bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overlapping volumes in re-irradiation for head and neck cancer – an important factor for patient selection
Authors: Embring Anna , Onjukka Eva , Mercke Claes , Lax Ingmar , Berglund Anders , Bornedal Sara , Wennberg Berit , Friesland Signe 
Published: June 2020

Abstract
Background

There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment.

Methods

Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded.

Results

The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC.

Conclusions

Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.
Effect of Achilles tendon on kinematic coupling relationship between tarsal bones: a pilot finite element study
Authors: Li Song-Jian , Tang Lei , Zhao Li , Liu Cheng-Long , Liu Yu-Bin 
Published: June 2020

Abstract
Background
The procedure of percutaneous Achilles tenotomy (PAT) is an important component of the Ponseti method. However, few studies reported the influence of Achilles tendon on kinematic coupling relationship between tarsal bones. The purpose of present study was to demonstrate the effect of Achilles tendon on the kinematic coupling relationship between tarsal bones, and to illustrate how kinematic coupling relationship between tarsal bones works in term of finite element analysis.

Methods
A three-dimensional finite element model of foot and ankle was constructed based on the Chinese digital human girl No.1 (CDH-G1) image database using the software of mimics, Geomagic studio, HyperMesh, and Abaqus. The last manipulation of the Ponseti method before the procedure of PAT was simulated. The talus head and the proximal tibia and fibula bone were fixed in all six degrees of freedom, and the outward pressure was added on the first metatarsal head to investigate the kinematic coupling relationship between tarsal bones.

Results
The least relationship of kinematic coupling between tarsal bones was found in calcaneus. Stress concentration was mainly observed at the navicular, talus and the medial malleolus. The difference in displacement of the navicular was only found with the Achilles tendon stiffness of 0 N/mm and others. No difference in the navicular displacement was found in the stiffness of Achilles tendon between 40, 80, 200, 400, and 1000 N/mm. The maximum displacement of navicular was observed at the ankle position of PF-20° (plantar flexion-20°). The difference in displacement of the navicular was greater at the ankle position of PF-20° with the Achilles tendon stiffness of 0 N/mm than that at the ankle position of PF-40° with the Achilles tendon stiffness of 40 N/mm.

Conclusions
Based on the findings from this study, it was demonstrated that the Achilles tendon existence or not and ankle position had great influence, while increased stiffness of Achilles tendon had no influence on kinematic coupling relationship between tarsal bones. For the cases with severe equinus, earlier implementation of PAT procedure (with the purpose of release the Achilles tendon and reduce the degree of ankle plantar flexion) may be beneficial to the deformity correction.
Structural durability of early-generation Transcatheter aortic valve replacement valves compared with surgical aortic valve replacement valves in heart valve surgery: a systematic review and meta-analysis
Authors: Ler Ashlynn , Ying Yeo Jie , Sazzad Faizus , Choong Andrew M. T. L. , Kofidis Theo 
Published: June 2020

Abstract
Background
The current treatment for aortic stenosis includes open surgical aortic valve replacement (SAVR) as well as endovascular transcatheter aortic valve replacement (TAVR). This study aims to compare the 1-year, 2–3 year and 5-year structural durability of TAVR valves with that of SAVR valves.

Method
A systematic literature search was conducted in July 2019 on Medline (via PubMed), Embase and Cochrane electronic databases according to the PRISMA guidelines.

Results
Thirteen randomized controlled trials were included. From the meta-analysis, we observed higher rates of 1-year (OR: 7.65, CI: 4.57 to 12.79, p < 0.00001), 2–3-year (OR: 13.49, CI: 5.66 to 32.16, p < 0.00001) and 5-year paravalvular regurgitation (OR: 14.51, CI: 4.47 to 47.09, p < 0.00001) associated with the TAVR valves than the SAVR valves. There were also higher rates of 1-year (OR: 5.00, CI: 3.27 to 7.67, p < 0.00001), 2–3-year (OR: 8.14, CI: 3.58 to 18.50, p < 0.00001) and 5-year moderate or severe aortic regurgitation (MD: 14.65, CI: 4.55 to 47.19, p < 0.00001), and higher rates of 1-year (OR: 3.55, CI: 1.86 to 6.77, p = 0.0001), 2–3-year (OR: 3.55, CI: 1.86 to 6.77, p = 0.0001) and 5-year reintervention (OR: 3.55, CI: 1.22 to 10.38, p = 0.02) in the TAVR valves as compared to SAVR valves.

Conclusion
TAVR valves appear to be more susceptible to structural valve deterioration and thus potentially less structurally durable than SAVR valves, given that they may be associated with higher rates of moderate or severe aortic regurgitation, paravalvular regurgitation and reintervention in the 1-year-, 2–3 year, and 5-year period.
Barriers and challenges in the process of including critically ill patients in clinical studies
Authors: Dahlberg Jørgen , Eriksen Camilla , Robertsen Annette , Beitland Sigrid 
Published: June 2020

AbstractBackgroundClinical research in severely ill or injured patients is required to improve healthcare but may be challenging to perform in practice. The aim of this study was to analyse barriers and challenges in the process of including critically ill patients in clinical studies.MethodsData from critically ill patients considered for inclusion in an observational study of venous thromboembolism in Norway were analysed. This included quantitative and qualitative information from the screening log, consent forms and research notes.ResultsAmong 279 eligible critically ill patients, 204 (73%) were omitted from the study due to challenges and barriers in the inclusion process. Reasons for omission were categorised as practical in 133 (65%), medical in 31 (15%), and legal or ethical in 40 (20%) of the patients. Among 70 included patients, 29 (41%) consents were from patients and 41 (59%) from their next of kin. Several challenges were described herein; these included whether patients were competent to give consent, and which next of kin that should represent the patient. Furthermore, some included patients were unable to recall what they have consented, and some appeared unable to separate research from treatment.ConclusionsBarriers and challenges in the inclusion process led to the omission of near three out of four eligible patients. This analysis provided information about where the problem resides and may be solved. The majority of challenges among included patients were related to issues of autonomy and validity of consent.Trial registrationClinicalTrials.gov(NCT03405766).
Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium
Authors: Erstad Brian L. , Barletta Jeffrey F. 
Published: June 2020

AbstractPractice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.
Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes
Authors: Sakthikumar Sharadha , Roy Ananya , Haseeb Lulu , Pettersson Mats E. , Sundström Elisabeth , Marinescu Voichita D. , Lindblad-Toh Kerstin , Forsberg-Nilsson Karin 
Published: June 2020

AbstractBackgroundGlioblastoma (GBM) has one of the worst 5-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.ResultsWe validate our GBM cohort, finding similar copy number aberrations and mutated genes based on coding mutations as previous studies. Performing analysis on non-coding constraint mutations and their position relative to nearby genes, we find a significant enrichment of non-coding constraint mutations in the neighborhood of 78 genes that have previously been implicated in GBM. Among them,SEMA3CandDYNC1I1show the highest frequencies of alterations, with multiple mutations overlapping transcription factor binding sites. We find that a non-coding constraint mutation in theSEMA3Cpromoter reduces the DNA binding capacity of the region. We also identify 1776 other genes enriched for non-coding constraint mutations with likely regulatory potential, providing additional candidate GBM genes. The mutations in the top four genes,DLX5,DLX6,FOXA1, andISL1, are distributed over promoters, UTRs, and multiple transcription factor binding sites.ConclusionsThese results suggest that non-coding constraint mutations could play an essential role in GBM, underscoring the need to connect non-coding genomic variation to biological function and disease pathology.
Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study
Authors: Kaur Ramanjot , Tchanque-Fossuo Catherine , West Kaitlyn , Hadian Yasmin , Gallegos Anthony , Yoon Daniel , Ismailyan Ligia , Schaefer Saul , Dahle Sara E. , Isseroff R. Rivkah 
Published: June 2020

Abstract
Background
Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (βAAs) on skin and skin-derived cells. We have shown that βAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the βAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs.

Methods/design
This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period.

Discussion
This is a clinical translation study, moving the investigators’ pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment.

Trial registration
ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.
Elbow hemiarthroplasty versus open reduction and internal fixation for AO/OTA type 13 C2 and C3 fractures of distal humerus in patients aged 50 years or above: a randomized controlled trial
Authors: Al-Hamdani Ali , Rasmussen Jeppe V. , Holtz Kenneth , Olsen Bo S. 
Published: June 2020

Abstract
Background
Intraarticular distal humeral fractures of AO/OTA type 13 C2 and C3 pose a surgical challenge despite the evolution of surgical implants and techniques. Open reduction and internal fixation (ORIF) is often preferred as the first choice of treatment, but the results vary and are sometimes disappointing. Total elbow arthroplasty (TEA) has been widely used for fractures that are not amenable to ORIF in elderly patients, but the mechanical complications remain a challenge, especially in active patients. Elbow hemiarthroplasty (EHA) provides a modern alternative that might avoid the mechanical complications and weight bearing restrictions related to the linked articulation in semi-constrained TEA. No studies have compared the results of EHA to that of ORIF, but case series have reported promising results.

Methods/design
This is a study protocol describing an investigator-initiated, non-blinded randomized controlled trial comparing the outcome of EHA with ORIF for AO/OTA type 13 C2 and C3 fractures of the distal humerus in patients who are 50 years or older. Forty-four patients with AO/OTA type 13 C2 and C3 fractures of distal humerus will be randomized to either EHA or ORIF. The Oxford Elbow Score (OES) will be used as primary outcome. Mayo Elbow Performance Score (MEPS), pain severity score (VAS), range of motion, and patient satisfaction will be used as secondary outcomes. Reoperations, complications, and the length of sick leave will be recorded. The patients will be examined after the operation and at 3 months and 1, 2, 5, and 10 years.

Discussion
The main objective of this study is to investigate the best treatment option for AO/OTA type 13 C2 and C3 fractures of distal humerus in patients aged 50 years or above. We hypothesize that EHA results in fewer complications and superior functional outcome compared with ORIF and that the mechanical complications related to the linked articulation of TEA can be avoided.

Trial registration
ClinicalTrials.gov, PRS, NCT04163172. Registered November 13, 2019. https://clinicaltrials.gov/ct2/results?cond=&term=evori&cntry=&state=&city=&dist= (Table 2).
The protocol has been approved by The Scientific Ethics Committee of the Capital Region of Denmark (Jr. no.: H− 19,035,590).
The processing of personal data has been approved by the Danish Data Protection Agency (Jr. no. P-2019-246). Inclusion started on February 1, 2020.
Implementation and evaluation of a nurse-led decision-coaching program for healthy breast cancer susceptibility gene (BRCA1/2) mutation carriers: a study protocol for the randomized controlled EDCP-BRCA study
Authors: Isselhard A. , Töpper M. , Berger-Höger B. , Steckelberg A. , Fischer H. , Vitinius F. , Beifus K. , Köberlein-Neu J. , Wiedemann R. , Rhiem K. , Schmutzler R. , Stock S. 
Published: June 2020

Abstract
Background
Female BRCA mutation carriers have an increased lifetime risk for breast and ovarian cancer compared to the general population. Women who carry this mutation have several options to deal with their cancer risk, such as risk-reducing surgeries or intensified breast cancer screening. Previous research has shown that preferences in this scenario are highly dependent on affected women’s personalities and value systems. To support these women in the decision-making process, a structured decision support consisting of decision coaching combined with a decision aid might be helpful.

Methods/design
A randomized controlled trial will be conducted in order to compare usual care with structured decision support alongside usual care. The decision support program entails nurse-led decision coaching as well as an evidence-based patient decision aid. Nurses are qualified by a 4-day training program in informed decision-making and decision coaching. Six centers for Familial Breast and Ovarian Cancer in Germany will be included in the study, with a planned sample size of 398 women.
The primary outcome is the congruence between the preferred and the actual played role in the decision-making process as measured by the Control Preferences Scale. It is hypothesized that the structured decision support will enable women to play the preferred role in the decision-making process. Secondary outcomes include the knowledge and attitudes about preventive options, decisional conflict, depression and anxiety, coping self-efficacy, impact of event, and self-concept. A process evaluation will accompany the study.

Discussion
The EDCP-BRCA study is the first study to implement and evaluate decision coaching combined with a decision aid for healthy BRCA mutation carriers worldwide.

Trial registration {2a}
DRKS-ID: DRKS00015527. Registered 30 October 2019.
Does internal limiting membrane peeling during epiretinal membrane surgery induce microscotomas on microperimetry? Study protocol for PEELING, a randomized controlled clinical trial
Authors: Ducloyer Jean-Baptiste , Ivan Juliette , Poinas Alexandra , Lebreton Olivier , Bonissent Alexandre , Fossum Paul , Volteau Christelle , Tadayoni Ramin , Creuzot-Garchet Catherine , Le Mer Yannick , Perol Julien , Fortin June , Chiffoleau Anne , Billaud Fanny , Ivan Catherine , Weber Michel 
Published: June 2020

Abstract
Background
The epiretinal membrane (ERM) is a degenerative condition associated with age, which can cause loss of vision and/or metamorphopsia. The treatment of symptomatic ERM involves surgical removal including a vitrectomy followed by peeling of the ERM using a microforceps. As the internal limiting membrane (ILM) is adherent to the ERM, it is sometimes removed with it (spontaneous peeling). If ILM remains in place, it can be removed to reduce ERM recurrence. However, it is important to clarify the safety of ILM peeling, while it increases surgical risks and cause histological disorganization of the retina that can lead to microscotomas, may be responsible for definitive visual discomfort.

Methods
PEELING is a prospective, randomized, controlled, single-blind, and multicentered trial with two parallel arms. This study investigates the benefit/risk ratio of active ILM peeling among individuals undergoing ERM surgery without spontaneous ILM peeling. Randomization is done in the operating room after ERM removal if ILM remains in place. After randomization, the two groups—“active peeling of the ILM” and “no peeling of the ILM”—are compared during a total of three follow-up visits scheduled at month 1, month 6, and month 12. Primary endpoint is the difference in microscotomas before surgery and 6 months after surgery. Patients with spontaneous peeling are not randomized and are included in the ancillary study with the same follow-up visits and the same examinations as the principal study.
Relevant inclusion criteria involve individuals aged > 18 years living with idiopathic symptomatic ERM, including pseudophakic patients with transparent posterior capsule or open capsule or lensed patients with age-related cataracts. The calculated sample size corresponds to 53 randomized eyes (one eye/patient) per arm that means 106 randomized eyes (106 randomized patients) in total and a maximum of 222 included patients (116 spontaneous peeling).

Discussion
ILM peeling is often practiced in ERM surgery to reduce ERM recurrence. It does not impair postoperative visual acuity, but it increases the surgical risks and causes anatomical damages. If active ILM peeling is significantly associated with more microscotomas, it may contraindicate the ILM peeling during primitive idiopathic ERM surgery.

Trial registration
ClinicalTrials.gov, NCT02146144. Registered on 22 May 2014. Recruitment is still ongoing.
Parallel isotope differential modeling for instationary 13C fluxomics at the genome scale
Authors: Zhang Zhengdong , Liu Zhentao , Meng Yafei , Chen Zhen , Han Jiayu , Wei Yimin , Shen Tie , Yi Yin , Xie Xiaoyao 
Published: June 2020

BackgroundA precise map of the metabolic fluxome, the closest surrogate to the physiological phenotype, is becoming progressively more important in the metabolic engineering of photosynthetic organisms for biofuel and biomass production. For photosynthetic organisms, the state-of-the-art method for this purpose is instationary 13C fluxomics, which has arisen as a sibling of transcriptomics or proteomics. Instationary 13C data processing requires solving high-dimensional nonlinear differential equations and leads to large computational and time costs when its scope is expanded to a genome-scale metabolic network.ResultHere, we present a parallelized method to model instationary 13C labeling data. The elementary metabolite unit (EMU) framework is reorganized to allow treating individual mass isotopomers and breaking up of their networks into strongly connected components (SCCs). A variable domain parallel algorithm is introduced to process ordinary differential equations in a parallel way. 15-fold acceleration is achieved for constant-step-size modeling and ~ fivefold acceleration for adaptive-step-size modeling.ConclusionThis algorithm is universally applicable to isotope granules such as EMUs and cumomers and can substantially accelerate instationary 13C fluxomics modeling. It thus has great potential to be widely adopted in any instationary 13C fluxomics modeling.