bluuebunny/crossref_metadata_2025 huggingface dataset:
Furlow Palatoplasty, Nasopharyngeal Size, and Sleep Oximetry
Authors: Gilbert Francis , Leclerc Jacques E. , Deschênes Marianne , Julien Anne-Sophie , Grenier-Ouellette Iseult
Published: February 2020

Objectives:

(1) To assess the evolution of prepalatoplasty sleep oximetry (PRESO) and postpalatoplasty sleep oximetry (POSSO) in cleft patients and (2) to evaluate the impact of the size of the nasopharynx on PRESO and POSSO values.

Study Design:

Retrospective cohort study.

Patients and Methods:

In 81 patients with cleft palate and/or cleft lip, the following data were prospectively collected: patient demographics and prepalatoplasty cleft palate measurements. All the patients had at least 1 PRESO and POSSO. A Kaplan-Meier curve was obtained from all the sleep oximetry results. Transverse nasopharyngeal area (TNA) pre- and postvalues were compared for each group with paired t tests, while analysis of variance was used to compare TNA pre- and postscores between the groups with a Bonferroni correction for multiple comparisons.

Results:

POSSO results were normal or showed mild desaturations in most patients in the few weeks following palatoplasty. For the cohort, no statistically significant changes were found between PRESO and POSSO values. A 2-fold variation in the area of the TNA was found before palatoplasty within identical cleft malformation cases. No statistically significant association was found between the TNA or the a/30 − b 1 parameter values and the sleep study scores.

Conclusions:

The patients with the smaller nasopharyngeal areas presented identical PRESO and POSSO results when compared to those with larger nasopharyngeal sizes. Future studies should address the possible association between prepalatoplasty and postpalatoplasty TNAs and the occurrence of velopharyngeal deficiency later in life.
Use of Preoperative Cervical Vascular Imaging in Patients With Velocardiofacial Syndrome and Velopharyngeal Dysfunction in the United Kingdom
Authors: Fallico Nefer , Timoney Norma , Atherton Duncan
Published: February 2020

Objective:

In patients with velocardiofacial syndrome (VCFS), medial displacement of the internal carotid arteries (ICAs) may increase the risk of vascular injury during the surgical correction of velopharyngeal dysfunction (VPD). Some surgeons advocate the use of vascular imaging studies prior to surgery. Nevertheless, the role of preoperative imaging is still controversial. This study aimed to review the current practice of the UK cleft units and also examine our own practice at the Evelina London Children’s Hospital in relation to children with VCFS undergoing speech surgery over the previous 7 years.

Design:

A questionnaire was sent to all UK cleft surgeons to enquire about the management and use of preoperative vascular imaging in patients with VPD and VCFS. A retrospective study was also conducted of the unit’s 7-year series of patients with VPD and VCFS.

Results:

Thirty-four completed questionnaires were returned (response rate 100%). Most UK surgeons (73.5%) do not regularly order preoperative vascular imaging for patients with VCFS although some reportedly would consider it if a posterior pharyngeal wall pulsation was visible. In our unit, between 2013 and 2019, a total of 40 patients affected by VCFS have been assessed for VPD. A magnetic resonance angiography (MRA) was performed for 23 patients. Medial deviation of the ICAs was identified in 7 (30%) patients.

Conclusions:

The results of the national survey showed no consensus on routine use of preoperative vascular imaging. Our retrospective study showed a 30% prevalence of medialized ICAs in our patient cohort. In these patients, the MRA findings influenced the choice of speech surgery.
Analytical responses of functionally graded beam under moving mass using Caputo and Caputo–Fabrizio fractional derivative models
Authors: Abu-Alshaikh Ibrahim M , Almbaidin Amro A
Published: February 2020

In this article, a functionally graded simply supported Euler–Bernoulli beam subjected to moving mass is considered in which the beam-damping is described using fractional Kelvin–Voigt model. A comparison between Caputo and Caputo–Fabrizio fractional derivatives for obtaining the analytical dynamic response of the beam is carried out. The equation of motion is solved by the decomposition method with the cooperation of the Laplace transform. Two verification studies were performed to check the validity of the solutions. The results show that the grading order, the velocity of the moving mass and the fractional derivative order have significant effects on the beam deflection, whereas the difference between the results of the two fractional derivative models is expressed by the determination of the correlation coefficient.
Tandem laser-gas metal arc welding joining of 20 mm thick super duplex stainless steel: An experimental and numerical study
Authors: Mathieu A , Tkachenko I , Jouvard JM , Tomashchuk I
Published: February 2020

The present work covers the topic of strains and stresses prediction in case of welded steel structures. Steel sheets of 20 mm thickness made in UR™2507Cu are welded using a laser and gas metal arc welding processes combination. The focused laser beam leads the arc in a Y-shape chamfer geometry. Both sources are 20 mm apart from each other in order to avoid any synergic effect with each other. In order to predict residual strain, a 3D unsteady numerical simulation has been developed in COMSOL finite element software. A volume heat source has been identified based on the temperature measurements made by 10 K-type thermocouples, implanted inside the workpiece. The 50 mm deep holes are drilled in the workpiece using dye-sinking Electrical Discharge Machining (EDM) machine. Before the implantation in the hole, each thermocouple is surrounded by Inconel sheathing. Hot junctions of the thermocouples are positioned in a way to feel two advancing molten pools. The equivalent heat source is composed of three sources. First one is a Goldak source that represents the molten pool induced by gas metal arc welding. The second one is a cylinder with an elliptic cross-section that represents the focused laser beam penetrating into the workpiece. The third one is a surface Gaussian source that represents energy radiated by arc and blocked by workpiece surface. Concerning mechanical simulation, an elasto-plastic behavior with isotropic hardening is implemented. A weak coupling is established between equations governing heat transfer and mechanics thanks to the temperature dependent coefficient of linear expansion. This numerical simulation made with some simplifying assumptions predicts an angular distortion and a longitudinal shrinkage of the welded structure. The numerical results are consistent with the displacements measured by digital image correlation method.
We were in one place, and the ethics committee in another: Experiences of going through the research ethics application process
Authors: Brindley Rob , Nolte Lizette , Nel Pieter W
Published: February 2020

This study aimed to explore postgraduate students’ lived experiences of managing research ethics committee processes. Whilst there is a wide range of research that explores ethics principles/guidance and committee perspectives upon research ethics processes, there is a lack of research into applicant experiences of these processes. Thus, interpretative phenomenological analysis (IPA) was utilised to explore the lived experiences and personal meaning-making of seven doctoral-level students participating in clinical psychology training. Three main themes emerged from participants’ accounts: (1) The emotional intensity and personal impact of the ethics process; (2) responses to and ways of managing the ethics process and (3) challenges within the ethics process. The results of this study highlight the importance of recognising the impact of the relationships between research students, courses and research ethics committees upon applicants’ progress through the research ethics process. In particular, an unhelpful ‘them and us’ dynamic may be maintained by misunderstandings about each other’s roles, uncertainty and stereotyping, amongst other factors. Potential ways to change this dynamic and to improve the research ethics process are explored.
High low-density lipoprotein cholesterol level is the independent risk factor of primary patency rate of arteriovenous fistula
Authors: Yamazaki Tomotaka , Shirai Hiroyuki , Yashima Jun , Tojimbara Tamotsu
Published: February 2020

Objectives

An arteriovenous fistula is the first choice of vascular access in dialysis patients. However, the correlations between patient factors and the arteriovenous fistula patency rate remain unclear. Therefore, we examined the effect of dialysis patient factors on arteriovenous fistula patency rate.

Methods

This study included 101 patients who received maintenance dialysis and used arteriovenous fistula for vascular access at Atami Hospital, International University of Health and Welfare in July 2018. A retrospective review was performed from the time of arteriovenous fistula creation to July 2018, and the primary and secondary arteriovenous fistula patency rates were investigated. The patency rate was calculated using the Kaplan–Meier method, and risk factor analysis was performed using Cox proportional hazards regression analysis.

Results

The primary patency rate of arteriovenous fistula was 71.2% at one year and 43.0% at five years, and the secondary patency rate was 92.7% at one year and 79.8% at five years. In the multivariate analysis, high low-density lipoprotein cholesterol (LDL-C) level and a history of diabetes were considered significant risk factors (HR 1.023, p value <0.01 and HR 2.550, p value <0.01, respectively). A log rank test was conducted on the groups of patients with LDL <90 mg/dl and LDL ≥90 mg/dl, and the <90 mg/dl group resulted in a good primary patency rate ( p value 0.0327).

Conclusions

High LDL-C level was considered the independent risk factors of arteriovenous fistula primary patency rate.
A Dai–Yuan conjugate gradient algorithm of linear equation constrained optimization approach for optimal robust controller of bipedal robots
Authors: Wang M , Sun ZB , Zhang BC , Pang ZX , Jiang DW
Published: February 2020

In this article, combined rapidly exponential control Lyapunov function with hybrid zero dynamics, a sufficiently descent projected Dai–Yuan approach is proposed, investigated, and analyzed for online solving optimal robust control problems with linear equation constraints of bipedal robots. Moreover, a new approach is developed for designing optimal robust controller. To demonstrate the effectiveness and feasibility of the proposed method, we will conduct numerical simulations on the model of three-link robot with nonlinear, impulsive, and under-actuated dynamics. Numerical results show that the bipedal robot can walk effectively and stability on the ground though the optimal robust controller when the parameters of the hybrid system model are disturbed three times. Furthermore, under the random noise condition, the bipedal robot can walk stably and effectively through online computing the nonlinear optimization problem for optimal robust controller. In addition, some classical control methods are compared with the developed approach in this article, numerical results are reported and analyzed to substantiate the feasibility and superiority of the proposed method for linear equation constrained optimization problem. Last, this article develops a systematic approach on exploiting optimal robust control technique to design hybrid system models for robustly and accurately via online solving linear equation constrained optimization problems.
Facilitating transfer through incorrect examples and explanatory feedback
Authors: Corral Daniel , Carpenter Shana K
Published: February 2020

This article examines whether studying correct versus incorrect examples produces differential learning. A prediction that follows from behaviourism is that learning should be best from studying correct examples. A contrasting prediction is that incorrect examples can highlight a concept’s properties that are missing in the example, and thereby enable concept learning. We test these ideas across two experiments, wherein subjects were shown hypothetical study scenarios and were asked to determine whether each was a true experiment. In Experiment 1, some subjects were only presented correct examples, some were only presented incorrect examples, and others were presented both. In addition, example type was crossed with feedback type: Some subjects were given explanatory feedback and some were not given any feedback; a control condition was also included, wherein subjects were not shown any study scenarios. All subjects completed a posttest involving novel scenarios; some questions asked subjects to indicate whether they were true experiments (classification questions), and some asked them to specify what was lacking in the design or to indicate how it could be fixed (application questions). Experiment 2 used a similar design, but compared explanatory feedback with corrective feedback. In both experiments, as long as some form of feedback was provided, subjects in the mixed example condition achieved the best classification performance. Furthermore, subjects in the incorrect and mixed example conditions performed best on application questions, particularly when explanatory feedback was provided. These findings offer insights into the mechanisms that might underlie learning from incorrect examples.
Influence of training on dorsal tangential radiographic view to detect screw protrusion after anterior plating of the distal radius: a cadaveric study
Authors: Bergsma Minke , Obdeijn Miryam C. , Janssen Stein J. , Bain Gregory I. , Jaarsma Ruurd L. , Doornberg Job N.
Published: February 2020

In this cadaveric study of anterior plating of the distal radius, we aimed to determine the interobserver agreement and diagnostic performance for detecting dorsally protruding screws using the dorsal tangential radiographic view before and after specific training. Without prior instruction, 13 observers interpreted the dorsal tangential view of cadaveric specimens, in which anterior radial plates were placed. After seeing a training video on the dorsal tangential view, they repeated the task. Though we found that accuracy and interobserver agreement was lower than described in some other clinical series, training led to statistically significant improvements of (1) the interobserver agreement on the decision to exchange screws, (2) the self-confidence of the surgeon in obtaining adequate views, and (3) the number of fluoroscopic images required to obtain these views. After training, the number of protruding screws missed was reduced by 36%, but 7% of dorsally protruding screws was still missed.
Mandibular Ramus Fractures: A Proposed Classification
Authors: Agarwal Padmanidhi , Mehrotra Divya
Published: February 2020

Aims:

The purpose of this article was to study and devise a classification of fracture patterns of the mandibular ramus to facilitate management.

Methods:

Mandibular ramus fracture demographics in literature were reviewed along with evaluation of the patients diagnosed with mandibular ramus fractures who had reported to the emergency/outpatient clinic of our Institute in the last 5 years. Epidemiology of these ramus fractures was studied, and these ramus fractures were categorized into repetitive patterns on the basis of radiological observations in an effort to achieve a simplified classification.

Results:

A total of 1372 trauma patients were diagnosed with mandibular fractures, of which an incidence of 2.4% was recorded for ramus fractures. These were predominantly in males and mainly due to road traffic accidents commonly in people driving two-wheeler vehicles (64%). Ramus fractures seldom occur in isolation. Five predictable fracture patterns were observed and accordingly classified as types I to V. Type I was the most common and type IV the least. Open reduction was done in 45.5% patients with non-compression plating systems. Satisfactory aesthetic and functional outcomes were achieved in all patients.

Conclusion:

The mandibular ramus fractures although rare need to be well understood and demarcated. The classification highlights the importance of this mandibular buttress and focuses on the importance of its technically and anatomically more complicated fracture treatment. Future studies are needed to compare the modalities of management.
Regulating for decent work: Reflections on classification of employees
Authors: Mangan David
Published: February 2020

The International Labour Organisation hosted the Sixth Regulating for Decent Work Conference in its centenary year of 2019. As part of these three days, I had the pleasure to chair a panel posing the prescient question: ‘Are the Categories of “Employee” and “Self-Employed” Still a Valid Tool to Allocate Labour Rights?’ In this brief introduction, I outline the product of that panel by situating classification as part of an interplay between labour and commercial law.
Use of combined transarticular pinning and external skeletal fixation for the reduction and stabilization of multiple metatarsophalangeal luxations in a cat
Authors: Verpaalen Valentine D , Lewis Daniel D , Porter Erin G
Published: February 2020

Case summary

A 1-year-old spayed female domestic shorthair cat presented for evaluation of a non-weight bearing right pelvic limb lameness after falling from a 4 m height. On orthopedic examination there was substantial swelling and pain on manipulation of the right pes. Radiographs were obtained under sedation, and these revealed dorsoproximal luxations of the third, fourth and fifth metatarsophalangeal joints, and lateral rotation of the second digit. Closed manual reduction under sedation was unsuccessful and open reduction under general anesthesia was therefore performed. Combined transarticular pinning and external skeletal fixation were performed to maintain reduction of the third and fourth digits. Marked postoperative swelling of the distal pes and internal rotation of the third and fourth digits were noted within 24 h of surgery. Three weeks postoperatively, the cat had a persistent weight bearing right pelvic limb lameness and minor pin tract inflammation. All implants were removed and the limb was splinted for 1 week. Internal rotation and pin tract inflammation had resolved at the time of splint removal, and the lameness resolved within 6 weeks of surgery. The cat was not lame, but radiographs revealed mild-to-moderate degenerative osteoarthrosis when the cat was evaluated 6 months after surgery.

Relevance and novel information

There are limited reports describing metatarsophalangeal luxations in cats. Although several surgical techniques have been advocated, specific outcomes in clinical cases have not been reported. This report describes the clinical application and outcome of combined transarticular pinning and external skeletal fixation for the management of multiple metatarsophalangeal luxations in a cat.
Efficiency of Life Insurance Companies: An Empirical Study in Mainland China and Taiwan
Authors: Shieh Hwai-Shuh , Hu Jin-Li , Ang Yong-Ze
Published: February 2020

The study employs metafrontier and four-stage data envelopment analysis (DEA) to measure the overall and individual efficiency of life insurance companies in mainland China and Taiwan, after applying the slack-based measure (SBM)-DEA model to adjust the differences in the operating environment across production units. The empirical findings show the following: (a) The environmental factors significantly affected the efficiency of all life insurance companies. After the adjustments, the efficiency score of life insurance companies in mainland China and Taiwan drops for 14.01% and 26.64% in regional frontier, and 38.31% and 12.22% in metafrontier frontier. (b) Before 2008, the life insurance companies in Taiwan are more efficient than those in mainland China.
Influence of intensity measure selection on simulation-based regional seismic risk assessment
Authors: Du Ao , Padgett Jamie E , Shafieezadeh Abdollah
Published: February 2020

This study investigates the influence of intensity measure (IM) selection on simulation-based regional seismic risk assessment (RSRA) of spatially distributed structural portfolios. First, a co-simulation method for general spectral averaging vector IMs is derived. Then a portfolio-level surrogate demand modeling approach, which incorporates the seismic demand estimation of the non-collapse and collapse states, is proposed. The derived IM co-simulation method enables the first comparative study of different IMs, including the conventional IMs and some more advanced scalar and vector IMs, in the context of RSRA. The influence of IM selection on the predictive performance of the portfolio-level surrogate demand models, as well as on the regional seismic risk estimates, is explored based on a virtual spatially distributed structural portfolio subjected to a scenario earthquake. The results of this study provide pertinent insights in surrogate demand modeling, IM co-simulation and selection, which can facilitate more accurate and reliable regional seismic risk estimates.
Introduction: The role of modern mineralogy in cultural heritage studies
Authors: ARTIOLI Gilberto , OBERTI Roberta
Published: February 2020

This short introduction aims to rethink the role of modern mineralogy and highlights the diverse and important contributions that it may provide in the study of materials and processes relevant to cultural heritage. It is argued that mineralogy lies in a very special position between Earth and materials sciences and that mineralogists have a profound perception of the structural and chemical complexity of natural materials. They possess knowledge of both the ancient and recent geological and physicochemical processes which produced the raw materials used by humans, and of the analogue processes used to transform them into artefacts. It is thus highly appropriate that a volume in the EMU series acknowledges some of the recent contributions of mineralogy to the investigation of human history, art and technology.
Ancient Mediterranean polychrome stones
Authors: LAZZARINI Lorenzo
Published: February 2020

The Romans, like the Egyptians and much more than the Greeks, used polychrome stones for decorative purposes in architectural elements, floor and wall facings and statuary. Throughout their Mediterranean provinces they systematically searched for and exploited a very large number of beautiful lithotypes, many of which they distributed to all corners of their empire. The most important of these stones were often re-used later in medieval-to-modern times; some of them are still offered on the market. They include granitoid rocks (granites, granodiorites/tonalities, gabbros, quartz-monzonites), a few lavas, many metamorphites (impure marbles, metabreccias and metandesites) and several sedimentary rocks (limestones, lumachellas, conglomerates, calcareous alabasters/travertines). The 40 most important and widespread of these lithotypes are considered here as regards their origin, the history of their use and their minero-petrographic characteristics, which can contribute to better knowledge of single species, to determination of the original quarries and to archaeometric solutions of several provenance problems.
WASP and Mst1 coregulate B-cell development and B-cell receptor signaling
Authors: Huang Lu , Sun Xiaoyu , Yang Di , Dai Xin , Jiang Panpan , Bai Xiaoming , Zhang Yongjie , Wang Jinzhi , Li Wenyan , Miller Heather , Song Wenxia , Treanor Bebhinn , Zhao Xiaodong , Liu Chaohong
Published: February 2020

Mst1 is a serine/threonine kinase involved in cell survival, proliferation, apoptosis, and tumorigenesis. In mice, Mst1 regulates actin dynamics required for T-cell adhesion and migration, which correlate with thymic egress and entry into lymphatic tissue. The role of Mst1 in B cells and how it may control actin-dependent processes has not been well characterized. Wiskott-Aldrich syndrome protein (WASP) deficiency only moderately affects development and B-cell receptor (BCR) signaling, suggesting WASP likely associates with other molecules. We investigated whether Mst1 associates with WASP to regulate B-cell development and activation. Experimenting on Mst1/WASP double knockout (DKO) mice, we found a severe defect in the bone marrow B-cell development, and BCR signaling in the DKO mice was severely reduced. Even though WASP or Mst1 could influence the early B-cell activation, we found that the early activation events such as B-cell spreading, BCR clustering, and BCR signaling were much more impaired in the B cells from DKO mice. Furthermore, reciprocal regulation between Mst1 and WASP was observed in WASP and Mst1 KO mice, whereby the localization and function of phosphorylated WASP were affected in Mst1 KO mice. Most importantly, Mst1 inhibits the expression of WASP by decreasing the expression of WASP-interacting protein. Interestingly, we also found that WASP deficiency in patients and mice interferes with phosphorylated Mst1 localization and therefore function in B cells. Overall, our study provides a partner for WASP to regulate B-cell development and BCR signaling, as well as the reciprocal regulating molecular mechanism of one another.
Tisagenlecleucel cellular kinetics, dose, and immunogenicity in relation to clinical factors in relapsed/refractory DLBCL
Authors: Awasthi Rakesh , Pacaud Lida , Waldron Edward , Tam Constantine S. , Jäger Ulrich , Borchmann Peter , Jaglowski Samantha , Foley Stephen Ronan , van Besien Koen , Wagner-Johnston Nina D. , Kersten Marie José , Schuster Stephen J. , Salles Gilles , Maziarz Richard T. , Anak Özlem , del Corral Christopher , Chu Jufen , Gershgorin Irina , Pruteanu-Malinici Iulian , Chakraborty Abhijit , Mueller Karen Thudium , Waller Edmund K.
Published: February 2020

The anti-CD19 chimeric antigen receptor (CAR)–T cell therapy tisagenlecleucel was evaluated in the global, phase 2 JULIET study in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We correlated tisagenlecleucel cellular kinetics with clinical/product parameters in 111 patients treated in JULIET. Tisagenlecleucel persistence in responders and nonresponders, respectively, was demonstrated for 554 and 400 days maximum by flow cytometry and for 693 and 374 days maximum by quantitative polymerase chain reaction (qPCR). No relationships were identified between cellular kinetics (qPCR) and product characteristics, intrinsic/extrinsic factors, dose, or immunogenicity. Most patients with 3-month response had detectable transgene at time of response and continued persistence for ≥6 months. Expansion (maximal expansion of transgene/CAR-positive T-cell levels in vivo postinfusion [Cmax]) was potentially associated with response duration but this did not reach statistical significance (hazard ratio for a twofold increase in Cmax, 0.79; 95% confidence interval, 0.61-1.01). Tisagenlecleucel expansion was associated with cytokine-release syndrome (CRS) severity and tocilizumab use; no relationships were observed with neurologic events. Transgene levels were associated with B-cell levels. Dose was associated with CRS severity, but this was not statistically significant after adjusting for baseline tumor burden. In contrast to the results from B-cell precursor acute lymphoblastic leukemia (B-ALL) and chronic lymphocytic leukemia, similar exposure was observed in DLBCL in this study regardless of response and expansion was lower in DLBCL than B-ALL, likely from differences in cancer location and/or T-cell intrinsic factors. Relationships between expansion and CRS severity, and lack of relationships between dose and exposure, were similar between DLBCL and B-ALL. Tisagenlecleucel cellular kinetics in adult relapsed/refractory DLBCL improve current understanding of in vivo expansion and its relationships with safety/efficacy endpoints. This trial was registered at www.clinicaltrials.gov as #NCT02445248.
Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses
Authors: Zhao Yating , Zhu Ruixia , Xiao Tongling , Liu Xu
Published: February 2020

Objective

Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations.

Methods

Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software.

Results

As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways “positive regulation of cytosolic calcium ion concentration” and “inositol phosphate-mediated signaling” and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility.

Conclusion

Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.
Molecular mechanism of azoles resistant Candida albicans in a patient with chronic mucocutaneous candidiasis
Authors: Zhang Ming-rui , Zhao Fei , Wang Shuang , Lv Sha , Mou Yan , Yao Chun-li , Zhou Ying , Li Fu-qiu
Published: February 2020

Background

More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. albicans isolated from the oral cavity of a patient with chronic mucocutaneous candidiasis (CMC).

Case presentation

CMC diagnosis was given based on clinical manifestations, laboratory test findings and gene sequencing technique. Minimum inhibitory concentration (MIC) of the fungal isolate, obtained from oral cavity termed as CA-R, was obtained by in vitro anti-fungal drugs susceptibility test. To further investigate the resistant mechanisms, we verified the mutations of drug target genes (i.e. ERG11 and ERG3) by Sanger sequencing, and verified the over-expression of ERG11 and drug efflux genes (i.e. CDR1 and CDR2) by RT-PCR. A heterozygous mutation of c.1162A > G resulting in p.K388E was detected in STAT1 of the patient. The expression of CDR1 and CDR2 in CA-R was 4.28-fold and 5.25-fold higher than that of type strain SC5314, respectively.

Conclusions

Up-regulation of CDR1 and CDR2 was mainly responsible for the resistance of CA-R. For CMC or other immunodeficiency patients, drug resistance monitoring is necessary.
Acute visual impairment as a main presenting symptom of non-convulsive status epilepticus: a case report
Authors: Yang Yi , Zhang Shunyuan , Duan Jinfeng , Zhang Xianwen , Tang Yufeng
Published: February 2020

Background

Nonconvulsive status epilepticus (NCSE) is a state of ongoing seizure activity without convulsions. The heterogeneous and subtle clinical features of NCSE make diagnosis and treatment challenging. Here, we report a patient with NCSE who showed a main presenting symptom of acute visual impairment, which is a rare and atypical clinical symptom of NCSE.

Case presentation

A 62-year-old man was admitted to the neurology department after complaining of an inability to see in the right eye for 2 days and progressive headache. He had a history of poststroke epilepsy and vascular dementia. Physical examination revealed right visual field hemianopia, visual neglect and cognitive impairment. T2 and diffusion-weighted magnetic resonance imaging showed high signal intensity in the left temporal, parietal and occipital lobes. Electroencephalography monitoring was performed, which found continuous sharp wave discharges, especially in the regions of the left temporal, parietal and occipital lobes. These findings were most consistent with the diagnosis of NCSE. Thus, a treatment of intravenous pumping of diazepam and an oral antiepileptic drug was added immediately. After that, the visual loss in the patient recovered quickly, and electroencephalography did not find epileptiform waves. On day 11, a follow-up MRI was performed, which showed that the abnormal signals of the left temporal, parietal and occipital lobes were markedly attenuated, and the patient returned to his premorbid state with a modified Rankin Scale score of 3.

Conclusions

Acute visual impairment can be seen in NCSE, and it can be reversed by administering effective antiepileptic treatment. Meanwhile, transient peri-ictal MRI abnormalities can be observed in NCSE.
Case report of one month and 15 days old baby with type V hyperlipoproteinemia (HLP)
Authors: Dildar Shabnam , Shamsi Tahir Sultan
Published: February 2020

Background

Most of the patients with type 1 and V hyperlipoproteinemia (HLP) present with symptoms and signs of acute pancreatitis due to marked elevation of triglycerides, but this baby presented with a chest infection, which was later diagnosed as type V HLP on laboratory workup.

Case presentation

We report a case of a 1 month and 15 days old baby boy, product of 2-nd degree consanguinity admitted to a nearby hospital with complaints of refusal to feed, cough and excessive crying. On examination his heart rate was 102 beats/min, respiratory rate was 55 breaths/min and temperature was within the normal range, provisional diagnosis of Pneumonia was made. His samples were tested at our laboratory, the lipid Profile at age of 1 month 15 days showed total cholesterol (TC) of 1400 mg/dl reference range (RR < 200 mg/dl), triglycerides (TG) of > 885 mg/dl after dilution it was 31,400 mg/dl (RR < 150 mg/dl), High density Cholesterol (HDL) of 35 mg/dl (RR > 40 mg/dl) and low density cholesterol (LDL) of 200 mg/dl (RR < 100 mg/dl). The patient’s blood sample was grossly milky and lipemic in appearance. A “Refrigerator test” was performed after overnight storage of the sample in refrigerator at 4 °C, which gave a creamy layer at the top and clear infranatant due to caking of the Chylomicrons. Lipoprotein electrophoresis performed 1 month later showed Chylomicrons of 4.7% (RR 0–2%), Pre-beta lipoproteins of 51.5% (RR 5–22%), beta lipoproteins of 16.5% (RR 39–70%) and alpha of 27.3% (RR 23–53%). Initially he was diagnosed as type 1 HLP, but later on he was correctly diagnosed as type V HLP. Cholestyramine (Questran sachet) powder was started at a dose of 100 mg/kg on t.i.d basis with NAN-1 formula Milk at the age of 1 month and 15 days. On follow up, detailed advices regarding the weaning food was given to the mother (using olive oil in cooking, giving proteins and avoiding heavy fatty meals). His lipid profile was repeated at age of 3 months, which showed some improvement, his TGs were 1986 mg/dl and TC 105 mg/dl.

Conclusion

There is no universal diagnostic criterion for diagnosing Type V HLP, most likely, due to a scanty literature on this disorder. It stimulated us to report this case so that our findings may help for a timely diagnosis of the affected patients.
RETRACTED ARTICLE: Cyanidin-3-glucoside activates Nrf2-antioxidant response element and protects against glutamate-induced oxidative and endoplasmic reticulum stress in HT22 hippocampal neuronal cells
Authors: Sukprasansap Monruedee , Chanvorachote Pithi , Tencomnao Tewin
Published: February 2020

Background

Cyanidin-3-glucoside (C3G), a major anthocyanin present in berries, exhibits a strong antioxidant and has been shown to possess a neuroprotection. Prolonged exposure to glutamate will lead to oxidative damage and endoplasmic reticulum stress which could play a key detrimental role in the development of neurodegenerative disorders (NDs). In the present study, we investigated the neuroprotective effect and underlying mechanisms of C3G on the reduction of oxidative/ER stress-induced apoptosis by glutamate in HT22 mouse hippocampal neuronal cells.

Method

Cells were pre-treated with C3G in various concentrations, followed by glutamate. Cell viability and toxicity were examined using MTT and LDH assays. The apoptotic and necrotic cell death were carried out by Annexin V-FITC/propidium iodide co-staining assays. Generation of intracellular reactive oxygen species (ROS) in cells was measured by flow cytometry using DCFH-DA probe. Expression of antioxidant genes was evaluated by Real-time polymerase chain reaction analysis. The possible signaling pathways and proteins involved were subsequently demonstrated by Western blot analysis.

Result

The pretreatment of the HT22 cells with C3G protected cell death from oxidative toxicity induced by glutamate. We demonstrated that treatment cells with glutamate caused several radical forms of ROS formation, and they were abolished by specific ROS inhibitors. Interestingly, C3G directly scavenged radical activity and inhibited intracellular ROS generation in our cell-based system. In addition, C3G pretreatment suppressed the up-regulation of specific ER proteins namely calpain, caspase-12 and C/EBP homologous proteins (CHOP) induced by glutamate-mediated oxidative and ER stress signal by up-regulating the expressions of survival proteins, including extracellular regulated protein kinase (ERK) and nuclear factor E2-related factor 2 (Nrf2). Furthermore, dramatically activated gene expression of endogenous antioxidant enzymes (i.e. superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPx)), and phase II enzymes (glutathione-S-transferases (GSTs)) was found in C3G-treated with cells.

Conclusions

Our finding suggest that C3G could be a promising neuroprotectant via inhibition of glutamate-induced oxidative and ER stress signal and activation of ERK/Nrf2 antioxidant mechanism pathways.
How do applicants, students and physicians think about the feminisation of medicine? - a questionnaire-survey
Authors: Laurence D. , Görlich Y. , Simmenroth A.
Published: February 2020

Background

The implications of the feminisation of medicine, which is characterised by a growing proportion of female doctors, is a topic currently being debated worldwide. To date, however, there has been no systematic survey of the viewpoint of present and future doctors on this subject. The aim of the present study is to determine how future and present doctors view this trend in terms of its relevance to the medical profession and its present impacts.

Methods

Of a total sample of 3813 people, 181 applicants for the winter term 2014, 590 medical students and 225 doctors of the UMG participated in this cross-sectional electronic questionnaire. The answers were analysed by means of the statistics program IBM SPSS Statistics 22. Open answers were qualitatively evaluated and categorised using the “Basiswissengeleitete offene Kategorienfindung” (Werner Früh) and coded for statistical analysis.

Results

The majority of our participants favoured a balanced gender-ratio among doctors: 77% of applicants, 68% of students and 61% of doctors rated this as important or very important. The results from the student and applicant groups differed concerning female gender. When answering in the role of a patient, the doctor’s gender was found to be more relevant than when the participants were answering in the role of the doctor. The majority of the respondents opined that feminisation had had an impact on their workplace: particular factors included part-time work, work-related organisation and the diversity of the medical profession. Commentaries were mostly categorised as negative.

Conclusions

The feminisation of medicine was viewed largely critically by the participants of this study. The respondents evaluated gender as being relevant for the medical profession and favoured a diverse workforce; however, the significance of one’s own gender in medical practice was underrated in comparison, implying a need for more awareness of the effect of a doctor’s gender on the patient-doctor-relationship. The mainly negative comments concerning the impact of feminisiation on work organisation, work satisfaction and patient care show the need for further research and action to adapt current medical work practices to the changing demographics in order to improve work satisfaction and quality of care.
A 19-isolate reference-quality global pangenome for the fungal wheat pathogen Zymoseptoria tritici
Authors: Badet Thomas , Oggenfuss Ursula , Abraham Leen , McDonald Bruce A. , Croll Daniel
Published: February 2020

Background

The gene content of a species largely governs its ecological interactions and adaptive potential. A species is therefore defined by both core genes shared between all individuals and accessory genes segregating presence-absence variation. There is growing evidence that eukaryotes, similar to bacteria, show intra-specific variability in gene content. However, it remains largely unknown how functionally relevant such a pangenome structure is for eukaryotes and what mechanisms underlie the emergence of highly polymorphic genome structures.

Results

Here, we establish a reference-quality pangenome of a fungal pathogen of wheat based on 19 complete genomes from isolates sampled across six continents. Zymoseptoria tritici causes substantial worldwide losses to wheat production due to rapidly evolved tolerance to fungicides and evasion of host resistance. We performed transcriptome-assisted annotations of each genome to construct a global pangenome. Major chromosomal rearrangements are segregating within the species and underlie extensive gene presence-absence variation. Conserved orthogroups account for only ~ 60% of the species pangenome. Investigating gene functions, we find that the accessory genome is enriched for pathogenesis-related functions and encodes genes involved in metabolite production, host tissue degradation and manipulation of the immune system. De novo transposon annotation of the 19 complete genomes shows that the highly diverse chromosomal structure is tightly associated with transposable element content. Furthermore, transposable element expansions likely underlie recent genome expansions within the species.

Conclusions

Taken together, our work establishes a highly complex eukaryotic pangenome providing an unprecedented toolbox to study how pangenome structure impacts crop-pathogen interactions.
Presenilin1 exerts antiproliferative effects by repressing the Wnt/β-catenin pathway in glioblastoma
Authors: Yang Wei , Wu Peng-fei , Ma Jian-xing , Liao Mao-jun , Xu Lun-shan , Xu Min-hui , Yi Liang
Published: February 2020

Background

Glioblastoma and Alzheimer’s disease (AD) are the most common and devastating diseases in the central nervous system. The dysfunction of Presenilin1 is the main reason for AD pathogenesis. However, the molecular function of Presenilin1 and its relative mechanism in glioblastoma remain unclear.

Methods

Expression of presenilin1 in glioma was determined by IHC. CCK-8, colony formation, Flow cytometry, Edu staining were utilized to evaluate functions of presenilin1 on glioblastoma proliferation. The mechanism of above process was assessed by Western blotting and cell immunofluorescence. Mouse transplanting glioblastoma model and micro-MRI detection were used to verified presenilin1 function in vivo.

Results

In this study, we found that all grades of glioma maintained relatively low Presenilin1 expression and that the expression of Presenilin1 in high-grade glioma was significantly lower than that in low-grade glioma. Moreover, the Presenilin1 level had a positive correlation with glioma and glioblastoma patient prognosis. Next, we determined that Presenilin1 inhibited the growth and proliferation of glioblastoma cells by downregulating CDK6, C-myc and Cyclin D1 to arrest the cell cycle at the G1/S phase. Mechanistically, Presenilin1 promoted the direct phosphorylation of β-catenin at the 45 site and indirect phosphorylation at the 33/37/41 site, then decreased the stabilized part of β-catenin and hindered its translocation from the cytoplasm to the nucleus. Furthermore, we found that Presenilin1 downregulation clearly accelerated the growth of subcutaneous glioblastoma, and Presenilin1 overexpression significantly repressed the subcutaneous and intracranial transplantation of glioblastoma by hindering β-catenin-dependent cell proliferation.

Conclusion

Our data implicate the antiproliferative effect of Presenilin1 in glioblastoma by suppressing Wnt/β-catenin signaling, which may provide a novel therapeutic agent for glioblastoma.
Immune response in piglets orally immunized with recombinant Bacillus subtilis expressing the capsid protein of porcine circovirus type 2
Authors: Zhang Shuai , Mou Chunxiao , Cao Yanan , Zhang En , Yang Qian
Published: February 2020

Background

Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome, and is associated with a number of other diseases. PCV2 is widely distributed in most developed swine industries, and is a severe economic burden. With an eye to developing an effective, safe, and convenient vaccine against PCV2-associated diseases, we have constructed a recombinant Bacillus subtilis strain (B. subtilis-Cap) that expresses the PCV2 capsid protein (Cap).

Methods

Electroporation of a plasmid shuttle vector encoding the PCV2 Cap sequence was use to transform Bacillus subtilis. Flow cytometry was used to evaluate in vitro bone marrow derived dendritic cell (BM-DC) maturation and T cell proliferation induced by B. subtilis-Cap. Orally inoculated piglets were used for in vivo experiments; ELISA and western blotting were used to evaluate B. subtilis-Cap induced PCV2-specific IgA and IgG levels, as well as the secretion of cytokines and the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 9 (TLR9).

Results

We evaluated the immune response to B. subtilis-Cap in vitro using mouse BM-DCs and in vivo using neonatal piglets orally inoculated with B. subtilis-Cap. Our results showed that the recombinant B. subtilis-Cap activated BM-DCs, significantly increased co-stimulatory molecules (CD40 and CD80) and major histocompatibility complex II, and induced allogenic T cells proliferation. Piglets immunized with B. subtilis-Cap had elevated levels of PCV2-specific IgA in the mucosal tissues of the digestive and respiratory tract, and PCV2-specific IgG in serum (P < 0.05 or P < 0.01). Ileal immunocompetent cells, such as the IgA-secreting cells (P < 0.01), intestinal intraepithelial lymphocytes (IELs) (P < 0.01), CD3+ T lymphocytes (P < 0.01) and CD4+ T lymphocytes (P < 0.01) increased significantly in the B. subtilis-Cap immunized piglets. Additionally, B. subtilis-Cap inoculation resulted in increased the expression of TLR2 and TLR9 (P < 0.01), and induced the secretion of cytokines IL-1β, IL-6, interferon-γ, and β-defensin 2 (P < 0.01).

Conclusions

We constructed a prototype PCV2 vaccine that can be administered orally and elicits a more robust humoral and cellular immunity than inactivated PCV2. B. subtilis-Cap is a promising vaccine candidate that is safe, convenient, and inexpensive. Further in vivo research is needed to determine its full range of efficacy in pigs.

Graphical abstract