bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roles of metabolic pathways in maintaining primary dormancy of Pinus koraiensis seeds
Authors: Song Yuan , Zhu Jiaojun 
Published: December 2019

AbstractBackgroundKorean pine seeds have primary dormancy following dispersal, leading to poor seed germination and seedling establishment. Metabolic homeostasis determines whether the seeds are dormant or non-dormant. However, the specific metabolic pathways that maintain the primary dormancy of pine seeds are poorly understood.ResultsMetabolic analysis was employed on the embryos of PDRS (seeds released from primary dormancy) and PDS (primary dormant seeds) on days 0, 5 and 11 after incubation under a germination-inductive temperature. A larger metabolic switch occurred in PDRS embryos from days 0 to 11. The contents of ninety metabolites were significantly changed from days 0 to 5, 83% of which (including most sugars, organic acids and amino acids) increased, reflecting that biosynthetic metabolism processes are initiated. The contents of ninety-two metabolites showed distinct variations from days 5 to 11, 71% of which (including most organic acids and almost all amino acids) reduced substantially. Fructose 6-phosphate, inositol-3-phosphate, 3-phosphoglyceric and D-glucose-6-phosphate contents showed the most decrease with decreasing 409-, 75-, 58- and 41-fold, indicating that the glycolysis and tricarboxylic acid (TCA) cycle strongly slowed down. The contents of the most metabolites in PDS embryos also displayed a relatively larger alteration only from days 0 to 5. Although 64% of metabolites increased from days 0 to 5, their levels were still lower compared with PDRS embryos. Furthermore, most metabolites were not further accumulated from days 5 to 11. Unlike PDRS embryos, almost all amino acids in PDS embryos did not exhibit a substantial decrease from days 5 to 11. Also, there was not a major decrease in the levels of metabolites involved mainly in glycolysis and TCA cycle, while some intermediates even increased.ConclusionsThe attenuated biosynthetic metabolism processes, the lower utilization rate of amino acids and the higher operation rate of glycolysis and TCA in embryos maintain primary dormancy.
Mutation in MPT64 gene influencing diagnostic accuracy of SD Bioline assay (capilia)
Authors: Singh Kamal , Kumari Richa , Tripathi Rajneesh , Gupta Ankush , Anupurba Shampa 
Published: December 2019

Abstract
Background
Success of India’s TB control program relies on rapid case detection, monitoring, care and treatment of drug resistance. Patients on multidrug resistance (MDR) treatment are monitored by follow up cultures. Discordant results (culture and smear positive while capilia negative) are usually declared negative Mycobacterium tuberculosis complex (MTBC). This study was designed to understand the possible causes of discordant results.

Methods
The capilia kit was evaluated to test its utility among 4737 follow up MDR patients enrolled during a period of 1 year. A total of 889 were liquid culture positive, 3375 were negative and 473 were contaminated. Of the 889 cultures positive, 829 were found positive by ZN smear, capilia test and MTBDR plus assay. The cultures which gave a positive result on Mycobacterium Growth Indicator Tube 960 (MGIT 960) and ZN smear but were negative on capilia test with no growth on Brain Heart Infusion agar (BHI) were included in this study. The conflicting results of capilia were compared with other molecular techniques; MTBDR plus assay and DNA sequence analysis of MPT64 gene.

Results
Out of 889 culture positive, 60 (6.7%) were found positive on liquid culture and ZN smear but were negative on capilia. Of these 60 cultures, 10 (16.7%) were found positive by both MTBDR plus assay and PCR. The sequencing analysis revealed that all of the capilia negative isolates had mutations within the MPT64 gene.

Conclusion
Re-evaluation of culture positive but capilia negative isolates should be done before declaring them as Mycobacterium other than tuberculosis (MOTT) because such cases can act as chronic carriers of TB in the population which can lead to the rise of this lethal disease.
Predicting recurrence of depression using lifelog data: an explanatory feasibility study with a panel VAR approach
Authors: Kumagai Narimasa , Tajika Aran , Hasegawa Akio , Kawanishi Nao , Horikoshi Masaru , Shimodera Shinji , Kurata Ken’ichi , Chino Bun , Furukawa Toshi A. 
Published: December 2019

AbstractBackgroundAlthough depression has a high rate of recurrence, no prior studies have established a method that could identify the warning signs of its recurrence.MethodsWe collected digital data consisting of individual activity records such as location or mobility information (lifelog data) from 89 patients who were on maintenance therapy for depression for a year, using a smartphone application and a wearable device. We assessed depression and its recurrence using both the Kessler Psychological Distress Scale (K6) and the Patient Health Questionnaire-9.ResultsA panel vector autoregressive analysis indicated that long sleep time was a important risk factor for the recurrence of depression. Long sleep predicted the recurrence of depression after 3 weeks.ConclusionsThe panel vector autoregressive approach can identify the warning signs of depression recurrence; however, the convenient sampling of the present cohort may limit the scope towards drawing a generalised conclusion.
Lessons learned from engaging communities for Ebola vaccine trials in Sierra Leone: reciprocity, relatability, relationships and respect (the four R’s)
Authors: Dada Sara , McKay Gillian , Mateus Ana , Lees Shelley 
Published: December 2019

Abstract
Background
Building trust and engaging the community are important for biomedical trials. This was core to the set up and delivery of the EBOVAC-Salone and PREVAC Ebola vaccine trials in Sierra Leone during and following the 2014–2016 West African Ebola epidemic. Local community liaison teams (CLT) engaged with the community through public meetings, radio chat shows, and other activities, while a social science team (SST) assessed community members’ and participants’ perceptions and regularly updated the clinical team to adapt procedures to improve the acceptability and compliance of the trial. The objective of this study was to examine the community engagement (CE) program in these trials and to identify potential barriers and facilitators.

Methods
Fifteen CLT and SST members participated in in-depth interviews and 23 community members attended three focus groups to discuss the Ebola vaccine trials and their experiences and perspectives of the CE activities.

Results
A key aim of the CE program was to build trust between the community and the trial. Four main principles (the “four R’s”) evolved from the discussions with team members and the community that influenced this trust: reciprocity, relatability, relationships and respect. The CLT and SST ensured reciprocal communication between the trial team and the community. The CLT delivered key messages from the trial, whilst the SST completed ethnographic research in the field to uncover rumors and perceptions of the trial in the community. These ethnographic findings were shared with the CLT and addressed in targeted messaging to the community. Both the CLT and SST approached the communities in an egalitarian manner, by dressing modestly, speaking local dialects, and using relatable examples. Appreciation and understanding of the importance of interpersonal relationships and respect for the people, their customs, and traditions also played a large role in the CE program.

Conclusion
These findings provide an in-depth understanding of how interdisciplinary community liaison and social science teams can work with a clinical team to strengthen trust. The four R’s suggest the ways in which trust relations are central to CE and confidence in vaccine trials, and could offer an approach to CE in vaccine trials.
Morphological analysis of Apolipoprotein E binding to Aβ Amyloid using a combination of Surface Plasmon Resonance, Immunogold Labeling and Scanning Electron Microscopy
Authors: Islam Tohidul , Gharibyan Anna L. , Lee Cheng Choo , Olofsson Anders 
Published: December 2019

Abstract
Background
Immunogold labeling in combination with transmission electron microscopy analysis is a technique frequently used to correlate high-resolution morphology studies with detailed information regarding localization of specific antigens. Although powerful, the methodology has limitations and it is frequently difficult to acquire a stringent system where unspecific low-affinity interactions are removed prior to analysis.

Results
We here describe a combinatorial strategy where surface plasmon resonance and immunogold labeling are used followed by a direct analysis of the sensor-chip surface by scanning electron microscopy. Using this approach, we have probed the interaction between amyloid-β fibrils, associated to Alzheimer’s disease, and apolipoprotein E, a well-known ligand frequently found co-deposited to the fibrillar form of Aβ in vivo. The results display a lateral binding of ApoE along the amyloid fibrils and illustrates how the gold-beads represent a good reporter of the binding.

Conclusions
This approach exposes a technique with generic features which enables both a quantitative and a morphological evaluation of a ligand-receptor based system. The methodology mediates an advantage compared to traditional immunogold labeling since all washing steps can be monitored and where a high stringency can be maintained throughout the experiment.
Assessment of anterior-posterior spinal curvatures in children suffering from hypopituitarism
Authors: Kobylińska Magdalena , Malak Roksana , Majewska Katarzyna , Kędzia Andrzej , Samborski Włodzimierz 
Published: December 2019

Abstract
Background
Body posture may be disordered by vestibular dysfunction, neurological disorders, problems with the distribution of muscle tone, brain injuries, and other dysfunctions. Growth hormone deficiency (GHD) can lead to many disorders, particularly of the musculoskeletal system. During treatment with recombinant human growth hormone (rhGH), an increase in muscle mass and an improvement in bone structure can be observed in children suffering from hypopituitarism from GHD.

Methods
The study involved 33 children suffering from hypopituitarism with GHD (9 girls and 24 boys), aged 10–14 years old. Measurements of the magnitude of their anterior–posterior spinal curvatures were made using an inclinometer. The children were examined at the medianus of the sacrum bone, the Th12–L1 intervertebral area, and the C7–Th1 intervertebral area. In order to characterize the anterior–posterior curvature of the spine, the results were compared with the general norms reported by Saunders. Statistical calculations were carried out using the statistical package Statistica 10 PL.

Results
Lumbar lordosis angles were higher in the patients currently receiving growth hormone (GH) treatment than in those who had yet to receive it. There is a statistically significant positive correlation between the length of growth hormone treatment and the alpha angle. There are also statistically significant correlations between age at the beginning of growth hormone therapy and the angle of lordosis. Statistically significant correlations were also seen between age at the beginning of growth hormone therapy and the alpha angle.

Conclusions
Although there may be changes in posture at the beginning of rhGH treatment, the sooner growth hormone therapy begins, the better the body posture. The longer the growth hormone treatment, the better the posture, as expressed by the alpha angle in the sagittal plane.
No increased risk of glucose metabolism disorders in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from an observational, longitudinal study
Authors: Beck-Peccoz Paolo , Höybye Charlotte , Murray Robert D. , Simsek Suat , Zabransky Markus , Zouater Hichem , Stalla Günter 
Published: December 2019

Abstract
Background
To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study.

Methods
PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%.

Results
Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29–84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45–72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD.

Conclusions
Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this.

Trial registration
Not applicable.
Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence
Authors: Perez-Calahorra Sofía , Laclaustra Martin , Marco-Benedi Victoria , Pinto Xavier , Sanchez-Hernandez Rosa M. , Plana Núria , Ortega Emilio , Fuentes Francisco , Civeira Fernando 
Published: December 2019

Abstract
Background
There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD.

Methods
This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction.

Results
Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time.

Conclusions
This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD.
Duodeno-pancreatic and extrahepatic biliary tree trauma: WSES-AAST guidelines
Authors:   WSES-AAST Expert Panel, Coccolini Federico , Kobayashi Leslie , Kluger Yoram , Moore Ernest E. , Ansaloni Luca , Biffl Walt , Leppaniemi Ari , Augustin Goran , Reva Viktor , Wani Imitiaz , Kirkpatrick Andrew , Abu-Zidan Fikri , Cicuttin Enrico , Fraga Gustavo Pereira , Ordonez Carlos , Pikoulis Emmanuil , Sibilla Maria Grazia , Maier Ron , Matsumura Yosuke , Masiakos Peter T. , Khokha Vladimir , Mefire Alain Chichom , Ivatury Rao , Favi Francesco , Manchev Vassil , Sartelli Massimo , Machado Fernando , Matsumoto Junichi , Chiarugi Massimo , Arvieux Catherine , Catena Fausto , Coimbra Raul 
Published: December 2019

AbstractDuodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines.
The largest reported intrathoracic lipoma: a case report and current perspectives review
Authors: Aldahmashi Mohammed , Elmadawy Abdalmotaleb , Mahdy Mahmoud , Alaa Mohamed 
Published: December 2019

Abstract
Background
The huge size intrathoracic lipomas are very rare. Few cases have been reported worldwide. To our knowledge, this presented case is one of the few cases reported. Here we report a single case as very huge intrathoracic lipoma compressing the right lung and displacing the diaphragm and liver downward. It has been managed by right posterolateral thoracotomy and complete excision, with excellent outcome.

Case presentation
A 32-year-old male presented with a symptomatic right intrathoracic mass, which was confirmed to be a lipomatous tumor using computed tomography. A penduculated tumor originating from the mediastinal pleura was resected through the conventional right posterior thoracotomy. Pathological examination indicated a diagnosis of fibrolipoma.

Conclusion
The tumor was symptomatic and relatively huge when detected during a medical checkup. This enabled the successful tumor resection via conventional thoracotomy approach. Although intrathoracic lipomas are histologically benign, careful observation and follow-up are crucial due to the possibility of recurrence.
An analysis of orphan medicine expenditure in Europe: is it sustainable?
Authors: Mestre-Ferrandiz Jorge , Palaska Christina , Kelly Tom , Hutchings Adam , Parnaby Adam 
Published: December 2019

Abstract
Background
Orphan medicinal product (OMP) prices are considered by some to be a challenge to the sustainability of healthcare expenditure. These concerns are compounded by the increasing number of OMPs receiving marketing authorisation (MA) annually. The aim of this study was to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure.

Methods
Using historical IQVIA data, an analysis was conducted on total pharmaceutical and OMP expenditure in eight countries (using values / volumes) in the branded, non-branded and overall pharmaceutical market. Country level and aggregated data was considered for EU5 countries, Austria, Belgium and Ireland.
Three key analyses were conducted:
The OMP share of total pharmaceutical expenditure was calculated from 2000 to 2017, to assess its evolution over time.The results of this analysis were compared with a 2011 forecast of OMP budget impact.The evolution of the total pharmaceutical market and its different segments (branded OMPs, non-OMP branded and unbranded) were assessed by estimating the compound annual growth rate (CAGR) and percentage of pharmaceutical expenditure for each market segment from 2010 to 2017.

Results
Across countries, OMP share of total pharmaceutical expenditure has increased each year since 2000, rising to 7.2% of total pharmaceutical expenditure in 2017. OMP expenditure has increased at a CAGR of 16% since 2010. The number of OMPs receiving MA each year showed a CAGR of 11% since 2001, four percentage points greater than the CAGR for all medicines receiving MA over the same period. OMP share of total pharmaceutical expenditure is higher than forecasted in 2011 due to slower than expected growth in the non-OMP market. OMP growth has been offset by reduced expenditure in the general market and increased use of generics and biosimilars.

Conclusions
Relative spending on OMPs has increased over the last 20 years, but this has been largely compensated for within the current allocation of total pharmaceutical spending by flat expenditure for non-OMPs and increased volumes of (lower-priced) generics/biosimilars, reflecting a shift towards expenditure in higher cost, lower volume patient populations and a shift in drug development towards more specialised targeting of diseases.
Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis
Authors: Nguyen Vu Hong Loan , Hough Rebecca , Bernaudo Stefanie , Peng Chun 
Published: December 2019

AbstractEpithelial ovarian cancer (EOC) is the deadliest female malignancy. The Wnt/β-catenin pathway plays critical roles in regulating embryonic development and physiological processes. This pathway is tightly regulated to ensure its proper activity. In the absence of Wnt ligands, β-catenin is degraded by a destruction complex. When the pathway is stimulated by a Wnt ligand, β-catenin dissociates from the destruction complex and translocates into the nucleus where it interacts with TCF/LEF transcription factors to regulate target gene expression. Aberrant activation of this pathway, which leads to the hyperactivity of β-catenin, has been reported in ovarian cancer. Specifically, mutations ofCTNNB1,AXIN, or APC,have been observed in the endometrioid and mucinous subtypes of EOC. In addition, upregulation of the ligands, abnormal activation of the receptors or intracellular mediators, disruption of the β-catenin destruction complex, inhibition of the association of β-catenin/E-cadherin on the cell membrane, and aberrant promotion of the β-catenin/TCF transcriptional activity, have all been reported in EOC, especially in the high grade serous subtype. Furthermore, several non-coding RNAs have been shown to regulate EOC development, in part, through the modulation of Wnt/β-catenin signalling. The Wnt/β-catenin pathway has been reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC. Emerging evidence also suggests that the pathway induces ovarian tumor angiogenesis and immune evasion. Taken together, these studies demonstrate that the Wnt/β-catenin pathway plays critical roles in EOC development and is a strong candidate for the development of targeted therapies.