bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of switching to bilastine, a histamine H1 receptor antagonist, in patients with chronic spontaneous urticaria (H1-SWITCH): study protocol for a randomized controlled trial
Authors: Fukunaga Atsushi , Oda Yoshiko , Washio Ken , Omori Takashi , Kakei Yasumasa , Hide Michihiro , Nishigori Chikako 
Published: January 2020

Abstract
Background
Chronic spontaneous urticaria (CSU) is characterized by the spontaneous appearance of wheals, angioedema, or both for > 6 weeks. Continuous treatment with H1-antihistamines is used as a first-line treatment for CSU. However, H1-antihistamine treatment leads to absence of symptoms in less than 50% of patients with CSU. Although Japanese guidelines for the diagnosis and treatment of urticaria recommend an increase in the H1-antihistamine dose or a switch to other H1-antihistamines, there is no evidence supporting a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.

Methods
We will conduct a multicenter, open-label, non-inferiority, randomized, parallel, comparison study to determine if the efficacy of bilastine 20 mg is not inferior to that of a twofold H1-antihistamine dose increase in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. This study will be performed at 15 academic hospitals in Japan, and the administration period (increasing the H1-antihistamine dose twofold vs. switching to bilastine 20 mg) will be 7 days. Participants (n = 150) will be randomized to either an increased H1-antihistamine dose or a switch to bilastine 20 mg at a 1:1 ratio. The primary endpoint, mean of the total symptom score of 5–7 days after the intervention, will be evaluated. The secondary objective is to determine if the safety of bilastine 20 mg regarding somnolence is superior to that of a twofold dose increase of H1-antihistamines. This will be measured by a change in the Japanese version of the Epworth Sleepiness Scale from baseline to 7 days after starting the intervention.

Discussion
This multicenter, open-label, non-inferiority, randomized, parallel, comparison study will be, to our knowledge, the first well-designed clinical study to evaluate the efficacy of a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed doses. This trial will provide evidence of the efficacy and safety of bilastine when treatment is switched in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.

Trial registration
Japan Registry of Clinical Trials (jRCT), jRCTs051180105. Registered on 8 March 2019.
Acupuncture treatment on the motor area of the scalp for motor dysfunction in children with cerebral palsy: study protocol for a multicenter randomized controlled trial
Authors: Wang Jun , Shi Wei , Khiati Dhiaedin , Shi Bingpei , Shi Xiaojuan , Luo Dandan , Wang Yin , Deng Rencai , Huang Huayu , Li Jian , Yan Weili , Yang Hong 
Published: January 2020

Abstract
Background
Scalp acupuncture has been widely used as treatment for motor dysfunction in children with cerebral palsy in China. Previous studies have failed to provide high-quality evidence to demonstrate the effectiveness of this treatment in children with cerebral palsy. No high-quality randomized controlled trials on scalp acupuncture have been published. The aim of this study is to evaluate the effectiveness of Jiao’s scalp acupuncture when combined with routine rehabilitation treatment versus routine rehabilitation treatment alone for motor dysfunction in children with cerebral palsy.

Methods/Design
This is a four-centre randomized controlled trial. One hundred cerebral palsy patients with motor dysfunction were enrolled. Patients will be allocated in a 1:1 ratio into either an acupuncture treatment group or a control group. Cerebral palsy patients in the control group will receive conventional rehabilitation treatment, whereas patients in the acupuncture group will receive a combination of scalp acupuncture and conventional rehabilitation treatment. Thirty-six treatment sessions will be performed over a 12-week period. The Gross Motor Function Measure and the Fine Motor Function Measure Scale will be assessed as the primary outcome measures. The Paediatric Evaluation of Disability Inventory and the Cerebral Palsy Quality of Life Questionnaire for Children will be selected as secondary outcome measures. All assessments will be conducted at baseline, week 4 (treatment 12), week 8 (treatment 24), week 12 (treatment 36) and week 24 (follow-up).

Discussion
This is the first trial evaluating the efficacy and safety of scalp acupuncture as a treatment for motor dysfunction in children with cerebral palsy. The results of this trial are expected to provide relevant evidence demonstrating that scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in children with cerebral palsy.

Trial registration
ClinicalTrials.gov, NCT03921281. Registered on 19 April 2019.
Enhanced lipid production by Yarrowia lipolytica cultured with synthetic and waste-derived high-content volatile fatty acids under alkaline conditions
Authors: Gao Ruiling , Li Zifu , Zhou Xiaoqin , Bao Wenjun , Cheng Shikun , Zheng Lei 
Published: January 2020

Abstract
Background
Volatile fatty acids (VFAs) can be effective and promising alternate carbon sources for microbial lipid production by a few oleaginous yeasts. However, the severe inhibitory effect of high-content (> 10 g/L) VFAs on these yeasts has impeded the production of high lipid yields and their large-scale application. Slightly acidic conditions have been commonly adopted because they have been considered favorable to oleaginous yeast cultivation. However, the acidic pH environment further aggravates this inhibition because VFAs appear largely in an undissociated form under this condition. Alkaline conditions likely alleviate the severe inhibition of high-content VFAs by significantly increasing the dissociation degree of VFAs. This hypothesis should be verified through a systematic research.

Results
The combined effects of high acetic acid concentrations and alkaline conditions on VFA utilization, cell growth, and lipid accumulation of Yarrowia lipolytica were systematically investigated through batch cultures of Y. lipolytica by using high concentrations (30–110 g/L) of acetic acid as a carbon source at an initial pH ranging from 6 to 10. An initial pH of 8 was determined as optimal. The highest biomass and lipid production (37.14 and 10.11 g/L) were obtained with 70 g/L acetic acid, whereas cultures with > 70 g/L acetic acid had decreased biomass and lipid yield due to excessive anion accumulation. Feasibilities on high-content propionic acid, butyric acid, and mixed VFAs were compared and evaluated. Results indicated that YX/S and YL/S of cultures on butyric acid (0.570, 0.144) were comparable with those on acetic acid (0.578, 0.160) under alkaline conditions. The performance on propionic acid was much inferior to that on other acids. Mixed VFAs were more beneficial to fast adaptation and lipid production than single types of VFA. Furthermore, cultures on food waste (FW) and fruit and vegetable waste (FVW) fermentate were carried out and lipid production was effectively improved under this alkaline condition. The highest biomass and lipid production on FW fermentate reached 14.65 g/L (YX/S: 0.414) and 3.20 g/L (YL/S: 0.091) with a lipid content of 21.86%, respectively. By comparison, the highest biomass and lipid production on FVW fermentate were 11.84 g/L (YX/S: 0.534) and 3.08 g/L (YL/S: 0.139), respectively, with a lipid content of 26.02%.

Conclusions
This study assumed and verified that alkaline conditions (optimal pH 8) could effectively alleviate the lethal effect of high-content VFA on Y. lipolytica and significantly improve biomass and lipid production. These results could provide a new cultivation strategy to achieve simple utilizations of high-content VFAs and increase lipid production. Feasibilities on FW and FVW-derived VFAs were evaluated, and meaningful information was provided for practical applications.
Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection
Authors: Gao Li , Song Xiumei , Wang Jingwen 
Published: January 2020

Abstract
Background
Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. Peptidoglycan recognition proteins (PGRPs), a family of pattern-recognition receptors (PRR), are responsible for initiating and regulating immune signaling pathways. PGRP-LA is involved in the regulation of immune defense against the Plasmodium parasite, however, the underlying mechanism needs to be further elucidated.

Methods
The spatial and temporal expression patterns of pgrp-la in Anopheles stephensi were analyzed by qPCR. The function of PGRP-LA was examined using a dsRNA-based RNA interference strategy. Western blot and periodic acid schiff (PAS) staining were used to assess the structural integrity of peritrophic matrix (PM).

Results
The expression of pgrp-la in An. stephensi was induced in the midgut in response to the rapid proliferating gut microbiota post-blood meal. Knocking down of pgrp-la led to the downregulation of immune effectors that control gut microbiota growth. The decreased expression of these immune genes also facilitated P. berghei infection. However, such dsLA treatment did not influence the structural integrity of PM. When gut microbiota was removed by antibiotic treatment, the regulation of PGRP-LA on immune effectors was abolished and the knock down of pgrp-la failed to increase susceptibility of mosquitoes to parasite infection.

Conclusions
PGRP-LA regulates the immune responses by sensing the dynamics of gut microbiota. A mutual interaction between gut microbiota and PGRP-LA contributes to the immune defense against Plasmodium parasites in An. stephensi.
CACTUS: cancer image annotating, calibrating, testing, understanding and sharing in breast cancer histopathology
Authors: Aksac Alper , Ozyer Tansel , Demetrick Douglas J. , Alhajj Reda 
Published: January 2020

Abstract
Objective
Develop CACTUS (cancer image annotating, calibrating, testing, understanding and sharing) as a novel web application for image archiving, annotation, grading, distribution, networking and evaluation. This helps pathologists to avoid unintended mistakes leading to quality assurance, teaching and evaluation in anatomical pathology. Effectiveness of the tool has been demonstrated by assessing pathologists performance in the grading of breast carcinoma and by comparing inter/intra-observer assessment of grading criteria amongst pathologists reviewing digital breast cancer images. Reproducibility has been assessed by inter-observer (kappa statistics) and intra-observer (intraclass correlation coefficient) concordance rates.

Results
CACTUS has been evaluated using a surgical pathology application—the assessment of breast cancer grade. We used CACTUS to present standardized images to four pathologists of differing experience. They were asked to evaluate all images to determine their assessment of Nottingham grade of a series of breast carcinoma cases. For each image, they were asked for their overall grade impression. CACTUS helps and guides pathologists to improve disease diagnosis with higher confidence and thereby reduces their workload and bias. CACTUS can be useful for both disseminating anatomical pathology images for teaching, as well as for evaluating agreement amongst pathologists or against a gold standard for evaluation or quality assurance.
Regular approximation of singular Sturm–Liouville problems with eigenparameter dependent boundary conditions
Authors: Zhang Maozhu , Li Kun , Song Hongxiang 
Published: January 2020

AbstractIn this paper we consider singular Sturm–Liouville problems with eigenparameter dependent boundary conditions and two singular endpoints. The spectrum of such problems can be approximated by those of the inherited restriction operators constructed. Via the abstract operator theory, the strongly resolvent convergence and norm resolvent convergence of a sequence of operators are obtained and it follows that the spectral inclusion of spectrum holds. Moreover, spectral exactness of spectrum holds for two special cases.
Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients
Authors: Rosa Neto Nilton Salles , Bento Judith Campos de Barros , Pereira Rosa Maria Rodrigues 
Published: January 2020

AbstractBackgroundFabry disease (FD) is an X-linked lysosomal disorder due to mutations in theGLAgene resulting in defective enzyme alpha-galactosidase A. FD patients are frequently misdiagnosed, commonly for rheumatic diseases. Determining pathogenicity of a mutation depends of in silico predictions but mostly on available clinical information and interpretation may change in light of evolving knowledge. Similar signs and symptoms in carriers ofGLAgene genetic variants of unknown significance or of benign variants may hamper diagnosis. This study reviews rheumatic and immune-mediated manifestations in a cohort of Brazilian FD patients with classic mutations and also in subjects withGLAgene A143T and R118C mutations. Misdiagnoses, time to correct diagnosis or determination of GLA gene status, time to treatment initiation and reasons for treatment prescription in A143T and R118C subjects are reviewed.MethodsGenotype confirmed classic FD patients (n = 37) and subjects with GLA gene mutations A143T and R118C (n = 19) were referred for assessment. Subjects with R118C and A143T mutations had been previously identified during screening procedures at hemodialysis units. All patients were interviewed and examined by a rheumatologist with previous knowledge of disease and/or mutation status. A structured tool developed by the authors was used to cover all aspects of FD and of common rheumatic conditions. All available laboratory and imaging data were reviewed.ResultsThirty-seven consecutive FD patients were interviewed – 16 male / 21 female (mean age: 43.1 years) and 19 consecutive subjects withGLAgene mutations R118C and A143T were evaluated – 8 male / 11 female (mean age: 39.6 years); 15 [R118C] / 4 [A143T]. Misdiagnosis in FD patients occurred in 11 males (68.8%) and 13 females (61.9%) of which 10 males and 9 females were previously diagnosed with one or more rheumatic conditions, most frequently rheumatic fever or “rheumatism” (unspecified rheumatic disorder). Median time for diagnosis after symptom onset was 16 years (range, 0–52 years). Twenty-two patients were treated with enzyme replacement therapy (ERT) – 13 male and 9 female. Median time to ERT initiation after FD diagnosis was 0.5 years (range, 0–15 years). Rheumatic manifestations occurred in 68.4% of R118C and A143T subjects. Two subjects had been prescribed ERT because of renal disease [R118C] and neuropsychiatric symptoms [A143T].ConclusionMisdiagnoses occurred in 64.8% of FD patients, most frequently for rheumatic conditions. Median time for correct diagnosis was 16 years. Rheumatic manifestations are also frequent in subjects withGLAgene R118C and A143T mutations. These results reinforce the need to raise awareness and increase knowledge about Fabry disease among physicians, notably rheumatologists, who definitely have a role in identifying patients and determining disease burden. Decision to start treatment should consider expert opinion and follow local guidelines.
Selective serotonin reuptake inhibitor ‘discontinuation syndrome’ or withdrawal
Authors: Massabki Ivana , Abi-Jaoude Elia 
Published: January 2020

SummaryAttempts to define selective serotonin reuptake inhibitor (SSRI) withdrawal with the term ‘discontinuation syndrome’ are not supported by evidence. Acknowledging that SSRI use can result in dependence and withdrawal allows patients to be better informed around decisions related to these drugs, and helps inform strategies for safe tapering as appropriate.
Risk for Acromegaly-related Comorbidities by Sex in Korean Acromegaly
Authors: Park Kyeong Hye , Lee Eun Jig , Seo Gi Hyeon , Ku Cheol Ryong 
Published: January 2020

Abstract

Context
Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce.

Objective
To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea.

Design
This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis.

Setting
A longitudinal case-control study using a nationwide population cohort.

Results
The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12–3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13–2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07–2.84).

Conclusion
Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea.
Sulfonated Poly(arylene perfluoroalkylene) Terpolymers as Novel Proton Exchange Membranes for High Performance Fuel Cells
Authors: Long Zhi , Miyake Junpei , Miyatake Kenji 
Published: January 2020

Abstract
We herein report a series of sulfonated poly(arylene perfluoroalkylene) terpolymers (SPAF-P) containing sulfophenylene, perfluoroalkylene, and meta- or para-phenylene groups in the main chain. The SPAF-P terpolymers with reasonable molecular weight and various ion exchange capacity (IEC = 1.85–3.18 meq g−1) provided transparent and flexible membranes. Compared with our previous membrane sharing the same perfluoroalkylene groups (SPAF-MM, IEC = 1.59 meq g−1), SPAF-P achieved higher proton conductivity over a wide range of humidity because of their higher IEC values. A fuel cell with SPAF-pP 1.85 membrane exhibited slightly higher performance than that of SPAF-MM at 30% RH with H2/air because of the improved proton conductivity. After the open-circuit voltage (OCV) hold test for 1000 h, the SPAF-pP fuel cell retained high OCV value (&gt;0.94 V), similar polarization curves, ohmic resistance curves, molecular weight and chemical structure, indicating the excellent chemical stability of the SPAF-pP 1.85 membrane.
ESTUDANTES DE ENSINO MÉDIO E REPRESENTAÇÕES SOBRE A RELAÇÃO ESCOLACOMUNIDADE : A EDUCAÇÃO PÚBLICA COMO CENTRALIDADE
Authors: Silva Lincoln Tavares 
Published: January 2020

Baseados na Teoria das Representações Sociais (Moscovici, Jodelet e Abric), buscamos conhecer melhor o que/como pensam estudantes do Ensino Médio de escolas públicas estaduais, situadas no Estado do Rio de Janeiro, sobre a relação escolacomunidade (entre os anos de 2008 e 2011). Os instrumentos aplicados forneceram informações sobre os processos que influenciam as concepções comunitárias e as relações com a escola. Analisamos que as representações e práticas amoldam-se às dinâmicas socioculturais, modificando ou transgredindo regras estabelecidas. A Educação tem centralidade nas representações. Idealizada ou não, como base, salvação, elo, fonte, meta, boa escolha, esforço, emancipação e direito. Articula-se à ajuda, à comunicação, aos alunos, ao professor e ao respeito na relação escolacomunidade, integrando e relacionando a experiência escolar às demais experiências. Tal centralidade sugere pensar em territórios educativos e não meramente escolares, ressignificando o trabalho escolar.
APRESENTAÇÃO – DOSSIÊ TEMÁTICO: ENSINO MÉDIO – PASSOS E IMPASSES NA ATUALIDADE
Authors: Frigotto Gaudêncio , Ramos Marise 
Published: January 2020

A Revista e-Mosaicos, nesta 19ª edição, optou por um Dossiê Temático que trata, especialmente, do ensino médio nas suas diferentes modalidades e em diferentes aspectos. O número de artigos enviados expressa o quanto o tema do ensino médio assume centralidade no debate da educação básica.
Mid-infrared electro-optic dual-comb spectroscopy with feedforward frequency stepping
Authors: Ren Xinyi , Dai Hu , Li Detian , Huang Kun , Hu Mengyun , Lv Tianjian , Yan Ming , Zeng Heping 
Published: January 2020

In this Letter, we utilize an acoustic-optic frequency shifter in a feedforward manner for automatic interpolation of dual-comb spectroscopy, where frequency tuning can be achieved at 5.45 THz/s with the step size precisely locked to the line spacing (54.5 MHz) of a referenced optical comb without complicated electronics or control programs. Our dual-comb spectrometer involves two near-infrared electro-optic combs at 25 GHz line spacings, nonlinearly converted into the mid-infrared region, revealing fundamental absorption lines of methane gas at 54.5 MHz resolution within a spectral range from 88.04 to 89.04 THz. The method and the system may be useful in many applications, including gas sensing.
Adaptive electrofluid-actuated liquid lens
Authors: Huang Xiang , Jin Hang , Lin Siying , Bu Zhenxiang , Lin Zhihong , Tu WenChang , Wang Lingyun 
Published: January 2020

We present a novel adaptive liquid lens actuated by electrofluid. The deformation of electrofluid under the combined action of vertical electric fields and magnetic fields controls the hydraulic pressure in the lens chamber. Both the study of electrohydrodynamics and the study of optical properties of the prototype have been carried out. The measured focal length of the liquid lens decreases from 34.55 mm to 5.12 mm, as the current increases from

−

3

A

to 5 A. However, the voltage across the electrofluid changed only from

−

0.24

V

to 0.4 V. The electrofluid-actuated lens exhibits some attractive features compared with the conventional mechanical driven lens, such as high integration, easy control, and low working voltage.
Ultrabroadband nonlinear optics in nanophotonic periodically poled lithium niobate waveguides
Authors: Jankowski Marc , Langrock Carsten , Desiatov Boris , Marandi Alireza , Wang Cheng , Zhang Mian , Phillips Christopher R. , Lončar Marko , Fejer M. M. 
Published: January 2020

Quasi-phase-matched interactions in waveguides with quadratic
nonlinearities enable highly efficient nonlinear frequency conversion.
In this paper, we demonstrate the first generation of devices that
combine the dispersion engineering available in nanophotonic
waveguides with quasi-phase-matched nonlinear interactions available
in periodically poled lithium niobate (PPLN). This combination enables
quasi-static interactions of femtosecond pulses, reducing the pulse
energy requirements by several orders of magnitude compared to
conventional devices, from picojoules to femtojoules. We
experimentally demonstrate two effects associated with second harmonic
generation (SHG). First, we observe efficient quasi-phase-matched SHG
with

<

100

f
J

of pulse energy. Second, in the limit
of strong phase-mismatch, we observe spectral broadening of both
harmonics with as little as 2 pJ of pulse energy. These results lay a
foundation for a new class of nonlinear devices, in which
coengineering of dispersion with quasi-phase-matching enables
efficient nonlinear optics at the femtojoule level.