bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a Novel Analytical Strategy for Profiling Altered Genes in Adjacent Tissue to Prostate Cancer: Unveiling Pathways and Clinical Implications
Authors: Payán-Gómez César , Guevara-Nieto Michelle , Rodriguez-Morales Dayana , Vargas Elizabeth , Ramierz-Clavijo Sandra , Parra-Medina Rafael 
Published: July 2024

PURPOSE Prostate cancer is a significant global health issue. The tumor microenvironment significantly influences cancer progression, treatment response, and metastasis. There's a lack of studies directly comparing adjacent tissue behavior to both tumor and normal tissue. An analytical strategy was developed to identify genes altered in the adjacent tissue to the tumor without the need for comparison with tumor or normal tissue. METHODS Data sets containing information on both adjacent tumor and normal tissue were searched. Also, transcriptomic data from the prostate cancer project in TCGA for adjacent tumor samples were searched. Differentially expressed genes (DEGs) were identified from the dataset enabling direct comparison between adjacent tissue and normal tissue. The DEGs were utilized as probes to identify other genes of interest within the TCGA database. We hypothesized that genes showing correlated expression with the DEGs would also exhibit altered expression in adjacent tissue within TCGA.A co-expression network was constructed using all genes displaying a correlation coefficient greater than 0.6 with at least one of the DEGs. Finally, a network analysis was conducted. RESULTS GSE6919 was the only dataset that allowed direct comparison of adjacent tissue to prostate cancer with normal tissue. Six DEGs were identified TRIB1, C18orf54, ARF1, NFKBIZ, and LINC00662, and MAFB. The transcriptomes of the 54 adjacent tissues to prostate cancer from TCGA were interrogated, revealing that the expression profiles of 3316 genes had a Pearson correlation coefficient greater than 0.6 with at least one of the 6 DEGs. With these genes, a co-expression network was constructed, retaining 3254 genes. Two networks were identified, one with 2234 genes and another with 395 genes. The first network was enriched with genes related to protein synthesis and vesicle transport from the endoplasmic reticulum to the Golgi apparatus. The second network was enriched with genes from the IL17 signaling pathway and the TNF signaling pathway. CONCLUSION The proposed method proved effective in identifying genes potentially altered in adjacent tissue to the tumor, even in the absence of normal tissue for comparison. Some pathways identified have been previously associated with cancer progression, metastasis, and treatment response. Further studies are warranted to determine whether the behavior of these and novel discovered pathways in adjacent tissue has clinical implications for prostate cancer.
Implementation of Self-Sampling-Based Human Papillomavirus Screening in HIV-Infected Women in Mali
Authors: Maiga Mamoudou , Diakite Brehima , Kassogue Yaya , Traore Ban , Diarra Fousseiyni , Kassogie Oumar , Kamate Bakarou , Traore Cheick B. , Holl Jane L. , Hou Lifang 
Published: July 2024

PURPOSE This study aimed to assess the implementation of self-sampling (SS)-based HPV screening among high-risk HIV-infected women in an HIV Care Center in Bamako, Mali. METHODS Participants received self-sampling kits after receiving explanations and answering questions regarding their preferences. The Cepheid Xpert HPV test, which detects the 14 most common HPV subtypes, was utilized. High-risk (hr)-HPV+ participants underwent visual inspection tests and histology if cancerous lesions were detected, followed by treatment. RESULTS Among the 100 enrolled HIV-infected women, 92% opted to conduct self-sampling on-site, while 8% preferred home sampling. Only four out of the eight women who chose home sampling returned their samples, whereas all participants who opted for on-site sampling provided their samples. The concept of self-sampling was well-received, with 40.6% of women testing positive for high-risk HPV, predominantly HPV18/45 (45%) and the P3 group (HPV31, 35, 33, 52, 58) (33%). Co-infections were common, and all positive cases agreed to undergo further testing and treatment as necessary. CONCLUSION The majority of women (92%) preferred on-site self-sampling. This self-sampling strategy for HPV screening appears to be acceptable among HIV-infected women in Mali and holds potential for widespread implementation to decrease cervical cancer incidence in resource-limited settings.
International Patients Paths to Chimeric Antigen Receptor T-Cell Therapy for B-ALL: No Two Journeys Are Alike
Authors: Zakieh Abdulhafiz , Vadlamudi Priya , Huth Hannah , Foley Toni , Little Lauren , Yates Bonnie , Silbert Sara , Shah Nirali , Sankaran Hari 
Published: July 2024

PURPOSE Chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) has a critical role in improving outcomes. Access to CAR T-cell therapy is limited for international patients for whom standard therapies have failed, forcing many to undertake substantial travel in search of a cure. Our institution offers phase I CAR T-cell clinical trials for pediatric, and adolescent and young adult (AYA) patients, and is one of few that can accept patients nationally and internationally. METHODS This was a retrospective study of international patients with r/r B-ALL enrolled on a CAR T-cell trial at the pediatric oncology branch (POB) from 6/2012 through 3/2021. Variables including demographics and prior therapies (among others) were manually extracted from the electronic medical records, and analyzed using Microsoft Excel and R software, version 4.3. RESULTS A total of 57 patients (71.9% male) were included, including 35 (61.4%) from high income countries (World Bank Classification), 14 (24.6%) from upper-middle income countries, and 8 (14.0%) from low-middle income countries. Most common referrals were for a relapse after hematopoietic stem cell transplantation (HSCT) and/or CAR T-cell (43.9%), followed by CD19 negative relapse/refractory disease (29.8%). Twenty-six patients (45.6%) were enrolled for CD22, 21 (36.8%) for CD19, and 10 (17.6%) for dual CD19/CD22 directed CAR T-cell therapy. The median number of prior therapy lines was 5 (range 2-12, Q1 = 4, Q2 = 6). Thirty-five patients (61.4%) underwent at least one prior HSCT, 29 (50.1%) had received prior immunotherapy, and 19 patients (33.3%) received at least one prior CAR T-cell at other institutions “Only 3 of 21 CAR T-cell products (14.3%) were received in the patient's home country. Twenty-six patients (45.6%) received chemotherapy to control the disease during travel to our institution for enrollment, 47 patients (82.5%) received at least one anti-microbial prophylactic agent, and 26 patients (49.1%) had central venous access on arrival. Median age at CAR T-cell infusion was 13 years (Q1 = 9, Q3 = 20). CONCLUSION Our study is the largest to describe prior lines of therapy and treatment paths for international pediatric and AYA patients with relapsed/refractory B-ALL undergoing CAR T-cell therapy. Characterizing prior therapies and paths of this heavily treated population will help inform future directions in expanding this novel immunotherapy availability and addressing access disparities across the world.
Knowledge, Perception, and Intended Healthcare-Seeking Behavior for Ovarian Cancer Among Female Undergraduate Students of the University of Ibadan, Nigeria
Authors: Temitan Imole , Oliwasanu Mojisola , John-Akinola Yetunde 
Published: July 2024

PURPOSE Ovarian cancer is the deadliest of all gynecological malignancies, making it a major public health concern. Major global research finding highlighted a low level of ovarian cancer knowledge and education among women of reproductive age especially the younger ones. Therefore, the study assessed knowledge, perception, and intended healthcare-seeking behavior for ovarian cancer among female undergraduate students of University of Ibadan, the first tertiary institution in Nigeria. METHODS This cross-sectional survey involved 275 female undergraduate students of the University of Ibadan selected by a four-stage sampling technique. A pre-tested and retested semi-structured self-administered questionnaire was used to obtain data on their socio-demographic characteristics, knowledge, perception, and intended healthcare-seeking behavior toward ovarian cancer. Data was analyzed using frequency distribution, Chi-square, Spearman’s rank order correlation, Mann-Whitney U and Kruskal-Wallis H tests with ±0.05. RESULTS Age was 22.12±2.2 years and 76% were Christians. Majority (95.3%) were aware of ovarian cancer however, only 33.2% had good knowledge. The top-two identified symptoms were abdominal pain (66%) and pelvic pain (63.8%). Over two third, (68.3%) had poor knowledge of its risk factors. Having ovarian cysts (29.5%) was the commonly recognized risk factor while the least was ‘menopause’ (16.4%). Majority had moderate perceived susceptibility and severity, but high perceived benefits, cues to action and self-efficacy. The majority (80.2%) intended to visit the health facility once they notice any symptoms of ovarian cancer and (66.0%) plan to do so within a few days. Knowledge was significantly and positively correlated with perception, the strongest was with perceived severity (p<0.001). CONCLUSION The knowledge of ovarian cancer is still very low when compared to other malignancies such as breast and cervical cancer. The female undergraduate students had low knowledge of ovarian cancer, but high intention to seek medical help. The results highlight the need for multi-component educational interventions and strengthening of the health system.
Knowlege, Attitudes and Perceptions of Traditional Healers on Cancer: A Pilot Survey
Authors: Madzudzo Michelle , Musosi Godwin , Muzvondiwa Ivan 
Published: July 2024

PURPOSE To assess traditional medical practitioners (TMP) conception of cancer and assess their understanding of cancer causes, symptoms, screening, diagnosis and treatment as well as their stance on collaborations between western and traditional medicine as part of the overall healthcare system. METHODS The qualitative survey was designed to identify knowledge levels, attitudes perceptions of TMPs in Manicaland province in Zimbabwe towards cancer. A workshop was organized and a questionnaire was given as pretest and post test to the participants. In depth interviews and focus group discussions were carried out, transcribed and thematically analysed. Emerging themes related to cancer causes, symptoms, screening, diagnosis and treatment modalities and their comparative effectiveness and the need for collaboration. RESULTS There was total of 135 participants with 58,5% being males. The age range was 17 to 60 years. 90% could not describe cancer but alluded to its causes and recurring theme was spiritual attack. None had knowledge on cancer screening and diagnosis and only one stated that he can diagnose cancer spiritually while the rest agreed to using diagnosis from western medicine. There was no uniform opinion on treatment effectiveness and there was a general consensus that collaboration between western and traditional medicine is important for improved cancer care. CONCLUSION A clear knowledge gap exists and there is need for health education and awareness of TMP. The survey revealed that they want to learn more about cancer and collaborate with western medicine. Traditional medicine should therefore be formally recognized as a component of the national health system in order to control cancer care and improve the quality of service across the continuum of cancer care.
Management and Outcomes of Low-Grade Lymphomas in a Prospective Lymphoma Cohort in Malawi
Authors: Chikaonda Tarsizious , Fedoriw Yuri , Chikasema Maria , Mponda Marriam , Kasonkanji Edwards , Simwinga Lusayo , Tomoka Tamiwe , Paindchab Matthew 
Published: July 2024

PURPOSE To outline the baseline characteristics, treatment, and outcomes of adults with low-grade lymphomas in Malawi. METHODS We describe a prospective, observational cohort of newly diagnosed low grade lymphomas at a national teaching hospital in Lilongwe, Malawi June 2013--December 2021; follow up was censored December 2022. Diagnoses were supported by histopathology and immunohistochemistry during weekly telepathology conferences between Malawi and U.S. Treatment guidelines were standardized and generally only started if patients met GELF criteria. Simple descriptive statistics and Kaplan Meier methods were used. RESULTS We enrolled 55 patients with low grade lymphoma. Median age was 58 (range 28-82), 35 (64%) were male, and three (9%) HIV-positive. Of 42 patients who required treatment, 37 received CVP (cyclophosphamide, vincristine, and prednisone) and 3 received CHOP (CVP plus doxorubicin), 1 received Mini-CHOP and 1 Received R-CHOP. Median chemotherapy cycles received was six (range 1-8). Of 39 evaluable patients, response was: seven (18%) complete response, 4 (10%) stable disease, 26 (67%) partial response, and 2 (5%) progressive disease. Median follow-up was 34 months (range 5-49 months) among those alive. One- and two-year overall survival were 60% (95% CI 48-75%) and 44% (95% CI 33-60%), respectively. One- and two-year progression free survival were 44% (95% CI 32-59%) and 28% (95% CI 18-43%), respectively. There were a total of four non-hematologic grade 3/4 adverse events and 44 deaths, 29 attributed to disease progression. CONCLUSION This is among the first prospective cohorts of low-grade lymphoma from sub-Saharan Africa. Patients with low grade lymphomas in Malawi have poor progression-free and overall survival compared to high income countries and all deaths in our cohort were from disease progression. Thus, increased resources (e.g., rituximab and other novel therapies) and investigation of the underlying biology of low-grade lymphoma in Malawi and similar contexts are needed to improve patient outcomes.
Mechanobiological Markers for Theragnostics in Breast Cancer
Authors: Maksimova Ksenia , Leonov Sergey , Pistovalova Margarita , Merkher Yulia 
Published: July 2024

PURPOSE Metastasis is the leading cause of cancer mortality. An accurate prediction of metastases helps to improve the patient's life quality. We have previously studied the relationship between mechanobiology (invasion, migration, endocytosis) and metastasis, where the actin cytoskeleton plays a key role in all these processes. The purpose of the study is to investigate associated with the actin cytoskeleton rearrangement genes, as potential markers of metastasis and targets for therapy. METHODS We have used genetic dependency data from the CRISPR screen from the 22Q2 public data release (DepMap, Broad Institute), including data for 17,386 genes across 1,086 cell-lines. Drug effects were taken from the PRISM Repurencing database (Broad Institute);4518 chemical compounds were evaluated. Data analysis was performed using RStudio software (2023 Posit Software, PBC). Ten previously defined mechanobiology-related markers were examined in 72 breast cancer (BC) and 52 non-cancerous cell-lines. Cell-lines were clustered by two methods: 1) isolated from metastatic, primary tumors and non-cancerous tissues;2) subgroups according to BC disease type. The parameters like gene effect, expression, copy number, RNAi, proteomics were evaluated. To analyze the correlation of drugs effect, Pearson's coefficient was calculated separately for metastatic and primary breast cancer cell lines. The effect of treatment on marker expression was considered significant when a coefficient was below -0.5 (at p < 0.001), chemical compounds with more significant effects on metastatic cells were identified separately, and matches were found in chemical connections between different markers. RESULTS The gene expression was the most significant parameter, enabling the statistically reliable differentiation of various BC cell-lines subgroups. Among the studied markers, TAGLN, FSCN1, ECM1 revealed differences in more than three explored parameters for two or more clusters, making them potential markers for metastasis. The most effective chemicals in terms of the combination of affected genes and dependent parameters were: DEHYDROEPIANDROSTERONE, RESIQUIMOD, LEVOMEPROMAZINE, BMS-806, MERBROMIN. Interestingly, among the studied markers the most influential were TAGLN, FSCN1, ECM1, making them potential targets for the therapy. CONCLUSION The markers defined by bioinformatical methods, TAGLN, FSCN1, and ECM1, have promising value for theragnostic purposes in breast cancer and should be further examined experimentally.
Vebreltinib for Advanced Non–Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study
Authors: Yang Jin-Ji , Zhang Yan , Wu Lin , Hu Jie , Wang Zhe-Hai , Chen Jing-Hua , Fan Yun , Lin Gen , Wang Qi-Ming , Yao Yu , Zhao Jun , Chen Yuan , Fang Jian , Song Yong , Zhang Wei , Cheng Ying , Guo Ren-Hua , Li Xing-Ya , Shi He-Peng , Xue Wei-Zhe , Han Di , Zhang Pei-Long , Wu Yi-Long 
Published: July 2024

PURPOSE

The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (
MET
), in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring c-Met alterations.

METHODS

This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with
MET
exon 14 skipping (
MET
ex14)–mutant NSCLC who had not previously received
MET
inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1.

RESULTS
As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%).

CONCLUSION

Vebreltinib has shown promising efficacy and a favorable safety profile in patients with
MET
ex14-mutant NSCLC.
All-cause Mortality and Incidence of Cardiovascular Diseases in Lean Patients With Newly Diagnosed Type 2 Diabetes
Authors: Song Do Kyeong , Oh Jongmin , Sung Yeon-Ah , Hong Young Sun , Lee Hyejin , Ha Eunhee 
Published: July 2024

Abstract

Context
A few studies have evaluated all-cause mortality or risk of cardiovascular diseases according to the body mass index (BMI) level in patients with type 2 diabetes.

Objective
We evaluated all-cause mortality and the incidence of cardiovascular diseases in lean patients with newly diagnosed type 2 diabetes in Korea. Additionally, we aimed to determine a difference in all-cause mortality and the incidence of cardiovascular diseases according to changes in BMI over time among patients with newly diagnosed type 2 diabetes in Korea.

Methods
We analyzed 419 509 patients with newly diagnosed type 2 diabetes who underwent health screening between 2010 and 2014 and followed up until 2019. We conducted a multivariate Cox proportional hazards model to determine the association between BMI and all-cause mortality or risk of cardiovascular diseases.

Results
Lean patients with type 2 diabetes had a higher risk of all-cause mortality [hazard ratio (HR): 2.106, 95% confidence interval (CI): 1.974-2.248], cardiovascular disease (HR: 1.132, 95% CI: 1.078-1.189), coronary heart disease (HR: 1.219, 95% CI: 1.124-1.323), heart failure (HR: 1.405, 95% CI: 1.279-1.543), stroke (HR: 1.155, 95% CI: 1.024-1.302), and ischemic stroke (HR: 1.205, 95% CI: 1.045-1.388) compared to patients with type 2 diabetes and normal BMI. Patients with newly diagnosed type 2 diabetes had the highest all-cause mortality when they remained lean during the follow-up.

Conclusion
Our findings underscore the critical role of maintaining an appropriate weight status to reduce all-cause mortality and incidence of cardiovascular diseases among lean patients with newly diagnosed type 2 diabetes.
Postnatal Cardiometabolic Health After Metformin Use in Gestational Diabetes: A Secondary Analysis of the EMERGE Trial
Authors: Dunne Fidelma , Newman Christine , Alvarez-Iglesias Alberto , O’Shea Paula , Devane Declan , Gillespie Paddy , Egan Aoife , O'Donnell Martin , Smyth Andrew 
Published: July 2024

Abstract

Aim
Women with gestational diabetes mellitus (GDM) display adverse lifetime cardiometabolic health. We examined whether early metformin in GDM could impact cardiometabolic risk factors postpartum.

Methods
EMERGE, a double-blind, placebo-controlled trial, randomized pregnancies 1:1 to placebo or metformin at GDM diagnosis and followed participants from randomization until 12 ± 4 weeks postpartum. In total, 478 pregnancies were available for postpartum maternal assessment, 237 and 241 assigned to metformin and placebo respectively. Weight (kg), body mass index (BMI) (kg/m2), waist circumference (cm), and blood pressure (mmHg) were measured, infant feeding method documented, and blood specimens drawn for a 75-gram oral glucose tolerance test, fasting insulin, C-peptide, and lipid analysis.

Results
Despite similar weight and BMI at trial randomization, participants receiving metformin had significantly lower weight (79.5 ± 15.9 vs 82.6 ± 16.9 kg; P = .04) and BMI (29.3 [5.6] vs 30.5 [5.4]; P = .018) at the postpartum visit. However, no difference in weight change from randomization to 12 weeks postpartum was observed between metformin and placebo groups. Overall, 29% (n = 139) of the cohort met criteria for prediabetes or diabetes, with no positive impact with metformin. There were also no differences in measurements of insulin resistance, blood pressure, or lipids between groups.

Conclusion
Early metformin use in GDM did not impact important cardiometabolic parameters in the early postpartum period despite significant benefits in weight gain and insulin use in pregnancy.