bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-center versus multi-center data sets for molecular prognostic modeling: a simulation study
Authors: Samaga Daniel , Hornung Roman , Braselmann Herbert , Hess Julia , Zitzelsberger Horst , Belka Claus , Boulesteix Anne-Laure , Unger Kristian 
Published: May 2020

AbstractBackgroundPrognostic models based on high-dimensional omics data generated from clinical patient samples, such as tumor tissues or biopsies, are increasingly used for prognosis of radio-therapeutic success. The model development process requires two independent discovery and validation data sets. Each of them may contain samples collected in a single center or a collection of samples from multiple centers. Multi-center data tend to be more heterogeneous than single-center data but are less affected by potential site-specific biases. Optimal use of limited data resources for discovery and validation with respect to the expected success of a study requires dispassionate, objective decision-making. In this work, we addressed the impact of the choice of single-center and multi-center data as discovery and validation data sets, and assessed how this impact depends on the three data characteristics signal strength, number of informative features and sample size.MethodsWe set up a simulation study to quantify the predictive performance of a model trained and validated on different combinations of in silico single-center and multi-center data. The standard bioinformatical analysis workflow of batch correction, feature selection and parameter estimation was emulated. For the determination of model quality, four measures were used: false discovery rate, prediction error, chance of successful validation (significant correlation of predicted and true validation data outcome) and model calibration.ResultsIn agreement with literature about generalizability of signatures, prognostic models fitted to multi-center data consistently outperformed their single-center counterparts when the prediction error was the quality criterion of interest. However, for low signal strengths and small sample sizes, single-center discovery sets showed superior performance with respect to false discovery rate and chance of successful validation.ConclusionsWith regard to decision making, this simulation study underlines the importance of study aims being defined precisely a priori. Minimization of the prediction error requires multi-center discovery data, whereas single-center data are preferable with respect to false discovery rate and chance of successful validation when the expected signal or sample size is low. In contrast, the choice of validation data solely affects the quality of the estimator of the prediction error, which was more precise on multi-center validation data.
Altered fractionation short-course radiotherapy for stage II-III rectal cancer: a retrospective study
Authors: Geinitz Hans , Nieder Carsten , Kocik Lukas , Track Christine , Feichtinger Johann , Weingartner Theresa , Spiegl Kurt , Füreder-Kitzmüller Barbara , Kaufmann Johanna , Seewald Dietmar H. , Függer Reinhold , Shamiyeh Andreas , Petzer Andreas L. , Kiesl David , Hammer Josef 
Published: May 2020

AbstractPurposeTo report the long-term outcomes of neoadjuvant altered fractionation short-course radiotherapy in 271 consecutive patients with stage II-III rectal cancer.Patients and Methods: This was a retrospective single institution study with median follow-up of 101 months (8.4 years). Patients who were alive at the time of analysis in 2018 were contacted to obtain functional outcome data (phone interview). Radiotherapy consisted of 25 Gy in 10 fractions of 2.5 Gy administered twice daily. Median time interval to surgery was 5 days.ResultsLocal relapse was observed in 12 patients (4.4%) after a median of 28 months. Overall survival after 5 and 10 years was 73 and 55.5%, respectively (corresponding disease-free survival 65.5 and 51%). Of all patients without permanent stoma, 79% reported no low anterior resection syndrome (LARS; 0–20 points), 9% reported LARS with 21–29 points and 12% serious LARS (30–42 points).ConclusionThe present radiotherapy regimen was feasible and resulted in low rates of local relapse. Most patients reported good functional outcomes.
A novel anatomically pre-contoured side-specific titanium plate versus the reconstruction plate for quadrilateral plate fractures of the acetabulum: a propensity-matched cohort study
Authors: Wu Haiyang , Shang Ranran , Liu Ximing , Song Chengjing , Chen Yanzhao , Cai Xianhua 
Published: May 2020

AbstractBackgroundSurgical treatment of acetabular fractures involving a quadrilateral plate is a challenge to orthopedic surgeons. We have developed a novel fixation technique using a specially shaped reconstruction plate combined with several buttress screws of a quadrilateral plate which was also called a dynamic anterior plate-screw system for quadrilateral plate (DAPSQ) to treat acetabular fractures involving quadrilateral plate since 2005 (RP group). And the long-term follow-up results have confirmed the effectiveness and safety of this technique. After 2016, standardized titanium plate (STP group) of DAPSQ have been designed and applied. The aim of the study was to compare the clinical efficacy of anatomical plate and the reconstruction plate of DAPSQ in the treatment of quadrilateral plate fractures.MethodsWe led a propensity-matched cohort study of quadrilateral plate fractures. Twenty-two patients were included in the STP group during the inclusion period (2016–2018) and were matched to 22 cases in our database of the RP group (2008–2016). The primary outcome measures were the quality of reduction and functional outcomes. Intraoperative conditions were also compared.ResultsOf these 22 consecutive patients in the STP group, the mean age was 46.7 years and the most common fracture pattern was a both-column fracture (12 cases, 54.5%) according to Letournel-Judet classification. The mean follow-up period was 23.1 months (range 12–37). There were no significant differences between the two groups with regard to the quality of reduction using the Matta radiological criteria and functional outcomes evaluated by the modified Merle d’Aubigné score (P> 0.05). Compared with the RP group, the STP group had a shorter operation time (245.1 min vs. 286.8 min,P= 0.020), less intraoperative blood loss (1136.4 mL vs. 1777.3 mL,P= 0.014), and transfusion (780.9 vs. 1256.8 mL,P= 0.035). The complication rate was 18.2% in the STP group, and there was no significant difference compared with the RP group (36.4%) (P> 0.05). None of the cases in the two groups had quadrilateral screws entering the hip or implant failure.ConclusionsThe fixation of standardized titanium plate in quadrilateral plate fractures showed a similar result to the reconstruction plate, in terms of quality of reduction and functional outcome. The standardized titanium plate of DAPSQ has the advantages of a short operation time, less intraoperative bleeding, and blood transfusion, and it is worth further promotion and research.
MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head
Authors: Fu Ligong , Liu Huawei , Lei Weijun 
Published: May 2020

Abstract
Background
It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear.

Methods
The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)—dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined.

Results
MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3.

Conclusion
MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.
Recurrent disc herniation following percutaneous endoscopic lumbar discectomy preferentially occurs when Modic changes are present
Authors: Hao Lu , Li Shengwen , Liu Junhui , Shan Zhi , Fan Shunwu , Zhao Fengdong 
Published: May 2020

Abstract
Objective
To investigate the relationship between Modic changes (MCs) and recurrent lumbar disc herniation (rLDH) and that between the herniated disc component and rLDH following percutaneous endoscopic lumbar discectomy (PELD).

Methods
We included 102 (65 males, 37 females, aged 20–66 years) inpatients who underwent PELD from August 2013 to August 2016. All patients underwent CT and MRI preoperatively. The presence and type of Modic changes were assessed. During surgery, the herniated disc component of each patient was classified into two groups: nucleus pulposus group and hyaline cartilage group. The association of herniated disc component with Modic changes was investigated. The incidence of rLDH was assessed based on a more than 2-year follow-up.

Results
In total, 11 patients were lost to follow-up; the other 91 were followed up during 24–60 months. Of the 91 patients, 99 discs underwent PELD; 28/99 (28.3%) had MCs. Type I and II MCs were seen in 9 (9.1%) and 19 (19.2%), respectively; no type III MCs were found. Among 28 endplates with MCs, according to the herniated disc component, 18/28 (64.3%) showed evidence of hyaline cartilage in the intraoperative specimens, including 6/9 and 12/19 endplates with type I and II MCs, respectively. Among 71 endplates without MCs, 14/71 (19.7%) showed evidence of hyaline cartilage in the intraoperative specimens. Hyaline cartilage was more common in patients with MCs (P < 0.05). We found 2 cases of rLDH in the non-MC group (n = 71); 6 cases of rLDH were found in the MC group (n = 28), including 2 and 4 cases for types I and II, respectively. There was no significant difference between types I and II (P > 0.05). rLDH was more common in patients with MCs (P < 0.05). We found 5 rLDH cases in the hyaline cartilage group (n = 32); 3 rLDH cases were found in the nucleus pulposus group (n = 67). rLDH was more common in the hyaline cartilage group (P < 0.05).

Conclusions
rLDH following PELD preferentially occurs when MCs or herniated cartilage are present.
Critical clinical situations in adult patients with Mucopolysaccharidoses (MPS)
Authors: Stepien Karolina M. , Gevorkyan Anait K. , Hendriksz Christian J. , Lobzhanidze Tinatin V. , Pérez-López Jordi , Tol Govind , del Toro Riera Mireia , Vashakmadze Nato D. , Lampe Christina 
Published: May 2020

Abstract
Background
Mucopolysaccharidoses (MPS) are rare, inherited disorders associated with enzyme deficiencies that result in glycosaminoglycan (GAG) accumulation in multiple organ systems. Management of MPS is evolving as patients increasingly survive to adulthood and undergo multiple surgeries throughout their lives. As surgeries in these patients are considered to be high risk, this can result in a range of critical clinical situations in adult patients.

Results
We discuss strategies to prepare for and manage critical clinical situations in adult patients with MPS, including supporting the multidisciplinary team, preoperative and airway assessments, surgical preparations, and postoperative care. We also present eight critical clinical cases (age range: 21–38 years) from four leading inherited metabolic disease centres in Europe to highlight challenges and practical solutions to optimise the care of adult patients with MPS. Critical clinical situations included surgical procedures, pregnancy and a thrombus in a port-a-cath.

Conclusions
Individualised strategies to manage critical clinical situations need to be developed for each patient to compensate for the heterogeneous symptoms that may be present and the potential complications that may occur. These strategies should include input from the wider MDT, and be coordinated by metabolic specialists with expertise in the management of MPS disorders and surgery in adult patients with MPS.
Formaldehyde formation in the glycine cleavage system and its use for an aldolase-based biosynthesis of 1,3-propanediol
Authors: Xu Yingying , Meng Hao , Ren Jie , Zeng An-Ping 
Published: May 2020

AbstractGlycine cleavage system (GCS) occupies a key position in one-carbon (C1) metabolic pathway and receives great attention for the use of C1 carbons like formate and CO2 via synthetic biology. In this work, we demonstrate that formaldehyde exists as a substantial byproduct of the GCS reaction cycle. Three causes are identified for its formation. First, the principal one is the decomposition of N5,N10-methylene-tetrahydrofolate (5,10-CH2-THF) to form formaldehyde and THF. Increasing the rate of glycine cleavage promotes the formation of 5,10-CH2-THF, thereby increasing the formaldehyde release rate. Next, formaldehyde can be produced in the GCS even in the absence of THF. The reason is that T-protein of the GCS can degrade methylamine-loaded H-protein (Hint) to formaldehyde and ammonia, accompanied with the formation of dihydrolipoyl H-protein (Hred), but the reaction rate is less than 0.16% of that in the presence of THF. Increasing T-protein concentration can speed up the release rate of formaldehyde by Hint. Finally, a certain amount of formaldehyde can be formed in the GCS due to oxidative degradation of THF. Based on a formaldehyde-dependent aldolase, we elaborated a glycine-based one carbon metabolic pathway for the biosynthesis of 1,3-propanediol (1,3-PDO) in vitro. This work provides quantitative data and mechanistic understanding of formaldehyde formation in the GCS and a new biosynthetic pathway of 1,3-PDO.
Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: analysis from a nationwide phase II DBCG trial
Authors: Skriver Signe Korsgaard , Jensen Maj-Britt , Knoop Ann Soegaard , Ejlertsen Bent , Laenkholm Anne-Vibeke 
Published: May 2020

Abstract
Background
The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.

Methods
Participants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs.

Results
Tumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range − 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53–0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40–0.78; p = 0.0007) for lower RCB index per 10% increase.

Conclusion
Increasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy.

Trial registration
ClinicalTrials.govNCT00908531, registered 27 May 2009.
Effect of acupuncture and its influence on cerebral activity in patients with persistent asthma: study protocol for a randomized controlled clinical trial
Authors: Yu Siyi , Dong Xiaohui , Sun Ruirui , He Zhaoxuan , Zhang Chuantao , Chen Mei , Hong Xiaojuan , Lan Lei , Zeng Fang 
Published: May 2020

Abstract
Background
Previous studies suggested that acupuncture was a promising adjunctive treatment for asthma. However, the underlying mechanism of acupuncture for asthma remains unclear. The aim of the present trial is to explore whether and how specific meridian acupuncture works in quality of life and symptomatic improvement by modulating brain function in patients with asthma.

Methods/design
This is a randomized controlled functional brain imaging trial currently being conducted in Sichuan, China. In total, 48 patients with mild to moderate persistent asthma will be recruited randomly and allocated to either of two acupuncture groups: acupuncture at the lung meridian or acupuncture at the heart meridian. The treatment period will last 4 weeks. The Asthma Quality of Life Questionnaire is the primary outcome. The Asthma Control Test, peak expiratory flow rate, forced expiratory volume in 1 s, Montreal Cognitive Assessment, Zung Self-rating Anxiety Scale, and Zung Self-rating Depression Scale will also be used to assess the clinical efficacy of different interventions. Functional magnetic resonance imaging (fMRI) will be performed to detect cerebral activity changes in each group. The clinical data and fMRI data will be analyzed between groups, then, the Pearson correlation analysis will be used to assess the association between the changes of cerebral activity features and the improvement of clinical outcomes in each group.

Discussion
The present study has been established on the basis of the “meridian–viscera relationship” theory of traditional Chinese medicine and the modern central mechanism of acupuncture. The results of this trial would be useful to identify the efficiency of the specific meridian acupuncture for asthma. The investigation of its central mechanism would further expand knowledge of acupuncture for asthma.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900027478. Registered on 15 November 2019.
OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose chest CT (OPTIMACT) trial—statistical analysis plan
Authors: Kanglie Maadrika M. N. P. , Bipat Shandra , van den Berk Inge A. H. , van Engelen Tjitske S. R. , Dijkgraaf Marcel G. W. , Prins Jan M. , Stoker Jaap , Bossuyt Patrick M. M. 
Published: May 2020

Abstract
Background
A chest X-ray is a standard imaging procedure in the diagnostic work-up of patients suspected of having non-traumatic pulmonary disease. Compared to a chest X-ray, an ultra-low-dose (ULD) chest computed tomography (CT) scan provides substantially more detailed information on pulmonary conditions. To what extent this translates into an improvement in patient outcomes and health care efficiency is yet unknown. The OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose chest CT (OPTIMACT) study is a multicenter, pragmatic, non-inferiority randomized controlled trial designed to evaluate replacement of chest X-ray by ULD chest CT in the diagnostic work-up of such patients, in terms of patient-related health outcomes and costs. During randomly assigned periods of 1 calendar month, either conventional chest X-ray or ULD chest CT scan was used as the imaging strategy. This paper presents in detail the statistical analysis plan of the OPTIMACT trial, developed prior to data analysis.

Methods/results
Functional health at 28 days is the primary clinical outcome. Functional health at 28 days is measured by the physical component summary scale of the Short Form (SF)-12 questionnaire version 1. Secondary outcomes are mental health (mental component summary scale of the SF-12), length of hospital stay, mortality within 28 days, quality-adjusted life year equivalent during the first 28 days (derived from the EuroQol five-dimension, five-level instrument), correct diagnoses at emergency department discharge as compared to the final post hoc diagnosis at day 28, number of patients in follow-up because of incidental findings on chest X-ray or ULD chest CT, and health care costs.

Conclusions
After this pragmatic trial we will have precise estimates of the effectiveness of replacing chest X-ray with ULD chest CT in terms of patient-related health outcomes and costs.

Trial registration
Netherlands National Trial Register: NTR6163. Registered on 6 December 2016.
Production, purification, and characterization of cellulase from Acinetobacter junii GAC 16.2, a novel cellulolytic gut isolate of Gryllotalpa africana, and its effects on cotton fiber and sawdust
Authors: Banerjee Sandipan , Maiti Tushar Kanti , Roy Raj Narayan 
Published: May 2020

Abstract
Purpose
The study aims to search for potent cellulase producer from the gut of Gryllotalpa africana as well as to characterize and determine the effect of the purified enzyme on the cellulosic waste materials.

Methods
The potent cellulolytic strain was identified through morphological, biochemical, physiological, and molecular characterization like 16S rRNA and fatty acid methyl ester profile. After the optimization of cellulase production, the enzyme was purified through DEAE-Sepharose column chromatographic separation. The molecular weight of the purified enzyme was determined by SDS-PAGE analysis. The purified enzyme was characterized in terms of its activity and its effect on cotton fiber, and sawdust was also studied.

Result
The selected potent strain GAC 16.2 was identified as Acinetobacter junii that was capable to produce enhanced cellulase (112.38 ± 0.87 U/ml) at standardized optimum fermentation conditions. The molecular weight of the purified enzyme was determined as 55 kDa. The utmost activity of the purified enzyme was detected pH 7.0, temperature 50 °C, and in the presence of metal ions like Mg2+ and Mn2+. The substantive degradation of cotton fiber and sawdust has been observed in a reasonably short period.

Conclusion
Purified cellulase from the selected isolate A. junii GAC16.2, a gut isolate of G. africana, has the potentiality to degrade cellulosic substances. This property can make the isolate a potent candidature for industrial application, as well as an effective biotechnological tool for environmental monitoring through cellulosic waste management.