bluuebunny/crossref_metadata_2025_split huggingface dataset:
Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis
Authors: Wang Wei , Hu Zaoxiu , Zhao Jie , Huang Yunchao , Rao Sunyin , Yang Jichen , Xiao Shouyong , Cao Run , Ye Lianhua 
Published: June 2020

Abstract
Objective
It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype.

Methods
Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses.

Results
Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20–2.21) and OS (HR 1.53, 95% CI 1.19–1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45–2.85) and OS (HR 2.26, 95% CI 1.46–3.52) were also poor in the subgroup of patients with the presence of an MP component.

Conclusions
Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.
Oncolytic viruses for cancer immunotherapy
Authors: Hemminki Otto , dos Santos João Manuel , Hemminki Akseli 
Published: June 2020

AbstractIn this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to elucidate how versatile viruses are, and how they can be used to complement other cancer therapies to gain optimal patient benefits. Historical reports from over a hundred years suggest treatment efficacy and safety with adenovirus and other oncolytic viruses. This is confirmed in more contemporary patient series and multiple clinical trials. Yet, while the first viruses have already been granted approval from several regulatory authorities, room for improvement remains.As good safety and tolerability have been seen, the oncolytic virus field has now moved on to increase efficacy in a wide array of approaches. Adding different immunomodulatory transgenes to the viruses is one strategy gaining momentum. Immunostimulatory molecules can thus be produced at the tumor with reduced systemic side effects. On the other hand, preclinical work suggests additive or synergistic effects with conventional treatments such as radiotherapy and chemotherapy. In addition, the newly introduced checkpoint inhibitors and other immunomodulatory drugs could make perfect companions to oncolytic viruses. Especially tumors that seem not to be recognized by the immune system can be made immunogenic by oncolytic viruses. Logically, the combination with checkpoint inhibitors is being evaluated in ongoing trials. Another promising avenue is modulating the tumor microenvironment with oncolytic viruses to allow T cell therapies to work in solid tumors.Oncolytic viruses could be the next remarkable wave in cancer immunotherapy.
Repeatability of plantar pressure assessment during barefoot walking in people with stroke
Authors: Rogers A. , Morrison S. C. , Gorst T. , Paton J. , Freeman J. , Marsden J. , Cramp M. C. 
Published: June 2020

AbstractPurposeStroke‐related changes in foot structure and function affect balance and mobility and quantifying foot function following stroke could offer clinically useful information to inform rehabilitation. The aim of this work was to explore the feasibility of undertaking plantar pressure assessment during barefoot walking in people with stroke, and evaluate the repeatability of the assessment protocol and regional footprint analysis as a measure of dynamic foot characteristics.Materials & methodsPlantar pressure analysis was undertaken using a pressure platform (Tekscan HR Mat) on two test sessions, approximately two weeks apart (mean = 15.64 ± 11.64 days). Peak plantar pressure (kPa) and contact area (cm2) for foot regions were extracted and repeatability analysis undertaken. Descriptive evaluation of field notes and experiences of the participants was undertaken to inform the feasibility of the data collection protocol.ResultsTwenty‐one participants (61.8 ± 9.2 years; 11 male, 10 female; 8 right‐sided, 13 left‐sided stroke) were recruited and 18 returned for retesting. Full data capture was achieved from 14 participants. Peak pressure and contact area demonstrated moderate to good repeatability for at the toes (ICC 0.76 and 0.58 respectively) and good to excellent repeatability for the other foot regions (ICC ≥ 0.82).ConclusionThe protocol adopted in this study was feasible and yielded good to excellent repeatability for the foot regions, except the toes. The challenges with data collection in our study cohort could help inform future studies adopting similar protocols. This work also has relevance for use of pressure technology in clinical practice for assessing and monitoring foot function following stroke.
Prevalence of short stature and malnutrition among Egyptian primary school children and their coexistence with Anemia
Authors: El-Shafie Ali M. , Kasemy Zeinab A. , Omar Zein A. , Alkalash Safa H. , Salama Amal A. , Mahrous Kerollos S. , Hewedy Shaimaa M. , Kotb Nessreen M. , Abd El-Hady Heba S. , Eladawy Eman S. , Zeid Mohamed A. , Abd El Hamid Manar E. , Hemeda Emad H. , El-shafie Mohamed A. , El-Meligy Esraa A. , Bahbah Wael A. 
Published: June 2020

Abstract
Background
Under nutrition and overweight typically occur during nutritional transition periods in developing countries including Egypt. Short stature and anemia are public health concern due to its strong link with malnutrition which is a preventable risk factor.

Objectives
to estimate the prevalence of overweight, obesity, underweight and short stature and its concurrence with anemia, also to determine the etiological profile of short stature among primary school children in Egypt.

Methods
A cross-sectional study was carried out on 33,150 Egyptian children aged 6–11 years old from January 2018 to January 2020, allocated in 59 primary schools from diverse geographical districts in Egypt. Complete anthropometric measurements were conducted and applied according to WHO growth charts. Hemoglobin level was measured. Systematic approach to detect the etiology of short stature was applied randomly to a sample of 380 stunted children.

Results
The prevalence of underweight was 8.2%, while obesity and overweight represented 21.8% (9.6 and 12.2% respectively). Overall short stature constituted 17%. The main etiologies of short stature were familial (40.8%) and constitutional (24.2%). Anemia was diagnosed in 26% of children; while concurrent anemia and stunting was reported in 9.9%. Regarding anemia and anemia with stunting were more common among girls (30.0% (OR = 1.50, CI95%: 1.43–1.58) and 11.4% (OR = 1.39, CI95%:1.29–1.49) respectively), who were living in rural areas (33.4% (OR = 1.96, CI 95%:1.87–2.06) &12.7% (OR = 1.72, CI 95%:1.60–1.85)) and those who had low socioeconomic status)34.6% (OR = 2.54, CI 95%:2.29–2.82) & 17.2% (OR = 3.32, CI 95%:2.85–3.88() respectively. Anemia with stunting was significantly higher among children aged ≥9 years old representing 12% (OR = 1.40, CI 95%:1.30–1.51).

Conclusion
Prevalence of short stature, obesity and anemia was high among primary school children in Egypt with a strong concurrence between anemia and stunting. Intensive parental health education and in-depth nutritional assessment are required.
Internet-based psychodynamic versus cognitive behaviour therapy for adolescents with depression: study protocol for a non-inferiority randomized controlled trial (the ERiCA study)
Authors: Mechler Jakob , Lindqvist Karin , Carlbring Per , Lilliengren Peter , Falkenström Fredrik , Andersson Gerhard , Topooco Naira , Johansson Robert , Midgley Nick , Edbrooke-Childs Julian , J. Dahl Hanne-Sofie , Sandell Rolf , Thorén Agneta , Ulberg Randi , Lindert Bergsten Katja , Philips Björn 
Published: June 2020

Abstract
Background
Adolescent depression is a common mental health problem and there is an urgent need for effective and accessible treatments. Internet-based interventions solve many obstacles for seeking and receiving treatment, thus increasing access to effective treatments. Internet-based cognitive behavioural therapy (ICBT) for adolescent depression has demonstrated efficacy in previous trials. In order to broaden the range of evidence-based treatments for young people, we evaluated a newly developed affect-focused Internet-based psychodynamic treatment (IPDT) in a previous study with promising results. The purpose of the planned study is to evaluate the efficacy of IPDT for adolescent depression in a non-inferiority trial, comparing it to ICBT.

Methods
The study will employ a parallel randomized non-inferiority design (ratio 1:1; n = 270). Eligible participants are adolescents 15–19 years suffering from depression. The primary hypothesis is that IPDT will be non-inferior to ICBT in reducing depressive symptoms from pre-treatment to end of treatment. Secondary research questions include comparing outcomes of IPDT and ICBT regarding anxiety symptoms, emotion regulation and self-compassion. Additional data will be collected to evaluate cost-effectiveness as well as investigating predictors, moderators and mediators of outcome. In addition, we will examine long-term outcome up to 1 year after end of treatment. Diagnostic interviews with MINI 7.0 will be used to establish primary diagnosis of depression as well as ruling out any exclusion criteria. Both treatments consist of eight modules over 10 weeks, complemented with therapist support through text messages and weekly chat sessions. Primary outcome measure is the Quick Inventory of Depressive Symptomatology in Adolescents Self-Rated (QIDS-A17-SR). Primary outcome will be analysed using data from all participants entering the study using a multilevel growth curve strategy based on the weekly measurements of QIDS-A17-SR. The non-inferiority margin is defined as d = 0.30.

Discussion
This trial will demonstrate whether IPDT is non-inferior to ICBT in the treatment of adolescent depression. The study might therefore broaden the range of evidence-based treatment alternatives for young people struggling with depression. Further analyses of data from this trial may increase our knowledge about “what works for whom” and the pathways of change for two distinct types of interventions.

Trial registration
ISRCTN12552584, Registered on 13 August 2019.
The effectiveness of radial extracorporeal shock wave therapy (rESWT), sham-rESWT, standardised exercise programme or usual care for patients with plantar fasciopathy: study protocol for a double-blind, randomised, sham-controlled trial
Authors: Heide Marte , Mørk Marianne , Røe Cecilie , Brox Jens Ivar , Fenne Hoksrud Aasne 
Published: June 2020

Abstract
Background
Plantar fasciopathy is a common cause of plantar heel pain, with a reported prevalence of up to 10%. The choice of best practice in these patients is debated. Two randomised studies reported that radial extracorporeal shock wave therapy is effective, but a meta-analysis concluded that due to methodological limitations, the evidence is questionable. There are few studies reporting the effect of exercise programs with high-load strength training, despite widespread use. The objective of this placebo-controlled, observer-blinded and partly patient blinded trial is to compare rESWT, sham-rESWT, standardised exercise programme and usual care for alleviating heel pain at 6 and 12 months follow-up.

Methods/design
A double-blind, randomised, sham-controlled trial is conducted at a hospital outpatient clinic of physical medicine and rehabilitation. Patients with chronic (> 3 months) pain due to plantar fasciopathy, aged 18 to 70 years old, are eligible for inclusion in the trial. Patients will be randomly allocated in 1:1 ratio to receive rESWT, sham-rESWT, standardised exercises or usual care. The sample size is estimated to 200 patients, 50 in each group. rESWT or sham-rESWT will be given once a week for 3 weeks. A physiotherapist will supervise the exercises, with a total of 8 sessions over 12 weeks. The patients in the usual care group will receive information, advice and foot orthosis only. All patients, regardless of group, will receive the same information and get an individual customised foot orthosis made by an orthopaedic technician. The primary outcome measure is heel pain intensity during activity in the last week, using a numeric rating scale (NRS, 0 to 10) at the 6 months follow-up adjusted for baseline pain intensity. The secondary outcomes are at the 6- and 12-month follow-up and include Foot Functional Index Revised Short Version (FFI-RS), Patient Global Impression of Change Scale (7-point Likert scale), RAND-12 Health Status Inventory (RAND-12), NRS during rest and NRS during activity (12 months). The patients receiving rESWT/sham-rESWT and the outcome assessor will be blinded to the group assignment.

Discussion
This trial is designed in order to provide results important for future clinical practice.

Trial registration
ClinicalTrials.gov NCT03472989. Registered on 14 March 2018
The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial
Authors: Metzger-Peter Katline , Kremer Laurent Daniel , Edan Gilles , Loureiro De Sousa Paulo , Lamy Julien , Bagnard Dominique , Mensah-Nyagan Ayikoe-Guy , Tricard Thibault , Mathey Guillaume , Debouverie Marc , Berger Eric , Kerbrat Anne , Meyer Nicolas , De Seze Jérôme , Collongues Nicolas 
Published: June 2020

Abstract
Background
Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair.
It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS.

Methods/design
This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes.

Discussion
The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality.
Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases.

Trial registration
ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.
Personalized dosing of nicotine replacement therapy versus standard dosing for the treatment of individuals with tobacco dependence: study protocol for a randomized placebo-controlled trial
Authors: Zawertailo Laurie , Hendershot Christian S. , Tyndale Rachel F. , Le Foll Bernard , Samokhvalov Andriy V. , Thorpe Kevin E. , Pipe Andrew , Reid Robert D. , Selby Peter 
Published: June 2020

Abstract
Background
Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive; as such, there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy are not effective for many smokers, and in many cases, the amount of nicotine provided is much less than when a smoker is smoking their usual number of cigarettes. The proposed study will test if titrating the dose of the nicotine patch (up to 84 mg) will improve quitting success compared to those receiving a 21-mg nicotine patch with increasing doses of placebo patch.

Methods
This is a multicenter, pragmatic, two-arm, placebo-controlled, block randomized controlled trial. We will recruit participants who smoke at least 10 cigarettes daily and are interested in making a quit attempt. After 2 weeks of usual treatment with a 21-mg patch, participants who fail to quit smoking (target n = 400) will be randomized to receive escalating doses of a nicotine patch vs matching placebo patches for an additional 10 weeks or up to a maximum dose of 84 mg per day. Those who stop smoking during the first 2 weeks of usual treatment will continue with 21 mg patch treatment for 10 weeks and will form an additional comparison arm. In addition to the medication, participants will receive brief behavioral counseling at each study visit. The primary outcome will be biochemically confirmed continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9 to 12).

Discussion
Research evidence supporting the effectiveness of personalized doses of nicotine replacement therapy could change current practice in a variety of healthcare settings. Given the evidence that quitting smoking at any age diminishes the risk of tobacco-related morbidity and mortality, even small increases in absolute quit rates can have a substantial population-level impact on reducing smoking-related disease, mortality rates, and associated healthcare costs.

Trial registration
ClinicalTrials.gov, NCT03000387. Registered on 22 December 2016.
Impact of different temperature profiles on simultaneous yeast and bacteria fermentation
Authors: Guzzon Raffaele , Roman Tomas , Larcher Roberto 
Published: June 2020

AbstractPurposeThe role of fermentation temperature was studied for its impact on the evolution of malolactic fermentation performed by simultaneous inoculum of yeast and bacteria in grape must. Results were discussed considering the different fermentative kinetics and the composition of obtained wines.MethodsTwo strains of bacteria belonging to theO. oeniandL. plantarumspecies were inoculated 24 h after the beginning of the alcoholic fermentation in 2 grape musts having different acidic and sugar profiles. Fermentations were conducted at 3 different temperature profiles (16/22 °C in 3 days, 18/24 °C in 3 days, 22/32 °C in 5 days). Evolution of microbiota was followed by flow cytometry and plate count. Chemical analysis of grape musts and wines were performed by instrumental approaches (FT-IR, enzymatic quantification of malic acid, GC-MS).ResultsL. plantarumresulted more efficient in malic acid consumption in the entire set of tests. These results are unexpected because, generally,Lactobacillushas been reported to be more sensitive to an oenological environment thanO. oeni. In our experiments,O. oeniresulted inhibited by the highest fermentation temperature profile, causing incomplete malic acid degradation. Similarly,S. cerevisiaeshowed a higher sensitivity to environmental limiting factors in respect to what is generally known. Differences in the chemical composition of wines were observed in relation to the bacteria strain and the temperature profile. However, the statistical treatment of data identified temperature as the main variable able to influence the features of wines.ConclusionsSimultaneous inoculum of yeast and bacteria in grape must is an alternative approach in the management of malolactic fermentation which showed some interesting features. However, it is necessary to consider that the dynamics of the microbial population are different to that observed in traditional winemaking and the environmental variables act against the microorganisms in a peculiar, and in certain cases unexpected, way.