bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combination of microfracture with induction of Wnt / β- Catenin pathway, leads to enhanced cartilage regeneration
Authors: Schizas Nikitas P. , Savvidou Olga , Diamantopoulou Kalliopi , Papadakis Stamatios , Papagelopoulos Panayiotis J. , Triantafyllopoulos Ioannis K. 
Published: December 2019

Abstract
Introduction
Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling.

Materials and methods
Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted.

Results
Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six.

Conclusion
The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model.
Knowledge, attitude and practice of surgical staff towards preoperative surgical antibiotic prophylaxis at an academic tertiary hospital in Sudan
Authors: Ahmed Ali Mohammed , Nasr Sara , Ahmed Almegdad Mohamed , Elkhidir Osama 
Published: December 2019

AbstractBackgroundSurgical site infections (SSIs) are among the most common serious complications after surgery and associated with preventable morbidity, mortality, and increased health care costs. The use of surgical antimicrobial prophylaxis (SAP) is an effective measure that helps to protect against SSIs. This study aims to evaluate the knowledge, attitude, and practice of surgical staff towards preoperative antibiotic prophylaxis in surgery department at an academic tertiary hospital in Sudan.MethodologyAn observational descriptive study was conducted among doctors in the surgery department at an academic tertiary hospital in Sudan in order to assess their knowledge, attitude, and practice (KAP) towards surgical antibiotic prophylaxis (SAP). A four-section multiple-choice questionnaire was designed and hand-delivered to registered doctors in the surgery department at an academic tertiary hospital in Sudan. The WHO guidelines were used to evaluate the answers of the participants.ResultsOut of 56 doctors requested to participate in this study, only 49 responded and their response rate was 87.5%. Six (12.5%) surgeons had good knowledge about appropriate SAP. However, 16.3 and 24.5% of the respondents were aware of appropriate SAP in the case of Ig E-mediated reaction to penicillin and risk of Gram-negative infections, respectively. The surgeon’s attitude score about the need for local and national guidelines for SAP was 98 and 100%, respectively. Accordance of the physician’s practice with ASHP guidelines regarding timing of the first dosage of SAP was 35.4% while correct administration of an intraoperative dose was 42.9% in agreement with the guideline. 53.1% knows when to stop SAP after surgery correctly.ConclusionAlthough the participants in this study showed a positive attitude towards antibiotic prophylaxis guidelines, their knowledge and strict adherence to a protocolized practice per WHO checklist should be improved in order to reduce the incidence of preventable surgical site infections.
Criteria for site selection in industry-sponsored clinical trials: a survey among decision-makers in biopharmaceutical companies and clinical research organizations
Authors: Dombernowsky Tilde , Haedersdal Merete , Lassen Ulrik , Thomsen Simon Francis 
Published: December 2019

Abstract
Background
Knowledge of what the pharmaceutical industry emphasizes when assessing trial sites during site selection is sparse. A better understanding of this issue can improve the collaboration on clinical trials and increase knowledge of how to attract and retain industry-sponsored trials. Accordingly, we investigated which site-related qualities multinational biopharmaceutical companies and clinical research organizations (CROs) find most important during site selection.

Methods
An online survey among decision-makers for trial site selection in the Nordic countries employed at multinational biopharmaceutical companies and CROs was conducted. The respondents’ experiences with and perceptions of site selection were addressed to evaluate the relative importance of site-related qualities. We included up to four respondents per company, representing different geographic regions. Descriptive statistics were used to summarize findings.

Results
Of 49 eligible companies, 20 biopharmaceutical companies and 23 CROs participated. In total, 83 responses were analyzed (estimated response rate 78%). A relative importance of site-related qualities was identified: For example, 88% (binomial 95% confidence interval [CI] ±7%) preferred reaching enrollment goals at trial sites in their region 10% quicker rather than cutting the costs at all sites by 20%. Likewise, 42% (CI ±11%) of the respondents preferred that trial sites were best at having the first patients ready for inclusion right after site initiation visit compared to having good data entry, documentation, and reporting practice (25% [CI ±9%]), easily reachable site personnel and backup (23% [CI ±9%]), fast contractual procedure times (6% [CI ±5%]), a key opinion leader associated with the site (3% [CI ±4%]), and updated equipment and facilities (1% [CI ±2%]). In total, 75% [CI ±9%] agreed that their company would be interested in cooperating with an inexperienced trial site if the site had access to a large patient population and 52% [CI ±11%] had experienced that their company selected an inexperienced trial site in favor of an experienced site due to a higher level of interest and commitment.

Conclusions
This study indicates that recruitment-related factors are pivotal to the pharmaceutical industry when assessing trial sites during site selection. Data quality-related factors seem highly valued especially in early phase trials whereas costs and investigator’s publication track record are less important. Experience in conducting clinical trials is not imperative. However, this applies primarily to late phase trials.
Budgeting of non-commercial clinical trials: development of a budget tool by a public funding agency
Authors: Nevens Hilde , Harrison Jillian , Vrijens France , Verleye Leen , Stocquart Nelle , Marynen Elisabeth , Hulstaert Frank 
Published: December 2019

Abstract
Background
Investigator-led multicentre randomised trials are essential to generate evidence on the optimal use of medical interventions. These non-commercial trials are often hampered by underfunding, which may lead to difficulties in gathering a team with the necessary expertise, a delayed trial start, slow recruitment and even early trial discontinuation. As a new public funder of pragmatic clinical trials, the KCE Trials programme was committed to correctly pay all trial activities in order to assure timely delivery of high-quality trial results. As no appropriate trial budget tool was readily publicly available that took into account the costs for the sponsor as well as the costs for participating sites, we developed a tool to make the budgeting of a clinical trial efficient, transparent and fair across applicants.

Methods
All trial-related activities of the sponsor and sites were categorised, and cost drivers were identified. All elements were included in a spreadsheet tool allowing the sponsor team to calculate in detail the various activities of a clinical trial and to appreciate the budget impact of specific cost drivers, e.g. a delay in recruitment. Hourly fees by role were adapted from published data. Fixed amounts per activity were developed when appropriate.

Results
This publicly available tool has already been used for 17 trials funded since the start of the KCE Trials programme in 2016, and it continues to be used and improved. This budget tool is used together with additional risk-reducing measures such as a multistep selection process with advance payments, a recruitment feasibility check by sponsor and funder, a close monitoring of study progress and a milestone-based payment schedule with the last payment made when the manuscript is submitted.

Conclusions
The budget tool helps the KCE Trials programme to answer relevant research questions in a timely way, within budget and with high quality, a necessary condition to achieve impact of this programme for patients, clinical practice and healthcare payers.
Landiolol, an ultra-short acting beta-1 blocker, for preventing postoperative lung cancer recurrence: study protocol for a phase III, multicenter randomized trial with two parallel groups of patients
Authors: Yamamoto Haruko , Hamasaki Toshimitsu , Onda Kaori , Nojiri Takashi , Aragaki Masato , Horie Nao , Sato Norihiro , Hida Yasuhiro 
Published: December 2019

Abstract
Background
Recurrence of cancer after curative surgery is a major problem after most cancer treatments. Increased sympathetic activity during the perioperative period could promote cancer cell invasion to blood vessels and angiogenesis, resulting in cancer metastasis. Recent studies showed that use of beta blockers can be associated with the prolonged survival of patients with cancer. The objective of this study is to evaluate the preventive effects of landiolol hydrochloride, which is an ultra-short-acting beta-1-selective blocker that has been developed in Japan, on reducing recurrence of cancer after curative surgery for patients with lung cancer.

Methods
The present study is a phase III, multicenter, randomized trial with two parallel groups of patients with lung cancer, comparing surgery alone and surgery with landiolol administration for three days during the perioperative period. A total of 400 patients will be enrolled from 12 Japanese institutions. The primary endpoint is two-year relapse-free survival and overall survival after curative surgery for lung cancer. The secondary endpoints are additional treatment after recurrence of cancer, safety events, and the incidence of postoperative complications.

Discussion
The principal question addressed in this trial is whether landiolol can reduce recurrence of cancer after curative surgery for lung cancer.

Trial registration
Japan Registry of Clinical Trials, jRCT2011180004. Registered 17 January 2019.
Contralateral migration of Kirschner wire from right acromioclavicular joint to left side of neck: a case report
Authors: Ko How-Yun , Lee Ka-Wo 
Published: December 2019

AbstractBackgroundKirschner wire migration is one of the most common complications after internal fixation of fracture or dislocation in the shoulder region. However, cases of contralateral wire migration are rare. We present a case of contralateral loosened Kirschner wire migration from the right acromioclavicular joint to the left side of the neck without damage to any important structures or great vessels.Case presentationWe report a case of a loosened Kirschner wire migrating from the right acromioclavicular joint to the left side of the neck in a 34-year-old Taiwanese man following a route of transversal, descendant, and then ascendant directions. The Kirschner wire was removed by exploratory neck dissection under C-arm fluoroscopy assistance without complication.ConclusionWire migration may occur after surgical treatment with or without clinical complaint. Several hypotheses for the mechanism of wire migration have been postulated, including muscular activity, respiratory motion, gravity, and motion of upper extremity. Therefore, the importance of follow-up should be communicated to the patient. Once wire loosening or migration is noted, the implant should be removed immediately under intraoperative C-arm fluoroscopy or ultrasound assistance.
Speech enhancement methods based on binaural cue coding
Authors: Wang Xianyun , Bao Changchun 
Published: December 2019

AbstractAccording to the encoding and decoding mechanism of binaural cue coding (BCC), in this paper, the speech and noise are considered as left channel signal and right channel signal of the BCC framework, respectively. Subsequently, the speech signal is estimated from noisy speech when the inter-channel level difference (ICLD) and inter-channel correlation (ICC) between speech and noise are given. In this paper, exact inter-channel cues and the pre-enhanced inter-channel cues are used for speech restoration. The exact inter-channel cues are extracted from clean speech and noise, and the pre-enhanced inter-channel cues are extracted from the pre-enhanced speech and estimated noise. After that, they are combined one by one to form a codebook. Once the pre-enhanced cues are extracted from noisy speech, the exact cues are estimated by a mapping between the pre-enhanced cues and a prior codebook. Next, the estimated exact cues are used to obtain a time-frequency (T-F) mask for enhancing noisy speech based on the decoding of BCC. In addition, in order to further improve accuracy of the T-F mask based on the inter-channel cues, the deep neural network (DNN)-based method is proposed to learn the mapping relationship between input features of noisy speech and the T-F masks. Experimental results show that the codebook-driven method can achieve better performance than conventional methods, and the DNN-based method performs better than the codebook-driven method.
View synthesis based on spatio-temporal continuity
Authors: Yao Li , Lu Qiurui , Li Xiaomin 
Published: December 2019

AbstractFree viewpoint video is generated on the basis of a video plus depth (V+D) virtual point rendering framework. Because of the limited bandwidth of video transmission, depth-image-based rendering (DIBR) has become a common method. Most DIBR methods not only have holes and ghost artifacts but also have problems with time continuity, leading to frequent flickers. In this paper, we make full use of time domain information in video sequences and adjacent frames to extract the static background image of the whole scene. Furthermore, we propose a weighted-fusion hole-filling method based on static background to fill holes and maintain time continuity. Experimental results show that the proposed method can improve the quality of virtual view images and strengthen spatio-temporal continuity.
Factors associated with alexithymia among the Lebanese population: results of a cross-sectional study
Authors: Obeid Sahar , Akel Marwan , Haddad Chadia , Fares Kassandra , Sacre Hala , Salameh Pascale , Hallit Souheil 
Published: December 2019

Abstract
Background
To our knowledge, no research project on alexithymia has been conducted in Lebanon. The objective of this study was to assess risk factors associated with alexithymia in a representative sample of the Lebanese population.

Methods
This is a cross-sectional study, conducted between November 2017 and March 2018, which enrolled 789 participants from al districts of Lebanon. The Toronto Alexithymia Scale (TAS-20) was used to measure alexithymia, the Alcohol Use Disorders Identification Test to assess alcohol use, drinking patterns, and alcohol-related issues, the Rosenberg self-esteem scale to evaluate self-worth, the Hamilton depression rating scale and Hamilton Anxiety Scale to screen for depression and anxiety respectively, the Three-Dimensional Work Fatigue Inventory to measure physical, mental and emotional work fatigue respectively, the Columbia–Suicide Severity Rating Scale to evaluate suicidal ideation and behavior, the Perceived Stress Scale to measure stress, the Liebowitz Social Anxiety Scale to help identify a social anxiety disorder and the Quick Emotional Intelligence Self-Assessment to measure emotional intelligence.

Results
The results showed that 395 (50.4%) were not alexithymic, 226 (28.8%) were possible alexithymic, whereas 163 (20.8%) were alexithymic according to established clinical cutoffs. Stress (Beta = 0.456), emotional exhaustion (Beta = 0.249), the AUDIT score (Beta = 0.225) and anxiety (Beta = 0.096) were associated with higher alexithymia, whereas low emotional work fatigue (Beta = −0.114) and being married (Beta = −1.933) were associated with lower alexithymia.
People in distress (Beta = 7.33) was associated with higher alexithymia scores, whereas people with high wellbeing (Beta = −2.18), an intermediate (Beta = −2.90) and a high (Beta = −2.71) family monthly income were associated with lower alexithymia compared to a low one.

Conclusion
Alexithymia appears to be influenced by many factors, including stress, anxiety, and burnout. To reduce its prevalence, it is important that health professionals educate the public about these factors. Further studies on a larger scale are needed to confirm our findings.
Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment
Authors: van Wageningen Thecla A. , Vlaar Eva , Kooij Gijs , Jongenelen Cornelis A. M. , Geurts Jeroen J. G. , van Dam Anne-Marie 
Published: December 2019

AbstractMultiple Sclerosis (MS) is the most common cause of acquired neurological disability in young adults, pathologically characterized by leukocyte infiltration of the central nervous system, demyelination of the white and grey matter, and subsequent axonal loss. Microglia are proposed to play a role in MS lesion formation, however previous literature has not been able to distinguish infiltrated macrophages from microglia. Therefore, in this study we utilize the microglia-specific, homeostatic markers TMEM119 and P2RY12 to characterize their immunoreactivity in MS grey matter lesions in comparison to white matter lesions. Furthermore, we assessed the immunological status of the white and grey matter lesions, as well as the responsivity of human white and grey matter derived microglia to inflammatory mediators. We are the first to show that white and grey matter lesions in post-mortem human material differ in their immunoreactivity for the homeostatic microglia-specific markers TMEM119 and P2RY12. In particular, whereas immunoreactivity for TMEM119 and P2RY12 is decreased in the center of WMLs, immunoreactivity for both markers is not altered in GMLs. Based on data from post-mortem human microglia cultures, treated with IL-4 or IFNγ+LPS and on counts of CD3+ or CD20+ lymphocytes in lesions, we show that downregulation of TMEM119 and P2RY12 immunoreactivity in MS lesions corresponds with the presence of lymphocytes and lymphocyte-derived cytokines within the parenchyma but not in the meninges. Furthermore, the presence of TMEM119+ and partly P2RY12+ microglia in pre-active lesions as well as in the rim of active white and grey matter lesions, in addition to TMEM119+ and P2RY12+ rod-like microglia in subpial grey matter lesions suggest that blocking the entrance of lymphocytes into the CNS of MS patients may not interfere with all possible effects of TMEM119+ and P2RY12+ microglia in both white and grey matter MS lesions.
Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis
Authors: Elkjaer Maria L. , Frisch Tobias , Reynolds Richard , Kacprowski Tim , Burton Mark , Kruse Torben A. , Thomassen Mads , Baumbach Jan , Illes Zsolt 
Published: December 2019

AbstractTo identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Compared to 25 WM controls, 6713 out of 18,609 genes were significantly differentially expressed in MS tissues (FDR < 0.05). A computational systems medicine analysis was performed to describe the MS lesion endophenotypes. The cellular source of specific molecules was examined by RNAscope, immunohistochemistry, and immunofluorescence. To examine common lesion specific mechanisms, we performed de novo network enrichment based on shared differentially expressed genes (DEGs), and found TGFβ-R2 as a central hub. RNAscope revealed astrocytes as the cellular source of TGFβ-R2 in remyelinating lesions. Since lesion-specific unique DEGs were more common than shared signatures, we examined lesion-specific pathways and de novo networks enriched with unique DEGs. Such network analysis indicated classic inflammatory responses in active lesions; catabolic and heat shock protein responses in inactive lesions; neuronal/axonal specific processes in chronic active lesions. In remyelinating lesions, de novo analyses identified axonal transport responses and adaptive immune markers, which was also supported by the most heterogeneous immunoglobulin gene expression. The signature of the normal-appearing white matter (NAWM) was more similar to control WM than to lesions: only 465 DEGs differentiated NAWM from controls, and 16 were unique. The upregulated marker CD26/DPP4 was expressed by microglia in the NAWM but by mononuclear cells in active lesions, which may indicate a special subset of microglia before the lesion develops, but also emphasizes that omics related to MS lesions should be interpreted in the context of different lesions types. While chronic active lesions were the most distinct from control WM based on the highest number of unique DEGs (n = 2213), remyelinating lesions had the highest gene expression levels, and the most different molecular map from chronic active lesions. This may suggest that these two lesion types represent two ends of the spectrum of lesion evolution in PMS. The profound changes in chronic active lesions, the predominance of synaptic/neural/axonal signatures coupled with minor inflammation may indicate end-stage irreversible molecular events responsible for this less treatable phase.