bluuebunny/crossref_metadata_2025 huggingface dataset:
AMEND study protocol: a case–control study to assess the long-term impact of invasive meningococcal disease in Australian adolescents and young adults
Authors: Marshall Helen , McMillan Mark , Wang Bing , Booy Robert , Afzali Hossein , Buttery Jim , Blyth Christopher C , Richmond Peter , Shaw David , Gordon David , Barton Belinda
Published: December 2019

Introduction

Invasive meningococcal disease (IMD) primarily causes disease in young children and adolescents and can cause long-term disability. Many countries are considering implementation of meningococcal B and/or meningococcal ACWY vaccines to control meningococcal disease. Estimating the cost-effectiveness of meningococcal vaccine programme is hampered due to a lack of good quality costing and burden of disease data. This study aims to address this evidence gap by assessing the clinical, physical, neurocognitive, economic and societal impact of IMD on adolescents and young adults.

Methods and analysis

A case–control study of 64 participants with confirmed IMD (15–24 years 11 months at time of disease) and 64 control participants (17–34 years 11 months) will be conducted in Australia from 2016 to 2020. All participants will undergo a neurocognitive assessment, full medical examination, pure tone audiometry assessment and complete quality of life and behavioural questionnaires. Meningococcal cases will be assessed 2–10 years posthospitalisation and a subset of cases will be interviewed to explore in depth their experiences of IMD and its impact on their life. Primary outcome measures include general intellectual functioning from the Wechsler Adult Intelligence Scale and overall quality of life from the Health Utilities Index. Secondary outcome measures include academic achievement, executive functioning, behaviour, hearing, psychological and physical functioning. Outcome measures will be compared between cases and controls using independent t-tests or ORs, or if any significant confounders are identified, adjusted analyses (analysis of covariance or adjusted ORs) will be conducted. Thematic analysis will be used to analyse transcribed interviews and a costing model will be used to project lifetime costs.

Ethics and dissemination

The Adolescent MENingococcal Disease (AMEND) study has been approved by the Human Research Ethics Committee of the Women’s and Children’s Health Network (HREC/14/WCHN/024). The results will be disseminated via peer-reviewed publications, conference presentations, study participants, and meningococcal and meningitis foundations.

Trial registration number

NCT03798574.
Effect of involving certified healthcare assistants in primary care in Germany: a cross-sectional study
Authors: Senft Jonas D , Wensing Michel , Poss-Doering Regina , Szecsenyi Joachim , Laux Gunter
Published: December 2019

Objectives

Growing prevalence of chronic diseases and limited resources are the key challenges for future healthcare. As a promising approach to maintain high-quality primary care, non-physician healthcare professionals have been trained to broaden qualifications and responsibilities. This study aimed to assess the influence of involving certified healthcare assistants (HCAs, German: Versorgungsassistent/in in der Hausarztpraxis) on quality and efficacy of primary care in Germany.

Design

Cross-sectional study.

Setting

Primary care.

Participants

Patients insured by the Allgemeine Ortskrankenkasse (AOK) statutory health insurer (AOK, Baden-Wuerttemberg, Germany).

Interventions

Since 2008 practice assistants in Germany can enhance their professional education to become certified HCAs.

Primary and secondary outcome measures

Claims data related to patients treated in practices employing at least one HCA were compared with data from practices not employing HCAs to determine frequency of consultations, hospital admissions and readmissions. Economic analysis comprised hospitalisation costs, prescriptions of follow-on drugs and outpatient medication costs.

Results

A total of 397 493 patients were treated in HCA practices, 463 730 patients attended to non-HCA practices. Patients in HCA practices had an 8.2% lower rate of specialist consultations (p<0.0001), a 4.0% lower rate of hospitalisations (p<0.0001), a 3.5% lower rate of readmissions (p=0.0463), a 14.2% lower rate of follow-on drug prescriptions (p<0.0001) and 4.7% lower costs of total medication (p<0.0001). No difference was found regarding the consultation rate of general practitioners and hospital costs.

Conclusions

For the first time, this high-volume claims data analysis showed that involving HCAs in primary care in Germany is associated with a reduction in hospital admissions, specialist consultations and medication costs. Consequently, broadening qualifications may be a successful strategy not only to share physicians’ work load but to improve quality and efficacy in primary care to meet future challenges. Future studies may explore specific tasks to be shared with non-physician workforces and standardisation of the professional role.
Cost-effectiveness analysis of a physician deployment program to improve access to healthcare in rural and underserved areas in the Philippines
Authors: Avanceña Anton L.V. , Tejano Kim Patrick S , Hutton David W.
Published: December 2019

Objectives

The objective of this study is to explore the cost-effectiveness of Doctor to the Barrios (DTTB), a physician deployment program in the Philippines.

Design

Cost-effectiveness analysis using decision tree models with a lifetime time horizon and probabilistic sensitivity analysis.

Setting

Societal and healthcare perspectives.

Population

Hypothetical cohort of children under 5 years in two provinces (Aklan and Nueva Ecija) and in a representative rural municipality.

Participants

None.

Interventions

DTTB’s impact on paediatric pneumonia and diarrhoea outcomes compared with a scenario without DTTB.

Main outcome measures

Costs, effectiveness (in terms of lives saved and quality-adjusted life years (QALYs) gained) and incremental cost-effectiveness ratio (ICER).

Results

DTTB is cost-effective in the two provinces that were included in the study from societal and healthcare perspectives. Looking at a representative rural municipality, base case analysis and probabilistic sensitivity analyses suggest that DTTB has an ICER of 27 192 per QALY gained from a societal perspective. From a healthcare perspective, the base case ICER of DTTB is Philippine pesos (PHP) 71 839 per QALY gained and PHP 2 064 167 per life saved, and 10 000 Monte Carlo simulations produced similar average estimates. The cost per QALY of DTTB from a healthcare perspective is lower than the WHO recommended willingness-to-pay threshold of 100% of the country’s per-capita gross domestic product.

Conclusions

DTTB can be a cost-effective intervention, but its value varies by setting and the conditions of the municipality where it is implemented. By focusing on a narrow set of paediatric outcomes, this study has likely underestimated the health benefits of DTTB. Additional research is needed to understand the full extent of DTTB’s impact on the health of communities in rural and remote areas. Future cost-effectiveness analysis should empirically estimate various parameters and include other health conditions in addition to pneumonia and diarrhoea in children.
Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D Feasibility): a randomised feasibility trial protocol
Authors: Farmer Andrew , Allen Julie , Bartlett Kiera , Bower Peter , Chi Yuan , French David , Gudgin Bernard , Holmes Emily A , Horne Robert , Hughes Dyfrig A , Kenning Cassandra , Locock Louise , McSharry Jenny , Miles Lisa , Newhouse Nikki , Rea Rustam , Riga Evgenia , Tarassenko Lionel , Velardo Carmelo , Williams Nicola , Williams Veronika , Yu Ly-Mee
Published: December 2019

Introduction

Type 2 diabetes is common, affecting over 400 million people worldwide. Risk of serious complications can be reduced through use of effective treatments and active self-management. However, people are often concerned about starting new medicines and face difficulties in taking them regularly. Use of brief messages to provide education and support self-management, delivered through mobile phone-based text messages, can be an effective tool for some long-term conditions. We have developed messages aiming to support patients’ self-management of type 2 diabetes in the use of medications and other aspects of self-management, underpinned by theory and evidence. The aim of this trial is to determine the feasibility of a large-scale clinical trial to test the effectiveness and cost-effectiveness of the intervention, compared with usual care.

Methods and analysis

The feasibility trial will be a multicentre individually randomised, controlled trial in primary care recruiting adults (≥35 years) with type 2 diabetes in England. Consenting participants will be randomised to receive short text messages three times a week with messages designed to produce change in medication adherence or non-health-related messages for 6 months. The aims are to test recruitment methods, retention to the study, the feasibility of data collection and the mobile phone and web-based processes of a proposed definitive trial and to refine the text messaging intervention. The primary outcome is the rate of recruitment to randomisation of participants to the trial. Data, including patient reported measures, will be collected online at baseline and the end of the 6-month follow-up period. With 200 participants (100 in each group), this trial is powered to estimate 80% follow-up within 95% CIs of 73.8% to 85.3%. The analysis will follow a prespecified plan.

Ethics and dissemination

Ethics approval was obtained from the West of Scotland Research Ethics Committee 05. The results will be disseminated through conference presentations, peer-reviewed journals and will be published on the trial website: www.summit-d.org (SuMMiT-D (SUpport through Mobile Messaging and digital health Technology for Diabetes)).

Trial registration number

ISRCTN13404264.
Realist evaluation of UK medical education quality assurance
Authors: Crampton Paul , Mehdizadeh Leila , Page Michael , Knight Laura , Griffin Ann
Published: December 2019

Objectives

The aim of the study was to explore what components of the General Medical Council’s (GMC) Quality Assurance Framework work, for whom, in what circumstances and how?

Setting

UK undergraduate and postgraduate medical education and training.

Participants

We conducted interviews with a stratified sample of 36 individuals. This included those who had direct experiences, as well as those with external insights, representing local, national and international organisations within and outside medicine.

Intervention

The GMC quality assure education to protect patient and public safety utilising complex intervention components including meeting standards, institutional visits and monitoring performance. However, the context in which these are implemented matters. We undertook an innovative realist evaluation to test an initial programme theory. Data were analysed using framework analysis.

Results

Across components of the intervention, we identified key mechanisms, including transparent reporting to promote quality improvement; dialogical feedback; partnership working facilitating interactions between regulators and providers, and role clarity in conducting proportionate interventions appropriate to risk. The GMC’s framework was commended for being comprehensive and enabling a broad understanding of an organisation’s performance. Unintended consequences included confusion over roles and boundaries in different contexts which often undermined effectiveness.

Conclusions

This realist evaluation substantiates the literature and reveals deeper understandings about quality assuring medical education. While standardised approaches are implemented, interventions need to be contextually proportionate. Routine communication is beneficial to verify data, share concerns and check risk; however, ongoing partnership working can foster assurance. The study provides a modified programme theory to explicate how education providers and regulators can work more effectively together to uphold education quality, and ultimately protect public safety. The findings have influenced the GMC’s approach to quality assurance which impacts on all medical students and doctors in training.
Simulation of motion of many ions in a linear Paul trap
Authors: Oral Martin , Číp Ondřej , Slodička Lukáš
Published: December 2019

The quadrupole linear Paul trap is one of the key instruments in building highly stable atomic clocks. However, a frequency reference based on a single trapped ion is limited in stability due to the time needed for the interrogation cycle which cannot be further shortened. A promising strategy is the utilization of multiple trapped ions. The ions of the same kind then repulse each other with the Coulomb force, which is countered by the ponderomotive force of the time depended field in the trap. A few ions form a chain along the axis of a linear Paul trap. Adding more ions (a few tens or hundreds) gives rise to Coulomb crystals. We created an efficient simulation code which calculates the motion of such collections of ions in quasi-static radiofrequency fields of real linear quadrupole traps (including the micromotion). We include a model for laser cooling of the ions. The simulation tool can be used to study the formation and the dynamics of Coulomb crystals under conditions corresponding to various experimental setups.
Effect of cold rolling on microstructural and mechanical properties of MG-7LI alloy
Authors: Cai Xiang , Qiao Yanxin , Wang Baojie , Zhou Huiling , Wang Yuxin
Published: December 2019

The influence of rolling on nanomechanical and mechanical behavior of Mg-7Li alloy was investigated by nanoindentation, tensile test and scanning electron microscopy (SEM), respectively. The [Formula: see text]-Mg phase elongated along the rolling direction and gradually cracked. As the rolling ratio increased from 3 to 10, the hardness of [Formula: see text]-Mg and [Formula: see text]-Li phase increased by 7.35% and 20.75%, respectively. The fracture of alloys changed from ductile fracture to quasi-cleavage fracture. The yield strength and ultimate tensile strength increased by 23 MPa and 12 MPa, respectively, while elongation reduced by 12.5%.
Investigation of PTCR characteristics in Nb2O5-doped BaTiO3-based chip-type ceramics prepared by reduction sintering-reoxidation method
Authors: Cheng Xuxin , Chen Xiaoming , Cui Haining , Wang Yuxin , Xiong Chao
Published: December 2019

This study investigates the influence of sintering conditions on electrical properties and positive temperature coefficient of resistance (PTCR) of [Formula: see text] (BTNO) ceramics, fired at [Formula: see text]C for different times from 1 to 6 h in a reducing atmosphere and reoxidised within the temperature range of [Formula: see text]–[Formula: see text]C for 1 h. The results showed that the room-temperature (RT) resistance and the resistance jump of the multilayer BTNO ceramics decreased with an increase in the firing time. Furthermore, the RT resistance of the BTNO samples gradually increased at first and then rapidly increased with increasing reoxidation temperature. In addition, the influence of sintering times on the microstructure of ceramics was also investigated.
Optimization of guide star catalog for daytime star sensors
Authors: Wu Feng , Zhu Xifang , Xu Qingquan , Xiang Ruxi , Yu Qiuyang , Zhou Jie , Yang Xiu
Published: December 2019

Daytime star sensor provides accuracy navigation information to air vehicles near the ground in the daytime by observing stars. It has been an important development of modern star sensors. In order to achieve a high signal-to-noise ratio, daytime star sensors work in the infrared band to avoid interferences from sky background. Daytime star sensors output accurate attitudes by identifying the observed stars in the field of view (FOV) according to the loaded guide star catalog. Guide stars are usually required to be distributed uniformly on the celestial sphere to improve the performance of star pattern identification. The parameters including limiting magnitude and FOV are determined by processing the 2MASS star catalog as the original star data and performing star distribution statistics. After constellation features are discussed, the idea of distributing stars in the local FOV to constellations is put forward by using the star pair angular separations. An optimization algorithm to build the guide star catalog for daytime stars is proposed to achieve evenly distributed guide stars. The guide star catalog is established and analyzed, proving that the proposed algorithm has simple calculation and easy realization. The Boltzmann entropy of obtained guide star catalog drops two orders of magnitude. Guide stars are distributed more uniformly.
Improved Single Image De-Hazing Via Sky Region Detection, Classification and Illumination Refinement
Authors: Nnolim Uche A.
Published: December 2019

This paper presents an automated sky detection technique based on statistical and fuzzy rule-based edge detection for improved hazy image contrast enhancement. This is significant since most conventional de-hazing approaches yield hazy images with over-enhanced sky regions and under-enhanced detail regions due to inability to adaptively determine and enhance such regions. Earlier and current schemes developed to remedy this issue are highly complex, usually require training with vast amount of images and manual tuning of one or several parameters. The proposed method utilizes standard deviation and fuzzy logic-based edge detection combined with thresholding algorithms to generate a homogeneity map identifying sky and non-sky regions. The areas of these regions are subsequently computed and used to obtain a homogeneity ratio. The ratio is then used to trigger a decision-based, switching scheme incorporated into a partial differential equation (PDE) de-hazing algorithm to improve results. Alternatively, a log illumination refinement method is proposed as a less complex alternative combined with the modified PDE algorithm to process hazy images without degrading sky regions, while yielding brighter images. Several image datasets from the literature were used to validate the proposed approaches and yielded mostly consistent and comparable results similar to or better than algorithms from the literature.
Highly Liquid Mortgage Bonds Using the Match Funding Principle
Authors: Dick-Nielsen Jens , Gyntelberg Jacob
Published: December 2019

We show that pass-through funding of mortgages with covered bonds supported by strong creditor rights is one way of providing highly liquid mortgage bonds. Despite a 30% drop in house prices during the 2008 crisis, these mortgage bonds remained as liquid as comparable government bonds with high trading volume and low bid-ask spreads. Market liquidity of these covered bonds is primarily driven by the availability of funding liquidity. Funding liquidity is the main concern because the pass-through funding approach effectively eliminates other types of risks from the investor’s perspective. Banking regulators should take into account the implications of these findings, particularly when it comes to the interplay between liquidity and capital requirements.
Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature
Authors: Yamasaki Evan , Thakore Pratish , Krishnan Vivek , Earley Scott
Published: December 2019

Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments.

NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.
Pattern Recognition Using Clustering Analysis to Support Transportation System Management, Operations, and Modeling
Authors: Saha Rajib , Tariq Mosammat Tahnin , Hadi Mohammed , Xiao Yan
Published: December 2019

There has been an increasing interest in recent years in using clustering analysis for the identification of traffic patterns that are representative of traffic conditions in support of transportation system operations and management (TSMO); integrated corridor management; and analysis, modeling, and simulation (AMS). However, there has been limited information to support agencies in their selection of the most appropriate clustering technique(s), associated parameters, the optimal number of clusters, clustering result analysis, and selecting observations that are representative of each cluster. This paper investigates and compares the use of a number of existing clustering methods for traffic pattern identifications, considering the above. These methods include the K-means, K-prototypes, K-medoids, four variations of the Hierarchical method, and the combination of Principal Component Analysis for mixed data (PCAmix) with K-means. Among these methods, the K-prototypes and K-means with PCs produced the best results. The paper then provides recommendations regarding conducting and utilizing the results of clustering analysis.
The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases
Authors: Yang Lingyi , Chen Shuli , Zhao Qiuyu , Sun Ying , Nie Hong
Published: December 2019

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.
Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats
Authors: Yuan Jian , Ding Wanghui , Wu Na , Jiang Shijie , Li Wen
Published: December 2019

Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-κB is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-κB signaling pathway in inflammatory disease. But so far, studies on the effects of genistein on TMJOA are very limited. So, the purpose of this study is to investigate the protective effect of genistein against experimentally induced condylar cartilage degradation through downregulating NF-κB expression in created osteoarthritis rats in vivo. Male SD rats were created as temporomandibular joint osteoarthritis models and administered through oral gavage with low and high dosage genistein (30 mg/kg and 180 mg/kg, respectively) daily for 4 weeks. The morphological changes of the condylar cartilage were studied with HE and Masson staining. The expressions of p65 and inflammatory cytokines (IL-1β and TNFα) were detected using immunohistochemistry and real-time PCR. The results showed that experimentally created osteoarthritis reduced the condylar cartilage thickness of rats and increased the gene expression of cytokines (IL-1β and TNFα) and positive cells of p65. Genistein treatment had positive effects on the condylar cartilage renovation, while high dose genistein treatment had more significant effects on the reversing of OA changes and reduction of the expression of p65 and inflammatory cytokines (IL-1β and TNFα). The results indicated that high dose genistein treatment had obvious therapeutic effects on condyle cartilage damages of OA rats. The mechanism may be that genistein suppresses the NF-κB expression activated by inflammatory cytokines.
KangFuXin Liquid in the Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis
Authors: Qu Ke Shen , Li Yang , Liang Yue , Hu Xiao Jie , Wang Xuan Yu , Chen Xin , Que Hua Fa
Published: December 2019

Background. Diabetic foot ulcer (DFU) is one of the most common complications of diabetes mellitus, with the wound not healing as expected and healing slowly. Poor control can develop into gangrene and even amputation. Currently, the existing treatments are not satisfactory enough. In China, KangFuXin liquid (KFXL) has been clinically used to treat DFU and has shown good clinical efficacy. In order to provide more reference to clinicians and experts, evidence of efficacy for it needs to be further rigorously evaluated. Methods. Eight electronic databases were searched to identify eligible randomized clinical trials (RCTs) published from construction of the library to April 2019. There is no language or data restriction; 11 trials involving 889 participants met the inclusion criteria. These RCTs compared the total effective rate, cure rate, cure time, and adverse events associated with KFXL. The Cochrane Handbook guidelines were used to assess the risk of bias and to evaluate the methodological quality of eligible studies. The methodological quality of included studies was generally low. Dichotomous and continuous data were presented using risk ratios (RRs) and mean differences (MDs), respectively. Results. Compared with the basic treatment, meta-analyses showed that KFXL combined with basic treatment can improve the total effective rate (RR = 1.38; 95% CI = 1.23–1.54; P<0.00001; fixed effect model: I2 = 32%) and cure rate (RR = 1.67; 95% CI = 1.17–2.38; P=0.005; random effect model: I2 = 65%), and shorten the healing time (MD = −5.73; 95% CI = −6.95 to −4.52; P<0.00001; random effect model). Moreover, under the same basic treatment, KFXL had a better effect than external use of pharmaceutical medications (RR = 1.95; 95% CI = 1.30–2.93; P=0.001), but the cure rate was not significantly different. Also, KFXL had nothing to do with adverse reactions. Conclusion. The evidence confirms that KFXL is an effective treatment for DFU. However, further large-scale, rigorously designed trials and high-quality studies are needed to confirm the role of KFXL in the treatment of DFU.
Experimental Investigation of Water-Inrush Risk Based on Permeability Evolution in Coal Mine and Backfill Prevention Discussion
Authors: Li Meng , Zhang Jixiong , Zhang Weiqing , Li Ailing , Yin Wei
Published: December 2019

Induced by coal mining, the fractures constantly occur in geologic strata until failure occurs, which provide channels for water flow. Therefore, it is essential to investigate the permeability evolution of rocks under load. Borehole sampling was conducted in a bedrock layer beneath an aquifer, and the permeability evolution of sandstone specimens under different confining pressures was tested in rock mechanics testing laboratories. The results indicated that the permeability gradually decreases with the increasing confining pressures, while the peak strength increases with the increase of confining pressures. The minimum and maximum permeabilities occurred in the sandstone specimens that were subjected to elastic deformation and strain-softening stages, respectively. The failure, and maximum permeability, of these sandstone specimens did not occur simultaneously. To prevent the flow channel being formed due to the development and failure of rock fractures, a method of backfill gob was proposed and also the influence of backfill on fracture development was discussed.
Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation
Authors: Truong Cao-Sang , Seo Eunhui , Jun Hee-Sook
Published: December 2019

Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in bothin vitroandin vivostudies.Psoralea corylifoliaseeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-αand IL-1βand iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.
Prevalence of Syndecan-1 (CD138) Expression in Different Kinds of Human Tumors and Normal Tissues
Authors: Kind Simon , Merenkow Christina , Büscheck Franziska , Möller Katharina , Dum David , Chirico Viktoria , Luebke Andreas M. , Höflmayer Doris , Hinsch Andrea , Jacobsen Frank , Göbel Cosima , Weidemann Sören , Fraune Christoph , Möller-Koop Christina , Hube-Magg Claudia , Clauditz Till S. , Simon Ronald , Sauter Guido , Wilczak Waldemar , Bawahab Ahmed Abdulwahab , Izbicki Jakob R. , Perez Daniel , Marx Andreas
Published: December 2019

Syndecan-1 (CD138) is a transmembrane proteoglycan known to be expressed in various normal and malignant tissues. It is of interest because of a possible prognostic role of differential expression in tumors and its role as a target for indatuximab, a monoclonal antibody coupled with a cytotoxic agent. To comprehensively analyze CD138 in normal and neoplastic tissues, we used tissue microarrays (TMAs) for analyzing immunohistochemically detectable CD138 expression in 2,518 tissue samples from 85 different tumor entities and 76 different normal tissue types. The data showed that CD138 expression is abundant in tumors. At least an occasional weak CD138 immunostaining could be detected in 71 of 82 (87%) different tumor types, and 58 entities (71%) had at least one tumor with a strong positivity. In normal tissues, a particularly strong expression was found in normal squamous epithelium of various organs, goblet and columnar cells of the gastrointestinal tract, and in hepatocytes. The highly standardized analysis of most human cancer types resulted in a ranking order of tumors according to the frequency and levels of CD138 expression. CD138 immunostaining was highest in squamous cell carcinomas such as from the esophagus (100%), cervix uteri (79.5%), lung (85.7%), vagina (89.7%) or vulva (73.3%), and in invasive urothelial cancer (76.2%). In adenocarcinomas, CD138 was also high in lung (82.9%) and colorectal cancer (85.3%) but often lower in pancreas (73.3%), stomach (54.2% in intestinal type), or prostate carcinomas (16.3%). CD138 expression was usually low or absent in germ cell tumors, sarcomas, endocrine tumors including thyroid cancer, and neuroendocrine tumors. In summary, the preferential expression in squamous cell carcinomas of various sites makes these cancers prime targets for anti-CD138 treatments once these might become available. Abundant expression in many different normal tissues might pose obstacles to exploiting CD138 as a therapeutic target, however.
MicroRNA Expression in Cutaneous Lupus: A New Window to Understand Its Pathogenesis
Authors: Méndez-Flores Silvia , Furuzawa-Carballeda Janette , Hernández-Molina Gabriela , Ramírez-Martinez Gustavo , Regino-Zamarripa Nora E. , Ortiz-Quintero Blanca , Jiménez-Alvarez Luis , Cruz-Lagunas Alfredo , Zúñiga Joaquín
Published: December 2019

Background. The role of miRNAs in the pathogenesis of cutaneous lupus has not been studied. Objective. It was to assess the levels of a selected panel of circulating miRNAs that could be involved in the regulation of the immune response, inflammation, and fibrosis in cutaneous lupus. Methods. It was a cross-sectional study. We included 22 patients with subacute (SCLE) and 20 with discoid (DLE) lesions, and 19 healthy donors (HD). qRT-PCR for miRNA analysis, flow cytometry in peripheral blood, and skin immunohistochemistry were performed to determine the distribution of CD4 T cells and regulatory cells and their correlation with circulating miRNAs. Results. miR-150, miR-1246, miR-21, miR-23b, and miR-146 levels were downregulated in SCLE vs. HD. miR-150, miR-1246, and miR-21 levels were downregulated in DLE vs. HD. Peripheral CD4+/CD25-/IL-4+ cells and CD4+/CD25hi/Foxp3+ were negatively associated with miR-23b, and CD4+/CD25-/IFN-γ+ with miR-1246 in SCLE, whereas CD123+/CD196+/IDO+ cells were positively associated with miR-150 in DLE. In the tissue, CD4+/IL-4+ and CD20+/IL-10+ cells were positively associated with miR-21 and CD4+/IFN-γ+ with miR-31 in SCLE, whereas CD4+/IL-4+ cells were positively associated with miR-150, and CD20+/IL-10+ cells with miR-1246 and miR-146a in DLE. In the SCLE, lower miR-150 levels were correlated with higher CLASI scores. The KEGG pathway enrichment analysis revealed that cell cycle regulation pathways, p53, TGF-β, thyroid hormone, and cancer signaling pathways were shared between miR-21, miR-31, miR-23b, miR-146a, miR-1246, and miR-150. Conclusions. A downregulation of miR-150, miR-1246, and miR-21 in both CLE varieties vs. HD was determined.
Vascularized Free Tissue Transfer in a Patient with Hemophilia B: Case Report and Literature Review
Authors: Qaisi Mohammed , Kierce Justin , Murphy James
Published: December 2019

Hemophilia is a blood disorder characterized by impairment of the coagulation cascade leading to an increased bleeding risk (Kauffman, 2014). As such, surgical management of these patients can become difficult and well-defined surgical guidelines are not yet in place (Assoumane et al., 2017). Close monitoring of perioperative factor levels may be even more crucial for those undergoing microvascular free tissue transfer. This is because either a hypercoagulable or hypocoagulable bleeding state has the potential to further increase the risk of vascular compromise to the flap. We report a successful case of mandibular reconstruction using a free fibular flap in a patient with severe hemophilia B and the protocols we used, as well as a review of the literature of similar cases. In the literature, we identified 6 cases of microvascular free tissue transfer in patients with hemophilia; two of these cases had complications which were both related to excess bleeding. It is crucial that these cases be managed in a multidisciplinary fashion in close consultation with a hematologist. The role of venothromboembolism (VTE) prophylaxis in the hemophilic patient undergoing free tissue transfer is discussed.
Gender-Specific Differences on the Association of Hypertension with Subclinical Thyroid Dysfunction
Authors: Zhang Jingkai , Huang Chao , Meng Zhaowei , Fan Yaguang , Yang Qing , Zhang Wenjuan , Gao Yuxia , Yang Zhenwen , Cai Heng , Bian Bo , Li Yongle , Yu Xuefang , Du Xin , Xu Shaopeng , Nie Jing , Liu Ming , Sun Jinhong , Zhang Qing , Gao Ying , Song Kun , Wang Xing , Zhao Li
Published: December 2019

Objective. Both hypertension and subclinical thyroid dysfunction (STD) have high prevalence and clinical importance, but their relationship is still a matter of debate. We aimed to explore gender-specific difference on the association between hypertension and STD in Chinese. Methods. We recruited 13,380 ostensible healthy participants (8,237 men and 5,143 women). The associations between hypertension and STD were analyzed on a gender-based setting after dividing STD into subclinical hypothyroidism, subclinical hyperthyroidism and further subgrouped euthyroidism. Crude and adjusted odds ratios of STD for hypertension were analyzed by binary logistic regression. Results. An increasing trend of hypertension prevalence was found along with aging in both genders. Yet, higher male hypertension prevalence was found until 65 years, and then it intersected with female hypertension prevalence. Women had significantly higher propensity for STD than men. Yet, in elderly participants, this gender-specific difference became less obvious. We displayed detrimental effects for subclinical hypothyroidism in both genders after multiple-covariate adjustments, yet no such effects were shown for subclinical hyperthyroidism. Moreover, females with subclinical hypothyroidism were more likely to be associated with hypertension than males, and the corresponding odds ratios were 1.619 (P<0.01) and 1.557 (P<0.05), respectively. For systolic blood pressure, the adjusted odds ratios were 1.371 (P<0.05) and 1.154 (P>0.05), and for diastolic blood pressure, 1.604 (P<0.01) and 1.564 (P<0.01), respectively. Conclusion. We demonstrate that hypertension is associated with subclinical hypothyroidism, but not with subclinical hyperthyroidism. Moreover, females with subclinical hypothyroidism are more likely to be associated with hypertension than males.
B-Doped Si@C Nanorod Anodes for High-Performance Lithium-Ion Batteries
Authors: Liu Shibin , Xu Jianwei , Zhou Hongyu , Wang Jing , Meng Xiangcai
Published: December 2019

B doping plays an important role in improving the conductivity and electrochemical properties of Si anodes for Li-ion batteries. Herein, we developed a facile and massive production strategy to fabricate C-coated B-doped Si (B-Si@C) nanorod anodes using casting intermediate alloys of Al-Si and Al-B and dealloying followed by C coating. The B-Si@C nanorod anodes demonstrate a high specific capacity of 560 mAg-1, with a high initial coulombic efficiency of 90.6% and substantial cycling stability. Notably, the melting cast approach is facile, simple, and applicable to doping treatments, opening new possibilities for the development of low-cost, environmentally benign, and high-performance Li-ion batteries.
Symptomatic Hypercalcemia in Patients with Primary Hyperparathyroidism Is Associated with Severity of Disease, Polypharmacy, and Comorbidity
Authors: Aresta C. , Passeri E. , Corbetta S.
Published: December 2019

Current primary hyperparathyroidism (PHPT) clinical presentation is asymptomatic in more than 90% of patients, while symptoms concern osteoporosis and rarely kidney stones. Here, we retrospectively investigated the prevalence of PHPT patients presenting with hypercalcemic-related symptoms (HS-PHPT) as cognitive impairment, changes in sensorium, proximal muscle weakness, nausea and vomiting, constipation, and severe dehydration, in a single center equipped with an emergency department and described their clinical features and outcome in comparison with a series of asymptomatic PHPT out-patients (A-PHPT). From 2006 to 2016, 112 PHPT patients were consecutively diagnosed: 16% (n = 18, 3M/15F) presented with hypercalcemic-related symptoms. Gastrointestinal symptoms occurred in 66% of HS-PHPT patients and cognitive impairment in 44%; one woman experienced hypertensive heart failure. Two-thirds of HS-PHPT patients were hospitalized due to the severity of symptoms. Comparing the clinical features of HS-PHPT patients with A-PHPT patients, no gender differences were detected in the two groups, while HS-PHPT patients were older at diagnosis (71 (61–81) vs. 64 (56–74) years, P=0.04; median (IQR)). HS-PHPT patients presented higher albumin-corrected calcium levels (12.3 (11.3–13.7) vs. 10.6 (10.3–11.3) mg/dl, P<0.001); 4 HS-PHPT presented corrected calcium levels >14 mg/dl. Serum PTH levels and total alkaline phosphatase activity were higher in HS-PHPT. Reduced kidney function (eGFR < 45 ml/min) was prevalent in HS-PHPT patients (42% vs. 5%, P=0.05). No differences in kidney stones and osteoporosis were detected, as well as in the rates of cardiovascular comorbidities and main cardiovascular risk factors. HS-PHPT patients had an age-adjusted Charlson Comorbidity Index higher than that of the A-PHPT patients and were on chronic therapy with a greater number of medications than A-PHPT patients. In conclusion, hypercalcemic-related symptoms occurred in 16% of PHPT patients. Risk factors were severity of the parathyroid tumor function, multimorbidity, and polypharmacy.
Epidemiology and Survival Outcomes of Lung Cancer: A Population-Based Study
Authors: Lin Huan-Tang , Liu Fu-Chao , Wu Ching-Yang , Kuo Chang-Fu , Lan Wen-Ching , Yu Huang-Ping
Published: December 2019

Purpose. Lung cancer has been the top-ranking cause of cancer deaths in Taiwan for decades. Limited data were available in global cancer surveillance regarding lung cancer epidemiology in Taiwan, and previous reports are outdated. Patients and Methods. This population-based cohort study extracted data of patients with lung cancer from the Taiwan National Health Insurance database and determined the lung cancer incidence and prevalence during 2002–2014. Histological subtypes were retrieved from the Taiwan Cancer Registry database; survival rates were gathered from the National Death Registry. Average annual percentage changes (APCs) of prevalence, incidence, and overall survival were estimated by joinpoint regression analysis. Results. Age-standardized incidence of lung cancer increased from 45.04 per 100,000 person-years in 2002 to 49.86 per 100,000 person-years in 2014, with an average APC of 0.7 (95% CI = 0.3–1.1; 0.2 in males, 2.0 in females). Lung cancer was more prevalent in male patients, but this increase gradually slowed down. Socioeconomic analysis showed that lung cancer has higher prevalence in patients with higher income level and urban residency. Adenocarcinoma was the most abundant histological subtype in Taiwan (adenocarcinoma-to-squamous cell carcinoma ratio = 4.16 in 2014), with a 2.4-fold increase of incident cases during 2002–2014 (from 43.47% to 64.89% of all lung cancer cases). The 5-year survival rate of lung cancer patients in 2010 was 17.34% (12.60% in male, 25.40% in female), with an average APC of 9.3 (6.3 in male, 11.8 in female) during 2002–2010. Conclusion. Average APCs of prevalence and incidence of lung cancer were 3.1 and 0.7, respectively, during 2002–2014 in Taiwan. The number of female patients and number of patients with adenocarcinoma have increased the most, with incident cases doubling in these years. Facing this fatal malignancy, it is imperative to improve risk stratification, encourage early surveillance, and develop effective therapeutics for lung cancer patients in Taiwan.
Normal Anatomy and Anomalies of the Rectus Extraocular Muscles in Human: A Review of the Recent Data and Findings
Authors: Haładaj Robert
Published: December 2019

Development of modern surgical techniques is associated with the need for a thorough knowledge of surgical anatomy and, in the case of ophthalmologic surgery, also functional aspects of extraocular muscles. Thus, the leading idea of this review was to summarize the most recent findings regarding the normal anatomy and anomalies of the extraocular rectus muscles (ERMs). Particular attention was paid to the presentation of detailed and structured data on the gross anatomy of the ERMs, including their attachments, anatomical relationships, vascularization, and innervation. This issue of ERMs innervation was presented in detail, considering the research that has recently been carried out on human material using advanced anatomical techniques such as Sihler’s technique of the nerves staining. The text was supplemented with a carefully selected graphic material (including anatomical specimens prepared specially for the purpose of this review) and discussion of the clinical cases and practical significance of the presented issues.