bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Prognostic Markers in Argentinian Acute Lymphoblastic Leukemia Pediatric Patients Through Transcriptome Analysis: Differential Gene Expression, Mutational Status and Immune Microenvironment
Authors: Abbate Mercedes , Ruiz María Sol , Avendaño Daniel , Riccheri María Cecilia , Vazquez Elba , Cotignola Javier 
Published: May 2022

PURPOSE Acute lymphoblastic leukemia (ALL) is the most incident pediatric cancer. Although considerable progress has been made on treatment efficacy and survival rates, 15%-30% of patients relapse and/or die. We aimed to identify molecular profiles and microenvironment makeup in leukemic bone marrow samples that could help to better predict disease outcome. METHODS We performed RNA-seq on bone marrow samples from pediatric ALL patients at diagnosis (n = 37). Patients were recruited under a multi-center clinical protocol in Argentina (median follow-up: 31 months). We analyzed differential gene expression, gene set variations, mutations in candidate genes, and fusion genes among clinico-pathological features. The abundance of immune-cell populations was inferred by digital cytometry (MIXTURE) and a “cytolytic score” based on the expression of five genes specific to cytotoxic cells. RESULTS We detected: (1) 37 differentially expressed genes (DEG) between poor vs good responders to prednisone; (2) 71 DEG between high vs standard-risk groups; (3) 13 DEG between patients who died/relapsed vs those who did not; and (4) 35 DEG between patients that developed severe therapy-related acute toxicity vs those who did not (|log2FC|> 1; P.adj < .05). We observed that 15%-30% of the DEG corresponded to lncRNAs. We found six differentially expressed pathways relevant to cancer and leukocyte biology among risk groups ( P < .01). We identified 17 mutations and three fusion genes in 44% of patients; the presence of these mutations shortened the relapse-free survival (Cox- P-val = .006). High cytolytic score was associated with activated CD8+T cells, immune cell trafficking, and bone marrow niche signaling genesets, suggesting potential candidates for immunotherapies. Higher CD8+T-cell/NK at diagnosis was marginally associated with worse event-free survival (hazard-ratio = 5.39; Cox- P-val = .08). CONCLUSION Transcriptomic sequencing allowed the analysis and integration of multiple molecular features that might improve pediatric ALL outcome prediction.
Impact of Patient Navigation on Timeliness of Diagnosis and Treatment, and Adherence to Treatment in Middle Income Asian Country
Authors: Jaganathan Maheswari , Rajoo Yamuna , Rajaram Nadia , Khairy Azuddin Mohd , Zainal Nur Hidayati , Zakaria Jasiah , Adi Mazwela , Halim Shahtirah , Sabtu Fizati , Sharif Siti Zubaidah , Jaafar Nur Shuhadah , Mohd Bahar Farhana Harzila , Nik Abdullah Nik Azim , Ali Adibah , Ashrina Sharifah , Julaihi Rokayah , Menon Isabella , Muniandy Kavitha , Zainal Hani , Muniandi Mallika , Roimin France Olovia , Ghazali Aini Fatimah , Ching Ling Clara Chong , Rahim Norlia , Tajuddin Nurul Ain , Ambia Fazilah , Cheng Nurizzati , Sapiee Norija , Teo Soo-Hwang , Abdul Wahab Mohamed Yusof 
Published: May 2022

PURPOSE Women in low to middle-income countries (LMICs), such as in Malaysia, face complex barriers to healthcare because of social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast cancer care. Patient Navigation has emerged as a cost-effective and impactful approach to enable women to access care. METHODS We have established a hospital-based partnership model between a non-profit organization and national healthcare service to address the barriers faced by low-income women to improve the timeliness of diagnosis and treatment and reduce poor adherence to treatment. The navigation team provides resources required to overcome financial and logistic barriers, counseling to address knowledge and emotional needs and to ensure treatment adherence. RESULTS To determine the effectiveness of the program, timeliness of diagnosis and treatment, and rates of treatment adherence were compared with a historical cohort from the same hospital. The proportion of patients who met the healthcare system's targets for timeliness to cancer diagnosis increased from 50.4% to 67.3% ( P < .05) and that for initiation of primary treatment increased from 36.5% to 49.5% ( P < .05). The overall treatment default rates reduced from 8.6% to 2.6% ( P < .05). CONCLUSION In summary, Patient Navigation is feasible and potentially effective for addressing barriers to cancer care and could be a key element of cancer control in LMICs.
Improving Tobacco Cessation Programs in Lao People's Democratic Republic: Perspectives of Healthcare Professionals
Authors: Xangsayarath Phonepadith , Kulkarni Shweta , Xayavong Dalouny , Soulaphy Chanthavy , Phandouangsy Khatthanaphone , Keopaseuth Phayvanh , Keothongkou Khamsing , Le Tina , Vidrine Damon , Vidrine Jennifer , Businelle Michael , Bui Thanh 
Published: May 2022

PURPOSE Tobacco use represents a major public health problem in Lao People's Democratic Republic (Lao PDR), however very few tobacco cessation programs are available. This formative, qualitative study of Lao healthcare professionals (HCP) aims to elicit both factors that help smokers quit and mechanisms to improve the effectiveness of tobacco treatment programs. METHODS We conducted in-depth interviews with 28 HCPs at two hospitals, Setthathirath Hospital in Vientaine Capital and Champasak Hospital in Champasak Province. We used purposive sampling to select a diverse sample with regard to age, sex, work position, and clinical speciality. Interviews were voice recorded and transcribed verbatim. Data were analyzed using thematic content analysis aided by the MAXQDA program. Codes and themes related to smoking cessation behavior were based on theoretical constructs of the Phase-Based Model (PBM). Codes and themes related to intervention implementation or dissemination were based on the Practical, Robust Implementation and Sustainability Model (PRISM). RESULTS Regarding PBM-based factors to help smokers quit, HCPs emphasized the need for medications to address craving, repeating quit-smoking advice, arranging follow-ups to monitor patients' progress, and advising patients on exercising or other distracting activities to cope with urges and stress. HCPs also identified visual education tools (e.g., short videos or images) as helpful, and that emphasis of smoking-related harms to patients' families increased smoker's motivation to quit. Salient PRISM-based factors for program implementation include the continuing dissemination of information regarding smoking-related harms in mass media, highlighting successful quit stories, the need for HCPs to be a model of becoming non-smokers, and the local enforcement of tobacco control policies (e.g., smoke-free environments). CONCLUSION This study identified several areas for improvement to increase the likelihood of success for tobacco treatment programs in Lao PDR, including individual-level (smokers') factors, provider-level factors, and external environment factors.
Protein Kinase A (PKA) as a Master Regulator of the Early Metabolic Reprogramming in Bone Metastatic Prostate Cancer Cells
Authors: Sanchis Pablo , Anselmino Nicolas , Lavignolle Rosario , Sabater Agustina , Labanca Estefania , Bizzotto Juan , Lage-Vickers Sofia , Pascual Gaston , Seniuk Rocio , Toro Ayelen , Navone Nora , Cotignola Javier , Vazquez Elba , Gueron Geraldine 
Published: May 2022

PURPOSE The arrival of metastatic prostate cancer (PCa) tumor cells to the bone niche requires a metabolic adaptation. We sought to identify metabolic dysregulations fueling PCa metastasis, modulated by bone secreted factors. METHODS By an indirect co-culture system of PCa (PC3) and bone progenitors (MC3T3, pre-osteoblasts, or Raw 264.7, pre-osteoclasts) we assessed the transcriptome of PC3 cells modulated by soluble factors released from bone precursors. We validated the transcriptional profile of metabolic genes in open-access transcriptomic datasets. We performed an Ingenuity Pathway Analysis (IPA) to delineate the regulators of these metabolic genes. Bone secretome was profiled on the conditioned media (CM) by ESI-MS/MS. RESULTS PC3 cells co-cultured with bone progenitors displayed an activation of lipidic categories, including PPAR-signaling and fat absorption/digestion. Principal Component and Unsupervised Clustering analyses using transcriptomic data from human PCa and bone metastatic samples (GSE74685) showed that the metabolic genes deregulated in PC3 accurately clustered samples in primary tumor or bone metastasis. Moreover, four lipid-associated genes, PPARA, VDR, SLC16A1 and GPX1, were associated with a shorter survival time (SU2C-PCF dataset), and were independent risk-predictors of death ( P < .05). An IPA revealed that these genes are regulated by the Protein Kinase A (PKA). Accordingly, PC3 cells treated with the CM of the co-culture presented a decreased ATP content compared to the treatment with the CM of PC3 grown alone, which was restored upon PKA inhibition. Finally, the secretome analysis revealed soluble factors secreted by bone progenitors (Col1a1, Fn1) which could regulate PKA activity. CONCLUSION We identified a novel lipid-associated gene signature important for metastatic PCa, triggered by the dialogue with bone cells. Moreover, PKA could regulate this signature in response to bone-secreted factors reprogramming the metabolic phenotype of metastatic cells, emerging as a potential druggable target for this disease.
Self-Efficacy and Willingness to Implement Narrative Communication Interventions: Mixed Methods Study Among Breast Cancer Patients and Survivors at the University College Hospital, Ibadan, Nigeria
Authors: Odukoya Oluwaponmile , Oluwasanu Mojisola , Okunnuga Ndidi , Ayandipo Omobolaji , Ntekim Atara , Arulogun Oyedunni , Olopade Olufunmilayo 
Published: May 2022

PURPOSE Globally, black women experience poorer breast cancer (BC) outcomes suggesting the need for effective health promotion approaches to increase perceived severity and improve screening practices for early detection. Although, narrative communication by patients or survivors are increasingly considered an effective approach for better BC outcomes, there is limited information on its use in Nigeria. This study assessed the self-efficacy and willingness of BC patients and survivors at the University College Hospital, Ibadan to implement narrative communication interventions. METHODS This study utilized a mixed-method convergent parallel design. Five patients were recruited for in-depth interviews (IDI). A semi-structured questionnaire was used to collect data from 102 patients on perception and the generalized self-efficacy to implement narrative communication interventions. Data were analyzed using thematic analysis for qualitative and descriptive and inferential statistics for quantitative data. RESULTS Mean age of the respondents was 49.3 ± 10.2 years. Over three quarters (79.4%) of respondents had good self-efficacy to implement narrative communication. Majority of respondents (87.3%) were willing to share lived experiences during narrative communication interventions. Over 90% (94.1%) agreed that health programs on BC anchored by patients and survivors will enable individuals make healthy decisions than interactions with clinicians only. Respondents' educational attainment was significantly associated with perception and self-efficacy to implement narrative communication intervention programs ( P < .05). Patients opined that a pre-diagnosis discussion with a BC patient or survivor would have increased their perceived severity and susceptibility. CONCLUSION This study highlights the potentials of BC patients and survivors as breast health educators sharing their lived experiences to empower and motivate women to act on health information on BC prevention and screening. Findings could guide the design of population-level interventions on BC prevention and screening.
Health System Costs of a Breast Cancer Early Diagnosis Program in a Rural District of Rwanda
Authors: Nambaziira Rashidah , Niteka Lysa Carolle , Vianney Dusengimana Jean Marie , Ruhumuriza John , Bhangdia Kayleigh , Mugunga Jean Claude , Uwineza Marie Louise , Rugema Vestine , Erfani Parsa , Shyirambere Cyprien , Shulman Lawrence N. , Rabideau Melany , Pace Lydia E. 
Published: May 2022

PURPOSE Low-and-middle-income countries require information about effective and pragmatic strategies to facilitate earlier breast cancer diagnoses. A Breast Cancer Early Detection (BCED) program training health workers and establishing breast clinics in Burera District, Rwanda was associated with increased evaluation of breast symptoms and higher incidence of early-stage breast cancer. We examined the program's cost from the health system perspective. METHODS The BCED program's first phase started in 2015 and included seven health centers (HCs) and Butaro Cancer Center of Excellence (BCCOE), the cancer referral center at Butaro Hospital. Patient volume and diagnoses from 2015 to 2017 were abstracted from existing databases. We retrospectively reviewed administrative data to identify start-up and ongoing operational costs. Using Time-Driven Activity-Based Costing, clinical costs per patient visit were estimated based on HC and BCCOE visits for breast health care observed in 2021. RESULTS Over the first 2 years, there were 1,010 HC visits for breast symptoms, 210 referrals to BCCOE, and 10 breast cancers diagnosed. The BCED program's total cost was $119,511, comprising of start-up costs ($36,917), recurring operational costs ($67,711) and clinical costs ($14,883). Clinical breast assessment (CBA) at HCs cost $3.27/visit. At BCCOE, CBA-only visits cost $13.47, CBA/ultrasound cost $14.79, and CBA/ultrasound/biopsy cost $147.81. Overall, the clinical cost per breast cancer diagnosed was $1,488. The primary cost drivers were personnel at HCs (55%) and biopsy supplies at BCCOE (46%). In other districts, patients must go to their local HC and district hospital before referral to BCCOE, adding about $14.00/patient. CONCLUSION The BCED program's cost at HCs was modest, similar to other outpatient HC services. Hospital-level care was more expensive and requiring multiple visits for biopsies increased costs. Start-up and operational costs could be reduced by using local trainers and virtual/mobile mentorship. For scalability in other districts, decentralizing ultrasound and/or biopsies to district hospitals could reduce costs.
Development of Culturally Adapted Media to Increase Community Awareness of Childhood Cancer in Tanzania
Authors: Abualhaj Dalia , Sanga Erica , Rajabu Shabani , Karia Francis , Makarushka Christina , Pollak Kathryn , Fish Laura , Schroeder Kristin 
Published: May 2022

PURPOSE There is low childhood cancer awareness in many low and middle income countries (LMICs), contributing to delayed hospital presentation, and treatment abandonment. In Tanzania, only 20% of the estimated 3,500 new cases per year present for treatment. While childhood cancer awareness media exist, they are not adapted for use in many LMIC communities, including Tanzania. METHODS To reach consensus on childhood cancer education content and education strategy selection, a Delphi process was completed with an expert advisory panel representing three Tanzanian referral hospitals. Focus groups discussions (FGD) were completed with rural and urban communities from each of the Mwanza, Dar Es Salaam and Kilimanjaro regions. Thematic analysis was guided by content consensus to identify community knowledge gaps. Sample education materials were reviewed to identify preferred delivery format. RESULTS A total of 14 and 72 participants formed the expert panel and community FGD respectively. Education strategies with the highest feasibility and impact included community health worker led education, a song, and social media messaging. The following key knowledge content areas were identified to have the lowest community awareness. (1) The cause of most childhood cancer is unknown: 83% felt untreated illnesses, cooking oil, witchcraft, immune system deficiency, and the environment were causes of childhood cancer; (2) Symptom recognition and hospital based studies can improve early detection: 66% reported that ill children see a traditional healer or pharmacist and only go a hospital if febrile or if symptoms do not improve; (3) Most childhood cancer can be cured with early detection: 50% felt that there is no cure. CONCLUSION This study identified key childhood cancer knowledge gaps within the Tanzanian community and culturally adapted strategies to disseminate education media. Additional studies are needed to evaluate the impact of culturally adapted media on community awareness and early hospital presentation in the region.
Long Non-Coding RNAs (lncRNAs) Dysregulated in Tumor Progression to Castration-Resistant Prostate Cancer
Authors: Ledesma-Bazan Sabrina , Vazquez Elba , Gueron Geraldine , Cotignola Javier 
Published: May 2022

PURPOSE The dysregulation of non-coding RNAs is implicated in the development and progression of different pathological processes, including cancer. Prostate cancer is known for having a wide spectrum of clinical outcomes, ranging from an indolent tumor to a lethal metastatic castration resistant cancer (CRPC). However, the biology of the processes leading to these phenotypes remains elusive. The aim of this study was to identify lncRNAs involved in the progression of prostate tumors to CRPC. METHODS We browed public repositories and downloaded raw RNAseq data from primary prostate adenocarcinomas (pre- and post-androgen deprivation therapy (ADT); n = 40 and n = 11 (paired to 11 pre-ADT), respectively) and CRPC (n = 8). We performed differential gene expression of 17,009 lncRNAs with R/Bioconductor using two statistical models: DESeq2 and edgeR. RESULTS We identified 12 lncRNAs that responded to ADT and were further dysregulated in CRPC; three of them were previously reported as players in prostate cancer development and progression (PCA3, PCAT18 and PCGEM1), validating the pipeline used in this study. Interestingly, all of them showed the same expression pattern: (1) post-ADT tumors had significantly lower expression compared with pre-ADT tumors; and (2) CRPCs showed significant higher levels compared with post-ADT tumors, and the expression was similar, or even higher, to primary pre-ADT tumors. Unsupervised clustering analysis revealed that the expression profile of these 12 lncRNAs could cluster post-ADT and CRPC samples apart. Primary tumors pre-ADT were more heterogeneous. This suggests that primary prostate tumors which might potentially progress to CRPC might be detected at the time of diagnosis according to their lncRNA expression profile. CONCLUSION Herein we describe a gene expression profile comprised of 12 lncRNAs that respond to hormone therapy and that are dysregulated in CRPC. The study of this expression signature might help to characterize primary tumors with low/high risk of progression to CRPC.
Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia
Authors: Ward Leanne M , Glorieux Francis H , Whyte Michael P , Munns Craig F , Portale Anthony A , Högler Wolfgang , Simmons Jill H , Gottesman Gary S , Padidela Raja , Namba Noriyuki , Cheong Hae Il , Nilsson Ola , Mao Meng , Chen Angel , Skrinar Alison , Roberts Mary Scott , Imel Erik A 
Published: May 2022

Abstract

Context
Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The effect of age on burosumab efficacy and safety in XLH is unknown.

Objective
This work aimed to explore the efficacy and safety of burosumab vs Pi/D in younger (&lt; 5 years) and older (5-12 years) children with XLH.

Methods
This post hoc analysis of a 64-week, open-label, randomized controlled study took place at 16 academic centers. Sixty-one children aged 1 to 12 years with XLH (younger, n = 26; older, n = 35) participated. Children received burosumab starting at 0.8 mg/kg every 2 weeks (younger, n = 14; older, n = 15) or continued Pi/D individually titrated per recommended guidelines (younger, n = 12; older, n = 20). The main outcome measure included the least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64.

Results
The LSMD in outcomes through 64 weeks on burosumab vs conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total Rickets Severity Score (younger, −0.86; older, −1.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (ALP) (younger, −31.15% of upper normal limit [ULN]; older, −52.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children.

Conclusion
Burosumab appears to improve outcomes both in younger and older children with XLH, including rickets, lower limb deformities, growth, and ALP, compared with Pi/D.
Effects of exercise training on cardiotoxicity in cancer survivors. A systematic review
Authors: Reddy C Ravindra , Samuel Stephen , Singh Vijay Pratap , Banerjee Sourjya 
Published: May 2022

Background: Cardiotoxicity is a major long-term complication of anti-cancer drugs such as anthracycline and androgen deprivation therapy (ADT). These drugs also impact the quality of life, reduced functional capacity, and life expectancy. Exercise attenuates the cardiotoxic effects of anticancer treatments, as indicated by a growing body of evidence. Methods: Studies for this review were retrieved from databases PubMed, SCOPUS, EMBASE, COCHRANE, and Web of Science and were restricted only to clinical trials. Study results were screened and synchronized to Mendeley. Studies that met the eligibility criteria were extracted into the spreadsheet, summarizing information regarding the site and cancer stages, adjuvant therapy, various exercise interventions, and outcome measures. Risk of bias quality analysis was done in accordance with the National Heart Lung Blood Institute. Results: In this systematic review, 9021 articles were screened. After the exclusion criteria, seven articles were included for qualitative analysis. Outcome measures analyzed were measures of cardiotoxicity such as left ventricular ejection fraction (LVEF), cardiac biomarkers, and global longitudinal strain. Conclusion: Although a structured exercise protocol including aerobic and resistance training has been found to improve, the functional capacity is an indirect measure of cardiotoxicity. There is a lack of data in terms of improvement seen in direct measurements of cardiotoxicity such as LVEF and cardiac biomarkers. A lack of evidence regarding the effects of exercise on the direct measurement of cardiotoxicity encourages the need for further research.