 10 and 20% (p= 0.0000033%). The Hazard Ratio for PC survival: Health insurance (HR= 0.51, 95% CI 0.36-0.73, p=0.003), age at diagnosis (≥64-years old) (HR=1.14, 95% CI: 0.81-1.61, p=0.47) and any treatment vs no-treatment received (HR= 1.16, 95% CI 0.817-1.64, p = 0.39). CONCLUSION The study demonstrated that a LMIC population-based cancer registry is a feasible platform for cancer survival estimations. The PC observed survival in this study is poor. More detailed data capturing of biochemical, stage of disease, Gleason score, and specific treatments received is needed in order to evaluate survival impact.
Quality and Diagnostic Characterization of Bone Marrow Biopsies at Kamuzu Central Hospital, Malawi: A Retrospective Study
Authors: Kasonkanji Edwards , Chikaonda Tarsizious , Fastburg Luke , Mulenga Maurice , Tomoka Tamiwe , Fedoriw Yuri , Painschab Matthew S. 
Published: July 2024

PURPOSE Diagnosis and management of many hematologic diseases depends on BM evaluation though data on diseases diagnosed and quality of bone marrow biopsies from Malawi is limited. METHODS We conducted a retrospective study of bone marrow biopsies taken for routine care from 2013-2023 at Kamuzu Central Hospital in Lilongwe, Malawi. We queried the laboratory database for patients age ≥18 with a pathology sample for “bone marrow biopsy” with location “iliac crest.” Patient characteristics were limited to those available from the pathology request request forms for each case including: age, sex, HIV status, details on history and laboratory findings. Diagnoses were made by routine care and recorded in the laboratory information system database (LIS), completed by the provider during the biopsy. Descriptive statistics were conducted in R. RESULTS 498 participants were identified; 273(55%) were male with median age of 41 (range 18-82). 305(61%) were HIV negative, 131(26%) HIV positive, and 62(12%) HIV unknown. Specimens collected and analyzed were either trephine and aspirates or both. Of the 498, 283(57%) were trephines, 88(18%) were aspirates and 127(25%) were both trephine and aspirate. Quality of biopsies was excellent, as only 29(6%) were sub-optimal or un-interpretable. Biopsy indications included unexplained anemia 40(8%), cancer staging 29(6%), pancytopenia 8(2%), lymphadenopathy 8(2%), and splenomegaly 5(1%). Indication was not given for 377(76%). The most common diagnosis was benign or reactive bone marrow (i.e., non-malignant) 275(60%). Other diagnoses included ALL 27(6%), AML 19(4%), Benign lesions-NOS 18(4%), DLBCL 16(4%), Aplastic anemias 11(2%), CLL 10(2%), Multiple myeloma 10(2%), MDS 8(2%), CML 8(2%), Carcinomas 8(2%), Hodgkin lymphoma 5(1%), HIV-infection 4(0.9%) among others. CONCLUSION Quality of bone marrow biopsies done under routine care is good in Malawi. However, the most common diagnosis in this population was a reactive bone marrow, for which the underlying cause was not evident to the treating provider. Therefore, further research is needed on the causes of cytopenia in this population.
Racial Disparities in Pediatric Patients With Acute Lymphoblastic Leukemia: An NCDB Analysis
Authors: Mishra Anjali , Mathews Maya , Becker Ashley , Al-Qurnas Mohammed , Silberstein Peter , Swedek Michelle 
Published: July 2024

PURPOSE Acute Lymphoblastic Leukemia (ALL) is the most common type of pediatric cancer. The American Cancer Society notes that the risk of ALL is higher in White patients than in Black patients. The goal of this study was to provide an updated investigation of racial disparities in overall survival (OS) of pediatric patients with ALL. METHODS Using the National Cancer Database, this retrospective cohort study identified 23,397 ALL patients between the ages of 0-18 who received chemotherapy from 2004-2020. Patients with race listed as “unknown” or “other” were excluded. Kaplan Meier survival analysis and cox multivariate analysis was used to evaluate OS across race categories. RESULTS OS was 196.8 months [95% confidence interval 195.8 – 197.8] for White patients, 189.7 months [187.6 - 191.8] for Spanish/Hispanic, 182.6 months [179.0 – 186.3] for Black patients, 183.6 months [174.5 to 192.7] for Native American patients, and 192.3 months [188.7 to 195.8] for AAPI patients. Multivariate analysis accommodated for sex, insurance status, median income quartiles, and Charlson-Deyo comorbidity score. Pairwise log rank test revealed Black patients had statistically significantly lower OS compared to White (p < 0.0001) and AAPI patients (p < 0.0001). Black patients had a higher survival hazard ratio compared to White (HR=1.309, 95% CI 1.117 to 1.533, p<0.001). Spanish/Hispanic patients had statistically significant lower OS (p < 0.0001) and higher hazard ratio (HR=1.188, 95% CI 1.058 to 1.334, p = 0.004) compared to non-Spanish/Hispanic patients. 5-year event-free survival (EFS) to be 90.9% for White patients, 87.1% for Black patients, 88.1% for Native American patients, and 92.4% for AAPI patients. CONCLUSION Black patients had decreased OS and greater hazard ratios compared to White patients with ALL. In addition, Hispanic patients had decreased OS and greater hazard ratios compared to non-Hispanic patients. After accommodating for sex, insurance status, median income quartiles, and Charlson-Deyo comorbidity score, we find these racial disparities continue to persist. Reducing the disparities in ALL incidence among pediatric patients from different racial backgrounds is not only a matter of health equity but also a testament to our commitment to ensuring the well-being of all children.
Regulation of Osteopontin in Prostate Cancer: Potential Therapeutic Implications for Bone Metastasis
Authors: Sanchis Pablo , Sabater Agustina , Bizzotto Juan , Valacco Pia , Vazquez Elba , Navone Nora , Gueron Geraldine , Anselmino Nicolas 
Published: July 2024

PURPOSE Prostate cancer (PCa) bone metastasis (BM) plays a crucial role in disease outcome and poses a significant clinical obstacle due to its heterogeneity. In this sense, Osteopontin (SPP1/OPN) is elevated in a subset of patients with advanced disease. However understanding its regulation is an unmet need. In this work we investigated the factors controlling SPP1/OPN expression in a subgroup of patients with BM. METHODS We performed a comprehensive transcriptomics analysis (DEG, Ingenuity Pathway Analysis (IPA)) of publicly available patients datasets (GSE74685, SU2C-PCF and Westbrooke et al), comparing PCa on different metastatic sites and/or treatment status. Using an indirect co-culture (24h) to mimic the dialogue between PCa cells (PC3/C42B) and osteoblast precursors (MC3T3) in vitro, we integrated transcriptomics (RT-qPCR and RNAseq) and secretomic (ESI-MS/MS of conditioned media (CM)) data to dissect key players involved in the bi-directional crosstalk between PCa and bone cells. Protein Kinase A (PKA) pathway implication was evaluated by its induction (forskolin 1uM) or suppression (H89 10uM). Clinically relevant patient derived xenograft (PDX) models growing intrafemorally (i.f.) were used for in vivo validation. RESULTS Across different datasets, we consistently found a sub-population of patients with BM characterized by high levels of SPP1 expression, associated with an active PKA pathway. By functionalizing this response experimentally, we demonstrated that specific bone secreted factors, particularly Col1a1 and Fn1, significantly induce SPP1 expression in PCa cells via PKA activation. Further, experimental and clinical settings suggest that the androgen receptor (AR) is implicated on this bone-induced PKA/SPP1 axis. Notably, longitudinal analysis of patients samples revealed an increased SPP1 expression alongside signs of PKA pathway activation, in a subpopulation of BM upon AR signaling inhibition with enzalutamide. CONCLUSION Herein, we uncovered PKA as a novel upstream regulator of SPP1/OPN expression in PCa triggered by the bone microenvironment that could possibly be implicated in treatment resistance. These results highlight the potential of SPP1/OPN as a marker of tumors with active PKA to improve disease management.