bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of response shift in health-related quality of life studies: a systematic review
Authors: Ortega-Gómez Estelina , Vicente-Galindo Purificación , Martín-Rodero Helena , Galindo-Villardón Purificación
Published: February 2022

Background

Response Shift (RS) refers to the idea that an individual may undergo changes in its health-related quality of life (HRQOL). If internal standard, values, or reconceptualization of HRQOL change over time, then answer to the same items by the same individuals may not be comparable over time. Traditional measures to evaluate RS is prone to bias and strong methodologies to study the existence of this phenomenon is required. The objective is to systematically identify, analyze, and synthesize the existing and recent evidence of statistical methods used for RS detection in HRQOL studies.

Methods

The analysis of selected studies between January 2010 and July 2020 was performed through a systematic review in MEDLINE/PubMed, Scopus, Web of Science, PsycINFO and Google Scholar databases. The search strategy used the terms “Health-Related Quality of Life” and “Response Shift” using the filters “Humans”, “Journal Article”, “English” and “2010/01/01–2020/07/31”. The search was made in August 2020.

Results

After considering the inclusion and exclusion criteria, from the total selected articles (675), 107 (15.9%) of the publications were included in the analysis. From these, 79 (71.0%) detected the existence of RS and 86 (80.4%) only used one detection method. The most used methods were Then Test (n = 41) and Oort’s Structural Equation Models (SEM) (n = 35). Other method used were Multiple Lineal Regression (n = 7), Mixed-Effect Regression (n = 6), Latent Trajectory Analysis (n = 6), Item Response Theory (n = 6), Logistics Regression (n = 5), Regression and Classification Trees (n = 4) and Relative Importance Method (n = 4). Most of these detected recalibration, including Then Test (n = 27), followed by Oort’s SEM that detected the higher combination of RS types: recalibration (n = 24), reprioritization (n = 13) and reconceptualization (n = 7).

Conclusions

There is a continuous interest of studying RS detection. Oort’s SEM becomes the most versatile method in its capability for detecting RS in all different types. Despite results from previous systematic reviews, same methods have been used during the last years. We observed the need to explore other alternative methods allowing same detection capacity with robust and highly precise methodology. The investigation on RS detection and types requires more study, therefore new opportunity grows to continue attending this phenomenon through a multidisciplinary perspective.
The Peterborough Exemplar: a protocol to evaluate the impact and implementation of a new patient-centred, system-wide community mental healthcare model in England
Authors: Efstathopoulou Lida , Jagger Grace , Mackenzie Jules , Faulkner Kathryn , Barker-Barrett Trish , Cameron Rory , Wagner Adam P. , Perez Jesus
Published: February 2022

Background

Community mental healthcare has significantly grown since de-institutionalization. Despite progress, service fragmentation and gaps in service provision remain key barriers to effective community care in England. Recent mental healthcare policies highlighted the need to transform service provision by developing patient-centred, joined-up community mental healthcare. In response to policy guidance, a system-wide community mental healthcare model was developed in Peterborough (England). The “Peterborough Exemplar” is based on two main pillars: (1) the creation of knowledge exchange pathways to strengthen interorganizational relationships, and (2) the development of new, accessible community services addressing existing service gaps. This paper presents the protocol developed to evaluate the Peterborough Exemplar.

Methods

A quasi-experimental design with an intervention group and a nonequivalent comparator group has been developed to compare service provision provided in Peterborough pre- and post-intervention with services provided in Fenland, a neighbouring area where service users access usual care. Two evaluation methods will be employed to compare service provision between the two groups: (1) outcome measures completed by service users and carers will be analysed to assess quality of life and service satisfaction, and (2) service activity data will be analysed to assess service usage. In addition, qualitative interviews will be conducted with staff members of participating organizations to explore the implementation of the Exemplar in Peterborough and evaluate knowledge exchange processes among local service providers. A matched control approach will be used to compare outcome measures between the two areas. Descriptive and inferential statistics, including chi-square tests, will be used to analyse service activity data and examine differences between the two areas. A thematic analysis will be adopted to analyse qualitative data.

Discussion

Outcomes of the evaluation will contribute to understanding the contribution of the Peterborough Exemplar on mental health service provision locally. Evaluation findings and intermediate reporting will be shared with organizations involved in the implementation of the Peterborough Exemplar and with local decision-makers to inform the Exemplar delivery. As the Peterborough Exemplar is an Early Implementer (EI) site funded by NHS England, findings will be shared with policy-makers to inform national policy on community mental healthcare and integrated care.
BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma
Authors: Chen Xing , Lin Shan , Lin Ying , Wu Songsong , Zhuo Minling , Zhang Ailong , Zheng Junjie , You Zhenhui
Published: February 2022

Background

Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated.

Methods

In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAFV600E (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAFV600E PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAFV600E PTC cells.

Results

The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAFV600E PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAFV600E PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAFV600E PTC cells.

Conclusion

All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAFV600E mutation.
Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer
Authors: Yin Yue , Jiang Ruilan , Shen Mingwang , Li Zhaofang , Yan Ni , Feng Junqiao , Jiang Hong , Lv Jiaxin , Shi Lijuan , Wang Lina , Liu Xi , Zhang Kaiyun , Chen Di
Published: February 2022

Background

Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required.

Methods

We used a simple suboptimal inoculation melanoma mouse model to obtain ‘pre-diagnostic samples’ of mice with macroscopic melanomas. High-throughput sequencing and bioinformatic analysis were employed to identify differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of melanoma cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. Moreover, 36 genes selected from the eDEGs via bioinformatics analysis were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was utilized to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice.

Results

These RNAs identified from eDEGs of mice injected with a suboptimal number of cancer cells were strongly enriched in pathways related to immune response and regulation. The prediction models generated by 36 gene qPCR verification data showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature includingCd19,Cdkn1a,S100a9,Tap1, andTnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature includingCcr7,Cd4,Kmt2d, andLy6e).

Conclusions

Our proof-of-concept study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer.
Membrane progesterone receptor α (mPRα) enhances hypoxia-induced vascular endothelial growth factor secretion and angiogenesis in lung adenocarcinoma through STAT3 signaling
Authors: Xia Zhi , Xiao Jian , Dai Ziyu , Chen Qiong
Published: February 2022

Lung cancer remains a huge challenge to public health because of its high incidence and mortality, and lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Hypoxia-induced vascular endothelial growth factor (VEGF) release and angiogenesis have been regarded as critical events in LUAD carcinogenesis. In the present study, membrane progesterone receptor α (mPRα) is deregulated within LUAD tissue samples; increased mPRα contributes to a higher microvessel density (MVD) in LUAD tissues. mPRα knockdown in A549 and PC-9 cells significantly inhibited STAT3 phosphorylation, as well as HIF1α and VEGF protein levels, decreasing cancer cell migration and invasion. The in vivo xenograft model further confirmed that mPRα enhanced the aggressiveness of LUAD cells. Furthermore, mPRα knockdown significantly inhibited hypoxia-induced upregulation in HIF1α and VEGF levels, as well as LUAD cell migration and invasion. Under the hypoxic condition, conditioned medium (CM) derived from mPRα knockdown A549 cells, namely si-mPRα-CM, significantly inhibited HUVEC migration and tube formation and decreased VEGF level in the culture medium. In contrast, CM derived from mPRα-overexpressing A549 cells, namely mPRα-CM, further enhanced HUVEC migration and tube formation and increased VEGF level under hypoxia, which was partially reversed by STAT3 inhibitor Stattic. In conclusion, in LUAD cells, highly expressed mPRα enhances the activation of cAMP/JAK/STAT3 signaling and increases HIF1α-induced VEGF secretion into the tumor microenvironment, promoting HUVEC migration and tube formation under hypoxia.
CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle
Authors: Huang Yu-gang , Li Dan , Wang Li , Su Xiao-min , Tang Xian-bin
Published: February 2022

Background

Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor and is prone to local invasion and metastasis. And, overexpressed Centromere Protein F (CENPF) is closely related to the oncogenesis of various neoplasms, including ACC. However, the prognosis and exact biological function of CENPF in ACC remains largely unclear.

Methods

In the present essay, the expression patterns and prognostic value of CENPF in ACC were investigated in clinical specimens and public cancer databases, including GEO and TCGA. The potential signaling mechanism of CENPF in ACC was studied based on gene-set enrichment analysis (GSEA). Furthermore, a small RNA interference experiment was conducted to probe the underlying biological function of CENPF in the human ACC cell line, SW13 cells. Lastly, two available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored.

Results

The expression of CENPF in human ACC samples, GEO, and TCGA databases depicted that CENPF was overtly hyper-expressed in ACC patients and positively correlated with tumor stage. The aberrant expression of CENPF was significantly correlated with unfavorable overall survival (OS) in ACC patients. Then, the GSEA analysis declared that CENPF was mainly involved in the G2/M-phase mediated cell cycle and p53 signaling pathway. Further, the in vitro experiment demonstrated that the interaction between CENPF and CDK1 augmented the G2/M-phase transition of mitosis, cell proliferation and might induce p53 mediated anti-tumor effect in human ACC cell line, SW13 cells. Lastly, immune infiltration analysis highlighted that ACC patients with high CENPF expression harbored significantly different immune cell populations, and high TMB/MSI score. The gene-drug interaction network stated that CENPF inhibitors, such as Cisplatin, Sunitinib, and Etoposide, might serve as potential drugs for the therapy of ACC.

Conclusion

The result points out that CENPF is significantly overexpressed in ACC patients. The overexpressed CENPF predicts a poor prognosis of ACC and might augment the progress of ACC. Thus, CENPF and related genes might serve as a novel prognostic biomarker or latent therapeutic target for ACC patients.
Ontogeny and ecological significance of metabolic rates in sea turtle hatchlings
Authors: Gatto Christopher R. , Jones T. Todd , Imlach Brittany , Reina Richard D.
Published: February 2022

Background

Sea turtle hatchlings must avoid numerous predators during dispersal from their nesting beaches to foraging grounds. Hatchlings minimise time spent in predator-dense neritic waters by swimming almost continuously for approximately the first 24 h post-emergence, termed the ‘frenzy’. Post-frenzy, hatchling activity gradually declines as they swim in less predator-dense pelagic waters. It is well documented that hatchlings exhibit elevated metabolic rates during the frenzy to power their almost continuous swimming, but studies on post-frenzy MRs are sparse.

Results

We measured the frenzy and post-frenzy oxygen consumption of hatchlings of five species of sea turtle at different activity levels and ages to compare the ontogeny of mass-specific hatchling metabolic rates. Maximal metabolic rates were always higher than resting metabolic rates, but metabolic rates during routine swimming resembled resting metabolic rates in leatherback turtle hatchlings during the frenzy and post-frenzy, and in loggerhead hatchlings during the post-frenzy. Crawling metabolic rates did not differ among species, but green turtles had the highest metabolic rates during frenzy and post-frenzy swimming.

Conclusions

Differences in metabolic rate reflect the varying dispersal stratagems of each species and have important implications for dispersal ability, yolk consumption and survival. Our results provide the foundations for links between the physiology and ecology of dispersal of sea turtles.
Early shape divergence of developmental trajectories in the jaw of galeomorph sharks
Authors: López-Romero Faviel A. , Berio Fidji , Abed-Navandi Daniel , Kriwet Jürgen
Published: February 2022

Background

The onset of morphological differences between related groups can be tracked at early stages during embryological development. This is expressed in functional traits that start with minor variations, but eventually diverge to defined specific morphologies. Several processes during this period, like proliferation, remodelling, and apoptosis for instance, can account for the variability observed between related groups. Morphological divergence through development is often associated with the hourglass model, in which early stages display higher variability and reach a conserved point with reduced variability from which divergence occurs again to the final phenotype.

Results

Here we explored the patterns of developmental shape changes in the lower jaw of two shark species, the bamboo shark (Chiloscyllium punctatum) and the catshark (Scyliorhinus canicula). These two species present marked differences in their foraging behaviour, which is reflected in their adult jaw morphology. By tracing the developmental sequence of the cartilage condensation, we identified the onset of cartilage for both species at around stage 31. Other structures that developed later without a noticeable anlage were the labial cartilages, which appear at around stage 33. We observed that the lower jaw displays striking differences in shape from the earliest moments, without any overlap in shape through the compared stages.

Conclusions

The differences observed are also reflected in the functional variation in feeding mechanism between both species. Likewise, the trajectory analysis shows that the main differences are in the magnitude of the shape change through time. Both species follow a unique trajectory, which is explained by the timing between stages.
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

Background

Menopause 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.

Methods

We 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.

Results

Overall, 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.

Conclusions

In 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

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

Background

Age 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.

Methods

We 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.

Results

Licit 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.

Conclusions

Normalization 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

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

Background

Artificial 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.

Methods

For 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.

Results

The 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.

Conclusions

Two 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

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

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

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

Non-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

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.
PROPENSIX: pressure garment therapy using compressive dynamic Lycra® sleeve to improve bi-manual performance in unilateral cerebral palsy: a multicenter randomized controlled trial protocol
Authors: Gerard A. , Toussaint-Thorin M. , Mohammad Y. , Letellier G. , Fritot S. , Masson S. , Duhamel A. , Donskoff C. , Zagame Y. , Beghin L. , Gottrand L.
Published: February 2022

Background

Upper limb impairment affects activity and participation in children with unilateral cerebral palsy (UCP). Pressure garment therapy (PGT) using compressive dynamic Lycra® garments is an innovative intervention proposed for the management of cerebral palsy consequences. The PROPENSIX study aims to evaluate the efficacy of a therapy using a Lycra® sleeve as compared to a placebo sleeve to improve bi-manual performance measured by the Assisting Hand Assessment (AHA) in children with unilateral cerebral palsy.

Methods

The PROPENSIX trial is a multicenter, prospective, placebo-controlled, double-blinded, randomized study. One hundred children with UCP, aged from 5 to 10, are randomly assigned as soon as they are recruited in a 1:1 ratio to perform usual daily activities, especially activities involving bimanual performances, with Lycra® sleeve or placebo sleeve during 6 months. The primary endpoint is the change in bimanual performance from inclusion to 6 months, evaluated by AHA. The secondary endpoints evaluate changes from inclusion to 6 months in other dimensions of the International Classification of Functioning (ICF), upper limb movement capacity assessed by Quality of Upper Extremity Skill Test (QUEST), and health-related quality of life evaluated by Pediatric Quality of Life Inventory 3.0 Cerebral Palsy Module (PedsQLTM 3.0 CP Module) and in body structures and functions domain assessed by neuro-orthopedic examination and somatosensory evoked potentials (SEP).

Discussion

The PROPENSIX study is the largest randomized controlled trial (RCT) aiming to evaluate the efficacy of a PGT using compressive dynamic Lycra® sleeve in UCP. Enhancement of children’s bimanual performance at the end of the 6 months wear of the Lycra® sleeve should improve evidence regarding this type of treatment and expand discussion about their recommendation in clinical practice. Data from secondary outcomes assessments should bring interesting arguments to discuss the Lycra® sleeve action on mobility, tonus, and sensory impairments in children with unilateral cerebral palsy.

Trial registration

ClinicalTrials.govNCT02086214. Retrospectively registered on March 13, 2014

Trial status

Study start data: December 2012. Recruitment status: completed. Primary completion date: April 2021. Estimated study completion date: December 2022. Protocol version 10 (date: February 2018).
Randomized phase III trial of intravenous and intraperitoneal paclitaxel with S-1 versus gemcitabine plus nab-paclitaxel for pancreatic ductal adenocarcinoma with peritoneal metastasis (SP study)
Authors: Yamamoto Tomohisa , Fujii Tsutomu , Hirano Satoshi , Motoi Fuyuhiko , Honda Goro , Uemura Kenichiro , Kitayama Joji , Unno Michiaki , Kodera Yasuhiro , Yamaue Hiroki , Shimokawa Toshio , Hashimoto Daisuke , Yamaki So , Yoshitomi Hideyuki , Miura Fumihiko , Ueno Hideki , Sekimoto Mitsugu , Satoi Sohei ,   on behalf of the Study Group of Pancreatic Ductal Adenocarcinoma with Peritoneal Metastasis
Published: February 2022

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 (https://jrct.niph.go.jp/).
Declining carbohydrate solubilization with increasing solids loading during fermentation of cellulosic feedstocks by Clostridium thermocellum: documentation and diagnostic tests
Authors: Kubis Matthew R. , Holwerda Evert K. , Lynd Lee R.
Published: February 2022

Background

For economically viable 2nd generation biofuels, processing of high solid lignocellulosic substrate concentrations is a necessity. The cellulolytic thermophilic anaerobe Clostridium thermocellum is one of the most effective biocatalysts for solubilization of carbohydrate harbored in lignocellulose. This study aims to document the solubilization performance of Clostridium thermocellum at increasing solids concentrations for two lignocellulosic feedstocks, corn stover and switchgrass, and explore potential effectors of solubilization performance.

Results

Monocultures of Clostridium thermocellum demonstrated high levels of carbohydrate solubilization for both unpretreated corn stover and switchgrass. However, fractional carbohydrate solubilization decreases with increasing solid loadings. Fermentation of model insoluble substrate (cellulose) in the presence of high solids lignocellulosic spent broth is temporarily affected but not model soluble substrate (cellobiose) fermentations. Mid-fermentation addition of cells (C. thermocellum) or model substrates did not significantly enhance overall corn stover solubilization loaded at 80 g/L, however cultures utilized the model substrates in the presence of high concentrations of corn stover. An increase in corn stover solubilization was observed when water was added, effectively diluting the solids concentration mid-fermentation. Introduction of a hemicellulose-utilizing coculture partner, Thermoanaerobacterium thermosaccharolyticum, increased the fractional carbohydrate solubilization at both high and low solid loadings. Residual solubilized carbohydrates diminished significantly in the presence of T. thermosaccharolyticum compared to monocultures of C. thermocellum, yet a small fraction of solubilized oligosaccharides of both C5 and C6 sugars remained unutilized.

Conclusion

Diminishing fractional carbohydrate solubilization with increasing substrate loading was observed for C. thermocellum-mediated solubilization and fermentation of unpretreated lignocellulose feedstocks. Results of experiments involving spent broth addition do not support a major role for inhibitors present in the liquid phase. Mid-fermentation addition experiments confirm that C. thermocellum and its enzymes remain capable of converting model substrates during the middle of high solids lignocellulose fermentation. An increase in fractional carbohydrate solubilization was made possible by (1) mid-fermentation solid loading dilutions and (2) coculturing C. thermocellum with T. thermosaccharolyticum, which ferments solubilized hemicellulose. Incomplete utilization of solubilized carbohydrates suggests that a small fraction of the carbohydrates is unaffected by the extracellular carbohydrate-active enzymes present in the culture.