bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer
Authors: Huang He , Deng Ting , Guo Yuntong , Chen Hao , Cui Xiaolong , Duan Jingjing , Yang Yuchong , Guo Zhixin , Ba Yi 
Published: June 2022

IntroductionFamily history is a high-risk factor for colorectal cancer (CRC). The risk comes not only from known germline mutations but also from the other family-related mechanisms. Uncovering them would be an important step to improve the diagnosis and treatment of these patients.MethodSamples from 168 patients with advanced CRC were collected and applied to next-generation sequencing of 624 pan-cancer genes. Genomic mutations and significantly mutated genes were identified. Significantly mutated genes and co-mutated genes were used to cluster patients. For each cluster of patients, mutational signatures were extracted. The identified mutational signatures were further validated in the other independent cohort.ResultSignificantly mutated genes including TP53, APC, KRAS, and SMAD4 were found associated with tumor mutational burden and microsatellite instability. LRP1, ACVR2A, and SETBP1 were found co-mutated. Patients with mutations in LRP1, ACVR2A, and SETBP1 tend to have a family history of cancer. Those patients tended to have right-sided tumors with high tumor mutational burden and microsatellite instability. Among them, signature analysis identified two possible etiologies, SBS10a (defective polymerase epsilon exonuclease domain) and SBS6 (defective DNA mismatch repair and microsatellite unstable tumors). These signatures were also found in another independent cohort.ConclusionThe gene cluster (LRP1, ACVR2A, and SETBP1) could be a good biomarker of these patients with a family risk, which was characterized by right-sidedness, high tumor mutational burden, and high microsatellite instability.
Predicting Kirsten Rat Sarcoma Virus Gene Mutation Status in Patients With Colorectal Cancer by Radiomics Models Based on Multiphasic CT
Authors: Hu Jianfeng , Xia Xiaoying , Wang Peng , Peng Yu , Liu Jieqiong , Xie Xiaobin , Liao Yuting , Wan Qi , Li Xinchun 
Published: June 2022

ObjectiveTo develop and validate radiomics models based on multiphasic CT in predicting Kirsten rat sarcoma virus (KRAS) gene mutation status in patients with colorectal cancer (CRC).Materials and MethodsA total of 231 patients with pathologically confirmed CRC were retrospectively enrolled and randomly divided into training(n=184) and test groups(n=47) in a ratio of 4:1. A total of 1316 quantitative radiomics features were extracted from non-contrast phase (NCP), arterial-phase (AP) and venous-phase (VP) CT for each patient. Four steps were applied for feature selection including Spearman correlation analysis, variance threshold, least absolute contraction and selection operator, and multivariate stepwise regression analysis. Clinical and pathological characteristics were also assessed. Subsequently, three classification methods, logistic regression (LR), support vector machine (SVM) and random tree (RT) algorithm, were applied to develop seven groups of prediction models (NCP, AP, VP, AP+VP, AP+VP+NCP, AP&amp;VP, AP&amp;VP&amp;NCP) for KRAS mutation prediction. The performance of these models was evaluated by receiver operating characteristics curve (ROC) analysis.ResultsAmong the three groups of single-phase models, the AP model, developed by LR algorithm, showed the best prediction performance with an AUC value of 0.811 (95% CI:0.685–0.938) in the test cohort. Compared with the single-phase models, the dual-phase (AP+VP) model with the LR algorithm showed better prediction performance (AUC=0.826, 95% CI:0.700-0.952). The performance of multiphasic (AP+VP+NCP) model with the LR algorithm (AUC=0.811, 95%CI: 0.679-0.944) is comparable to the model with the SVM algorithm (AUC=0.811, 95%CI: 0.695-0.918) in the test cohort, but the sensitivity, specificity, and accuracy of the multiphasic (AP+VP+NCP) model with the LR algorithm were 0.810, 0.808, 0.809 respectively, which were highest among these seven groups of prediction models in the test cohort.ConclusionThe CT radiomics models have the potential to predict KRAS mutation in patients with CRC; different phases may affect the predictive efficacy of radiomics model, of which arterial-phase CT is more informative. The combination of multiphasic CT images can further improve the performance of radiomics model.
Knowing to Ask and Feeling Safe to Tell - Understanding the Influences of HCP-Patient Interactions in Cancer Care for LGBTQ+ Children and Young People
Authors: Gannon Tamsin , Phillips Bob , Saunders Daniel , Berner Alison May 
Published: June 2022

BackgroundLesbian, gay, bisexual, transgender, queer or questioning (LGBTQ+) people experience healthcare inequalities in cancer care. Previous studies have focused on knowledge, attitudes and behaviours of healthcare professionals (HCPs) treating adults with cancer and how these contribute to inequalities. To date, no research has focused on HCPs treating LGBTQ+ children and adolescents with cancer in the UK. This is important given that this group may be at a critical time for exploring their gender identity and sexual orientation, whilst also facing a cancer diagnosis. We aimed to explore the knowledge, attitudes and behaviours of paediatric, teenage and young adult oncology HCPs treating LGBTQ+ patients in the UK.MethodsWe carried out semi-structured interviews with 8 HCPs in paediatric, teenage and young adult (TYA) oncology from the Royal Marsden NHS Foundation Trust. Eight questions were asked, which centred around participants’ knowledge, attitudes and behaviours regarding management of LGBTQ+ patients in oncology. Interview transcripts were analysed by inductive thematic analysis.ResultsWe identified 10 themes, including novel themes (how HCPs acquire knowledge and expectations of a ‘third party’ to be the expert) which may underlie previously observed trends in knowledge, attitudes and behaviours of HCPs. We highlight other themes and HCP concerns specific to care of LGBTQ+ patients in paediatrics (influence of the parental-carer dynamic, concerns around patient age and development as a barrier to disclosure) which require further research. We found evidence of the interrelatedness of HCP knowledge, attitudes and behaviours and the ability of these elements to positively influence each other. We mapped our themes across these elements to form a new suggested framework for improving HCP-patient interactions in LGBTQ+ Cancer Care. We found a need both for individual HCP education and organisational change, with creation of a culture of psychological safety to improve patient care.ConclusionKnowledge, attitudes and behaviours of HCPs are closely interdependent when providing care to young LGBTQ+ patients with cancer. The authors suggest that future efforts to improve care of these patients address this complexity by spanning the domains of our suggested framework. Whilst HCP education is essential, change must also occur at an organisational level.
Survival Analysis and Prediction Model of ASCP Based on SEER Database
Authors: Lv Sun-Yuan , Lin Min-Jie , Yang Zhao-Qun , Xu Chen-Nan , Wu Zhi-Ming 
Published: June 2022

BackgroundThis study aims to compare the incidence and clinical and survival characteristics of adenosquamous carcinoma of the pancreas (ASCP) and adenomatous carcinoma of the pancreas (ACP), analyze the survival factors of ASCP and construct a prognostic model.MethodPatients diagnosed with pancreatic cancer from 2000 to 2018 are selected from the SEER database. ASCP and ACP are compared in terms of epidemiology, clinical characteristics and prognosis. Cases are matched in a 1:2 ratio, and survival analysis is performed. The Cox proportional hazard model is used to determine covariates related to overall survival (OS), and an ASCP prognosis nomogram is constructed and verified by consistency index (C-index), calibration chart and decision curve analysis (DCA). The accuracy of the model is compared with that of AJCC.Stage and SEER.Stage to obtain the area under the receiver operating characteristic (ROC) curve.Resultsthe age-adjusted incidence of ACP increased significantly over time from 2000 to 2008 and from 2008 to 2018 (P &lt; 0.05). APC was 2.01% (95% CI: 1.95–2.21) and 1.08% (95% CI: 0.93–1.25) respectively. The age-adjusted incidence of ASCP increased with time from 2000 to 2018 (P &lt; 0.05) and APC was 3.64% (95% CI: 3.25–4.01).After propensity score matching (PSM), the OS and cancer-specific survival (CSS) of ACP are better than those of ASCP. The survival time of ASCP is significantly improved by the combined treatment of surgery + chemotherapy + radiotherapy, with a median OS of 31 months. Cox proportional hazard regression analysis shows that age, race, surgery, radiotherapy, chemotherapy and tumor size are independent factors affecting the prognosis. DCA and area under the curve (AUC) value shows that the model has good discrimination ability.ConclusionThe OS prognosis of ASCP is worse than that of ACP, and the nomogram has high accuracy for the prognosis prediction of ASCP.
Cancer-Testis Antigen LDH-C4 in Tissue, Serum, and Serum-Derived Exosomes Serves as a Promising Biomarker in Lung Adenocarcinoma
Authors: Peng Wei , Chen Jin , Xiao Yanping , Su Guangjian , Chen Yan , Cui Zhaolei 
Published: June 2022

ObjectiveAs a cancer-testis antigen (CTA), human lactate dehydrogenase C4 (LDH-C4) enzyme protein encoded by the LDHC gene has been reported to be involved in the occurrence and development of various malignancies, while its expression and clinical significance in lung adenocarcinoma (LUAD) remain unclear. This study aims to investigate the expression of LDH-C4 in LUAD and its diagnostic and prognostic value.MethodsThe mRNA and protein levels of LDH-C4 in LUAD and adjacent normal tissues were analyzed based on the UALCAN database, and the prognostic significance was assessed using the LOGpc database. The LDHC mRNA level in serum and serum secretion of LUAD patients was determined by quantitative real-time PCR (qRT-PCR). Based on the high-throughput LUAD tissue chip combined with immunohistochemistry (IHC), the protein level of LDH-C4 in LUAD tissues was measured, and its correlation with clinicopathological features and prognosis was analyzed.ResultsLDHC expression was upregulated in LUAD, which was related to the clinical stage and poor prognosis of patients. The positive rates of LDHC mRNA expression in serum and exosome of LUAD patients were 78.3% and 66.7%, respectively. The area under the curve (AUC) of serum and exosomal LDHC in the diagnosis of LUAD was 0.8121 and 0.8925, respectively. The expression of LDHC in serum and serum-derived exosomes from LUAD patients was negatively correlated with medical treatment and positively correlated with the recurrence of LUAD. The positive expression rate of LDH-C4 in LUAD tissues was 96.7% (89/92), which was significantly higher than that in adjacent normal tissues 22.6% (19/84) (p &lt; 0.001). The median overall survival (OS) time of patients with a high expression of LDH-C4 was significantly shorter than that of patients with low expression (34 months versus 62 months) (p = 0.016). Further relative risk analysis exhibited that the expression of LDH-C4 was an independent prognostic factor of OS in patients with LUAD.ConclusionsLDHC/LDH-C4 expression was upregulated in LUAD, and LDH-C4 could be used as a molecular indicator of the prognosis of LUAD. Serum and serum-derived exosomes of LDHC can be used as an important biomarker for the diagnosis, efficacy evaluation, and recurrence monitoring of LUAD.
Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study
Authors: Musiime Victor , Kiggwe Andrew , Beinomugisha Judith , Kakooza Lawrence , Thembo-Mwesige Josam , Nkinzi Sharafat , Naguti Erusa , Atuhaire Loice , Segawa Ivan , Ssengooba Willy , Mukonzo Jackson K. , Babirekere-Iriso Esther , Musoke Philippa 
Published: June 2022

BackgroundChildren living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition.MethodsThis is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone (n = 150) or standard-of-care (ampicillin/gentamicin) (n = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. Furthermore, all the CLHIV on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) 0−12h, maximum concentration (Cmax) and concentration at 12 h after dose (C12h)] will be determined. They will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population.DiscussionThis study will ascertain whether antibiotics with higher sensitivity patterns to common organisms in Uganda and similar settings, will produce better treatment outcomes. The study will also provide insights into the current pattern of organisms isolated from blood cultures and their antimicrobial sensitivities, in this population. In addition, the study will ascertain whether there has been a significant change in the prevalence of HIV-infection among children presenting with severe malnutrition in the WHO recommended option B plus era, while determining the social/structural factors associated with HIV-infection. There will also be an opportunity to study PK parameters of antiretroviral drugs among severely malnourished children which is rarely done, and yet it is very important to understand the dosing requirements of this population.Trial RegistrationClinicalTrials.gov, identifier: NCT05051163.
LINC01001 Promotes Progression of Crizotinib-Resistant NSCLC by Modulating IGF2BP2/MYC Axis
Authors: Zhang Meiling , Wang Qian , Ke Zihao , Liu Yijing , Guo Huijin , Fang Shencun , Lu Kaihua 
Published: June 2022

Background: Crizotinib is a microtubule-related protein-4-anaplastic lymphoma kinase (EML4-ALK) multi-target tyrosine kinase inhibitor applied in the treatment of ALK-rearranged NSCLC. However, the specific molecular mechanism underlying its therapeutic effect remains unclear. Therefore, the purpose of this research is to explore the mechanism by which crizotinib targets NSCLC with ALK-rearrangement, mainly whether it is related to LINC01001 in regulating NSCLC progression via IGF2BP2/MYC axis.Methods: RT-qPCR is conducted to evaluate the mRNA levels of LINC01001, IGF2BP2 and MYC in A549/R and H1299/R cells. CCK-8 and EdU assays are performed to assess the viability and proliferation of A549/R and H1299/R cells. Western blot is conducted to measure the levels of PCNA and Ki-67 proteins in A549/R and H1299/R cells. FACs and TUNEL are performed to detect apoptosis of A549/R and H1299/R cells. Immunohistochemical staining is performed to assess the levels of Ki67 in crizotinib-resistant NSCLC tissue. Bioinformatics analysis of multiple CLIP (crosslinking-immunoprecipitation) data found potential binding sites between LINC01001 and IGF2BP2, IGF2BP2 and MYC, that are confirmed by RIP assay and RNA pulldown assay.Results: Our findings illustrated that LINC01001 is highly expressed in crizotinib-resistant NSCLC cells and associated with poor overall survival of NSCLC patients. Inhibition of LINC01001 depresses crizotinib resistance of NSCLC cells. LINC01001 interacts with IGF2BP2, and inhibition of IGF2BP2 depresses crizotinib resistance of NSCLC cells. IGF2BP2 interacts with the mRNA of MYC, and LINC01001 overexpression increases crizotinib resistance of NSCLC via MYC.Conclusion: LINC01001 promotes the progression of crizotinib-resistant NSCLC by modulating the IGF2BP2/MYC axis. Our research clarifies the specific mechanism of crizotinib-resistance in NSCLC treatment.
Metabolic Energy Contributions During High-Intensity Hatha Yoga and Physiological Comparisons Between Active and Passive (Savasana) Recovery
Authors: Lee Kwang-Ho , Ju Hyo-Myeong , Yang Woo-Hwi 
Published: June 2022

Purpose: The objective of this study was to investigate metabolic energy contributions during high-intensity hatha yoga (HIHY) and to compare changes in physiological variables between active and passive recovery methods.Methods: The study involved 20 women yoga instructors (n = 20) who performed 10 min of HIHY (vigorous sun salutation). Upon completion, they were randomly assigned to either active (walking; n = 10) or passive (savasana; n = 10) recovery groups for a period of 10 min. During HIHY, physiological variables such as heart rate (HRpeak and HRmean), oxygen uptake (VO2peak and VO2mean), and blood lactate concentrations (peak La−) were measured. Energetic contributions (phosphagen; WPCR, glycolytic; WGly, and oxidative; WOxi) in kJ and % were estimated using VO2 and La− data. Furthermore, the metabolic equivalents (METs) of VO2peak and VO2mean were calculated. To compare different recovery modes, HRpost, ΔHR, VO2post, ΔVO2, recovery La−, and recovery ΔLa− were analyzed.Results: The results revealed that HRpeak, VO2peak, and peak La− during HIHY showed no differences between the two groups (p &gt; 0.05). Values of HRpeak, HRmean, METs of VO2peak and VO2mean, and La− during HIHY were 95.6% of HRmax, 88.7% of HRmax, 10.54 ± 1.18, 8.67 ±.98 METs, and 8.31 ± 2.18 mmol·L−1, respectively. Furthermore, WOxi was significantly higher compared with WPCR, WGly, and anaerobic contribution (WPCR + WGly), in kJ and % (p &lt; 0.0001). VO2post and recovery ΔLa− were significantly higher in the active recovery group (p &lt; 0.0001, p = 0.0369, respectively). Values of ΔVO2 and recovery La− were significantly lower in the active group compared with the passive group (p = 0.0115, p = 0.0291, respectively).Conclusions: The study concluded that high-intensity hatha yoga which was performed for 10 min is a suitable option for relatively healthy people in the modern workplace who may have hatha yoga experience but do not have time to perform a prolonged exercise. Following active recovery, they can participate in further HIHY sessions during short breaks. Furthermore, a faster return to work can be supported by physiological recovery.
The Six-Minute Stepper Test Is Valid to Evaluate Functional Capacity in Hospitalized Patients With Exacerbated COPD
Authors: Ribeiro Diego Britto , Terrazas Aline Carleto , Yamaguti Wellington Pereira 
Published: June 2022

Background: The six-minute stepper test (6MST) is a self-paced test considered a valid tool to assess functional capacity in stable COPD patients. However, a high floor effect, where a large proportion of participants reach the minimum score when using the measurement instrument, might compromise the test validity in the hospital setting. Therefore, this study aimed at verifying the concurrent validity of 6MST in hospitalized patients with acute exacerbation of COPD (AECOPD).Methods: A cross-sectional study was conducted in a tertiary hospital. Patients who were hospitalized due to AECOPD were considered for inclusion. On the first day, when patients reached minimum clinical criteria considered as the use of non-invasive ventilation less than 2 h for 6 h/period, dyspnea at rest less than 7 (very severe) on the modified Borg scale, a respiratory rate less than 25 breaths per minute, oxygen pulse saturation greater than 88% (considering use of supplemental oxygen) and absence of paradoxical breathing pattern, they underwent a lung function evaluation and answered three questionnaires: Chronic Respiratory Questionnaire (CRQ), Modified Medical Research Council Dyspnea Scale (MMRC), and COPD Assessment Test (CAT). Then, on two consecutive days, patients performed 6MST or six-minute walk test (6MWT), in random order. Each test was performed twice, and the best performance was recorded. Also, the patient’s severity was classified according to the BODE index. Inspiratory capacity measurements were performed before and after each test execution.Results: Sixteen patients (69.4 ± 11.4 years) with a mean FEV₁ of 49.4 ± 9.9% predicted were included (9 females). There was a strong correlation of the performance in 6MST (number of cycles) with 6MWT (distance walked in meters) in absolute values (r = 0.87, p &lt; 0.001) as well as with the percentage of predicted normal 6MWT (r = 0.86, p &lt; 0.001). There was a strong correlation between the performance in 6MST with the dynamic hyperinflation (r = 0.72, p = 0.002) and a moderate correlation between 6MST with the percentage of reduction of inspiratory capacity (r = 0.68, p = 0.004). We also identified that 6MST showed moderate negative correlations with CAT (r = −0.62, p = 0.01) and BODE index (r = −0.59, p = 0.01).Conclusion: It could be concluded that 6MST is valid for evaluating functional capacity in hospitalized patients with exacerbated COPD.