bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial
Authors: McLaughlin Pamela M. J. , Klar Maximilian , Zwimpfer Tibor A. , Dutilh Gilles , Vetter Marcus , Marth Christian , du Bois Andreas , Schade-Brittinger Carmen , Reuss Alexander , Bommer Claudine , Kurzeder Christian , Heinzelmann-Schwarz Viola 
Published: May 2022

Abstract
Background
A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL).

Methods
In this international multicenter randomized, placebo-controlled phase III trial at clinical centers in Switzerland, Germany and Austria, we plan to include 540 patients with primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low- or high-grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer. Patients are randomized in a 1:1 ratio into two groups: receiving blinded study treatment (letrozole or placebo tablets). When assuming a HR of 0.7, a median PFS of 18 months in the control arm and a median PFS of 25.7 months in the treatment arm, a two-sided alpha level of 5%, 3.5 years recruitment and 1.5 years observation time, we expect 330 events to have occurred within these 5 years in the total cohort yielding a power of 90%. Follow-up data for the whole cohort will be collected for up to 10 years and for the low-grade cancer for up to 12 years.

Discussion
The here proposed randomized phase III trial aims to identify patients with EOC in the maintenance setting, who benefit from the effectiveness of the letrozole, by proving its efficacy whilst maintaining a high standard of QoL due to the limited toxicity expected in comparison to the current alternative drugs on the market for this treatment phase.

Trial registration
This trial is registered at clinicaltrials.gov under the identifier NCT04111978. Registered 02 October 2019.
Image-guided navigation for locally advanced primary and locally recurrent rectal cancer: evaluation of its early cost-effectiveness
Authors: Lindenberg Melanie , Kramer Astrid , Kok Esther , Retèl Valesca , Beets Geerard , Ruers Theo , van Harten Wim 
Published: May 2022

AbstractBackgroundA first pilot study showed that an image-guided navigation system could improve resection margin rates in locally advanced (LARC) and locally recurrent rectal cancer (LRRC) patients. Incremental surgical innovation is often implemented without reimbursement consequences, health economic aspects should however also be taken into account. This study evaluates the early cost-effectiveness of navigated surgery compared to standard surgery in LARC and LRRC.MethodsA Markov decision model was constructed to estimate the expected costs and outcomes for navigated and standard surgery. The input parameters were based on pilot data from a prospective (navigation cohortn = 33) and retrospective (control groupn = 142) data. Utility values were measured in a comparable group (n = 63) through the EQ5D-5L. Additionally, sensitivity and value of information analyses were performed.ResultsBased on this early evaluation, navigated surgery showed incremental costs of €3141 and €2896 in LARC and LRRC. In LARC, navigated surgery resulted in 2.05 Quality-Adjusted Life Years (QALYs) vs 2.02 QALYs for standard surgery. For LRRC, we found 1.73 vs 1.67 QALYs respectively. This showed an Incremental Cost-Effectiveness Ratio (ICER) of €136.604 for LARC and €52.510 for LRRC per QALY gained. In scenario analyses, optimal utilization rates of the navigation technology lowered the ICER to €61.817 and €21.334 for LARC and LRRC. The ICERs of both indications were most sensitive to uncertainty surrounding the risk of progression in the first year after surgery, the risk of having a positive surgical margin, and the costs of the navigation system.ConclusionAdding navigation system use is expected to be cost-effective in LRRC and has the potential to become cost-effective in LARC. To increase the probability of being cost-effective, it is crucial to optimize efficient use of both the hybrid OR and the navigation system and identify subgroups where navigation is expected to show higher effectiveness.
Three-arm phase II trial comparing camrelizumab plus chemotherapy versus camrelizumab plus chemoradiation versus chemoradiation as preoperative treatment for locally advanced esophageal squamous cell carcinoma (NICE-2 Study)
Authors: Yang Yang , Zhu Li , Cheng Yan , Liu Zhichao , Cai Xiaoyue , Shao Jinchen , Zhang Ming , Liu Jun , Sun Yifeng , Li Yin , Yi Jun , Yu Bentong , Jiang Hongjing , Chen Hezhong , Yang Hong , Tan Lijie , Li Zhigang 
Published: May 2022

Abstract
Background
Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240).

Methods
The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events.

Discussion
This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021.

Trial registration
ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered.
The oncogenic role of tubulin alpha-1c chain in human tumours
Authors: Hu Xinyao , Zhu Hua , Chen Biao , He Xiaoqin , Shen Yang , Zhang Xiaoyu , Xu Yangtao , Xu Ximing 
Published: May 2022

AbstractTubulin alpha-1c chain (TUBA1C), a subtype of α-tubulin, has been shown to be involved in cell proliferation and cell cycle progression in several cancers and to influence cancer development and prognosis. However, a pancancer analysis of TUBA1C to reveal its immunological and prognostic roles has not been performed. In this study, we first downloaded raw data on TUBA1C expression in cancers from The Cancer Genome Atlas (TCGA) database and multiple other databases and analysed these data with R software to investigate the prognostic and immunological value of TUBA1C in cancers. Immunohistochemical analysis was performed in gliomas to further validate our findings. Overall, TUBA1C was overexpressed in most cancers, and overexpression of TUBA1C was linked to poor prognosis and higher tumour grade in patients. In addition, TUBA1C expression was associated with tumour mutation burden (TMB), microsatellite instability (MSI), the tumour microenvironment (TME) and the infiltration of immune cells. TUBA1C was also coexpressed with most immune-related genes and influenced immune-related pathways. Immunohistochemical analysis showed that TUBA1C expression was highest in glioblastoma (GBM) tissues, second highest in low-grade glioma (LGG) tissues and lowest in normal tissues. Our study indicated that TUBA1C might be a biomarker for predicting the immune status and prognosis of cancers, offering new ideas for cancer treatment.
A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor
Authors: Pantaleo Maria A. , Heinrich Michael C. , Italiano Antoine , Valverde Claudia , Schöffski Patrick , Grignani Giovanni , Reyners Anna K. L. , Bauer Sebastian , Reichardt Peter , Stark Daniel , Berhanu Ghimja , Brandt Ulrike , Stefanelli Tommaso , Gelderblom Hans 
Published: May 2022

Abstract
Background
Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib.

Methods
This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion.

Results
Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8–4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%).

Conclusions
The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing.

Trial registration
ClinicalTrials.govNCT01735968 (date of initial registration 28/11/2012).
Cost-effectiveness of using artificial intelligence versus polygenic risk score to guide breast cancer screening
Authors: Mital Shweta , Nguyen Hai V. 
Published: May 2022

Abstract
Background
Current guidelines for mammography screening for breast cancer vary across agencies, especially for women aged 40–49. Using artificial Intelligence (AI) to read mammography images has been shown to predict breast cancer risk with higher accuracy than alternative approaches including polygenic risk scores (PRS), raising the question whether AI-based screening is more cost-effective than screening based on PRS or existing guidelines. This study provides the first evidence to shed light on this important question.

Methods
This study is a model-based economic evaluation. We used a hybrid decision tree/microsimulation model to compare the cost-effectiveness of eight strategies of mammography screening for women aged 40–49 (screening beyond age 50 follows existing guidelines). Six of these strategies were defined by combinations of risk prediction approaches (AI, PRS or family history) and screening frequency for low-risk women (no screening or biennial screening). The other two strategies involved annual screening for all women and no screening, respectively. Data used to populate the model were sourced from the published literature.

Results
Risk prediction using AI followed by no screening for low-risk women is the most cost-effective strategy. It dominates (i.e., costs more and generates fewer quality adjusted life years (QALYs)) strategies for risk prediction using PRS followed by no screening or biennial screening for low-risk women, risk prediction using AI or family history followed by biennial screening for low-risk women, and annual screening for all women. It also extendedly dominates (i.e., achieves higher QALYs at a lower incremental cost per QALY) the strategy for risk prediction using family history followed by no screening for low-risk women. Meanwhile, it is cost-effective versus no screening, with an incremental cost-effectiveness ratio of $23,755 per QALY gained.

Conclusions
Risk prediction using AI followed by no breast cancer screening for low-risk women is the most cost-effective strategy. This finding can be explained by AI’s ability to identify high-risk women more accurately than PRS and family history (which reduces the possibility of delayed breast cancer diagnosis) and fewer false-positive diagnoses from not screening low-risk women.
Stigma and mental health challenges among adolescents living with HIV in selected adolescent-specific antiretroviral therapy clinics in Zomba District, Malawi
Authors: Kip Esther C. , Udedi Michael , Kulisewa Kazione , Go Vivian F. , Gaynes Bradley N. 
Published: May 2022

Abstract
Background
Of the 1.8 million adolescents between the ages of 10 and 19 living with HIV globally in 2020; approximately 1.5 million of these live in sub-Saharan Africa. These adolescents living with HIV (ALHIV) are at higher risk of experiencing mental health problems than those without; in Malawi, 18.9% have a depressive disorder. ALHIV can face numerous psychosocial challenges, but little is known about how ALHIV in Malawi perceive these stressors. Understanding psychosocial challenges of ALHIV is a key step in ensuring good mental health care. The aim of this study was to assess the psychosocial challenges faced by ALHIV attending adolescent-specific ART program in Zomba, Malawi.

Methods
Between April and May 2019, we engaged a purposive sample of ALHIV ages 12–18 (n = 80) in a series of eight focus groups drawing from four Teen Clubs linked to an adolescent-specific ART program. Data were analyzed inductively and deductively to identify themes related to ALHIV psychosocial experiences.

Results
Two themes that emerged from the study include: 1) stigma and discrimination within communities and families; 2) non-adherence to medications. HIV-related stigma was associated with increased psychological distress; physical and emotional/verbal abuse; low social support, isolation, and a feeling of rejection; and risky health behaviors such as medication hiding and non-adherence to ART. Discriminatory actions were manifested in a form of being given separate utensils for their meals and mistreatment at school. Furthermore, some parents did not allow their children to play with the participants out of fear that HIV transmission.

Conclusions
Stigma and discrimination are overlooked potential barriers to HIV treatment and care. If HIV services are to effectively meet ALHIVs' needs, mental health interventions are needed to prevent and manage depression and improve adherence to ART. These findings highlight the crucial need to develop culturally relevant mental interventions aimed at helping ALHIV to cope with these diverse challenges.
Population exposure to alcohol and junk food advertising during the 2018 FIFA world cup: implications for public health
Authors: Alfayad Khaldoon , Murray Rachael L. , Britton John , Barker Alexander B. 
Published: May 2022

Abstract
Background
Advertising alcoholic drinks and food high in fat, sugar, and salt (HFSS) is a driver of alcohol use and HFSS consumption, among children and young people. Whilst advertising legislation and broadcasting regulation protect children from alcohol and HFSS imagery, the 2018 FIFA World Cup, which attracted a global audience, was sponsored and partnered by alcohol and HFSS brands. This study investigated the exposure of viewers to HFSS and alcohol imagery in a selection of group matches, and the final match, of the FIFA 2018 World Cup.

Methods
The frequency and duration of appearances (to the nearest second) of branding from two sponsors (McDonald’s and Budweiser), one official partner (Coca-Cola) and the official sports drink (Powerade) were recorded during all active play in live coverage of a sample of 13 matches (Six in Group A, which included the host nation, Russia, which has stringent alcohol promotion regulations in place; six in Group G, which featured England; and the final) broadcast in the UK. We used census and viewing data to calculate gross and per capita impressions generated by this imagery in the UK population.

Results
The 13 matches included 1262 min of active play and a total of 1806 appearances of alcohol and HFSS food advertisements, delivering approximately 7.5 billion branded HFSS impressions, including 759 million to children (age < 16 years), and 3.3 billion alcohol impressions, including 385 million to children, in the UK. Appearances of HFSS and alcohol brands were not statistically different between the games in either group.

Conclusion
UK advertising legislation and broadcasting regulations intended to prevent exposure to alcohol and HFSS imagery and advertising in UK television was circumvented completely by sponsorship arrangements in the 2018 FIFA World Cup. Preventing this exposure therefore requires revision of existing advertising and broadcasting controls to include sponsorship.
Accuracy of death certifications of diabetes, dementia and cancer in Australia: a population-based cohort study
Authors: Xu Zhiwei , Hockey Richard , McElwee Paul , Waller Michael , Dobson Annette 
Published: May 2022

AbstractBackgroundNational mortality statistics are only based on the underlying cause of death, which may considerably underestimate the effects of some chronic conditions.MethodsThe sensitivity, specificity, and positive and negative predictive values for diabetes (a common precursor to multimorbidity), dementia (a potential accelerant of death) and cancer (expected to be well-recorded) were calculated from death certificates for 9 056 women from the 1921–26 cohort of the Australian Longitudinal Study on Women’s Health. Log binomial regression models were fitted to examine factors associated with the sensitivity of death certificates with these conditions as underlying or contributing causes of death.ResultsAmong women who had a record of each of these conditions in their lifetime, the sensitivity was 12.3% (95% confidence interval, 11.0%, 13.7%), 25.2% (23.7%, 26.7%) and 57.7% (55.9%, 59.5%) for diabetes, dementia and cancer, respectively, as the underlying cause of death, and 40.9% (38.8%, 42.9%), 52.3% (50.6%, 54.0%) and 67.1% (65.4%, 68.7%), respectively, if contributing causes of death were also taken into account. In all cases specificity (> 97%) and positive predictive value (> 91%) were high, and negative predictive value ranged from 69.6% to 84.6%. Sensitivity varied with age (in different directions for different conditions) but not consistently with the other sociodemographic factors.ConclusionsDeath rates associated with common conditions that occur in multimorbidity clusters in the elderly are underestimated in national mortality statistics, but would be improved if the multiple causes of death listed on a death certificate were taken into account in the statistics.
Adolescent health outcomes: associations with child maltreatment and peer victimization
Authors: Salmon Samantha , Garcés Dávila Isabel , Taillieu Tamara L. , Stewart-Tufescu Ashley , Duncan Laura , Fortier Janique , Struck Shannon , Georgiades Katholiki , MacMillan Harriet L. , Kimber Melissa , Gonzalez Andrea , Afifi Tracie O. 
Published: May 2022

Abstract
Background
Child maltreatment (CM) and peer victimization (PV) are serious issues affecting children and adolescents. Despite the interrelatedness of these exposures, few studies have investigated their co-occurrence and combined impact on health outcomes. The study objectives were to determine the overall and sex-specific prevalence of lifetime exposure to CM and past-month exposure to PV in adolescents, and the impact of CM and PV co-occurrence on non-suicidal self-injury, suicidality, mental health disorders, and physical health conditions.

Methods
Adolescents aged 14–17 years (n = 2,910) from the 2014 Ontario Child Health Study were included. CM included physical, sexual, and emotional abuse, physical neglect, and exposure to intimate partner violence. PV included school-based, cyber, and discriminatory victimization. Logistic regression was used to compare prevalence by sex, examine independent associations and interaction effects in sex-stratified models and in the entire sample, and cumulative effects in the entire sample.

Results
About 10% of the sample reported exposure to both CM and PV. Sex differences were as follows: females had increased odds of CM, self-injury, suicidality, and internalizing disorders, and males had greater odds of PV, externalizing disorders, and physical health conditions. Significant cumulative and interaction effects were found in the entire sample and interaction effects were found in sex-stratified models, indicating that the presence of both CM and PV magnifies the effect on self-injury and all suicide outcomes for females, and on suicidal ideation, suicide attempts, and mental health disorders for males.

Conclusions
Experiencing both CM and PV substantially increases the odds of poor health outcomes among adolescents, and moderating relationships affect females and males differently. Continued research is needed to develop effective prevention strategies and to examine protective factors that may mitigate these adverse health outcomes, including potential sex differences.
Risk factors and prognosis of spinal cord injury without radiological abnormality in children in China
Authors: Liang Jianmin , Wang Linyun , Hao Xiaosheng , Wang Guangliang , Wu Xuemei 
Published: May 2022

Abstract
Background
Compared to adults, spinal cord injury without radiographic abnormality (SCIWORA) is more common in children due to the congenital spinal soft tissue elasticity and immature vertebral bodies. In this study, we aimed to investigate the risk factors and prognosis associated with SCIWORA in China.

Method
We retrospectively examined patient records at the First Hospital of Jilin University from January 2007 to December 2020. Patients diagnosed with SCIWORA were included in the study group (n=16). The age, gender, history of trauma, symptoms, injury level of the spinal cord, the American Spinal Injury Association (ASIA) impairment score according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), as well as laboratory and imaging findings were analyzed.

Result
The study group included 16 patients with SCIWORA with a mean age of 6.69±2.51 y. The ISNCSCI impairment scale was significantly different between the pre-school age patients (≤7 years old) and school age patients (>7 years old) before (P=0.044) and after therapy (P=0.002). Similarly, magnetic resonance imaging demonstrated a significant difference in the spinal injury level between pre-school age and school age patients (P=0.041). Further, the study group was subdivided into three subgroups according to the cause of trauma: Dance, Taekwondo, or Falls. Magnetic resonance imaging revealed significant differences among the three subgroups (P=0.041).

Conclusion
Compared to school-age patients, pre-school-age patients were more vulnerable to SCIWORA with more severe ISNCSCI scores. Dance and Taekwondo are among the risk factors associated with SCIWORA in Chinese children.