bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalised purulent peritonitis and small bowel obstruction due to a spontaneously perforated ovarian dermoid cyst
Authors: Simillis Constantinos , Cribb Emily , Gurtovaya Yulia , Pawa Nikhil
Published: October 2019

We outline the narrative of a 28-year-old woman who initially presented to the emergency department with vomiting, diarrhoea, abdominal pain and fever. Blood tests revealed significantly raised inflammatory markers and acute renal failure. Initially, this was attributed to gastroenteritis due to a recent foreign travel, but further investigations and radiological imaging revealed a large right ovarian dermoid cyst with a significant amount of free intra-abdominal fluid and small bowel dilation. She underwent laparotomy, which revealed a spontaneously perforated right ovarian dermoid cyst resulting in generalised purulent peritonitis and small bowel obstruction due to bowel adherence at the perforation site. Meticulous adhesiolysis, right salpingo-oophorectomy and extensive peritoneal lavage were performed, with a good postoperative recovery. Spontaneous perforation of an ovarian dermoid cyst, without an associated torsion, is extremely rare, but it should be considered in cases of peritonitis and bowel obstruction of unclear cause with a concomitant finding of a dermoid cyst.
Non-ST elevation myocardial infarction, non-obstructive coronary arteries and severe regional microvascular dysfunction in a patient with dilated cardiomyopathy
Authors: Kite Thomas A , Marrow Benjamin A , Nduwayo Sarah , McCann Gerry P
Published: October 2019

Cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) is a key modality in providing localisation and characterisation of myocardial injury in patients diagnosed with myocardial infarction with non-obstructive coronary arteries (MINOCA). We present a case that demonstrates the unique ability of CMR to provide crucial information in instances of uncertainty. A 71-year-old patient with dilated cardiomyopathy (DCM) presented with symptoms suggestive of acute myocardial infarction. The diagnosis of MINOCA was confirmed following coronary angiography. CMR imaging with LGE confirmed presence of apical infarction. Quantitative myocardial perfusion mapping demonstrated severely reduced blood flow in the non-infarcted septal segments proximal to the distal infarcted territory. The precise aetiology of apical infarction remains uncertain and is likely attributed to coronary plaque rupture. However, concomitant severe regional microvascular dysfunction is also appreciated. This is a recognised, but not well described, phenomenon in DCM and may contribute to repetitive ischaemic injury and disease progression.
Intractable pruritus in chronic myelomonocytic leukaemia and myelodysplastic syndromes: a case series
Authors: Ceesay M Mansour , Basu Tanya N , du Vivier Anthony , Mufti Ghulam J
Published: October 2019

Intractable pruritus without visible primary skin lesions and refractory to antihistamines as a primary presentation of chronic myelomonocytic leukaemia (CMML) and myelodysplastic syndrome (MDS) is not well recognised. We present two cases of CMML and two cases of MDS with this challenging symptom. In two of them, the pruritus preceded the diagnosis of MDS/CMML by months. Various chemotherapeutic and immunosuppressive options were used with variable success. In one of the cases, the pruritus persisted despite achieving morphological remission of CMML with azacitidine but had a remarkable complete response to cladribine. The pathogenesis of intractable itching in CMML and MDS remains unclear but seems to be linked to the biology of these diseases and could precede definitive diagnostic features. Earlier diagnosis of these myeloid disorders may therefore be aided by increasing awareness among clinicians of the association with pruritus.
Five-year nationwide incidence of macular hole requiring surgery in Korea
Authors: Cho Soo Chang , Park Sang Jun , Byun Seong Jun , Woo Se Joon , Park Kyu Hyung
Published: October 2019

Background/aims

To estimate the incidence and demographics of macular hole (MH) requiring surgery in Korea.

Methods

Patients who underwent surgery for MH in Korea from 2011 to 2015 with the diagnostic code for MH and the surgical code for vitrectomy were retrospectively identified using the Korean national health claims database. The average incidence rate of MH during the 5-year study period was estimated by applying the direct method of standardisation using the 2015 census data as a reference population.

Results

A total of 7301 patients with MH requiring surgery were identified. The average incidence of MH requiring surgery was 3.14 (95 % CI, 3.07 to 3.21) per 100 000 person-years . The incidence in women (4.29 per 100 000 person-years; 95% CI, 4.17 to 4.40) was significantly higher than that in men (2.00 per 100 000 person-years; 95% CI, 1.92 to 2.07; p<0.001). The incidence rate of MH increased exponentially with increasing age between the ages of 35 years and 69 years and was highest among patients aged 65–69 years. The female-to-male ratio for the incidence of MH was 2.15:1.

Conclusions

This study represents the largest nationwide population-based investigation of the incidence of MH, using a database that covers the entire population of South Korea. MH is the disease of elderly peaked 70 years old and more common in women.
Security and Privacy Approaches in Mixed Reality
Authors: De Guzman Jaybie A. , Thilakarathna Kanchana , Seneviratne Aruna
Published: October 2019

Mixed reality (MR) technology development is now gaining momentum due to advances in computer vision, sensor fusion, and realistic display technologies. With most of the research and development focused on delivering the promise of MR, the privacy and security implications of this technology are yet to be thoroughly investigated. This survey article aims to put in to light these risks and to look into the latest security and privacy work on MR. Specifically, we list and review the different protection approaches that have been proposed to ensure user and data security and privacy in MR. We extend the scope to include work on related technologies such as augmented reality, virtual reality, and human-computer interaction as crucial components, if not the origins, of MR, as well as numerous related work from the larger area of mobile devices, wearables, and Internet-of-Things. We highlight the lack of investigation, implementation, and evaluation of data protection approaches in MR. Further challenges and directions on MR security and privacy are also discussed.
The Anthropology of Water
Authors: Ballestero Andrea
Published: October 2019

The anthropology of water is a self-declared relational field that attempts to transcend nature/culture distinctions by attending to the fact that the social and ecological aspects of water are separated only by convention. Despite its recent coming of age, the anthropology of water is incredibly expansive. It attends to molecular, embodied, ecosystemic, and planetary issues. I provide an overview of that breadth in four thematic clusters: (in)sufficiency, bodies and beings, knowledge, and ownership. These clusters highlight issues of materiality, ontological politics, and political economy. They are the grounds on which questions of water justice are elucidated. Furthermore, I show how water is always more than itself; its force and material presence constantly frame people's efforts to address the fundamental question of what it means to live life collectively in a world that is always more than human. I close with two directions for research: the denaturalization of water's materiality and the diversification of the moral undertones of our analytic vocabularies.
Sociolinguistics of the Spanish-Speaking World
Authors: Díaz-Campos Manuel , Escalona Torres Juan M. , Filimonova Valentyna
Published: October 2019

This review provides a state-of-the-art overview of Spanish sociolinguistics and discusses several areas, including variationist sociolinguistics, bilingual and immigrant communities, and linguistic ethnography. We acknowledge many recent advances and the abundant research on several classic topics, such as phonology, morphosyntax, and discourse-pragmatics. We also highlight the need for research on understudied phenomena and emphasize the importance of combining both quantitative and ethnographic methodologies in sociolinguistic research. Much research on Spanish has shown that the language's wide variation across the globe is a reflection of Spanish-speaking communities’ rich sociohistorical and demographic diversity. Yet, there are many areas where research is needed, including bilingualism in indigenous communities, access to bilingual education, attitudes toward speakers of indigenous languages, and language maintenance and attrition. Language policy, ideology, and use in the legal and health care systems have also become important topics of sociolinguistics today as they relate to issues of human rights.
Using an integrated teaching approach to facilitate student achievement of the learning outcomes in a preclinical medical curriculum in India
Authors: Vashe Asha , Devi Vasudha , Rao Raghavendra , Abraham Reem Rachel , Pallath Vinod , Umakanth Shashikiran
Published: October 2019

Today most education institutions around the world have adopted the philosophy of outcome-based education. The emphasis in outcome-based education is achievement of outcomes; hence the curriculum should be designed in a way that it includes the components targeted specifically at achieving these outcomes. A discipline-based approach results in fragmentation of learning and lack of clinical applicability. Integrated teaching could be a solution to achieve required outcomes in a holistic way. Hence, the aim of this study was to develop, implement, and evaluate an integrated teaching module. Temporal coordination of the basic sciences, along with correlation of learned topics to clinical settings, was done in the first year of the undergraduate medical program. The module was evaluated by obtaining qualitative and quantitative feedback from students. Student assessment was conducted with a test that had case vignettes and multiple-choice questions. In addition, students’ change in learning approaches and self-directed learning readiness were collected. Students’ perception regarding the educational environment was also obtained. Analysis of the data showed positive feedback from the students regarding the integrated teaching. Students’ average score in the test was 86%. There was a significant increase in the scores for the deep approach and self-directed learning readiness in the posttest compared with the pretest. Moreover, students were found to be satisfied with the educational environment. Evaluation of integrated teaching revealed that it was well accepted by the students. Moreover, it facilitated the achievement of the students’ outcomes.
Nucleolin mediates the binding of cancer cells to L-selectin under conditions of lymphodynamic shear stress
Authors: Goldson Tovë M. , Turner Kevin L. , Huang Yinan , Carlson Grady E. , Caggiano Emily G. , Oberhauser Andres F. , Fennewald Susan M. , Burdick Monica M. , Resto Vicente A.
Published: October 2019

Head and neck squamous cell carcinoma (HNSCC) cells bind to lymphocytes via L-selectin in a shear-dependent manner. This interaction takes place exclusively under low-shear stress conditions, such as those found within the lymph node parenchyma. This represents a novel functional role for L-selectin-selectin ligand interactions. Our previous work has characterized as-of-yet unidentified L-selectin ligands expressed by HNSCC cells that are specifically active under conditions of low shear stress consistent with lymph flow. Using an affinity purification approach, we now show that nucleolin expressed on the surface of HNSCC cells is an active ligand for L-selectin. Parallel plate chamber flow-based experiments and atomic force microscopy (AFM) experiments show that nucleolin is the main functional ligand under these low-force conditions. Furthermore, AFM shows a clear relationship between work of deadhesion and physiological loading rates. Our results reveal nucleolin as the first major ligand reported for L-selectin that operates under low-shear stress conditions.
ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue
Authors: Kawabe Yasuhiro , Mori Jun , Morimoto Hidechika , Yamaguchi Mihoko , Miyagaki Satoshi , Ota Takeshi , Tsuma Yusuke , Fukuhara Shota , Nakajima Hisakazu , Oudit Gavin Y. , Hosoi Hajime
Published: October 2019

The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1–7 (Ang 1–7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1–7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg−1·day−1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1–7 axis represent a potential therapeutic approach to prevent the development of obesity.
Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2
Authors: Zheng Hong , Liu Xuefei , Katsurada Kenichi , Patel Kaushik P.
Published: October 2019

Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN was performed. The expression of ENaC, NHE3, and AQP2 in both renal cortex and medulla were measured. As a functional test for ENaC activation, diuretic and natriuretic responses to ENaC inhibitor benzamil were monitored in four groups of rats (Sham, Sham+RDN, CHF, CHF+RDN). Western blot analysis indicated that RDN (1 wk later) significantly reduced protein levels of α-ENaC, β-ENaC, γ-ENaC, and AQP2 in the renal cortex of CHF rats. RDN had no significant effects on the protein expression of kidney NHE3 in both Sham and CHF rats. Immunofluorescence studies of kidney sections confirmed the reduced signaling of ENaC and AQP2 in the CHF+RDN rats compared with the CHF rats. There were increases in diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. RDN reduced the diuretic and natriuretic responses to benzamil in CHF rats. These findings suggest a critical role for renal nerves in the enhanced expression of ENaC and AQP2 and subsequent pathophysiology of renal sodium and water retention associated with CHF.

NEW & NOTEWORTHY This is the first study to show in a comprehensive way that renal denervation initiated after a period of chronic heart failure reduces the expression of epithelial sodium channels and aquaporin 2 leading to reduced epithelial sodium channel function and sodium retention.
Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia
Authors: Willis Kent A. , Siefker David T. , Aziz Michael M. , White Catrina T. , Mussarat Naiha , Gomes Charles K. , Bajwa Amandeep , Pierre Joseph F. , Cormier Stephania A. , Talati Ajay J.
Published: October 2019

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.
The asynchronous state's relation to large-scale potentials in cortex
Authors: Alishbayli A. , Tichelaar J. G. , Gorska U. , Cohen M. X. , Englitz B.
Published: October 2019

Understanding the relation between large-scale potentials (M/EEG) and their underlying neural activity can improve the precision of research and clinical diagnosis. Recent insights into cortical dynamics highlighted a state of strongly reduced spike count correlations, termed the asynchronous state (AS). The AS has received considerable attention from experimenters and theorists alike, regarding its implications for cortical dynamics and coding of information. However, how reconcilable are these vanishing correlations in the AS with large-scale potentials such as M/EEG observed in most experiments? Typically the latter are assumed to be based on underlying correlations in activity, in particular between subthreshold potentials. We survey the occurrence of the AS across brain states, regions, and layers and argue for a reconciliation of this seeming disparity: large-scale potentials are either observed, first, at transitions between cortical activity states, which entail transient changes in population firing rate, as well as during the AS, and, second, on the basis of sufficiently large, asynchronous populations that only need to exhibit weak correlations in activity. Cells with no or little spiking activity can contribute to large-scale potentials via their subthreshold currents, while they do not contribute to the estimation of spiking correlations, defining the AS. Furthermore, third, the AS occurs only within particular cortical regions and layers associated with the currently selected modality, allowing for correlations at other times and between other areas and layers.
Bibliometric Study of the Comorbidity of Pain and Depression Research
Authors: Wang Xue-Qiang , Peng Meng-Si , Weng Lin-Man , Zheng Yi-Li , Zhang Zhi-Jie , Chen Pei-Jie
Published: October 2019

Background. Comorbid pain and depression occur with high prevalence in clinical observations, and published academic journals about them have been increasing in number over time. However, few studies used the bibliometric method to analyze the general aspects of scientific researches on the comorbidity of pain and depression. The aim of this study is to systematically provide global scientific research in the comorbidity of pain and depression from 1980 to 2018. Methods. The published papers were searched between 1980 and 2018 in Web of Science. Publications related to comorbid pain and depression research were included. The language was restricted to English, and no species limitations were specified. Results. A total of 2,519 papers met the inclusion criteria in our study. The results revealed that the publications had a significant growth over time in the comorbidity of pain and depression research (P<0.001) by linear regression analyses. The United States had the largest number of publications and citations and the highest value of H-index. According to subject categories of Web of Science, research areas of the 2,519 papers mainly focused on clinical neurology (28.78%), neurosciences (22.9%), and psychiatry (22.23%). In accordance with types of pain, headache (19.09%) was the most popular topic in the included papers on comorbid pain and depression research. Conclusions. The findings provide useful information for pain and depression researchers to detect new areas related to collaborators, cooperative institutions, popular topics, and research frontiers.
A Lumped-Element Decoupling and Matching Network for a Four-Element Mobile Handset MIMO Antenna
Authors: Kormilainen Riku , Luomaniemi Rasmus , Lehtovuori Anu , Viikari Ville
Published: October 2019

This paper presents the first realization of a lumped-element decoupling and matching network (DMN) for more than two-element mobile MIMO arrays. The realization of the DMN is based on an existing method, which is improved in terms of bandwidth and the number of network elements. The array is designed to operate in the 2.6–2.7 GHz LTE band. The DMN is applied to a four-element MIMO antenna array located on one side of the mobile phone chassis. The array initially has a strong coupling of −3 dB, which is improved to −7 dB with the DMN. In other words, this denotes a reduction of 30 percentage points in coupled power. The DMN also improves the total efficiency by 21 percentage points at best.
Evaluation of Occurrence, Concentration, and Removal of Pathogenic Parasites and Fecal Coliforms in Three Waste Stabilization Pond Systems in Tanzania
Authors: Zacharia Abdallah , Ahmada Wajihu , Outwater Anne H. , Ngasala Billy , Van Deun Rob
Published: October 2019

In Tanzania, waste stabilization ponds (WSPs) are employed to treat wastewater, and effluents are used for urban agricultural activities. The use of untreated or partially treated wastewater poses risks of disease transmission, including parasitic and bacterial infections, to exposed communities. Little is known about the occurrence, concentration, and removal of parasites and fecal coliform (FC) bacteria in WSPs in Tanzania. This study evaluates the occurrence and concentration of parasites and FCs in wastewater, the efficiency of WSPs in removing parasites and FCs, and the validity of using FCs as an indicator of parasites. This was a cross-sectional study conducted between February and August 2018. Wastewater samples were collected from three WSPs located in the Morogoro, Mwanza, and Iringa regions. APHA methods were used to test physicochemical parameters. The modified Bailenger method and Ziehl–Neelsen stain were used to analyse parasites. Membrane filtration method was used to analyse FCs. Data were analysed using IBM SPSS version 20. Helminth egg removal ranged from 80.8% to 100%. Protozoan (oo)cyst removal ranged from 98.8% to 99.9%. The Mwanza WSP showed the highest FC reduction (3.8 log units (100 mL)−1). Both the parasites and FCs detected in the effluents of assessed WSPs were of higher concentrations than World Health Organization and Tanzania Bureau of Standards limits, except for helminths in the Morogoro WSP and FCs in the Mwanza WSP. FCs were significantly correlated with protozoa (p<0.01) and predicted protozoa occurrence well (p=0.011). There were correlations between physicochemical parameters, parasites, and FC bacteria in the WSP systems. Inadequate performance of these systems may be due to lack of regular maintenance and/or systems operating beyond their capacity. FC indicators were observed to be a good alternative for protozoa monitoring, but not for helminths. Therefore, during wastewater quality monitoring, helminths should be surveyed independently.
New Circumpapillary Retinal Nerve Fiber Layer Thickness and Bruch’s Membrane Opening-Minimum Rim Width Assessment in Nonglaucomatous Eyes with Large Discs
Authors: Bayraktar Serife , Sultanova Gulnar , Cebeci Zafer , Altinkurt Emre , Izgi Belgin
Published: October 2019

Purpose. To compare the new spectral-domain optical coherence tomography (SD-OCT) algorithm for measuring circumpapillary retinal nerve fiber layer (RNFL) thickness centered on Bruch’s membrane opening (BMO), RNFLBMO1, with the conventional circumpapillary RNFL thickness measurement centered on the optic disc (RNFLDİ), and assess the BMO-minimum rim width (BMO-MRW) in nonglaucomatous eyes with large discs. Methods. This prospective, cross-sectional, observational study included a total of 91 eyes of 91 patients having nonglaucomatous eyes with large discs (Group 1) and 50 eyes of 50 healthy subjects (Group 2). The optic nerve head (ONH) parameters obtained by confocal scanning laser ophthalmoscopy (CSLO), peripapillary RNFL thickness, BMO area, and BMO-MRW were imaged with SD-OCT. Results. The mean disc size was 3.06 ± 0.42 mm2 (range, 2.61–4.68) in Group 1 and 1.95 ± 0.23 mm2 (range, 1.6–2.43) in Group 2 (p=0.0001). The mean BMO area was 2.9 ± 0.58 mm2 (range, 1.26–4.62) in Group 1 and 2.05 ± 0.31 mm2 (range, 1.51–2.82) in Group 2 (p=0.0001). The difference between RNFLDİ and RNFLBMO1 measurements in Group 1 was stronger than in Group 2 because it was significant in all sectors in large discs. The mean global BMO-MRW thickness was significantly thinner in large discs; it was 252.95 ± 42.16 µ (range, 170–420) in Group 1 and 326.06 ± 73.39 µ (range, 210–440) in Group 2 (p=0.0001). There was a positive correlation between BMO-MRW thickness measurements and RNFL thickness parameters, both with RNFLDİ and RNFLBMO1, in global and all optic nerve sectors except temporal quadrants with r = 0.257–0.431 (p≤0.001–0.01) in Group 1. But in control group, Group 2, there was a weak correlation or no correlation between BMO-MRW thickness measurements and RNFL thickness parameters with r = −0.256–0.328 (p=0.797–0.02). Conclusion. The new circumpapillary RNFL scanning algorithm centered on BMO is better to assess the RNFL thickness and BMO-MRW in large discs for the early diagnosis of glaucoma.
Dynamic Spreading Model of Passenger Group Panic considering Official Guidance Information in Subway Emergencies
Authors: Li Jiayang , Tang Jiafu , Wang Dan
Published: October 2019

Safety concerns are increasing as rail transportation develops at a fast pace. When emergencies erupt in the course of transportation, panic will spread among passengers. Subway operators should understand how the emotions of passengers spread and how the guidance instructions work, in order to effectively deter the transmission of panic. Based on the models of system dynamics, transmission dynamics, and contagious disease, the essay constructs a dynamic transmission model for passenger panic inside the carriage, incorporating the official guidance instructions. Then, the essay utilizes Routh–Hurwitz criteria and analyzes the stability equilibrium of the dynamic differential equation. Mathematical analysis and simulation tests have verified the validity of the model and stability conditions. Finally, it is proved in the essay by mathematical analysis and simulation tests that official guidance instructions can effectively control the spread of panic and quickly stabilize the system. Thus, the essay helps subway operators to come up with clear official guidance, so as to find quick solutions and prevent escalation of panic due to lack of trust.
Impact of Hypoglycemia on Health-Related Quality of Life among Type 2 Diabetes: A Cross-Sectional Study in Thailand
Authors: Pratipanawatr Thongchai , Satirapoj Bancha , Ongphiphadhanakul Boonsong , Suwanwalaikorn Sompongse , Nitiyanant Wannee
Published: October 2019

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases. Patients are generally advised lifestyle changes with antihyperglycemic agents prescribed. The major drawback of prescribing antihyperglycemic agents is the risk of hypoglycemia which subsequently impacts on health-related quality of life (HRQoL). This study is aimed at examining association between previous history of hypoglycemia and HRQoL. The study was a multicenter cross-sectional study, conducted from February 2013 to March 2015 at 5 tertiary care hospitals in Thailand (Srinagarind, Phramongkutklao, Ramathibodi, King Chulalongkorn Memorial, and Siriraj hospitals). The study population were males or females diagnosed with type 2 DM according to ADA criteria, 30 years of age or older, who had been treated with sulfonylurea (SU) monotherapy or SU and metformin combination for at least 6 months. Prespecified medical factors were extracted from medical records 12 months prior to patients’ enrolment. The experience of hypoglycemia questionnaire was used to collect and measure severity of hypoglycemia experienced during the previous 6 months. HRQoL was assessed using the 3-level version of EuroQol-5-dimension (EQ-5D-3L) and visual analogue scale (EQ-VAS) questionnaires. Of 659 eligible patients surveyed, 202 patients (30.65%) had experienced symptoms of hypoglycemia. HRQoL was significantly lower among patients reporting at least one of hypoglycemic symptoms, measured by EQ-VAS scores (mean±SD; 73.66±13.18, 73.56±15.10, or 68.93±14.76 vs. 77.01±13.02, one-way ANOVA; p=0.006) and EQ-5D-3L index scores (0.62±0.47, 0.68±0.38, or 0.58±0.51 vs. 0.79±0.31, one-way ANOVA; p<0.001) for mild, moderate, or severe/very severe hypoglycemic patients compared with patients without hypoglycemic symptoms. After adjusting for confounding factors in a multiple linear regression model, patients with hypoglycemic symptoms either mild, moderate, or severe/very severe demonstrated significantly higher impairment for EQ-VAS and EQ-5D indexes than those who did not experience hypoglycemic symptoms. In conclusion, our study showed decreased HRQoL determined by EQ-5D and EQ-VAS in patients reporting symptoms of hypoglycemia compared with patients not reporting hypoglycemic symptoms, relative to severity of hypoglycemia.
A New 3D Method for Reactor Core Vibration Based on Silicon Steel Lamination Rules and Application in UHV Shunt Reactors
Authors: Lü Fangcheng , Guo Jiayi , Niu Leilei , Geng Jianghai , Pan Yirui
Published: October 2019

A new three‐dimensional (3D) analysis method is proposed as the existing two‐dimensional (2D) method has low accuracy in analysing the vibration characteristics of oil‐immersed shunt reactors, such as ultrahigh‐voltage (UHV) shunt reactors. First of all, a set of 3D laminated coordinate systems was defined based on silicon steel lamination rules, in which the anisotropy of magnetic properties for laminated silicon steel in the rolling direction (RD), the transverse direction (TD), and the lamination direction (LD) were considered. Then, the mapping between laminated coordinate systems and space rectangular coordinate system was established to unify the parameters in different laminated coordinate systems. With the mapping, the anisotropy of the magnetic properties in the laminated coordinate systems was transformed into a rectangular coordinate system. Next, two sets of comparative studies between the new 3D method and the traditional 2D method were carried out, which show that the 3D method has high precision and a wide application range. Finally, the relationship between air gap number and core vibration of UHV shunt reactors was studied by the new 3D method. The results show that, as the number of air gaps increases, the magnetic flux density and the total force area of Maxwell force are increased, resulting in the intensification of core vibration. The conclusions of this paper are helpful for the design of large oil‐immersed reactors.
A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice
Authors: Akimoto Hidetoshi , Fukuda-Kawaguchi Emi , Duramad Omar , Ishii Yasuyuki , Tanabe Kazunari
Published: October 2019

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β cells by autoantigen-reactive diabetogenic cells. Antigen-specific therapies using islet autoantigens for restoring immune tolerance have emerged as promising approaches for the treatment of T1D but have been unsuccessful in humans. Herein, we report that RGI-3100-iB, a novel liposomal formulation carrying both α-galactosylceramide (α-GalCer), which is a representative ligand for invariant natural killer T (iNKT) cells, and insulin B chain 9–23 peptide, which is an epitope for CD4+ T cells, could induce the accumulation of regulatory T cells (Tregs) in islets in a peptide-dependent manner, followed by the remarkable prevention of diabetes onset in nonobese diabetic (NOD) mice. While multiple administrations of a monotherapy using either α-GalCer or insulin B peptide in a liposomal formulation was confirmed to delay/prevent T1D in NOD mice, RGI-3100-iB synergistically enhanced the prevention effect of each monotherapy and alleviated insulitis in NOD mice. Immunopathological analysis showed that Foxp3+ Tregs accumulated in the islets in RGI-3100-iB-treated mice. Cotransfer of diabetogenic T cells and splenocytes of NOD mice treated with RGI-3100-iB, but not liposomal α-GalCer encapsulating an unrelated peptide, to NOD-SCID mice resulted in the prevention of diabetes and elevation of Foxp3 mRNA expression in the islets. These data indicate that the migration of insulin B-peptide-specific Tregs to islet of NOD mice that are involved in the suppression of pathogenic T cells related to diabetes onset and progression could be enhanced by the administration of liposomes containing α-GalCer and insulin B peptide.
Ceramide–Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations
Authors: Khiste Sachin K. , Liu Zhijun , Roy Kartik R. , Uddin Mohammad B. , Hosain Salman B. , Gu Xin , Nazzal Sami , Hill Ronald A. , Liu Yong-Yu
Published: October 2019

Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramide–rubusoside (Cer–RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. Natural RUB encapsulated short-chain C6-Cer so as to form Cer–RUB nanomicelles (∼32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer–RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer–RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer–RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H/+ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer–RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations.
The First Clinical Use of a RecombinantLactococcus lactisExpressing Human Papillomavirus Type 16 E7 Oncogene Oral Vaccine: A Phase I Safety and Immunogenicity Trial in Healthy Women Volunteers
Authors: Mohseni Amir Hossein , Taghinezhad-S Sedigheh , Keyvani Hossein
Published: October 2019

A dose-escalation, randomized, double-blind, placebo-controlled phase I clinical trial was performed in healthy Iranian volunteer women to assess the safety, tolerability, and immunogenicity of NZ8123-HPV16-optiE7 vaccine involving recombinant Lactococcus lactis expressing the codon-optimized human papillomavirus (HPV)-16 E7 oncogene. Fifty-five eligible subjects were divided into 6 cohorts based on the dosages (1 × 109, 5 × 109, and 1 × 1010 CFU/mL) of either vaccine or placebo, which were administrated orally a total of 4 times at weeks 1, 2, 4, and 8. Then, adverse events, specific serum IgG and vaginal IgA, and E7-specific IFNγ-secreting CD8+ CTL responses were evaluated. The vaccination was well tolerated by 40 subjects who completed the immunization schedule, and no serious adverse effects were reported. The IgG and IgA levels peaked at day 60, and the levels for the 5 × 109 CFU/mL and 1 × 1010 CFU/mL dose groups were higher than those for the 1 × 109 CFU/mL dose group. Time-to-peak stimulation in E7-specific IFNγ-secreting CD8+ CTL responses was seen in cervical lymphocytes 1 month after the last vaccination. Again, no significant increase was seen in the peripheral blood mononuclear cells (PBMC) of the same volunteers. CTL responses in cervical lymphocytes and PBMCs at day 90 were markedly higher in the 5 × 109 and 1 × 1010 CFU/mL groups than in the 1 × 109 CFU/mL group, demonstrating the dose dependency of NZ8123-HPV16-optiE7 vaccine following oral administration. The 6-month follow-up revealed that antibody levels decreased up to day 240; nevertheless, long-term E7-specific IFNγ-secreting CD8+ CTL responses were recorded during follow-up. Overall, the safety and immunogenicity profile achieved in this study encourages further phase II trials with the 5 × 109 CFU/mL dose vaccine.
An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance
Authors: Deng Shanshan , Krutilina Raisa I. , Wang Qinghui , Lin Zongtao , Parke Deanna N. , Playa Hilaire C. , Chen Hao , Miller Duane D. , Seagroves Tiffany N. , Li Wei
Published: October 2019

Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases in the United States. TNBC has poorer overall prognosis relative to other molecular subtypes due to rapid onset of drug resistance to conventional chemotherapies and increased risk of visceral metastases. Taxanes like paclitaxel are standard chemotherapies that stabilize microtubules, but their clinical efficacy is often limited by drug resistance and neurotoxicities. We evaluated the preclinical efficacy of a novel, potent, and orally bioavailable tubulin inhibitor, VERU-111, in TNBC models. VERU-111 showed potent cytotoxicity against TNBC cell lines, inducing apoptosis and cell-cycle arrest in a concentration-dependent manner. VERU-111 also efficiently inhibited colony formation, cell migration, and invasion. Orally administered VERU-111 inhibited MDA-MB-231 xenograft growth in a dose-dependent manner, with similar efficacies to paclitaxel, but without acute toxicity. VERU-111 significantly reduced metastases originating from the mammary fat pad into lung, liver, and kidney metastasis in an experimental metastasis model. Moreover, VERU-111, but not paclitaxel, suppressed growth of luciferase-labeled, taxane-resistant, patient-derived metastatic TNBC tumors. In this model, VERU-111 repressed growth of preestablished axillary lymph node metastases and lung, bone, and liver metastases at study endpoint, whereas paclitaxel enhanced liver metastases relative to vehicle controls. Collectively, these studies strongly suggest that VERU-111 is not only a potent inhibitor of aggressive TNBC phenotypes, but it is also efficacious in a taxane-resistant model of metastatic TNBC. Thus, VERU-111 is a promising new generation of tubulin inhibitor for the treatment of TNBC and may be effective in patients who progress on taxanes.

Results presented in this study demonstrate the efficacy of VERU-111 in vivo and provide strong rationale for future development of VERU-111 as an effective treatment for metastatic breast cancer.
Evidence-Based Clinical Practice Guidelines for the Management of Patients with Lentigo Maligna
Authors: Robinson Mitchell , Primiero Clare , Guitera Pascale , Hong Angela , Scolyer Richard A. , Stretch Jonathan R. , Strutton Geoffrey , Thompson John F. , Soyer H. Peter
Published: October 2019

Introduction: Lentigo maligna (LM) is a subtype of melanoma in situ that usually occurs in sun-damaged skin and is characterised by an atypical proliferation of melanocytes within the basal epidermis. If left untreated, LM can develop into invasive melanoma, termed lentigo maligna melanoma, which shares the same prognosis as other types of invasive melanoma. The incidence rates of LM are steadily increasing worldwide, in parallel with increases in the incidence rates of invasive melanoma, and establishing appropriate guidelines for the management of LM is therefore of great importance. Methods: A multidisciplinary working party established by Cancer Council Australia has recently produced up-to-date, evidence-based clinical practice guidelines for the management of melanoma and LM. Following selection of the most relevant clinical questions, a comprehensive literature search for relevant studies was conducted, followed by systematic review of these studies. Data were summarised and the evidence was assessed, leading to the development of recommendations. After public consultation and approval by the full guidelines working party, these recommendations were published on the Cancer Council Australia wiki platform (https://wiki.cancer.org.au/australia/Clinical_question:Effective_interventions_to_improve_outcomes_in_lentigo_maligna%3F). Main Recommendations: Surgical removal of LM remains the standard treatment, with 5- to 10-mm clinical margins when possible. While yet to be fully validated, the use of peri-operative reflectance confocal microscopy to assess margins should be considered where available. There is a lack of high-quality evidence to infer the most effective non-surgical treatment. When surgical removal of LM is not possible or refused, radiotherapy is recommended. When both surgery and radiotherapy are not appropriate or refused, topical imiquimod is the recommended treatment. Cryotherapy and laser therapy are not recommended for the treatment of LM.
Complications after Radiofrequency Ablation for Hepatocellular Carcinoma: A Multicenter Study Involving 9,411 Japanese Patients
Authors: Maeda Masaki , Saeki Issei , Sakaida Isao , Aikata Hiroshi , Araki Yasuyuki , Ogawa Chikara , Kariyama Kazuya , Nouso Kazuhiro , Kitamoto Mikiya , Kobashi Haruhiko , Sato Shuichi , Shibata Hiroshi , Joko Kouji , Takaki Shintaro , Takabatake Hiroyuki , Tsutsui Akemi , Takaguchi Koichi , Tomonari Tetsu , Nakamura Shinichiro , Nagahara Takakazu , Hiraoka Atsushi , Matono Tomomitsu , Koda Masahiko , Mandai Mari , Mannami Tomohiko , Mitsuda Akeri , Moriya Takashi , Yabushita Kazuhisa , Tani Joji , Yagi Takahito , Yamasaki Takahiro
Published: October 2019

Introduction: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered a safe and minimally invasive procedure. We previously reported that the mortality and complication rates for RFA were 0.038% (5/13,283 patients) and 3.54% (579 complications/16,346 procedures), respectively, from 1999 to 2010 (previous period). In this study, we investigated the clinical criteria for RFA and the mortality and complication rates from 2011 to 2015 (recent period). Methods: Data were collected from 25 centers by using a questionnaire developed by the Chugoku-Shikoku Society for Local Ablation Therapy of HCC. The criteria for RFA, RFA modification, use of image-guidance modalities, mortality, and complications during the previous and recent periods were compared. Results: We evaluated 11,298 procedures for 9,411 patients, including those that involved new devices (bipolar RFA and internally adjustable electrode system). The criterion of hepatic function for RFA increased from a Child-Pugh score ≤8 during the previous period to ≤9 during the recent period. The criteria regarding the tumor location and other risk factors have been expanded recently because of the increased use of several modifications of the RFA procedure and image-guidance modalities. The mortality rate was 0.064% (6/9,411 patients), and the complication rate was 2.92% (330 complications/11,298 procedures). There was no difference in mortality rates between the 2 periods (p = 0.38), but the complication rates was significantly lower during the recent period (p = 0.038). Discussion and Conclusions: Our findings confirmed that RFA, including the use of new devices, is a low-risk procedure for HCC, despite the expansion of the criteria for RFA during the recent period.
Early Phonological Predictors of Toddler Language Outcomes
Authors: Gerhold Kayla , Torrington Eaton Catherine , Newman Rochelle S. , Bernstein Ratner Nan
Published: October 2019

Purpose: Several studies have explored relationships between children’s early phonological development and later language performance. This literature has included a more recent focus on the potential for early phonological profiles to predict later language outcomes. Methods: The present study longitudinally examined the nature of phonetic inventories and syllable structure patterns of 48 typically developing children at 7, 11, and 18 months, and related them to expressive language outcomes at 2 years of age. Results: Findings provide evidence that as early as 11 months, phonetic inventory and mean syllable structure level are related to 24-month expressive language outcomes, including mean length of utterance and vocabulary diversity in spontaneous language samples, and parent-reported vocabulary scores. Consonant inventories in particular differed at 11 and 18 months for 2-year-olds with lower versus higher language skills. Conclusion: Limited inventories and syllable repertoires may add to risk profiles for later language delays.
Comparison of Conservative versus Surgical Treatment Protocols in Treating Idiopathic Granulomatous Mastitis: A Meta-Analysis
Authors: Zhou Fei , Liu Lu , Liu Liyuan , Yu Lixiang , Wang Fei , Xiang Yujuan , Zheng Chao , Huang Shuya , Cai Han , Yu Zhigang
Published: October 2019

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign breast disease without any definitive therapeutic strategy. It is controversial whether to use conservative or surgical treatment of IGM and high-level evidence-based medicine data are lacking. The purpose of this study was to systemically evaluate the clinical effectiveness of the conservative versus surgical treatment for IGM. Methods: In this meta-analysis, we searched PubMed, EMbase, ScienceDirect, and Web of Science for comparative studies about the conservative versus surgical treatment of IGM. Two researchers independently identified reports and extracted data. We used Stata 11 for data analysis. A meta-analysis was performed to investigate the differences in the recurrence rate of conservative and surgical treatment using a random effects model. Results: A total of 10 studies involving 1,101 patients were included. The results demonstrated that there was no significant difference in the recurrence rate among patients who were treated by nonsurgical therapy and surgical treatment. No publication bias was detected. Conclusion: This meta-analysis demonstrates that both the conservative and surgical treatment approaches have appropriate efficacy in IGM treatment and relapse. Further randomized controlled trials with longer follow-up periods are required to confirm the advantages of each approach.