bluuebunny/crossref_metadata_2025_split huggingface dataset:
Menopausal status, age at natural menopause and risk of diabetes in China: a 10-year prospective study of 300,000 women
Authors: Wang Meng , Gan Wei , Kartsonaki Christiana , Guo Yu , Lv Jun , Chen Zhengming , Li Liming , Yang Ling , Yu Min 
Published: February 2022

AbstractBackgroundMenopause characteristics have been implicated in future health consequences, yet little is known about its relevance to diabetes. We examined the associations of menopausal status and age at natural menopause with diabetes risk in Chinese women.MethodsWe used prospective data of the China Kadoorie Biobank study that recruited 302,522 women aged 30–79 years in 2004–2008 from 10 areas across China. During average 10.8 years of follow-up, 11,459 incident diabetes cases were recorded among 281,319 women without prior diabetes diagnosis at baseline. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for incident diabetes associated with menopausal status and age at natural menopause.ResultsOverall, the mean (SD) age at natural menopause was 48.2 (4.4) years among 141,789 post-menopausal women. Naturally peri-, or post-menopausal women were at higher risk of diabetes, with HRs of 1.17 (95% CI 1.06–1.29) and 1.15 (1.06–1.25) compared with pre-menopausal women, adjusting for several potential confounders. Among women who had natural menopause, the HR of diabetes was 1.14 (1.01–1.30), 1.01 (0.93–1.09), 1.10 (1.04–1.16), and 1.10 (1.01–1.20) for menopause at ages less than 40, 40–44, 50–53, and 54 years or older, respectively, relative to 45–49 years.ConclusionsIn this study, we found that women with naturally peri-, or post-menopausal status had higher risk of developing diabetes. Besides, among the post-menopausal women, both earlier and later age at natural menopause were associated with increased risk of diabetes.
FCTC ratification, smoking prevalence, and GDP per capita: lessons for Indonesia and the rest of the world
Authors: Ahsan Abdillah , Afin Rifai , Amalia Nadira , Hindriyani Martha , Jacinda Ardhini Risfa , Kramer Elisabeth 
Published: February 2022

Abstract
Background
Indonesia’s stagnated progress towards tobacco control could be addressed through the implementation of a comprehensive national framework, such as the World Health Organization’s (WHO) Framework Convention of Tobacco Control (FCTC). However, national tobacco industry supporters argue that accepting the FCTC will have negative economic implications for the country. These arguments have, thus far, discouraged the Indonesian government from ratifying the FCTC. Drawing from an analysis of the impact of the FCTC on other countries’ smoking rates and Gross Domestic Product (GDP) per capita, this study offers empirical evidence against industry arguments concerning the potential negative economic impacts of FCTC adoption. This study applies a two stage least square estimation strategy to unbalanced panel data at country level. In the first stage we estimate the impact of FCTC ratification on smoking rates, and in the second step, we estimate the influence of smoking activity on macroeconomic performance.

Results
The result of this study shows that FCTC ratification has a negative impact on a country’s smoking prevalence. While FCTC ratification positively correlates with reduced smoking prevalence, a decline in smoking prevalence is not related to a decline in GDP per capita.

Conclusions
The results of this study shows that FCTC ratification, which can be an important driver for more effective tobacco control, does not necessarily have a negative impact on the economy. Instead, FCTC ratification may be beneficial for both health and economic outcomes, as it provides comprehensive guidance for reducing smoking prevalence that take into account social and economic factors.
Youth substance use service provider’s perspectives on use and service access in ontario: time to reframe the discourse
Authors: Ali Farihah , Russell Cayley , Nafeh Frishta , Chaufan Claudia , Imtiaz Sameer , Rehm Jürgen , Spafford Adrienne , Elton-Marshall Tara 
Published: February 2022

AbstractBackgroundAge is a critical factor in substance use and related outcomes, with adolescence being a particularly sensitive period. Early initiation of substance use has been linked with higher risk for developing substance use disorders. In Ontario, Canada, substance use is common among youth, yet treatment is underutilized, suggesting the potential for an unmet need in terms of substance use care. Despite these challenges, there is limited research examining factors that contribute to youth substance use and youth-specific barriers to substance use care. To fill this knowledge gap, this study sought to include the unique perspectives of service providers who work directly with youth to examine these issues.MethodsWe used a cross-sectional mixed-methods design to examine factors that contribute to substance use among youth and identify youth-specific barriers to substance use among a sample of 54 Ontario-based youth service providers. Data collection included an online survey completed by all study participants followed by qualitative interviews of a subsample of 16 participants. Data analysis included basic frequency tabulations for survey results and thematic qualitative analyses to identify common themes.ResultsLicit substances were identified as the most commonly used among youth, where 94% of respondents identified cannabis use and 81% identified alcohol use. Thematic analyses identified the role of dominant substance use discourses in normalizing certain substances (i.e., cannabis and alcohol) while also endorsing stigmatizing beliefs and sentiments. According to youth service providers, the intersection of these two discourses simultaneously lead to an increase in substance use while deterring youth from seeking substance use care.ConclusionsNormalization and stigmatization are two dominant discourses around youth substance use, with important implications for public health interventions. Key public health strategies, as identified by participants, to reduce the overall negative effect of these factors include the need to reframe substance use discourse, from a moral failing to a public health issue and to educate youth about the impacts of use. To accomplish this goal educational campaigns to raise awareness around the health effects of use and address stigmatization are needed. Educational reforms are also needed to ensure that these programs are integrated into the school system.
Adaptive dose escalated radiotherapy in oropharyngeal cancers: a treatment planning feasibility study
Authors: Grocutt Laura , Paterson Claire , Valentine Ronan M. 
Published: February 2022

Abstract
Background
A significant proportion of patients with poor prognosis squamous cell cancer of the oropharynx relapse loco-regionally despite radical (chemo)radiotherapy. If a predictive biomarker for disease control can be identified during treatment then individualised and adaptive treatment strategies may be employed. The aim of this study is to assess the feasibility of adaptive and dose-escalated RT to the gross tumour volume without increasing surrounding planning target volume doses and maintaining clinically acceptable organs at risk doses.

Materials and methods
Twenty representative patients with poor prognosis locally advanced OPSCC who were known to have relapsed post RT, were re-planned retrospectively using Eclipse TPS v15.5, RapidPlan™ and multi-criteria optimisation. In our centre, PTV65 is treated with 65 Gy in 30 fractions while areas at risk of containing microscopic disease (PTV54) are treated synchronously to 54 Gy in 30 fractions. The original clinical plans were re-optimised to act as controls (Group I). These plans were split into two plans of 15 fractions each, with the latter 15 fractions used to escalate the dose to the GTV to 73 Gy (Group II) and 82 Gy (Group III). Plan sums were created for the total 30 fractions to record plan evaluation parameters along with assessments of plan deliverability.

Results
For all groups, the dose coverage at D98% and D50% for the PTVs were comparable. The D2% dose levels for PTV65-GTV increased. All dose levels associated with PTV54 remained largely unaffected by the dose escalation regimens. Conformity indices for PTV65 and PTVAll (PTV65 plus PTV54) reveal comparable target volume coverage across all three groups. Despite the GTV being escalated by 12.3% and 26.2% in groups II and III, the volume of GTV receiving > 84 Gy was considerably less than 1.75 cc. While OAR doses increased for the escalated groups, these increases were not clinically significant.

Conclusion
This planning feasibility study exploring RapidPlan™ combined with multi-criteria optimisation has demonstrated that doses to the GTV may be escalated without increasing PTV65-GTV, PTV54 or OAR doses considerably, suggesting an interventional clinical trial using this approach would be feasible.
Clinical evaluation of two AI models for automated breast cancer plan generation
Authors: Kneepkens Esther , Bakx Nienke , van der Sangen Maurice , Theuws Jacqueline , van der Toorn Peter-Paul , Rijkaart Dorien , van der Leer Jorien , van Nunen Thérèse , Hagelaar Els , Bluemink Hanneke , Hurkmans Coen 
Published: February 2022

AbstractBackgroundArtificial intelligence (AI) shows great potential to streamline the treatment planning process. However, its clinical adoption is slow due to the limited number of clinical evaluation studies and because often, the translation of the predicted dose distribution to a deliverable plan is lacking. This study evaluates two different, deliverable AI plans in terms of their clinical acceptability based on quantitative parameters and qualitative evaluation by four radiation oncologists.MethodsFor 20 left-sided node-negative breast cancer patients, treated with a prescribed dose of 40.05 Gy, using tangential beam intensity modulated radiotherapy, two model-based treatment plans were evaluated against the corresponding manual plan. The two models used were an in-house developed U-net model and a vendor-developed contextual atlas regression forest model (cARF). Radiation oncologists evaluated the clinical acceptability of each blinded plan and ranked plans according to preference. Furthermore, a comparison with the manual plan was made based on dose volume histogram parameters, clinical evaluation criteria and preparation time.ResultsThe U-net model resulted in a higher average and maximum dose to the PTV (median difference 0.37 Gy and 0.47 Gy respectively) and a slightly higher mean heart dose (MHD) (0.01 Gy). The cARF model led to higher average and maximum doses to the PTV (0.30 and 0.39 Gy respectively) and a slightly higher MHD (0.02 Gy) and mean lung dose (MLD, 0.04 Gy). The maximum MHD/MLD difference was ≤ 0.5 Gy for both AI plans. Regardless of these dose differences, 90–95% of the AI plans were considered clinically acceptable versus 90% of the manual plans. Preferences varied between the radiation oncologists. Plan preparation time was comparable between the U-net model and the manual plan (287 s vs 253 s) while the cARF model took longer (471 s). When only considering user interaction, plan generation time was 121 s for the cARF model and 137 s for the U-net model.ConclusionsTwo AI models were used to generate deliverable plans for breast cancer patients, in a time-efficient manner, requiring minimal user interaction. Although the AI plans resulted in slightly higher doses overall, radiation oncologists considered 90–95% of the AI plans clinically acceptable.
Effectiveness and safety of surgical treatment of carpal tunnel syndrome via a mini-transverse incision and a bush hook versus a mid-palmar small longitudinal incision
Authors: Wang Dongyue , Ma Tianxiao , Hu Yuqing , Zhao Xiaocui , Song Lihua 
Published: February 2022

Abstract
Background
Minimally invasive surgery for carpal tunnel syndrome has been consistently the mainstay of treatment. In this study, we developed a novel bush hook via a mini-transverse incision at proximal wrist crease to surgically treat carpal tunnel syndrome and our aim was to compare the results with those of mid-palmar small longitudinal incision in carpal tunnel release.

Methods
This is a retrospective study on patients who received a mini-transverse incision and a novel bush hook or a mid-palmar small longitudinal incision for treatment of carpal tunnel syndrome. The decision to receive either technique was made mainly based on patients' choice. The clinical results were evaluated at 1 week, 1 month, 3 and 6 months postoperatively and compared.

Results
In total, 58 patients in mini-transverse incision group and 74 in mid-palmar longitudinal incision group were include. The follow-up period was 6.8 ± 1.6 months. The mini-transverse incision group had a significantly smaller incision (4.3 ± 0.4 mm vs. 26.2 ± 1.6 mm), shorter surgical time (7.8 ± 2.6 min vs. 19.7 ± 2.8 min), but not for hospital stay (3.2 ± 1.9 vs. 3.6 ± 2.2 days). Both groups showed significant improvement from baseline level at any time points postoperatively (all P < 0.001). At 1 month and 3 months, the mini-transverse incision group showed a significantly better improvement of VAS, SSS and FSS score (P < 0.05). At 6 months, the differences were no longer significant (P > 0.05). In addition, the mini-transverse incision group showed a significantly reduced time to return to the work and activities, tendency to higher rate of excellence and good outcomes and fewer complications.

Conclusions
This novel technique via a mini-transverse incision and bush hook showed better clinical effectiveness and safety, and can be considered as an alternative for wrist tunnel release after the results are validated by higher-level evidence studies.
Evidence level: III.
Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency
Authors: Kühnen Peter , Wabitsch Martin , von Schnurbein Julia , Chirila Costel , Mallya Usha G. , Callahan Patrick , Gnanasakthy Ari , Poitou Christine , Krabusch Philipp M. , Stewart Murray , Clément Karine 
Published: February 2022

Abstract
Introduction
Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL).

Methods
Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9).

Results
In total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6–12 years old; n = 2) and adolescents (13–17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52.

Conclusions
Patients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.
Neuroradiological differentiation of white matter lesions in patients with multiple sclerosis and Fabry disease
Authors: Rath Jakob , Foesleitner Olivia , Haider Lukas , Bickel Hubert , Leutmezer Fritz , Polanec Stephan , Arnoldner Michael A. , Sunder-Plassmann Gere , Prayer Daniela , Berger Thomas , Rommer Paulus , Kasprian Gregor 
Published: February 2022

Abstract
Objective
White matter lesions (WML) in multiple sclerosis (MS) differ from vascular WML caused by Fabry disease (FD). However, in atypical cases the discrimination can be difficult and may vary between individual raters. The aim of this study was to evaluate interrater reliability of WML differentiation between MS and FD patients.

Materials and methods
Brain MRI scans of 21 patients with genetically confirmed FD were compared to 21 matched patients with MS. Pseudonymized axial FLAIR sequences were assessed by 6 blinded raters and attributed to either the MS or the FD group to investigate interrater reliability. Additionally, localization of WML was compared between the two groups.

Results
The median age of patients was 46 years (IQR 35–58). Interrater reliability was moderate with a Fleiss' Kappa of 0.45 (95%CI 0.3–0.59). Overall, 85% of all ratings in the MS group and 75% in the FD group were correct. However, only 38% of patients with MS and 33% of patients with FD were correctly identified by all 6 raters. WML involving the corpus callosum (p < 0.001) as well as juxtacortical (p < 0.001) and infratentorial lesions (p = 0.03) were more frequently observed in MS patients.

Conclusion
Interrater reliability regarding visual differentiation of WML in MS from vascular WML in FD on standard axial FLAIR images alone is only moderate, despite the distinctive features of lesions in each group.
Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy
Authors: Zhao Rongyan , Fu Jiahui , Zhu Lingjuan , Chen Yi , Liu Bo 
Published: February 2022

AbstractNon-coding RNAs (ncRNAs) have been defined as a class of RNA molecules transcribed from the genome but not encoding proteins, such as microRNAs, long non-coding RNAs, Circular RNAs, and Piwi-interacting RNAs. Accumulating evidence has recently been revealing that ncRNAs become potential druggable targets for regulation of several small-molecule compounds, based on their complex spatial structures and biological functions in cancer therapy. Thus, in this review, we focus on summarizing some new emerging designing strategies, such as high-throughput screening approach, small-molecule microarray approach, structure-based designing approach, phenotypic screening approach, fragment-based designing approach, and pharmacological validation approach. Based on the above-mentioned approaches, a series of representative small-molecule compounds, including Bisphenol-A, Mitoxantrone and Enoxacin have been demonstrated to modulate or selectively target ncRNAs in different types of human cancers. Collectively, these inspiring findings would provide a clue on developing more novel avenues for pharmacological modulations of ncRNAs with small-molecule drugs for future cancer therapeutics.
“It was an important part of my treatment”: a qualitative study of Norwegian breast Cancer patients’ experiences with mainstreamed genetic testing
Authors: Strømsvik Nina , Olsson Pernilla , Gravdehaug Berit , Lurås Hilde , Schlichting Ellen , Jørgensen Kjersti , Wangensteen Teresia , Vamre Tone , Heramb Cecilie , Mæhle Lovise , Grindedal Eli Marie 
Published: February 2022

Abstract
Background
In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed “mainstreamed genetic testing”. The aim of this study was to learn about patients’ experience of this healthcare service.

Methods
Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data.

Results
The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing.

Conclusions
Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment.