bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone health in symptomatic carriers of haemophilia A: a protocol for a multicentre prospective matched-cohort study
Authors: Tang Grace H , Norris Erin , Petrucci Jessica , James Paula D , Lee Adrienne , Poon Man-Chiu , Floros Georgina , Boma-Fischer Laurence , Teitel Jerry , Nisenbaum Rosane , Sholzberg Michelle 
Published: December 2019

IntroductionHaemophilia A is an X linked inherited bleeding disorder, caused by a decrease in coagulation factor VIII. Persons with haemophilia experience repeated musculoskeletal bleeding, which can lead to decreased range of motion, irreversible joint damage, low bone mineral density (BMD), and are at greater risk for osteoporosis. Women heterozygous for this mutation, also known as haemophilia A carriers, can have bleeding symptoms and even experience joint bleeding evidenced by radiological soft tissue and osteochondral changes. The prevalence of low BMD as a risk factor for osteoporosis has never been evaluated in carriers of haemophilia, and given the recent findings which suggest subclinical musculoskeletal bleeding in carrier women, we hypothesise that they too are at risk of impaired bone health.Methods and analysisThis is a national multicentre prospective matched-cohort study to compare BMD T-scores among symptomatic haemophilia A carriers, 50 years of age or older, with age-matched and body mass index-matched non-carriers (1:1). A total of 40 symptomatic carriers and 40 matched non-carriers will be recruited from St. Michael’s Hospital, Kingston General Hospital in Ontario, Canada and Foothills Medical Centre in Alberta, Canada. Multivariable linear regression models will be used to estimate the effect of haemophilia carriership on BMD T-scores, adjusting for age, body mass index and other relevant covariates.Ethics and disseminationThe protocol was designed and will be conducted in compliance with applicable laws, rules and regulations. Research ethics approval was obtained from St. Michael’s Hospital, Foothills Medical Centre, and Kingston General Hospital. Findings will be presented at international venues such as the American Society of Haematology and the World Federation of Haemophilia World Congress. The authors of this study will seek publication in journals such as Blood, Journal of Thrombosis and Haemostasis, American Journal ofHematology and British Journal ofHaematology.
Twelve-month outcome in patients with stroke and atrial fibrillation not suitable to oral anticoagulant strategy: the WATCH-AF registry
Authors: Guidoux Celine , Meseguer Elena , Ong Elodie , Lavallée Philippa C , Hobeanu Cristina , Monteiro-Tavares Linsay , Charles Hugo , Cabrejo Lucie , Martin-Bechet Anna , Rigual Ricardo , Nighoghossian Norbert , Amarenco Pierre 
Published: December 2019

AimsLong-term oral anticoagulant (LTOAC) reduces ischaemic stroke recurrences. Because of bleeding history, frailty, cognitive impairment, comorbidities or patient refusal, many cannot be discharged from stroke unit on LTOAC. Proportion and outcome of these patients is not well known.MethodsThe Warfarin Aspirin Ten-a inhibitor Cerebral infarction and Haemorrhage and atrial fibrillation (AF) prospective registry enrolled consecutive patients with an acute stroke associated with AF. Scales to evaluate stroke severity, disability, functional independence, cognition, risk of fall, ischaemic and haemorrhagic risk stratification were systematically collected at admission, discharge, 3 and 12 months poststroke. The two main 12-month endpoints were death or dependency (modified Rankin Scale >3) and recurrent stroke.ResultsAmong 400 patients (370 brain infarctions, 30 brain haemorrhages), 274 were discharged on LTOAC, 31 died before discharge and 95 (24%) were not discharge on anticoagulant (frailty, bedridden or demented, EHRA/ESC contraindication to anticoagulant). Death or dependency and recurrent stroke occurred in 19.8% and 9.9%, respectively, in patient on anticoagulant, and 33.5% and 27.2% in those not on anticoagulant (both p<0.001). Patient not anticoagulated at discharge had a 1.6-fold increase in the risk of death or dependency at 12 months (HR 1.65; 95% CI 1.05 to 2.61; p=0.032) and a 2.5-fold increase in the risk of stroke (HR 2.46; 95% CI 1.36 to 4.44; p=0.003).ConclusionsOne-fourth of patients with stroke associated with AF are not discharged on anticoagulation and have a dramatic increase in the risk of death or dependency at 12 months as well as recurrent stroke. Alternative treatments should be trialled in these patients.
Holographic complexity of Born–Infeld black holes
Authors: Meng Kun 
Published: December 2019

AbstractIn this paper, according to CA duality, we study complexity growth of Born–Infeld (BI) black holes. As a comparison, we study action growth of dyonic black holes in Einstein–Maxwell gravity at the beginning. We study action growth of electric BI black holes in dRGT massive gravity, and find BI black holes in massive gravity complexify faster than the Einstein gravity counterparts. We study action growth of the purely electric and magnetic Einstein–Born–Infeld (EBI) black holes in general dimensions and the dyonic EBI black holes in four-dimensions, and find the manners of action growth are different between electric and magnetic EBI black holes. In all the gravity systems we considered, we find action growth rates vanish for the purely magnetic black holes, which is unexpected. In order to ameliorate the situation, we add the boundary term of matter field to the action and discuss the outcomes of the addition.
Community-Based Pilot Study of a Screening Program for Gastric Cancer in a Chinese Population
Authors: Ji Lin , Liu Zengchao , Zhou Bin , Cai Ying , An Fangmei , Wang Lei , Lv Zhifa , Xia Min , Yang Jianbo , Yuan Jianfen , Wang Hui , Zhou Zhiyi , Yang Shudong , Hu Lei , Zhan Qiang 
Published: December 2019

Abstract
A majority of gastric cancer cases in China are diagnosed at advanced stages, chiefly due to lack of an established routine nationwide screening program. This study evaluated the effectiveness of a novel screening program for gastric cancer. Seven geographic communities were randomly selected, and residents ages 40–69 years were screened. Serologic tests of Helicobacter pylori antibodies and pepsinogens, and positive family history of gastric cancer in first-degree relatives (FDR), were used to differentiate individuals for further gastroscopic examination and gastric mucosal biopsies. Among 7,773 individuals who underwent examination of serum markers, gastric cancer was detected in 14 (1.8%; 10 men). The rate in terms of gastric cancer cases per 100 gastroendoscopies was 1.6% (14/872), which was greater than 0.87% previously reported. Eleven of 14 patients with gastric cancer (78.6%) were FDRs of patients with gastric cancer. Two-thirds of the subjects with cardia gastric cancer were FDRs of individuals with gastric cancer rather than cardia gastric cancer. Comparative analysis indicated that the gastric cancer subjects were significantly more likely to be FDRs of patients with gastric cancer, in contrast to those without gastric cancer. All the individuals with gastric cancer were aged ≥50 years. After conducting a reverse analysis, we propose a novel screening program for gastric cancer. In conclusions, the populations most vulnerable to gastric cancer are those with positive family history of gastric cancer in FDRs, male gender, and aged 50 years or older. This screening program using fewer serum markers combined individual risk factors, mainly FDRs, is novel for identification of high-risk individuals for further gastroscopy in detecting early gastric cancer.
Implications for the monitoring of patients with multiple myeloma undergoing treatment with the anti-CD38 monoclonal daratumumab
Authors: Thirkettle Sally , Russell Joanne , Wilson Sarah , Ganijee Tasneem , Kulkarni Samar , Cavet Jim , Monaghan Phillip J 
Published: December 2019

Background The novel daratumumab immunotherapy is a human IgG1 kappa antibody targeted against CD38, which is almost universally expressed on myeloma plasma cells. Daratumumab has efficacy in clinical trials for the treatment of multiple myeloma; however, it complicates laboratory monitoring of the serological response to treatment, as it is detected by serum electrophoresis and/or immunofixation. Methods Laboratory reports of electrophoresis patterns serially performed in a single laboratory of six patients with relapsed multiple myeloma receiving daratumumab therapy as part a clinical trial were reviewed retrospectively. Results Post administration of daratumumab therapy, an additional band was visible by serum electrophoresis, migrating to the mid-gamma region, which was confirmed as IgG kappa by immunofixation. In five out of the six patients, this band was quantified at <2.0 g/L. For one patient, this band co-migrated with the patient’s disease paraprotein band, so both bands were quantified together. The appearance of an apparent second paraprotein band while receiving treatment for multiple myeloma can cause anxiety for patients, confusion for healthcare workers and may also underestimate complete remission rates. Conclusions The clinical laboratory must be aware of the interference of daratumumab in serum electrophoresis. Effective communication between clinicians and the laboratory is essential for the production of clinically valuable, non-misleading reports for these patients.
Distance Traveled to Head and Neck Cancer Provider: A Measure of Socioeconomic Status and Access
Authors: Massa Sean T. , Liebendorfer Adam P. , Zevallos Jose P. , Mazul Angela L. 
Published: December 2019

ObjectiveImproved head and neck cancer survival has been associated with traveling farther distances for treatment, potentially due to patients seeking higher‐quality facilities. This study investigates the role of both facility and confounding patient factors on this relationship.Study DesignReview of national registry data.SettingNational Cancer Database.Subjects and MethodsAdults with head and neck cancer diagnosed from 2004 to 2014 were identified. Overall survival was compared among distance‐to‐facility quartiles via univariate and multivariate survival models. Then, the analysis was stratified by facility and patient factors, and the association between distance and survival was compared among strata.ResultsOverall survival was worst in the shortest‐distance quartile (<5 miles; median survival, 80.7 months; 95% CI, 79.2‐82.3), while other distance groups showed similar survival (range, 96.4‐104 months). This finding remained in the multivariate model (adjusted hazard ratio vs first distance quartile: 0.88; 95% CI, 0.87‐0.89). The association between survival and distance persisted in all subgroups when stratified by facility volume and type (adjusted hazard ratio range, 0.82‐0.91), suggesting that facility quality does not fully account for this association. When stratified by income, distance remained statistically associated with survival but with a smaller effect size than that of income.ConclusionThe association between distance to treating facility and head and neck cancer survival is limited to patients with worse survival outcomes living within 5 miles of the facility and is not fully explained by measures of facility quality.
Prognosis comparison between wait and watch and surgical strategy on rectal cancer patients after treatment with neoadjuvant chemoradiotherapy: a meta-analysis
Authors: Pang Kai , Rao Quan , Qin Shengqi , Jin Lan , Yao Hongwei , Zhang Zhongtao 
Published: December 2019

Background: After achieving a clinical complete response through neoadjuvant chemoradiotherapy, a nonoperative management approach for rectal cancer patients known as Wait and Watch (W&W) has gained increasing attention. However, the W&W strategy has been related to higher local recurrence and ambiguous long-term survival. This meta-analysis compared key prognosis indicators between W&W and surgical treatment in an effort to clarify some long-standing points of confusion. Methods: Pubmed, Web of Science, EMbase, Cochrane Library were searched for relevant researches comparing W&W with surgery treatment, with a time criteria set from 1 January 2002 to 4 July 2019. Endpoints were 2-year local regrowth/recurrence, 2-year distant metastasis (plus local regrowth/recurrence), 3- and 5-year disease-free survival (DFS), and overall survival (OS). Results: In total, nine studies with 801 patients were enrolled, of which 348 were managed by W&W and 453 by surgery. Surgery patients were further divided into a pathological complete response (pCR) group (all included patients achieved pCR) and a surgery group (consisting of both pCR and non-pCR patients without deliberate screening). Compared with the surgery group, W&W patients have higher 3- and 5-year OS, and are not inferior on 2-year local regrowth (LR), 2-year distant metastasis (DM)/DM+LR, and 3- and 5-year DFS. On the other hand, compared with the pCR group, the W&W group is inferior on 2-year LR, 3- and 5-year DFS, and 5-year OS, and not inferior on 2-year DM/DM+LR and 3-year OS. Conclusions: In contrast with patients undergoing surgical treatment, the W&W group has higher 3- and 5-year OS, and is not inferior on other major prognostic indicators, which, however, is based on the fact that the tumor stage in the W&W group is generally earlier. Versus surgically treated patients who acquired pCR, W&W group is inferior on all major prognostic indicators except 2-year DM/DM+LR and 3-year OS. Additionally, by comparison of cCR definitions across different studies, we conclude that implementation of the strictest cCR criteria is critical for W&W patients to acquire maximum prognostic benefit.
Hounsfield unit and its correlation with spontaneous expulsion of lower ureteric stone
Authors: Bokka Sriharsha , Jain Amit 
Published: December 2019

Background: Hounsfield unit (HU) is the measure of stone density, and is utilized in the predetermination of type of stone. The purpose of this study was to identify some factors in noncontrast computed tomography (NCCT) of kidney, ureter, and bladder (KUB) that are easily extractable and can be used to determine the outcome of expectant management. Methods: All patients 18–50 years of age who presented with flank pain and diagnosed as having lower ureteric calculi of size 5–10 mm by NCCT KUB were included in the study. HU of stone was calculated from the mean HU at three different regions of interest. We prescribed tamsulosin for 4 weeks as medical expulsive therapy. We divided the patients into two groups: group A included patients with successful expulsion of stone, and group B included patients who failed to pass stone. We compared age, gender, laterality, stone size in axial and coronal section of NCCT, HU of stone, blood urea, creatinine, and renal parenchymal thickness. Results: A total of 180 patients with lower ureteric calculus were included in the study. The mean age of patients was 34 years, with male:female ratio of 2.3:1. Of these 180 patients, 119 (66%) successfully expelled the stone and were included in group A, with the remaining 61 (34%) forming group B. In univariate analysis, longitudinal diameter of stone ( p < 0.001), transverse diameter of stone ( p < 0.001) and high HU ( p < 0.001) were significantly associated with failure of expulsion. However, in multivariate analysis only longitudinal diameter of stone ( p < 0.001) differed significantly among groups. Differences in HU ( p = 0.179) and transverse diameter of stone ( p = 0.108) did not reach significance level. Conclusions: Lower ureteric calculi are definitely amenable to conservative management. Longitudinal diameter of stone can be a useful parameter; however, HU and its derivatives cannot be used as a predictor of outcome.
Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing–remitting multiple sclerosis in a real-world clinical setting: PROTEC
Authors: Berger T , Brochet B , Brambilla L , Giacomini PS , Montalbán X , Vasco Salgado A , Su R , Bretagne A 
Published: December 2019

Background Patient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing–remitting multiple sclerosis (RRMS) disease. Objective The aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic. Methods PROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated. Results Unadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall ( n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline. Conclusion At 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective. Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708, https://clinicaltrials.gov/ct2/show/NCT01930708 .
Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling
Authors: Yu Xin , Wan Qilong , Ye Xiaoling , Cheng Yuet , Pathak Janak L. , Li Zubing 
Published: December 2019

AbstractBackgroundHypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown.MethodsIn this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model.ResultsThe peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and μ-CT results showed that CoCl2treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect.ConclusionsThe in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.
Renal cell carcinoma lung metastases treated by radiofrequency ablation integrated with systemic treatments: over 10 years of experience
Authors: Gonnet Alexis , Salabert Laura , Roubaud Guilhem , Catena Vittorio , Brouste Véronique , Buy Xavier , Gross Goupil Marine , Ravaud Alain , Palussière Jean 
Published: December 2019

Abstract
Background
To determine safety and efficacy of radiofrequency ablation (RFA) for local treatment of lung metastases of renal cell carcinoma (RCC), sequenced or combined with systemic treatments.

Methods
Retrospectively, we studied 53 patients treated by RFA for a maximum of six lung metastases of RCC. The endpoints were local efficacy, overall (OS), disease-free (DFS), pulmonary progression-free (PPFS) and systemic treatment-free (STFS) survivals, complications graded by the CTCAE classification and factors associated with survivals. Potential factors analysed were: clinical and pathological data, tumoral staging of TNM classification, primary tumor histology, Fuhrman’s grade, age, number and size of lung metastases and extra-pulmonary metastases pre-RFA.

Results
One hundred metastases were treated by RFA. Median follow-up time was 61 months (interquartile range 90–34). Five-year OS was 62% (95% confidence interval (CI): 44–75). Median DFS was 9.9 months (95% CI: 6–16). PPFS at 1 and 3 years was 58.9% (95%CI: 44.1–70.9) and 35.2% (95%CI: 21.6–49.1), respectively. We observed 3% major complications (grade 3 and 4 of CTCAE classification). Local efficacy was 91%. Median STFS was 28.3 months. Thirteen patients (25%) with lung recurrence could be treated by another RFA. T3/T4 tumors had significantly worse OS, PPFS and STFS. Having two or more lung metastases increased the risk of pulmonary progression more than threefold.

Conclusion
Integrated to systemic treatment strategy, RFA is safe and effective for the treatment strategy of lung metastasis from RCC with good OS and long systemic treatment-free survival. RFA offers the possibility of repeat procedures, with low morbidity.
Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness
Authors: Rutkowska Daria A. , Mokoena Nobalanda B. , Tsekoa Tsepo L. , Dibakwane Vusi S. , O’Kennedy Martha M. 
Published: December 2019

Abstract
Background
African horse sickness (AHS) is a severe arthropod-borne viral disease of equids, with a mortality rate of up to 95% in susceptible naïve horses. Due to safety concerns with the current live, attenuated AHS vaccine, alternate safe and effective vaccination strategies such as virus-like particles (VLPs) are being investigated. Transient plant-based expression systems are a rapid and highly scalable means of producing such African horse sickness virus (AHSV) VLPs for vaccine purposes.

Results
In this study, we demonstrated that transient co-expression of the four AHSV capsid proteins in agroinfiltrated Nicotiana benthamiana dXT/FT plants not only allowed for the assembly of homogenous AHSV-1 VLPs but also single, double and triple chimeric VLPs, where one capsid protein originated from one AHS serotype and at least one other capsid protein originated from another AHS serotype. Following optimisation of a large scale VLP purification procedure, the safety and immunogenicity of the plant-produced, triple chimeric AHSV-6 VLPs was confirmed in horses, the target species.

Conclusions
We have successfully shown assembly of single and double chimeric AHSV-7 VLPs, as well as triple chimeric AHSV-6 VLPs, in Nicotiana benthamiana dXT/FT plants. Plant produced chimeric AHSV-6 VLPs were found to be safe for administration into 6 month old foals as well as capable of eliciting a weak neutralizing humoral immune response in these target animals against homologous AHSV virus.