bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study
Authors: Kawai Akira , Narahara Hiroyuki , Takahashi Shunji , Nakamura Tomoki , Kobayashi Hiroshi , Megumi Yasunori , Matsuoka Toshiyuki , Kobayashi Eisuke 
Published: May 2022

Abstract
Background
Soft tissue sarcomas (STSs) are a heterogeneous group of cancers with over 100 described subtypes. While these cancers are infrequent, the prognosis is quite poor, particularly for those with stage IV metastatic disease. Patients for whom curative resection is difficult or those with recurrent metastatic disease are treated with chemotherapy, although the options are very limited. Eribulin is an approved treatment of all STS subtypes in Japan. Efficacy and safety data for the treatment of rare STS subtypes other than liposarcoma and leiomyosarcoma (L-type sarcomas) are limited. This nationwide, multicenter, prospective, post-marketing observational study was conducted to assess the real-world effectiveness and safety of eribulin in Japanese patients with STS.

Methods
Patients with all types of STS and who consented to eribulin treatment were eligible to participate. The observation period was 1 year, starting at treatment initiation, and clinical outcomes were followed up for 2 years after initiating treatment. The primary endpoint was overall survival (OS). Additional outcomes included time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. ORR and DCR were evaluated using imaging findings. Effectiveness results were analyzed both for all patients and by STS subtype.

Results
A total of 256 patients were enrolled; 252 and 254 were included in the effectiveness and safety analysis set, respectively. Most patients (83.1%) received an initial eribulin dose of 1.4 mg/m2 (standard dose). Respective median OS (95% confidence interval [CI]) was 10.8 (8.5–13.1), 13.8 (10.1–22.3) and 6.5 (5.7–11.1) months for all, L-type, and non-L-type subtypes. The respective median TTF (95% CI) was 2.5 (2.1–2.8), 2.8 (2.3–3.7), and 2.2 (1.6–2.6) months. The ORR and DCR were 8.1 and 42.6%, respectively. Adverse drug reactions (ADRs) and serious ADRs were reported for 83.5 and 18.9% of patients, respectively. The main ADRs were associated with myelosuppression. No significant difference was observed in the incidence of ADRs for patients ≥65 versus <65 years old.

Conclusions
Eribulin demonstrated effectiveness and a manageable safety profile for patients with STS, although the effectiveness of eribulin was not demonstrated for some non-L-type subtypes.

Trial registration
NCT03058406 (ClinicalTrials.gov).
Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer
Authors: Nguyen Van Long Flora , Lardy-Cleaud Audrey , Carène Dimitri , Rossoni Caroline , Catez Frédéric , Rollet Paul , Pion Nathalie , Monchiet Déborah , Dolbeau Agathe , Martin Marjorie , Simioni Valentin , Bray Susan , Le Beherec Doris , Mosele Fernanda , Bouakka Ibrahim , Colombe-Vermorel Amélie , Odeyer Laetitia , Diot Alexandra , Jordan Lee B. , Thompson Alastair M. , Jamen Françoise , Dubois Thierry , Chabaud Sylvie , Michiels Stefan , Treilleux Isabelle , Bourdon Jean-Christophe , Pérol David , Puisieux Alain , André Fabrice , Diaz Jean-Jacques , Marcel Virginie 
Published: May 2022

Abstract
Background
A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated.

Methods
Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours.

Results
We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct.

Conclusion
Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.
Assessment of the masseter stiffness in patients during conservative therapy for masticatory muscle disorders with shear wave elastography
Authors: Olchowy Anna , Seweryn Piotr , Olchowy Cyprian , Wieckiewicz Mieszko 
Published: May 2022

Abstract
Background
The complex structure of the stomatognathic system plays a vital role in chewing, digestion, speaking, breathing, facial expression and swallowing. Its complexity is the primary reason for creating multidisciplinary teams to manage temporomandibular disorders (TMD). We aimed to assess the masseter stiffness in patients undergoing conservative therapy for masticatory muscle disorders and evaluate the efficacy of manual therapy and stabilization occlusal splint in the treatment of masticatory muscle disorders.

Methods
This uncontrolled prospective cohort study included 35 patients with masticatory muscle disorders. The study lasted for eight weeks. The patients were treated with manual therapy and stabilization occlusal splint and evaluated using shear wave elastography of the masseter muscles and patient-reported outcome measures (PROMs) to assess pain, anxiety, quality of sleep, satisfaction with life and perceived stress.

Results
After the treatment, the stiffness of both masseter muscles decreased significantly (by 4.21 kPa). The patients reported a significant reduction in pain. At baseline, the median scores ranged from 5 to 8; after treatment, they ranged from 0 to 1 (p < 0.0001). The patients also reported significant improvement in terms of all patient-reported outcome measures. The reduction in stiffness corresponded to the improvement in pain and PROMs, as shown by correlations which were insignificant for all measures.

Conclusions
Conservative therapy of masticatory muscle disorders involving manual therapy and stabilization occlusal splint is effective. It reduces the masseter stiffness as objectively shown in shear wave elastography and improves subjective PROMs scores, including numerical pain assessment and selected questionnaires. Shear wave elastography has the potential for broad application in clinical practice to monitor masticatory muscle disorders treatment effects due to its objectivity and non-invasive character. Further research is recommended on larger patient populations and longer follow-up.

Trial registration
The study was registered at clinicaltrials.gov (NCT03844854). First posted date: 19/02/2019.
A comparative study of two robotic thyroidectomy procedures: transoral vestibular versus bilateral axillary-breast approach
Authors: He Qingqing , Zhu Jian , Li Xiaolei , Wang Meng , Wang Gang , Zhou Peng , Wang Dan , Liu Changrui , Zheng Luming , Zhuang Dayong , Fan Ziyi , Yu Fang , Ma Yunhan , Cao Xianjiao , Wang Suai , Yue Tao , Hu Jinzhi 
Published: May 2022

Abstract
Objective
To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART).

Methods
A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed.

Results
There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P < 0.05). There was no significant difference in lymph node metastasis, hospital stay and postoperative pain score (under numerical rating scale, NRS) between the two groups (P > 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case).

Conclusion
Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck.
Impact of anxiety, depression and disease-related distress on long-term glycaemic variability among subjects with Type 1 diabetes mellitus
Authors: Déniz-García Alejandro , Díaz-Artiles Alba , Saavedra Pedro , Alvarado-Martel Dácil , Wägner Ana M. , Boronat Mauro 
Published: May 2022

AbstractBackgroundAnxiety, depression, and disease-related distress are linked to worse overall glycaemic control, in terms of HbA1c. This study was aimed to evaluate whether traits of these emotional disorders are associated with long-term glycaemic variability in subjects with Type 1 diabetes.MethodsLongitudinal retrospective study. Six-year HbA1c data (2014–2019) from 411 subjects with Type 1 diabetes who had participated in a previous study to design a diabetes-specific quality of life questionnaire in the year 2014 were included. Scores for Spanish versions of the Hospital Anxiety and Depression Scale (HADS) and Problem Areas in Diabetes (PAID) scale were obtained at baseline, along with sociodemographic and clinical data. Long-term glycaemic variability was measured as the coefficient of variation of HbA1c (HbA1c-CV). The association between HADS and PAID scores and HbA1c-CV was analysed with Spearman correlations and multiple regression models, both linear and additive, including other covariates (age, sex, diabetes duration time, type of treatment, baseline HbA1c, use of anxiolytic or antidepressant drugs, education level and employment status).ResultsScores of depression, anxiety and distress were positively and significantly correlated to HbA1c-CV in univariate analyses. Multiple regression study demonstrated an independent association only for diabetes distress score (p < 0.001). Age, diabetes duration time, baseline HbA1c, education level and employment status were also significantly associated with HbA1c-CV. However, when subjects were analyzed separately in two age groups, distress scores were associated with HbA1c-CV only among those aged 25 years or older, while anxiety scores, but not distress, were associated with HbA1c-CV among those younger than 25 years.ConclusionsPsychological factors, particularly disease-related distress and anxiety, are associated with long-term glycaemic variability in subjects with Type 1 diabetes.
Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality
Authors: Bae Yoon-Jong , Shin Sang-Jun , Kang Hee-Taik 
Published: May 2022

Abstract
Objective
The prevalence of diabetes mellitus (DM), cardio-cerebrovascular diseases (CCVDs) has increased during recent decades. We aimed to investigate the relationship between body mass index (BMI) and each of several outcomes (DM, CCVDs, or mortality) based on the Korean National Health Insurance Service-Health Screening cohort.

Methods
BMI was categorized as appropriate for Asian populations, into underweight (< 18.5 kg/m2), normal (18.5–< 23 kg/m2), overweight (23–< 25 kg/m2), grade 1 obesity (25–< 30 kg/m2), grade 2 obesity (30–< 35 kg/m2), and grade 3 obesity (≥35 kg/m2). In addition, BMI was further stratified into one unit. Multivariate Cox proportional hazards regression analyses were conducted to examine the association between BMI category and the primary outcomes (DM, CCVDs, or mortality).

Results
A total of 311,416 individuals were included. The median follow-up was 12.5 years. Compared to normal BMI, underweight, overweight, and grade 1–3 obese individuals had a higher risk of the primary outcomes (hazard ratio [95% confidence intervals] 1.293 [1.224–1.365], 1.101 [1.073–1.129], 1.320 [1.288–1.353], 1.789 [1.689–1.897], and 2.376 [2.019–2.857], respectively, in men and 1.084 [1.010–1.163], 1.150 [1.116–1.185], 1.385 [1.346–1.425], 1.865 [1.725–2.019], and 2.472 [2.025–3.028], respectively, in women). Setting the reference BMI to 20–< 21 kg/m2 and categorizing into one unit increment, BMI was associated with the primary outcomes in a J-shaped manner in both sexes. The risk of DM increased with higher BMI in both sexes, while all-cause mortality decreased in men with a BMI 21–< 31 kg/m2 and women with BMI 22–< 30 kg/m2.

Conclusions
BMI was associated with all-cause mortality in a J-shaped manner in both sexes, while it was associated with risk of DM in a dose-response relationship. The relationship between BMI and the primary outcomes was J-shaped.
Mentoring in palliative medicine in the time of covid-19: a systematic scoping review
Authors: Goh Sherill , Wong Ruth Si Man , Quah Elaine Li Ying , Chua Keith Zi Yuan , Lim Wei Qiang , Ng Aubrey Ding Rui , Tan Xiu Hui , Kow Cheryl Shumin , Teo Yao Hao , Lim Elijah Gin , Pisupati Anushka , Chong Eleanor Jia Xin , Kamal Nur Haidah Ahmad , Tan Lorraine Hui En , Tay Kuang Teck , Ong Yun Ting , Chiam Min , Lee Alexia Sze Inn , Chin Annelissa Mien Chew , Mason Stephen , Krishna Lalit Kumar Radha 
Published: May 2022

Abstract
Introduction
The redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program.

Methods
A Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles.

Results
Fifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA’s Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP’s structured virtual and near-peer mentoring process complement IPT’s accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program.

Conclusion
This systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out.
Can a multitiered copayment system affect people’s healthcare-seeking behavior? A case study of Wenzhou, China
Authors: Ge Lizheng , Zhang Xiangyang , Huang Yunyun , Xu Tingke , Zhao Qianru , Zhu Tingting , Pan Jingye , Chen Chun 
Published: May 2022

Abstract
Background
Facilitating the primary health care (PHC) system and maintaining people’s reasonable healthcare-seeking behavior are key to establishing a sustainable healthcare system. China has employed a multitiered copayment system/medical insurance differentiated payment policies to incentivize the public to utilize PHC services through its hierarchical medical care system; however, most people still prefer visiting tertiary care hospitals. We question whether the quality gap in healthcare services reduces the effect of the multitiered copayment system, which is considered an important factor in the lack of reform in the Chinese healthcare system. Thus, we explore the effect and influencing factors of the multitiered copayment system that drives primary healthcare-seeking behavior under the current situation with a large quality gap. We also consider the hypothetical situation of a reduced gap in the future.

Methods
This study used the hypothetical quality improvement scenario to elicit people’s hypothetical behaviors, and a multistage stratified cluster random sampling method. This preliminary study was conducted in 2016 using 1829 individuals from four regions of Wenzhou in Zhejiang Province: Ouhai, Ruian, Yongjia, and Taishun. A descriptive statistical analysis, chi-square analysis, Fisher’s exact test, and multinomial logistic regression model were performed to introduce the effect of the multitiered copayment system, and to explore the factors affecting the selection of PHC institutions at pre- and post-change phases.

Result
The results show that compared with the large quality gap phase, the number of respondents who believed the multitiered copayment system had an effect on their selection of PHC institutions after the equalization of healthcare services quality increased threefold (from 14.0% to 50.8%). Moreover, the main determinants in people’s selection of PHC institutions changed from age and needs variables (self-rated health status) to age, needs variables (self-rated health status) and enabling variables (distance to a medical care facility).

Conclusion
The results indicate limited initial effects of the multitiered copayment system. However, they become more pronounced after the equalization of healthcare services quality. This study confirms that changes in the quality gap in healthcare services influence the effect of the multitiered copayment system. Hence, reducing this gap can help achieve the intended outcome of the tiered healthcare insurance schedule.
Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study
Authors: Xin Junyi , Jiang Xia , Ben Shuai , Yuan Qianyu , Su Li , Zhang Zhengdong , Christiani David C. , Du Mulong , Wang Meilin 
Published: May 2022

Abstract
Background
The association between vitamin E and cancer risk has been widely investigated by observational studies, but the findings remain inconclusive. Here, we aimed to evaluate the causal effect of circulating vitamin E on the risk of ten common cancers, including bladder, breast, colorectal, esophagus, lung, oral and pharynx, ovarian, pancreatic, prostate, and kidney cancer.

Methods
A Mendelian randomization (MR) analytic framework was applied to data from a cancer-specific genome-wide association study (GWAS) comprising a total of 297,699 cancer cases and 304,736 controls of European ancestry. Three genetic instrumental variables associated with circulating vitamin E were selected. Summary statistic-based methods of inverse variance weighting (IVW) and likelihood-based approach, as well as the individual genotyping-based method of genetic risk score (GRS) were used. Multivariable IVW analysis was further performed to control for potential confounding effects. Furthermore, the UK Biobank cohort was used as external validation, supporting 355,543 European participants (incident cases ranged from 437 for ovarian cancer to 4882 for prostate cancer) for GRS-based estimation of circulating vitamin E, accompanied by a one-sample MR analysis of dietary vitamin E intake underlying the time-to-event analytic framework.

Results
Specific to cancer GWAS, we found that circulating vitamin E was significantly associated with increased bladder cancer risk (odds ratios [OR]IVW = 6.23, PIVW = 3.05×10-3) but decreased breast cancer risk (ORIVW = 0.68, PIVW = 8.19×10-3); however, the significance of breast cancer was dampened (Pmultivariable IVW > 0.05) in the subsequent multivariable MR analysis. In the validation stage of the UK Biobank cohort, we did not replicate convincing causal effects of genetically predicted circulating vitamin E concentrations and dietary vitamin E intake on the risk of ten cancers.

Conclusions
This large-scale population study upon data from cancer-specific GWAS and a longitudinal biobank cohort indicates plausible non-causal associations between circulating vitamin E and ten common cancers in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.