bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer
Authors: Zhang Xiaomeng , Ma Ningyi , Yao Weiqiang , Li Shuo , Ren Zhigang 
Published: December 2019

Abstract
Background
The DNA damage and repair pathway is considered a promising target for developing strategies against cancer. RAD51, also known as RECA, is a recombinase that performs the critical step in homologous recombination. RAD51 has recently received considerable attention due to its function in tumor progression and its decisive role in tumor resistance to chemotherapy. However, its role in pancreatic cancer has seldom been investigated. In this report, we provide evidence that RAD51, regulated by KRAS, promotes pancreatic cancer cell proliferation. Furthermore, RAD51 regulated aerobic glycolysis by targeting hypoxia inducible factor 1α (HIF1α).

Methods
TCGA (The Cancer Genome Atlas) dataset analysis was used to examine the impact of RAD51 expression on overall survival of pancreatic cancer patients. Lentivirus-mediated transduction was used to silence RAD51 and KRAS expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown effect. Analysis of the glycolysis process in pancreatic cancer cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay.

Results
Pancreatic cancer patients with higher levels of RAD51 exhibited worse survival. In pancreatic cancer cells, RAD51 positively regulated cell proliferation, decreased intracellular reactive oxygen species (ROS) production and increased the HIF1α protein level. KRAS/MEK/ERK activation increased RAD51 expression. In addition, RAD51 was a positive regulator of aerobic glycolysis.

Conclusion
The present study reveals novel roles for RAD51 in pancreatic cancer that are associated with overall survival prediction, possibly through a mechanism involving regulation of aerobic glycolysis. These findings may provide new predictive and treatment targets for pancreatic cancer.
Deletion of low-density lipoprotein-related receptor 5 inhibits liver Cancer cell proliferation via destabilizing Nucleoporin 37
Authors: Chen Jinxiao , Wo Da , Ma En , Yan Hongwei , Peng Jun , Zhu Weidong , Fang Yong , Ren Dan-ni 
Published: December 2019

Abstract
Background
LRP5/6 are co-receptors in Wnt/β-catenin pathway. Recently, we discovered multiple β-catenin independent functions of LRP5/6 in tumor cells and in the diseased heart. Nucleoporin 37 (NUP37) is an important component of the nuclear pore complex (NPC), whose elevated expression is associated with worsened prognosis in liver cancer. Previous studies have shown that NUP37 interacted with YAP and activated YAP/TEAD signaling in liver cancer. Our preliminary findings showed a nuclear location of LRP5. We thus tested the hypothesis that LRP5 may act as a genuine regulator of YAP/TEAD signaling via modulating NUP37 in a β-catenin-independent way.

Methods
We performed siRNA knockdown of LRP5, LRP6, or β-catenin in liver cancer HepG2 cells to determine the effect on tumor cell proliferation. Protein expressions and interaction between LRP5 and NUP37 were determined using immunoprecipitation and western blot analyses.

Results
HepG2 cell proliferation was markedly inhibited by knockdown of LRP5 but not LRP6 or β-catenin, suggesting that LRP5 has a specific, β-catenin-independent role in inhibiting HepG2 cell proliferation. Knockdown of NUP37 by siRNA inhibited the proliferation of HepG2 cells, whereas overexpression of NUP37 reversed the decrease in cell proliferation induced by LRP5 knockdown. Immunoprecipitation assays confirmed that LRP5 bound to NUP37. Furthermore, LRP5 overexpression restored NUP37 knockdown-induced downregulation of YAP/TEAD pathway.

Conclusions
LRP5 deletion attenuates cell proliferation via destabilization of NUP37, in a β-catenin-independent manner. LRP5 therefore acts as a genuine regulator of YAP/TEAD signaling via maintaining the integrity of the NPC, and implicates a therapeutic strategy in targeting LRP5 for inhibiting liver cancer cell proliferation.
Oncologic and visual outcomes after postoperative proton therapy of localized conjunctival melanomas
Authors: Thariat Juliette , Salleron Julia , Maschi Celia , Fevrier Edouard , Lassalle Sandra , Gastaud Lauris , Baillif Stephanie , Claren Audrey , Baumard Florent , Herault Joel , Caujolle Jean Pierre 
Published: December 2019

Abstract
Introduction
conjunctival melanomas have high local relapse rates. Oncologic and visual outcomes can be improved with proton therapy and no-touch surgery.

Material and methods
a monocentric retrospective study of consecutive patients treated with surgery and proton therapy for conjunctival melanoma was conducted. Proton therapy was performed to a total dose of 45 Grays physical dose delivered in eight fractions over two weeks.

Results
Ninety-two patients were included. The mean age was 63-year-old. 65.2% of patients had primary acquired melanosis. The mean tumor thickness and diameter was 2.5 mm and 7.0 mm respectively. The clinical stage was T1 in 71.6% of cases, with a quadrangular involvement of more than 90° in 69% of cases. Conjunctival melanomas were of epithelioid cell-type in 40% of cases. Mean follow-up was 4.7 years. Five-year local failure rate was 33.2%. Of 25 local recurrences, 14 were marginal/out-of-field, 4 in-field, others were undetermined. First surgery at expert center resulted in 24.3% of local failure at 5 years versus 38.7% if performed elsewhere (p = 0.41). Salvage exenteration was performed in 13 patients. Tumor stage and quadrangular involvement were significant factors for local failure. Five-year progression-free survival and cause-specific death rates were 61.5 and 3.6%. Stage and epithelioid type were associated with poorer progression-free survival. Trophic toxicity occurred in 22.9% of patients and was treated locally, with grafts in 7 patients. Glaucoma and cataract occurred in 13 and 22 patients respectively. Prognostic factors for visual deterioration were age, tumor extent (multifocality, quadrangular involvement > 180°) and cryotherapy.

Conclusions
5-year local failure rate after postoperative proton therapy for conjunctival melanoma was of 33.2%. Radiation-induced complications were overall manageable.
Comparison of the dose on specific 3DCT images and the accumulated dose for cardiac structures in esophageal tumors radiotherapy: whether specific 3DCT images can be used for dose assessment?
Authors: Tong Ying , Gong Guanzhong , Su Ming , Yin Yong 
Published: December 2019

Abstract
Background
Cardiac activity could impact the accuracy of dose assessment for the heart, pericardium and left ventricular myocardium (LVM). The purpose of this study was to explore whether it is possible to perform dose assessment by contouring the cardiac structures on specific three-dimensional computed tomography (3DCT) images to reduce the impact of cardiac activity.

Methods
Electrocardiograph-gated 4DCT (ECG-gated 4DCT) images of 22 patients in breath-hold were collected. MIM Maestro 6.8.2 (MIM) was used to reconstruct specific 3DCT images to obtain the Maximal intensity projection (MIP) image, Average intensity projection (AIP) image and Minimum intensity projection (Min-IP) image. The heart, pericardium and LVM were contoured in 20 phases of 4DCT images (0, 5%... 95%) and the MIP, AIP and Min-IP images. Then, a radiotherapy plan was designed at the 0% phase of the 4DCT images, and the dose was transplanted to all phases of 4DCT to acquire the dose on all phases, the accumulated dose of all phases was calculated using MIM. The dose on MIP, AIP and Min-IP images were also obtained by deformable registration of the dose. The mean dose (Dmean), V5, V10, V20, V30 and V40 for the heart, pericardium and LVM in MIP, AIP and Min-IP images were compared with the corresponding parameters after dose accumulation.

Results
The mean values of the difference between the Dmean in the MIP image and the Dmean after accumulation for the heart, pericardium and LVM were all less than 1.50 Gy, and the dose difference for the pericardium and LVM was not statistically significant (p > 0.05). For dose-volume parameters, there was no statistically significant difference between V5, V10, and V20 of the heart and pericardium in MIP, AIP, and Min-IP images and those after accumulation (p > 0.05). For the LVM, only in the MIP image, the differences of V5, V10, V20, V30 and V40 were not significant compared to those after dose accumulation (p > 0.05).

Conclusions
There was a smallest difference for the dosimetry parameters of cardiac structures on MIP image compared to corresponding parameters after dose accumulation. Therefore, it is recommended to use the MIP image for the delineation and dose assessment of cardiac structures in clinical practice.
Posterior percutaneous endoscopic lumbar discectomy combined with the vertical anchoring technique for lumbar disc herniation with distant upward migration
Authors: Xia Yu , Zhang Qiongyue , Gao Xiang , Wang Keran , Zhang Xun , Du Yu , Chen Liang 
Published: December 2019

Abstract
Background
Posterior percutaneous endoscopic lumbar discectomy (PELD) has become a preferred procedure for the treatment of simple lumbar disc herniation (LDH) but has rarely been reported for distant upward migration. The purpose of this research was to investigate the feasibility, safety, clinical efficacy and technical points of posterior PELD combined with the vertical anchoring technique (VAT) for the treatment of LDH with distant upward migration.

Methods
Thirteen patients with distant upward migrated LDH who underwent posterior PELD combined with the VAT from March 2016 to May 2018 were selected. Among these cases, the herniated disc was located at L3/4 in 2 patients, L4/5 in 9 patients and L5/S1 in 2 patients. The operative time, length of hospital stay and postoperative complications were recorded. The visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores and modified MacNab criteria were used to assess surgical efficacy.

Results
All 13 patients underwent successful surgery. We compared the VAS, ODI and JOA scores before and after surgery. The differences were statistically significant (P < 0.05). According to the modified MacNab criteria, 10 patients were assessed as “excellent”, 2 patients were assessed as “good” and 1 patient was assessed as “fair” at the last follow-up. The rate of satisfactory outcomes was 92.3%.

Conclusion
Posterior PELD combined with the VAT is a safe and feasible procedure for the treatment of LDH with distant upward migration and represents a new approach for this type of surgery.
Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes
Authors: Yang Yang , Hao Wang 
Published: December 2019

Abstract
Background
Isodicentric Y chromosomes [idic(Y)] are one of the most common structural abnormalities of the Y chromosome. The prenatal diagnosis of isodicentric Y chromosomes is of vital importance, and the postnatal phenotypes vary widely. Therefore, we present six patients prenatally diagnosed with isodicentric Y chromosomes and review the literature concerning the genotype-phenotype correlations.

Method
The clinical materials of six patients were obtained. Cytogenetic and molecular approaches were carried out for these six patients.

Results
Isodicentric Y chromosomes were found in all sixpatients. Among them, four patients presented with a mosaic 45,X karyotype, one patient had a 46,XY cell line, and one patient was nonmosaic. Five of these six isodicentric Y chromosomes had a breakpoint in Yq11.2, and the other had a breakpoint in Yp11.3. The molecular analysis demonstrated different duplications and deletions of the Y chromosome. Finally, three patients chose to terminate the pregnancy, two patients gave birth to normal-appearing males, and one patient was lost to follow-up.

Conclusion
The incorporation of multiple cytogenetic and molecular techniques would offer a more comprehensive understanding of this structural chromosomal abnormality for genetic counselling.
A multi-etiological model of childhood obesity: a new biobehavioral perspective for prevention?
Authors: Valerio Giuliana , Bernasconi Sergio 
Published: December 2019

AbstractCurrent prevention strategies focusing only around the energy balance model have been found insufficient to tackle the childhood obesity epidemic. Originating from the paper by Baranowski et al., recently published in Current Nutrition Report, this Commentary is aimed at discussing the complex etiology of obesity, on the ground of new biological models, which open a novel biobehavioral perspective of prevention.
Mindfulness-based cognitive therapy and cognitive behavioral therapy for chronic pain in multiple sclerosis: a randomized controlled trial protocol
Authors: Ehde Dawn M. , Alschuler Kevin N. , Day Melissa A. , Ciol Marcia A. , Kaylor Makena L. , Altman Jennifer K. , Jensen Mark P. 
Published: December 2019

AbstractBackgroundChronic pain is one of the most prevalent and disabling symptoms associated with multiple sclerosis (MS). Individuals with MS are interested in nonpharmacologic pain management approaches. Cognitive-behavioral therapy (CBT) is efficacious in improving MS-related pain outcomes. Mindfulness-based cognitive therapy (MBCT) is a promising, alternative approach. Little is known about moderators of these treatments’ outcomes, however. This article describes the study protocol for the first randomized controlled trial comparing MBCT, CBT, and usual care and examining treatment effect moderators in individuals with chronic pain and MS.MethodsWe will conduct a single-center, randomized, single blind, parallel-group trial comparing MBCT, CBT, and usual care in adults with MS and chronic pain. Both interventions will be delivered via eight group sessions using videoconferencing technology. Primary (average pain intensity) and secondary outcomes (including pain interference, depressive symptoms, fatigue, and sleep) will be assessed pre-treatment, mid-treatment, post-treatment, and at 6-month follow up. Potential treatment moderators will be assessed pre-treatment. We hypothesize that participants randomly assigned to MBCT or CBT will report significantly greater reductions in average pain intensity than participants assigned to usual care at post-treatment (primary study endpoint) and 6-month follow up. We also hypothesize that mindfulness, pain catastrophizing, and behavioral activation pre-treatment will moderate response to both active treatments, but not response to usual care.DiscussionFindings will provide important new information about the efficacy and moderators of two nonpharmacologic pain management approaches delivered using technology to overcome common barriers to treatment access. The knowledge gained may lead to better patient-treatment matching and, ultimately, better pain treatment outcomes in MS.Trial registrationClinicalTrials.gov,NCT03782246. Registered on 20 December 2018.
The effect of daily consumption of different doses of fortified Lavash bread versus plain bread on serum vitamin-D status, body composition, metabolic and inflammatory biomarkers, and gut microbiota in apparently healthy adult: study protocol of a randomized clinical trial
Authors: Tangestani Hadith , Djafarian Kurosh , Shab-Bidar Sakineh 
Published: December 2019

Abstract
Background
Due to the high prevalence of vitamin-D deficiency worldwide and its health consequences, intervention studies at the community level are warranted. The present study has been conducted to evaluate the effectiveness of vitamin-D-fortified bread on serum vitamin-D levels, inflammatory and metabolic biomarkers, and gut microbiota composition in vitamin-D-deficient individuals.

Methods/design
A double-blind, randomized controlled clinical trial is conducted on apparently healthy individuals with vitamin-D deficiency. The random allocation is done to divide participants into intervention groups including daily intake of vitamin-D-3-fortified bread (FB) with 500 IU/100 g bread (n = 30), FB with 1000 IU/100 g bread (n = 30), and 100 g plain bread (PD) (n = 30). At baseline and after 3 months of the intervention period, blood, stool, and urine samples are taken. Anthropometric measures, body composition, blood pressure, and dietary assessment are made. The gut microbiome composition is measured by the 16S rRNA approach. Data is analyzed by SPSS software version 21.

Discussion
This study may partly explain for the first time the conflicting results from recent critical and systematic reviews regarding the role of vitamin D in microbiota composition.

Trial registration
Iranian Registry of Clinical Trials (IRCT), ID: IRCT20170812035642N3. Registered on 11 March 2018; http://www.irct.ir/user/trial/28134/view.
Use of a smartphone app combined with gamification to increase the level of physical activity of adults and older adults: protocol of a sequential multiple assignment randomized trial
Authors: Morais Pereira Simões Maria do Socorro , de Barros Gonze Bárbara , Leite Proença Neli , Tonon Lauria Vinicius , Demarchi Silva Terra Vinícius , da Costa Padovani Ricardo , Zuniga Dourado Victor 
Published: December 2019

Abstract
Background
There is scientific evidence suggesting that app-based interventions targeted to increase the level of physical activity might be effective, although multicomponent interventions appear to be more effective than app-based interventions alone. Despite the motivating results, it remains unclear whether or not app-based interventions can increase the level of physical activity and cardiovascular health. Our study aims to investigate the effect of a smartphone app combined with gamification on the level of physical activity of adults and older adults. The specific aims are (1) to verify the effects of the intervention on cardiometabolic and cardiovascular health, lung function, and cardiorespiratory fitness; and (2) to verify the relationship between age group and the response rate.

Methods/design
We will conduct a sequential multiple assignment randomized trial (SMART). The adaptive intervention protocol will last 6 months. After baseline assessments, participants will be randomized into one of three groups (group 1: app + tailored messages; group 2: app + tailored messages + gamification I; control group: physical activity counseling). For 12 weeks, we will record the average number of steps per day of participants from groups 1 and 2. At 6 weeks from initiation of recording, participants will be classified into responders and non-responders according to their increase in the average number of daily steps; all those considered as non-responders will be re-randomized, with the chance to participate in a third group – group 3: app + tailored messages + gamification II. Finally, at 12 weeks, participants will continue using the app but will no longer receive direct intervention from investigators. All participants will be reassessed at 3 and 6 months from baseline. Our pilot SMART will require 42 participants (14 per arm). Following the SMART pilot, we will calculate the sample size for the trial based on the variation of the average number of steps/day, including an up to 40% loss to follow-up and a less optimistic nonresponse rate of 65%.

Discussion
To our knowledge, this will be the first trial with adaptive intervention to test the effectiveness of using a smartphone app to increase the level of physical activity of adults and older adults.

Trial registration
Brazilian Clinical Trials Registry: RBR-8xtc9c. Registered on 3 August 2018, http://www.ensaiosclinicos.gov.br; UTN number: U1111–1218-1092.
The BrainACT study: acceptance and commitment therapy for depressive and anxiety symptoms following acquired brain injury: study protocol for a randomized controlled trial
Authors: Rauwenhoff Johanne , Peeters Frenk , Bol Yvonne , Van Heugten Caroline 
Published: December 2019

Abstract
Background
Following an acquired brain injury, individuals frequently experience anxiety and/or depressive symptoms. However, current treatments for these symptoms are not very effective. A promising treatment is acceptance and commitment therapy (ACT), which is a third-wave behavioural therapy. The primary goal of this therapy is not to reduce symptoms, but to improve psychological flexibility and general well-being, which may be accompanied by a reduction in symptom severity. The aim of this study is to investigate the effectiveness of an adapted ACT intervention (BrainACT) in people with acquired brain injury who experience anxiety and/or depressive symptoms.

Methods
The study is a multicenter, randomized, controlled, two-arm parallel trial. In total, 94 patients who survive a stroke or traumatic brain injury will be randomized into an ACT or control (i.e. psycho-education and relaxation) intervention. The primary outcome measures are the Hospital Anxiety and Depression Scale and the Depression Anxiety Stress Scale. Outcomes will be assessed by trained assessors, blinded to treatment condition, pre-treatment, during treatment, post-treatment, and at 7 and 12 months.

Discussion
This study will contribute to the existing knowledge on how to treat psychological distress following acquired brain injury. If effective, BrainACT could be implemented in clinical practice and potentially help a large number of patients with acquired brain injury.

Trial registration
Dutch Trial Register, NL691, NTR 7111. Registered on 26 March 2018. https://www.trialregister.nl/trial/6916.
The OMACS-PIL study: a randomised controlled trial within the OMACS observational study
Authors: Culliford Lucy , Brierley Rachel , Clout Madeleine , Evans Rebecca , Maishman Rachel , Phillips Dawn , Tabusa Hana , Reeves Barney , Rogers Chris A. 
Published: December 2019

Abstract
Background
There has been little research to investigate whether the appearance of paper patient information leaflets (PILs) used to describe research studies to potential participants influences their decision to take part. Embedding a study within a trial (SWAT) is an efficient way of answering this type of methodological question. We included a randomised SWAT within a large cohort study, Outcome Monitoring after Cardiac Surgery (OMACS), to address this question.

Methods
Potential participants for the OMACS study were randomised to receive one of three PILs, which were identical in content but with varying formatting and use of colour: PIL A (enhanced format), PIL B (hybrid format) and PIL C (standard format). Consent to OMACS was the primary outcome. Consent rates using the three different PIL formats were collected and compared. Qualitative feedback on the different formats was obtained from a public and patient involvement (PPI) group.

Results
For the SWAT, 1517 PILs were sent to potential participants, of whom 640 (42%) consented to take part in OMACS. PIL B had the highest recruitment rate, with 45% of patients consenting to participation; 40% and 41% of patients consented to participation after receiving PILs A and C, respectively. Compared to PIL C, the consent rate was 4% higher with PIL B (45% versus 41%, 95% confidence interval (CI) -2% to + 10%, p = 0.16) and 1% lower with PIL A (40% versus 41%, 95% CI − 7% to + 5%, p = 0.72).

Conclusions
Consent rates were similar for all three PIL formats. PIL B is being used for the remainder of the host study and will be used to inform the design of PILs for other research studies, as it was the preferred format of the PPI group.

Trial registration
International Clinical Trials Registry, ISRCTN90204321. Registered on 21 January 2015.