bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal allocation of HIV resources among geographical regions
Authors: Kedziora David J. , Stuart Robyn M. , Pearson Jonathan , Latypov Alisher , Dierst-Davies Rhodri , Duda Maksym , Avaliani Nata , Wilson David P. , Kerr Cliff C.
Published: November 2019

Background

Health resources are limited, which means spending should be focused on the people, places and programs that matter most. Choosing the mix of programs to maximize a health outcome is termed allocative efficiency. Here, we extend the methodology of allocative efficiency to answer the question of how resources should be distributed among different geographic regions.

Methods

We describe a novel geographical optimization algorithm, which has been implemented as an extension to the Optima HIV model. This algorithm identifies an optimal funding of services and programs across regions, such as multiple countries or multiple districts within a country. The algorithm consists of three steps: (1) calibrating the model to each region, (2) determining the optimal allocation for each region across a range of different budget levels, and (3) finding the budget level in each region that minimizes the outcome (such as reducing new HIV infections and/or HIV-related deaths), subject to the constraint of fixed total budget across all regions. As a case study, we applied this method to determine an illustrative allocation of HIV program funding across three representative oblasts (regions) in Ukraine (Mykolayiv, Poltava, and Zhytomyr) to minimize the number of new HIV infections.

Results

Geographical optimization was found to identify solutions with better outcomes than would be possible by considering region-specific allocations alone. In the case of Ukraine, prior to optimization (i.e. with status quo spending), a total of 244,000 HIV-related disability-adjusted life years (DALYs) were estimated to occur from 2016 to 2030 across the three oblasts. With optimization within (but not between) oblasts, this was estimated to be reduced to 181,000. With geographical optimization (i.e., allowing reallocation of funds between oblasts), this was estimated to be further reduced to 173,000.

Conclusions

With the increasing availability of region- and even facility-level data, geographical optimization is likely to play an increasingly important role in health economic decision making. Although the largest gains are typically due to reallocating resources to the most effective interventions, especially treatment, further gains can be achieved by optimally reallocating resources between regions. Finally, the methods described here are not restricted to geographical optimization, and can be applied to other problems where competing resources need to be allocated with constraints, such as between diseases.
Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis
Authors: Pang Bing , Shi Li-Wei , Du Li-juan , Li Yun-Chu , Zhang Mei-Zhen , Ni Qing
Published: November 2019

Background

Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells.

Methods

HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 μg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively.

Results

SMS treatments at 25, 50, 100 μg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 μg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 μg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group.

Conclusion

SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.
Potential cost-savings from the use of the biosimilars filgrastim, infliximab and insulin glargine in Canada: a retrospective analysis
Authors: Mansell Kerry , Bhimji Hishaam , Eurich Dean , Mansell Holly
Published: November 2019

Background

In 2014 and 2015, biosimilars for the drugs filgrastim, infliximab, and insulin glargine were approved for use in Canada. The introduction of biosimilars in Canada could provide significant cost savings for the Canadian healthcare system over originator biologic drugs, however it is known that the use of biosimilars varies widely across the world. The aim of this study was to estimate the use of biosimilars in Canada and potential cost-savings from their use.

Methods

We performed a retrospective analysis of Canadian drug purchases for filgrastim, infliximab, and insulin glargine from July 2016 to June 2018. This was a cross-sectional study and the time horizon was limited to the study period. As a result, no discounting of effects over time was included. Canadian drugstore and hospital purchases data, obtained from IQVIA™, were used to estimate the costs per unit and unit volume for biosimilars and originator biologic drugs within each province. Potential cost-savings were calculated as a product of the units of reference originator product purchased and the cost difference between the originator biologic and its corresponding biosimilar.

Results

The purchase of biosimilars varied by each province in Canada, ranging from a low of 0.1% to a high of 81.6% of purchases. In total, $1,048,663,876 Canadian dollars in savings could have been realized with 100% use of biosimilars over the originator products during this 2 year time period. The potential savings are highest in the province of Ontario ($349 million); however, even in smaller markets (PEI and Newfoundland), $28 million could have potentially been saved. Infliximab accounted for the vast majority of the potential cost-savings, whereas the purchases of the biosimilar filgrastim outpaced that of the originator drug in some provinces. In sensitivity analyses assuming only 80% of originator units would be eligible for use as a biosimilar, $838 million dollars in cost savings over this two-year time period would still have been realized.

Conclusions

The overall use of biosimilar drugs in Canada is low. Policy makers, healthcare providers, and patients need to be informed of potential savings by increased use of biosimilars, particularly in an increasingly costly healthcare system.
Community participation and private sector engagement are fundamental to achieving universal health coverage and health security in Africa: reflections from the second Africa health forum
Authors: Olu Olushayo , Drameh-Avognon Pamela , Asamoah-Odei Emil , Kasolo Francis , Valdez Thomas , Kabaniha Grace , Karamagi Humphrey , Good Suvajee , O’Malley Helena , Yoti Zabulon , Razakazoa Nirina , Minkoulou Etienne , Dangou Jean-Marie , Mbola Mbassi Symplice , Castellon Mariano Salazar , Cabore Joseph , Moeti Matshidiso
Published: November 2019

Background

Inadequate access to quality health care services due to weak health systems and recurrent public health emergencies are impediments to the attainment of Universal Health Coverage and health security in Africa. To discuss these challenges and deliberate on plausible solutions, the World Health Organization Regional Office for Africa, in collaboration with the Government of Cabo Verde, convened the second Africa Health Forum in Praia, Cabo Verde on 26–28 March 2019, under the theme Achieving Universal Health Coverage and Health Security: The Africa We Want to See.

Methods

The Forum was conducted through technical sessions consisting of high-level, moderated panel discussions on specific themes, some of them preceded by keynote addresses. There were booth exhibitions by Member States, World Health Organization and other organizations to facilitate information exchanges. A Communiqué highlighting the recommendations of the Forum was issued during the closing ceremony. More than 750 participants attended. Relevant information from the report of the Forum and notes by the authors were extracted and synthesized into these proceedings.

Conclusions

The Forum participants agreed that the role of community engagement and participation in the attainment of Universal Health Coverage, health security and ultimately the Sustainable Development Goals cannot be overemphasized. The public sector of Africa alone cannot achieve these three interrelated goals; other partners, such as the private sector, must be engaged. Technological innovations will be a key driver of the attainment of these goals; hence, there is need to harness the comparative advantages that they offer. Attainment of the three goals is also intertwined – achieving one paves the way for achieving the others. Thus, there is need for integrated public health approaches in the planning and implementation of interventions aimed at achieving them.

Recommendations

To ensure that the recommendations of this Forum are translated into concrete actions in a sustainable manner, we call on African Ministers of Health to ensure their integration into national health sector policies and strategic documents and to provide the necessary leadership required for their implementation. We also call on partners to mainstream these recommendations into their ongoing support to World Health Organization African Member States.
A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali
Authors: Diakité Seidina A. S. , Traoré Karim , Sanogo Ibrahim , Clark Taane G. , Campino Susana , Sangaré Modibo , Dabitao Djeneba , Dara Antoine , Konaté Drissa S. , Doucouré Fousseyni , Cissé Amadou , Keita Bourama , Doumbouya Mory , Guindo Merepen A. , Toure Mahamoudou B. , Sogoba Nafomon , Doumbia Seydou , Awandare Gordon A. , Diakité Mahamadou
Published: November 2019

Background

Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission.

Methods

Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger’s 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species.

Results

The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel.

Conclusions

This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel.
Epithelial and interstitial Notch1 activity contributes to the myofibroblastic phenotype and fibrosis
Authors: Hong Weilong , Zhang Ge , Lu Hong , Guo Yangyang , Zheng Shizhang , Zhu Hengyue , Xiao Yanyi , Papa Akuetteh Percy David , Wu Cunzao , Sun Linxiao , Chen Bicheng , Bai Yongheng
Published: November 2019

Background

Notch1 signalling is a stem-cell-related pathway that is essential for embryonic development, tissue regeneration and organogenesis. However, the role of Notch1 in the formation of myofibroblasts and fibrosis in kidneys following injury remains unknown.

Methods

The activity of Notch1 signalling was evaluated in fibrotic kidneys in CKD patients and in ureteral obstructive models in vivo and in cultured fibroblasts and TECs in vitro. In addition, the crosstalk of Notch1 with TGF-β1/Smad2/3 signalling was also investigated.

Results

Notch1 activity was elevated in fibrotic kidneys of rat models and patients with chronic kidney disease (CKD). Further study revealed that epithelial and interstitial Notch1 activity correlated with an α-SMA-positive myofibroblastic phenotype. In vitro, injury stimulated epithelial Notch1 activation and epithelial-mesenchymal transition (EMT), resulting in matrix deposition in tubular epithelial cells (TECs). Additionally, interstitial Notch1 activation in association with fibroblast-myofibroblast differentiation (FMD) in fibroblasts mediated a myofibroblastic phenotype. These TGF-β1/Smad2/3-dependent phenotypic transitions were abolished by Notch1 knockdown or a specific antagonist, DAPT, and were exacerbated by Notch1 overexpression or an activator Jagged-1-Fc chimaera protein. Interestingly, as a major driving force behind the EMT and FMD, TGF-β1, also induced epithelial and interstitial Notch1 activity, indicating that TGF-β1 may engage in crosstalk with Notch1 signalling to trigger fibrogenesis.

Conclusion

These findings suggest that epithelial and interstitial Notch1 activation in kidneys following injury contributes to the myofibroblastic phenotype and fibrosis through the EMT in TECs and to the FMD in fibroblasts by targeting downstream TGF-β1/Smad2/3 signalling.
Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma
Authors: Chen Yan , Li Zhonghu , Zhang Mengyun , Wang Bo , Ye Jiaxin , Zhang Yang , Tang Di , Ma Dandan , Jin Weidong , Li Xiaowu , Wang Shuguang
Published: November 2019

Background

Circular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.

Methods

circRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.

Results

We identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.

Conclusions

circ-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.
Correction to: Identifying significantly impacted pathways: a comprehensive review and assessment
Authors: Nguyen Tuan-Minh , Shafi Adib , Nguyen Tin , Draghici Sorin
Published: November 2019

Following publication of the original paper [1], the authors reported the following update to the competing interests declaration.
Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome
Authors: Chen Jing , Luo Yi , Zhao Mengzhu , Wu Di , Yang Yunjiao , Zhang Wen , Shen Min
Published: November 2019

Objectives

Blau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who were treated with tumor necrosis factor (TNF)α inhibitors.

Methods

A total of four patients with BS were diagnosed and treated with infliximab (IFX) at the Peking Union Medical College Hospital during 2015 to 2018 and were followed up for 18 months. All patients were systematically studied for treatment outcomes including the clinical manifestations and inflammatory markers. We also conducted a comprehensive literature review about TNFα inhibitor therapy in BS.

Results

Four BS patients were all Chinese Han, and three were women. The mean age of disease onset was 4 ± 3.5 years, and the mean time of diagnosis delay was 19 ± 11 years. All patients received IFX plus methotrexate, and all achieved clinical remission of skin lesions and polyarthritis rapidly, as well as normalization of erythrocyte sedimentation rate and C-reactive protein and improvements in inflammatory cytokines, patient visual analogue scale, physician global assessment, and Short Form (SF)-36, at the first follow-up of 6 months. The disease relapsed in two patients after they lengthened the interval of IFX and discontinued methotrexate. According to the 38 English-language publications, 62 patients with BS were reported who underwent TNFα inhibitor therapy, including IFX used in 31, adalimumab in 24, and etanercept in 7. IFX was well tolerated in 27 patients, while 2 still had uveitis, and the other 2 experienced an adverse drug reaction.

Conclusions

Early recognition and effective treatment of BS are very important to avoid irreversible organ damage. TNFα inhibitors such as IFX may be a promising approach for BS patients who have unsatisfactory response to corticosteroids and traditional disease-modifying antirheumatic drugs.
Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats
Authors: Sui Yi , Kong Xianhe , Fan Rongrong , Ye Yanbin , Mai Haiyan , Zhuo Shuyu , Lu Wei , Ruan Peishan , Fang Shi , Yang Tao
Published: November 2019

Background

Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats.

Methods

Male ZDF rats and Zucker lean rats aged 4–8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed.

Results

Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats.

Conclusions

These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.
Exploring semantic deep learning for building reliable and reusable one health knowledge from PubMed systematic reviews and veterinary clinical notes
Authors: Arguello-Casteleiro Mercedes , Stevens Robert , Des-Diz Julio , Wroe Chris , Fernandez-Prieto Maria Jesus , Maroto Nava , Maseda-Fernandez Diego , Demetriou George , Peters Simon , Noble Peter-John M. , Jones Phil H. , Dukes-McEwan Jo , Radford Alan D. , Keane John , Nenadic Goran
Published: November 2019

Background

Deep Learning opens up opportunities for routinely scanning large bodies of biomedical literature and clinical narratives to represent the meaning of biomedical and clinical terms. However, the validation and integration of this knowledge on a scale requires cross checking with ground truths (i.e. evidence-based resources) that are unavailable in an actionable or computable form. In this paper we explore how to turn information about diagnoses, prognoses, therapies and other clinical concepts into computable knowledge using free-text data about human and animal health. We used a Semantic Deep Learning approach that combines the Semantic Web technologies and Deep Learning to acquire and validate knowledge about 11 well-known medical conditions mined from two sets of unstructured free-text data: 300 K PubMed Systematic Review articles (the PMSB dataset) and 2.5 M veterinary clinical notes (the VetCN dataset). For each target condition we obtained 20 related clinical concepts using two deep learning methods applied separately on the two datasets, resulting in 880 term pairs (target term, candidate term). Each concept, represented by an n-gram, is mapped to UMLS using MetaMap; we also developed a bespoke method for mapping short forms (e.g. abbreviations and acronyms). Existing ontologies were used to formally represent associations. We also create ontological modules and illustrate how the extracted knowledge can be queried. The evaluation was performed using the content within BMJ Best Practice.

Results

MetaMap achieves an F measure of 88% (precision 85%, recall 91%) when applied directly to the total of 613 unique candidate terms for the 880 term pairs. When the processing of short forms is included, MetaMap achieves an F measure of 94% (precision 92%, recall 96%). Validation of the term pairs with BMJ Best Practice yields precision between 98 and 99%.

Conclusions

The Semantic Deep Learning approach can transform neural embeddings built from unstructured free-text data into reliable and reusable One Health knowledge using ontologies and content from BMJ Best Practice.
Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death
Authors: Shah Anoop D. , Bailey Emily , Williams Tim , Denaxas Spiros , Dobson Richard , Hemingway Harry
Published: November 2019

Background

Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events – heart attack and death – there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.

Results

We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.

Conclusions

Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.
On extended interpolative Ćirić–Reich–Rus type F-contractions and an application
Authors: Mohammadi Babak , Parvaneh Vahid , Aydi Hassen
Published: November 2019

The goal of this work is to introduce an extended interpolative Ćirić–Reich–Rus type contraction by the approach of Wardowski. We establish some related fixed point results (for single and multivalued-mappings). Some examples are presented to illustrate the main result. Moreover, we give an application to integral equations.
Improving exposure for transoral oropharyngeal surgery with the floor of mouth window: A cadaveric feasibility study
Authors: Chung Jeffson , Bender-Heine Adam , Lambert H. Wayne
Published: November 2019

Background

Transoral robotic and laser surgery is rising in popularity due to the increasing incidence of Human Papilloma Virus (HPV) related oropharyngeal cancer. However, adequate exposure of the tongue base remains a major hurdle in many cases. This study introduces a novel surgical technique called the Floor of Mouth Window, which can be used to improve tongue base exposure at the time of transoral surgery.

Methods

This is a preclinical anatomic cadaver study. Seven fresh cadavers were used for this study. Exposure of the tongue base was compared between conventional mouth gags – the Feyh-Kastenbauer and McIvor – and our novel procedure, the Floor of Mouth Window. Exposure was compared subjectively using endoscopic and extracorporeal photographs, as well as objective measurements of inter-incisor distance, and oral cavity volume.

Results

The exposure achieved by the Floor of Mouth Window technique was superior to the mouth gags. Inter-incisor distance and oral cavity volume measurements were all more favorable with the Floor of Mouth Window. This technique allowed for successful transoral laser tongue base and tonsil resection without the use of gags or scopes.

Conclusion

The Floor of Mouth Window is an adjunctive procedure that simply and reliably improved exposure for transoral oropharyngeal surgery in this cadaveric feasibility study. This improved exposure may help increase the adoption of transoral surgery and reduce the number of aborted cases due to anatomic limitations.
First in-orbit results of the vector magnetic field measurement of the High Precision Magnetometer onboard the China Seismo-Electromagnetic Satellite
Authors: Zhou Bin , Cheng Bingjun , Gou Xiaochen , Li Lei , Zhang Yiteng , Wang Jindong , Magnes Werner , Lammegger Roland , Pollinger Andreas , Ellmeier Michaela , Xiao Qi , Zhu Xinghong , Yuan Shigeng , Yang Yanyan , Shen Xuhui
Published: November 2019

The High Precision Magnetometer (HPM) is one of the main payloads onboard the China Seismo-Electromagnetic Satellite (CSES). The HPM consists of two Fluxgate Magnetometers (FGM) and the Coupled Dark State Magnetometer (CDSM), and measures the magnetic field from DC to 15 Hz. The FGMs measure the vector components of the magnetic field; while the CDSM detects the magnitude of the magnetic field with higher accuracy, which can be used to calibrate the linear parameters of the FGM. In this paper, brief descriptions of measurement principles and performances of the HPM, ground, and in-orbit calibration results of the FGMs are presented, including the thermal drift and magnetic interferences from the satellite. The HPM in-orbit vector data calibration includes two steps: sensor non-linearity corrections based on on-ground calibration and fluxgate linear parameter calibration based on the CDSM measurements. The calibration results show a reasonably good stability of the linear parameters over time. The difference between the field magnitude calculated from the calibrated FGM components and the magnitude directly measured by the CDSM is just 0.5 nT (1σ) when the linear parameters are fitted separately for the day- and the night-side. Satellite disturbances have been analyzed including soft and hard remanence as well as magnetization of the magnetic torquer, radiation from the Tri-Band Beacon, and interferences from the rotation of the solar wing. A comparison shows consistency between the HPM and SWARM magnetic field data. Observation examples are introduced in the paper, which show that HPM data can be used to survey the global geomagnetic field and monitor the magnetic field disturbances in the ionosphere.
Determinants of p14/ARF methylation in healthy females: association with reproductive and non-reproductive risk factors of breast cancer
Authors: Ezzat Ghada M. , El-Shoeiby Mahmoud H.
Published: November 2019

Background

DNA methylation is associated with the risk factors of breast cancer. However, the impact of the reproductive and non-reproductive risk factors of breast cancer on p14/ARF methylation is not well known. Therefore, we investigated the relationships between p14/ARF methylation percentage and risk factors of breast cancer including age, family history, obesity, and reproductive risk factors in 120 breast cancer-free subjects; 60 women with a first-degree family history of breast cancer and 60 age-matched women with no family history of breast cancer. Extracted DNA from the whole blood was bisulfite-treated by EZ DNA modification kit. Quantitative methylation of p14/ARF was analyzed by methylation-specific PCR then methylation percentage of p14/ARF was calculated.

Results

P14/ARF methylation percentage was not related to any of the risk factors of breast cancer except age. Our study showed that p14/ARF methylation percentage was significantly higher in females with age ≥ 40 years than in females with age <  40 years (p=0.029). Also, a positive significant correlation between the p14/ARF methylation percentage and age was detected (r = 0.285, p = 0.014). Furthermore, univariate regression analysis showed that the age is independently associated with high p14/ARF methylation percentage (β = 1. 46, p = 0.029).

Conclusion

Among healthy females, the age is strongly linked to the peripheral p14/ARF methylation percentage. The present study suggests that p14/ARF methylation is not associated with other breast cancer risk factors. These results need oncoming research on a large cohort to define the interactions between p14/ARF methylation and the risk factors of breast cancer.
Assessing asylum seekers, refugees and undocumented migrants
Authors: Waterman Lauren Z. , Katona Cara , Katona Cornelius
Published: November 2019

Identifying the causes of psychiatric and physical symptoms in asylum seekers, refugees and other migrants and making definitive diagnoses can be challenging. Ethical and legal challenges in the UK include the likely deterrent effects of upfront charging for National Health Service (NHS) services. This paper focuses on the fictitious case of an asylum seeker presenting to a mental health service in England, highlighting some of the difficulties in assessing and treating this patient group and providing advice to clinicians on clinical and practical management. Current NHS entitlements for migrants are summarised and a list is presented in the online supplement of non-governmental organisations that can provide further support.
A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia
Authors: Mulla Christopher M , Zavitsanou Stamatina , Laguna Sanz Alejandro Jose , Pober David , Richardson Lauren , Walcott Pamela , Arora Ipsa , Newswanger Brett , Cummins Martin J , Prestrelski Steve J , Doyle Francis J , Dassau Eyal , Patti Mary Elizabeth
Published: November 2019

Background

Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective.

Methods

Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the artificial pancreas system connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during 2 study visits. The system delivered up to 2 doses of study drug (300/150 μg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose <55 mg/dL or neuroglycopenia.

Results

Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n = 11/12) and vehicle (n = 10/12). No other adverse events were observed.

Conclusion

A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH.

Clinical Trials Registration

NCT03255629
Mark1 regulates distal airspace expansion through type I pneumocyte flattening in lung development
Authors: Fumoto Katsumi , Takigawa-Imamura Hisako , Sumiyama Kenta , Yoshimura Shige H. , Maehara Natsumi , Kikuchi Akira
Published: November 2019

During the later stages of lung development, two types of pneumocytes, cuboidal type II (AECII) and flattened type I (AECI) alveolar epithelial cells, form distal lung saccules. Here, we highlight how fibroblasts expressing MAP-microtubule affinity regulating kinase 1 (Mark1) are required for the terminal stages of pulmonary development, called lung sacculation. In Mark1-knockout (KO) mice, distal sacculation and AECI flattening are significantly impaired. Fetal epithelial cells generate alveolar organoids and differentiate into pneumocytes when co-cultured with fibroblasts. However, the size of organoids decreased and AECI flattening was impaired in the presence of Mark1 KO fibroblasts. In Mark1 KO fibroblasts themselves, cilia formation and the Hedgehog pathway were suppressed, resulting in the loss of type I collagen expression. The addition of type I collagen restored AECI flattening in organoids co-cultured with Mark1 KO fibroblasts and rescued the decreased size of organoids. Mathematical modeling of distal lung sacculation supports the view that AECI flattening is necessary for the proper formation of saccule-like structures. These results suggest that Mark1-mediated fibroblast activation induces AECI flattening and thereby regulates distal lung sacculation.
The ethical adoption of artificial intelligence in radiology
Authors: Mudgal Keshav Shree , Das Neelanjan
Published: November 2019

Artificial intelligence (AI) is rapidly transforming healthcare—with radiology at the pioneering forefront. To be trustfully adopted, AI needs to be lawful, ethical and robust. This article covers the different aspects of a safe and sustainable deployment of AI in radiology during: training, integration and regulation.

For training, data must be appropriately valued, and deals with AI companies must be centralized. Companies must clearly define anonymization and consent, and patients must be well-informed about their data usage. Data fed into algorithms must be made AI-ready by refining, purification, digitization and centralization. Finally, data must represent various demographics.

AI needs to be safely integrated with radiologists-in-the-loop: guiding forming concepts of AI solutions and supervising training and feedback. To be well-regulated, AI systems must be approved by a health authority and agreements must be made upon liability for errors, roles of supervised and unsupervised AI and fair workforce distribution (between AI and radiologists), with a renewal of policy at regular intervals. Any errors made must have a root-cause analysis, with outcomes fedback to companies to close the loop—thus enabling a dynamic best prediction system.

In the distant future, AI may act autonomously with little human supervision. Ethical training and integration can ensure a "transparent" technology that will allow insight: helping us reflect on our current understanding of imaging interpretation and fill knowledge gaps, eventually moulding radiological practice. This article proposes recommendations for ethical practise that can guide a nationalized framework to build a sustainable and transparent system.
Mandibular cortical indices and their relation to gender and age in the cone-beam computed tomography
Authors: Goyushov Samir , Dursun Erhan , Tözüm Tolga Fikret
Published: November 2019

Objectives

The purpose of this study is to evaluate normal ranges of cortical bone Hounsfield units indices through cone beam CT images, and to investigate their relationships with age and sex.

Methods

700 adult human cone beam CT images were evaluated retrospectively, and divided into 4 age groups. Six different cortical bone Hounsfield unit measurements were applied bilaterally, where gender and age were recorded. Collected data were subjected to statistical analysis and ANOVA tests were used for various comparisons.

Results

The cortical bone measurements between female and male patients were significantly different (p<0.05). Cortical bone thickness indices showed greater values in male patients compare to female patients (p<0.05). Quantitative mandibular indices were significantly lower in first age group (18–30 years) than other three older age groups (p<0.01).

Conclusion

The results of this study seems to propose a persistent alteration in the mandibular cortical bone with age and that this influced by sex. Further studies with larger patient groups are needed to clarify and understand these mandibular indices.
An overview of radiological manifestations of acquired dental developmental disturbances in paediatric head and neck cancer survivors
Authors: Hoogeveen Reinier C. , Hol Marinka L.F. , Pieters Bradley R. , Balgobind Brian V. , Berkhout Erwin W.E.R. , Schoot Reineke A. , Smeele Ludi E. , Merks Hans J.H.M. , Becking Eddy A.G.
Published: November 2019

Objectives:

In paediatric cancer survivors treated with chemotherapy and radiotherapy therapy, late effects on dental development are quite common. Oral radiologists are not familiar with the radiographic images of these specific dental consequences of chemotherapy and radiotherapy. With the goal of educating colleagues, to raise awareness of the needs of survivors, and to identify directions for future research, we present dental radiographs of survivors treated for head and neck rhabdomyosarcoma with chemotherapy and radiotherapy. Also, based on the survivors reviewed, a radiographic inventory of commonly found late dental developmental effects seen in conjunction with treatment is presented.

Methods:

Panoramic radiographic findings of five illustrative cases are presented, from a group of 42 survivors of head and neck rhabdomyosarcoma treated at the Academic Medical Center Amsterdam, The Netherlands over the past 25 years.

Results:

Five cases showing dental developmental disorders are presented. These cases show an association of the location of the radiation field and the developmental stage of the teeth with the severity of the effect on dental development. We also report an inventory of severe and moderate effects of chemotherapy and radiotherapy on the development of molars and anterior teeth.

Conclusions:

This paper presents five cases and a radiographic inventory to illustrate disturbances of dental development associated with chemotherapy and radiotherapy in children. Medical and dental professionals involved in the treatment of cancer survivors are relatively unaware of the dental consequences of radiation therapy and the age dependency of specific regional effects. These effects can be severe, with great impact on quality of life. Further research in this area could help improve planning of radiation therapy for children, potentially preventing or limiting dental or maxillofacial sequelae.
Deep sequencing of tRNA's 3′-termini sheds light on CCA-tail integrity and maturation
Authors: Czech Andreas
Published: November 2019

The 3′-termini of tRNA are the point of amino acid linkage and thus crucial for their function in delivering amino acids to the ribosome and other enzymes. Therefore, to provide tRNA functionality, cells have to ensure the integrity of the 3′-terminal CCA-tail, which is generated during maturation by the 3′-trailer processing machinery and maintained by the CCA-adding enzyme. We developed a new tRNA sequencing method that is specifically tailored to assess the 3′-termini of E. coli tRNA. Intriguingly, we found a significant fraction of tRNAs with damaged CCA-tails under exponential growth conditions and, surprisingly, this fraction decreased upon transition into stationary phase. Interestingly, tRNAs bearing guanine as a discriminator base are generally unaffected by CCA-tail damage. In addition, we showed tRNA species-specific 3′-trailer processing patterns and reproduced in vitro findings on preferences of the maturation enzyme RNase T in vivo.
Diffusion of ethical governance policy on sharing of biological materials and related data for biomedical research
Authors: Vaz Manjulika , Palmero Ana G. , Nyangulu Wongani , Diallo Alpha A. , Ho Calvin W. L.
Published: November 2019

This paper considers how ethical norms on sharing of human biological materials and related data in international policy documents diffuse from global forums to national policies and practices. With focus on the domestic policies of four countries (i.e. Guinea, Argentina, India and Malawi), this paper seeks to explain policy diffusion by broadly applying an analytical framework wherein policy learning is one of four theories used to explain how countries learn policy norms from expert epistemic communities and international organizations. While the governance structures of all four countries broadly incorporate key ethical provisions in international policy documents on sharing of biological materials and related data for biomedical research, relative emphasis on certain provisions differ among them. In three of these countries (i.e. Guinea, Argentina and India), international ethical norms have had direct influence over their domestic governance policies. Their impact has been greatest for Guinea and Argentina, whose governance policies had to be adapted in response to the Ebola virus epidemic in West Africa and the Zika virus epidemic in Latin America. In both countries, sharing of biological materials and related data with international organisations increased significantly to meet therapeutic and research needs during the outbreaks. International organisations have had a comparatively greater role in bringing about policy change in Guinea when compared with Argentina, mainly due to the fragility of the health system in Guinea in 2014. In contrast, policy in India and in Malawi occurred under less strenuous conditions. This may account for the relatively greater emphasis on control and limits to cross-border transferability in their policies when compared with those of Guinea and Argentina. While all four countries have made significant progress in establishing accountable governance arrangements, still more needs to be done to ensure that the ethical goal of equitable sharing of benefits is realised.
The Important Element Of Revenue Sharing In Arbitrate Client By Indonesian Islamic Banking Profitability
Authors: Mubarok Endang Saefuddin , Khairuddin Khairuddin , Hidayat Rachmat , Saputra Surya Adi
Published: November 2019

This research aimed at understanding the effects of financing risk, cost efficiency, and liquidity on profitability and the impacts on profit sharing. The method used for the research was causality with purposive sampling data collection technique. The analysis model selected was the regression using panel data, namely the data repeatedly observed on the same unit of objects from time to time. The objects of the research was10 Islamic Commercial Banks in Indonesia with secondary data in the form of financial statements for 2010 - 2017 period. The results of the statistical study indicated that the NPF, OCR (BOPO), and FDR variables simultaneously influenced the profitability (ROA) with contribution value of 93.5%. Partially, the three variables had a negative and significant effect on profitability (ROA). NPF, OCR, and FDR simultaneously had a positive and significant effect on profit sharing with a contribution value of 94.53%. Partially, NPF had a negative and significant effect on profit sharing, while OCR and FDR had a positive and significant effect on profit sharing. Profitability (ROA) had a positive and significant effect on customer profit sharing. The NPF and FDR for profit sharing did not mediate their effects on profit sharing. At the same time, OCR for profit sharing through ROA, was able to mediate the OCR of the effect on profit sharing.