bluuebunny/crossref_metadata_2025_split huggingface dataset:
An efficient system composed of maize protoplast transfection and HPLC–MS for studying the biosynthesis and regulation of maize benzoxazinoids
Authors: Gao Lei , Shen Guojing , Zhang Lingdan , Qi Jinfeng , Zhang Cuiping , Ma Canrong , Li Jing , Wang Lei , Malook Saif Ul , Wu Jianqiang 
Published: November 2019

Abstract
Background
Insect herbivory poses a major threat to maize. Benzoxazinoids are important anti-insect secondary metabolites in maize, whose biosynthetic pathway has been extensively studied. However, yet little is known about how benzoxazinoids are regulated in maize, partly due to lack of mutant resources and recalcitrance to genetic transformation. Transient systems based on mesophyll- or cultured cell-derived protoplasts have been exploited in several plant species and have become a powerful tool for rapid or high-throughput assays of gene functions. Nevertheless, these systems have not been exploited to study the regulation of secondary metabolites.

Results
A protocol for isolation of protoplasts from etiolated maize seedlings and efficient transfection was optimized. Furthermore, a 10-min-run-time and highly sensitive HPLC–MS method was established to rapidly detect and quantify maize benzoxazinoids. Coupling maize protoplast transfection and HPLC–MS, we screened a few genes potentially regulating benzoxazinoid biosynthesis using overexpression or silencing by artificial microRNA technology.

Conclusions
Combining the power of maize protoplast transfection and HPLC–MS analysis, this method allows rapid screening for the regulatory and biosynthetic genes of maize benzoxazinoids in protoplasts, before the candidates are selected for in planta functional analyses. This method can also be applied to study the biosynthesis and regulation of other secondary metabolites in maize and secondary metabolites in other plant species, including those not amenable to transformation.
Functional outcomes after total joint arthroplasty are related to the severity of Parkinson’s disease: a mid-term follow-up
Authors: Rong Xiao , Dahal Suraj , Luo Ze-yu , Zhou Kai , Yao Shun-Yu , Zhou Zong-Ke 
Published: November 2019

Abstract
Background
Performing total joint arthroplasty (TJA) in Parkinson’s disease (PD) patients may encounter a higher complication rate or worse functional outcomes compared with common patients. The relationship between PD and clinical outcomes after TJA is not fully understood.

Methods
Retrospectively, we used manual charts to investigate the clinical outcomes in 41 patients including 24 total hip arthroplasty (THA) patients (28 hips) and 18 total knee arthroplasty (TKA) patients (22 knees) with a diagnosis of PD from 2009 to 2016. The stage of PD was confirmed by Hoehn and Yahr scale. Prosthesis survivorship was estimated with revision for any reason as the endpoint.

Result
All the clinical outcomes improved significantly (p < 0.05). Subgroup analysis revealed worse functional outcomes in mid- or end-stage PD patients. Sixteen short-term mild to moderate complications were noted. Two revisions were conducted for hip periprosthetic osteolysis and postoperative knee pain. The prosthesis survivorship at 60 months for TJA, total hip arthroplasty (THA), or total knee arthroplasty (TKA) was 91.6%, 94.1%, and 87.5%, respectively.

Conclusion
Patients with PD who underwent TJA would result in excellent pain relief and gain of function. However, patients at late-stage PD may suffer from functional loss. The effectiveness of TJA in patients with severe PD remains a concern. Physician should help delay the progression of PD which may optimize and stabilize the functional outcomes of TJA.
Supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization for varus ankle osteoarthritis with excessive talar tilt angle
Authors: Qu Wenqing , Xin Dajiang , Dong Shengjie , Li Wenliang , Zheng Yanping 
Published: November 2019

Abstract
Background
Although supramalleolar osteotomy is the main joint-preserving method for the treatment of varus ankle osteoarthritis, it tends to be ineffective when ankle osteoarthritis presents in combination with an excessive talar tilt angle. The purpose of this study was to present a new surgical technique, supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization, for the treatment of varus ankle osteoarthritis with an excessive talus tilt angle and to evaluate the clinical and radiological results.

Methods
From January 2013 to October 2016, a total of 17 patients with 17 cases of varus ankle arthritis with excessive talar tilt angles (larger than 7.3°) underwent surgical treatment using our new technique. The American Orthopaedic Foot and Ankle Society (AOFAS) clinical ankle-hindfoot scale and a visual analogue scale (VAS) were used to evaluate ankle function and pain before surgery and at the last follow-up. The medial distal tibial angle (MDTA), anterior distal tibial angle (ADTA), talar tilt angle (TTA), and hindfoot moment arm values (HMAVs) were evaluated on weight-bearing radiographs acquired preoperatively and at the last follow-up.

Results
The AOFAS score improved significantly from 45.8 ± 2.1 before surgery to 84.8 ± 1.8 after surgery (p < 0.001), and the VAS score decreased from 4.9 ± 0.4 to 1.1 ± 0.2 (p < 0.001). The MDTA, TTA, and HMAV changed from 80.9° ± 0.4° to 90.1° ± 0.4°, 11.7° ± 0.6° to 1.4° ± 0.3°, and 12.6 mm ± 0.8 mm to 4.2 mm ± 0.6 mm, respectively (each p < 0.001). The ADTA showed no obvious change (p = 0.370). The staging of 11 cases (65%) improved. Intramuscular vein thrombosis of the lower limbs occurred in 1 patient 1 week after surgery, and superficial infection occurred in 1 patient.

Conclusions
Supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization can correct the load of the weight-bearing ankle and effectively improve the ankle function. As the talar tilt angle can be significantly improved after surgery, this technique can be used for the treatment of varus ankle osteoarthritis with an excessive TTA.
RETRACTED ARTICLE: Effect of sagittal femoral component alignment on biomechanics after mobile-bearing total knee arthroplasty
Authors: Koh Yong-Gon , Lee Jin-Ah , Lee Hwa-Yong , Suh Dong-Suk , Kim Hyo-Jeong , Kang Kyoung-Tak 
Published: November 2019

AbstractBackgroundRecently, there has been increasing interest in mobile-bearing total knee arthroplasty (TKA). However, changes in biomechanics with respect to femoral component alignment in mobile-bearing TKA have not been explored in depth. This study aims to evaluate the biomechanical effect of sagittal alignment of the femoral component in mobile-bearing TKA.MethodsWe developed femoral sagittal alignment models with − 3°, 0°, 3°, 5°, and 7°. We also examined the kinematics of the tibiofemoral (TF) joint, contact point on the TF joint, contact stress on the patellofemoral (PF) joint, collateral ligament force, and quadriceps force using a validated computational model under a deep-knee-bend condition.ResultsPosterior kinematics of the TF joint increased as the femoral component flexed. In addition, contact stress on the PF joint, collateral ligament force, and quadriceps force decreased as the femoral component flexed. The results of this study can assist surgeons in assessing risk factors associated with femoral component sagittal alignment for mobile-bearing TKA.ConclusionsOur results showed that slight flexion implantation may be an effective alternative technique because of its advantageous biomechanical effect. However, excessive flexion should be avoided because of potential loosening of the TF joint.
Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial
Authors:   on behalf of the Magic Bullet Working Group WP1, Cisneros José M. , Rosso-Fernández Clara María , Roca-Oporto Cristina , De Pascale Gennaro , Jiménez-Jorge Silvia , Fernández-Hinojosa Esteban , Matthaiou Dimitrios K. , Ramírez Paula , Díaz-Miguel Ramón Ortiz , Estella Angel , Antonelli Massimo , Dimopoulos George , Garnacho-Montero José 
Published: November 2019

Abstract
Background
Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined.

Methods
A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved.

Results
A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015).

Conclusions
This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.

Trial registration
ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.
Ductal tree ablation by local delivery of ethanol prevents tumor formation in an aggressive mouse model of breast cancer
Authors: Kenyon Elizabeth , Westerhuis Jennifer J. , Volk Maximilian , Hix Jeremy , Chakravarty Shatadru , Claucherty Ethan , Zaluzec Erin , Ramsey Lisa , Madaj Zach , Hostetter Galen , Eagleson Bryn , Shapiro Erik , Moore Anna , Sempere Lorenzo F. 
Published: November 2019

Abstract
Background
Prophylactic mastectomy is the most effective intervention to prevent breast cancer. However, this major surgery has life-changing consequences at the physical, emotional, psychological, and social levels. Therefore, only high-risk individuals consider this aggressive procedure, which completely removes the mammary epithelial cells from which breast cancer arises along with surrounding tissue. Here, we seek to develop a minimally invasive procedure as an alternative to prophylactic mastectomy by intraductal (ID) delivery of a cell-killing solution that locally ablates the mammary epithelial cells before they become malignant.

Methods
After ID injection of a 70% ethanol-containing solution in FVB/NJ female animals, ex vivo dual stained whole-mount tissue analysis and in vivo X-ray microcomputed tomography imaging were used to visualize ductal tree filling, and histological and multiplex immunohistochemical assays were used to characterize ablative effects and quantitate the number of intact epithelial cells and stroma. After ID injection of 70% ethanol or other solutions in cancer-prone FVB-Tg-C3(1)-TAg female animals, mammary glands were palpated weekly to establish tumor latency and examined after necropsy to record tumor incidence. Statistical difference in median tumor latency and tumor incidence between experimental groups was analyzed by log-rank test and logistic mixed-effects model, respectively.

Results
We report that ID injection of 70% ethanol effectively ablates the mammary epithelia with limited collateral damage to surrounding stroma and vasculature in the murine ductal tree. ID injection of 70% ethanol into the mammary glands of the C3(1)-TAg multifocal breast cancer model significantly delayed tumor formation (median latency of 150 days in the untreated control group [n = 25] vs. 217 days in the ethanol-treated group [n = 13], p value < 0.0001) and reduced tumor incidence (34% of glands with tumors [85 of 250] in the untreated control group vs. 7.3% of glands with tumor [7 of 95] in the ethanol-treated group, risk ratio = 4.76 [95% CI 1.89 to 11.97, p value < 0.0001]).

Conclusions
This preclinical study demonstrates the feasibility of local ductal tree ablation as a novel strategy for primary prevention of breast cancer. Given the existing clinical uses of ethanol, ethanol-based ablation protocols could be readily implemented in first-in-human clinical trials for high-risk individuals.
RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants
Authors: Lin Hai , Hargreaves Katherine A. , Li Rudong , Reiter Jill L. , Wang Yue , Mort Matthew , Cooper David N. , Zhou Yaoqi , Zhang Chi , Eadon Michael T. , Dolan M. Eileen , Ipe Joseph , Skaar Todd C. , Liu Yunlong 
Published: November 2019

AbstractSingle nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis.
Common DNA sequence variation influences 3-dimensional conformation of the human genome
Authors: Gorkin David U. , Qiu Yunjiang , Hu Ming , Fletez-Brant Kipper , Liu Tristin , Schmitt Anthony D. , Noor Amina , Chiou Joshua , Gaulton Kyle J. , Sebat Jonathan , Li Yun , Hansen Kasper D. , Ren Bing 
Published: November 2019

AbstractBackgroundThe 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation.ResultsTo address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk.ConclusionOur results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized.
Safety and efficacy of PG102P for the control of pruritus in patients undergoing hemodialysis (SNUG trial): study protocol for a randomized controlled trial
Authors: Kim Yong Chul , Park Jae Yoon , Oh Sohee , Cho Jang-Hee , Chang Jae Hyun , Choi Dae Eun , Park Jung Tak , Lee Jung Pyo , Kim Sejoong , Kim Dong Ki , Ryu Dong-Ryeol , Lim Chun Soo 
Published: November 2019

AbstractBackgroundPruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared fromActinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo.MethodsThis multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck’s Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated.DiscussionThe SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis.Trial registrationClinical Trials.gov,NCT03576235. Registered on 4 July 2018.
The effects of oral vitamin D supplementation on the prevention of peritoneal dialysis-related peritonitis: study protocol for a randomized controlled clinical trial
Authors: Zhang Yu-hui , Xu Xiao , Pi Hai-chen , Yang Zhi-kai , Johnson David W. , Dong Jie 
Published: November 2019

Abstract
Background
Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis.

Methods
This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset).

Discussion
This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients.

Trial registration
Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.
ENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis
Authors: Cotton S. M. , Berk M. , Watson A. , Wood S. , Allott K. , Bartholomeusz C. F. , Bortolasci C. C. , Walder K. , O’Donoghue B. , Dean O. M. , Chanen A. , Amminger G. P. , McGorry P. D. , Burnside A. , Uren J. , Ratheesh A. , Dodd S. 
Published: November 2019

Abstract
Background
First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups.

Methods/design
ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15–25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration.

Discussion
Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry.

Trial registration
Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.