bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming challenges in delivering integrated motivational interviewing and cognitive behavioural therapy for bipolar disorder with co-morbid alcohol use: therapist perspectives
Authors: Berry Katherine , Barrowclough Christine , Fitsimmons Mike , Hartwell Rosalyn , Hilton Claire , Riste Lisa , Wilson Ian , Jones Steven
Published: May 2020

Background:

Alcohol misuse is common in bipolar disorder and is associated with worse outcomes. A recent study evaluated integrated motivational interviewing and cognitive behavioural therapy for bipolar disorder and alcohol misuse with promising results in terms of the feasibility of delivering the therapy and the acceptability to participants.

Aims:

Here we present the experiences of the therapists and supervisors from the trial to identify the key challenges in working with this client group and how these might be overcome.

Method:

Four therapists and two supervisors participated in a focus group. Topic guides for the group were informed by a summary of challenges and obstacles that each therapist had completed at the end of therapy for each individual client. The audio recording of the focus group was transcribed and data were analysed using thematic analysis.

Results:

We identified five themes: addressing alcohol use versus other problems; impact of bipolar disorder on therapy; importance of avoidance and overcoming it; fine balance in relation to shame and normalising use; and ‘talking the talk’ versus ‘walking the walk’.

Conclusions:

Findings suggest that clients may be willing to explore motivations for using alcohol even if they are not ready to change their drinking, and they may want help with a range of mental health problems. Emotional and behavioural avoidance may be a key factor in maintaining alcohol use in this client group and therapists should be aware of a possible discrepancy between clients’ intentions to reduce misuse and their actual behaviour.
Disarmed principals: institutional resilience and the non-enforcement of delegation
Authors: Weiss Moritz , Heinkelmann-Wild Tim
Published: May 2020

Governments across the world increasingly rely on non-state agents for managing even the most sensitive tasks that range from running critical infrastructures to protecting citizens. While private agents frequently underperform, governments as principals tend nonethelessnotto enforce delegation contracts. Why? We suggest the mechanism of institutional resilience. A preexisting set of rules shapes non-enforcement through the combination of (i) itsstructural misfitwith the delegation contract and (ii)asymmetric interdependencethat favors the agent over time. To demonstrate the plausibility of our argument, we trace the political process behind Europe’s largest military transport aircraft, the A400M. Governments delegated the development and production of this complex program to a private firm, Airbus. They layered a ‘commercial approach’ onto traditionally state-run defense industries. Yet, resilience caused these new formal rules to fail and eventually disarmed principals. Our mechanism constitutes an innovative approach by theorizing an alternative path toward dynamic continuity.
Effect of antidepressants for cessation therapy in betel-quid use disorder: a randomised, double-blind, placebo-controlled trial
Authors: Hung Chung-Chieh , Lee Chien-Hung , Ko Albert Min-Shan , Lane Hsien-Yuan , Lee Chi-Pin , Ko Ying-Chin
Published: May 2020

Aims

More than one-half of betel-quid (BQ) chewers have betel-quid use disorder (BUD). However, no medication has been approved. We performed a randomised clinical trial to test the efficacy of taking escitalopram and moclobemide antidepressants on betel-quid chewing cessation (BQ-CC) treatment.

Methods

We enrolled 111 eligible male BUD patients. They were double-blinded, placebo-controlled and randomised into three treatment groups: escitalopram 10 mg/tab daily, moclobemide 150 mg/tab daily and placebo. Patients were followed-up every 2 weeks and the length of the trial was 8 weeks. The primary outcome was BQ-CC, defined as BUD patients who continuously stopped BQ use for ⩾6 weeks. The secondary outcomes were the frequency and amount of BQ intake, and two psychological rating scales. Several clinical adverse effects were measured during the 8-week treatment.

Results

Intention-to-treat analysis shows that after 8 weeks, two (5.4%), 13 (34.2%) and 12 (33.3%) of BUD patients continuously quit BQ chewing for ⩾6 weeks among placebo, escitalopram, moclobemide groups, respectively. The adjusted proportion ratio of BQ-CC was 6.3 (95% CI 1.5–26.1) and 6.8 (95% CI 1.6–28.0) for BUD patients who used escitalopram and moclobemide, respectively, as compared with those who used placebo. BUD patients with escitalopram and moclobemide treatments both exhibited a significantly lower frequency and amount of BQ intake at the 8th week than those with placebo.

Conclusions

Prescribing a fixed dose of moclobemide and escitalopram to BUD patients over 8 weeks demonstrated treatment benefits to BQ-CC. Given a relatively small sample, this study provides preliminary evidence and requires replication in larger trials.
Poor implementation of the EU clinical trial regulation is a major threat for pragmatic trials in European countries
Authors: Ostuzzi Giovanni , Gastaldon Chiara , Petrini Carlo , Godman Brian , Barbui Corrado
Published: May 2020

The principle of pragmatism in clinical trials has been broadly recognised as a way to close the gap between research and practice. In this contribution, we argue that the conduct of pragmatic clinical trials in Europe may be hampered by poor implementation of current European Union's Clinical Trial Regulation No. 536/2014.
The Quasipersistent Feature of Highly Structured Field‐Aligned Currents in the Duskside Auroral Oval: Conjugate Observation Via Swarm Satellites and a Ground All‐Sky Imager
Authors: Yokoyama Y. , Taguchi S. , Iyemori T. , Hosokawa K.
Published: May 2020

During northward interplanetary magnetic field (IMF), irregular magnetic perturbations were observed in the duskside aurora oval via Swarm satellites instead of large‐scale Region 1/2 magnetic perturbations. By taking advantage of Swarm constellation measurements, and their conjugate observations with an all‐sky imager on the ground, the features of the irregular magnetic perturbations were examined. Detailed analysis of the data from Swarm A and Swarm C for two events demonstrated that the irregular magnetic perturbations are a result of highly structured quasistatic field‐aligned currents (FACs), not dynamic Alfvén waves. The typical latitudinal size of the upward FACs is 20–30 km. In each region of the upward FACs, 630‐nm aurora emissions are relatively strong, indicating that the energy flux of precipitating electrons having energies of a few hundred electron volts is high in each of the upward FAC regions. The enhanced mesoscale auroras continued to exist for at least approximately 30 min. These indicate that the mesoscale FAC structures also have quasipersistent features. The precipitating particle data from the Defense Meteorological Satellite Program satellite, which passed through the field of view of the all‐sky imager, indicate that the source of the precipitating particles is the duskside low‐latitude boundary layer (LLBL). We suggest that the highly structured quasipersistent FACs flow along the magnetic field lines connected to the duskside LLBL where cold dense ions exist. The highly structured FACs in the duskside aurora oval are the phenomena that are pertinent to the magnetosphere for a northward IMF condition, not a simple remnant of the typical Region 1.
A Case Study of the Enhancements in Ionospheric Electron Density and Its Longitudinal Gradient at Chinese Low Latitudes
Authors: Liu Libo , Ding Zonghua , Zhang Ruilong , Chen Yiding , Le Huijun , Zhang Hui , Li Guozhu , Wu Jian , Wan Weixing
Published: May 2020

The day‐to‐day variability of the ionospheric electron density and its longitudinal gradient challenges our description and understanding of the ionosphere, which is also essential for reliable applications of the Global Navigation Satellite System (GNSS). In this paper we conduct a case study of the anomalous enhancements in ionospheric electron density and its longitudinal gradient to reveal the spatial extent and related drivers of the enhancements. The ionospheric data analyzed include the vertical total electron content (TEC) by the Global Navigation Satellite System receivers, peak electron density (NmF2) and height (hmF2) of the F layer by a chain of ionosondes, and electron density profiles recorded by the Qujing incoherent scatter radar (103.8°E, 25.6°N) during the period from 29 May to 2 June 2015. Electron density enhancements are found in the region around the northern crest of equatorial ionization anomaly on the first 2 days of June 2015. It is the first time to report that, during the anomalous enhancement, the increase in electron density over Qujing depends on altitude, being stronger at higher altitudes. Further, there are strong longitudinal gradients in vertical TEC in the regions during the course of the electron density enhancements. Low latitude hmF2 and especially the equatorial electrojet become much larger on the enhancement days, implying the important role of equatorial zonal electric fields in the formation of the electron density enhancements at low latitudes.
Arctic Plankton Populations Vary by Season
Authors: Shultz David
Published: May 2020

Planktonic foraminifera and sea snail numbers swell from April to June in the Barents Sea, but contrary to predictions, the organisms do not appear to be affected directly by high methane levels.
Revisited Reference Solar Proton Event of 23 February 1956: Assessment of the Cosmogenic‐Isotope Method Sensitivity to Extreme Solar Events
Authors: Usoskin Ilya G. , Koldobskiy Sergey A. , Kovaltsov Gennady A. , Rozanov Eugene V. , Sukhodolov Timofei V. , Mishev Alexander L. , Mironova Irina A.
Published: May 2020

Our direct knowledge of solar eruptive events is limited to several decades and does not include extreme events, which can only be studied by the indirect proxy method over millennia, or by a large number of Sun‐like stars. There is a gap, spanning 1–2 orders of magnitude, in the strength of events between directly observed and reconstructed ones. Here, we study the proxy method sensitivity to identify extreme solar particle events (SPEs). First, the strongest directly observed SPE (23 February 1956), used as a reference for proxy‐based reconstructions, was revisited using the newly developed method. Next, sensitivity of the cosmogenic‐isotope method to detect a reference SPE was assessed against the precision and number of individual isotopic records, showing that it is too weak by a factor ≈30 to be reliably identified in a single record. Uncertainties of 10Be and 14C data are shown to be dominated by local/regional patterns and measurement errors, respectively. By combining several proxy records, a SPE 4–5 times stronger than the reference one can be potentially detected, increasing the present‐day sensitivity by an order of magnitude. This will allow filling the observational gap in SPE strength distribution, thus enriching statistics of extreme events from 3–4 presently known ones to several tens. This will provide a solid basis for research in the field of extreme events, both for fundamental science, namely solar and stellar physics, and practical applications, such as the risk assessments of severe space‐based hazards for modern technological society.
The role of bone marrow biopsy in patients with plasma cell disorders: should all patients with a monoclonal protein be biopsied?
Authors: Sidiqi M. Hasib , Aljama Mohammed , Kumar Shaji K. , Jevremovic Dragan , Buadi Francis K. , Warsame Rahma , Lacy Martha Q. , Dingli David , Gonsalves Wilson I. , Fonder Amie L. , Hobbs Miriam A. , Hwa Yi Lisa , Kapoor Prashant , Kourelis Taxiarchis , Leung Nelson , Muchtar Eli , Lust John A. , Kyle Robert A. , Go Ronald S. , Rajkumar Vincent S. , Gertz Morie A. , Dispenzieri Angela
Published: May 2020

We conducted a retrospective review of multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) patients seen at Mayo Clinic to determine whether a bone marrow biopsy (BM) is necessary in all patients diagnosed with a monoclonal protein. A total of 2254 MM, 397 SMM, and 5836 MGUS patients were included in the study. A total of 29 (1.3%) MM patients “without CRAB/FLC” were identified where BM or advanced imaging was critical for diagnosis, 8 (0.3% MM cohort) of whom were diagnosed with MM solely on BM findings (plasma cells > 60%). Without BM or advanced imaging none of these patients would be classified low-risk MGUS. A total of 314 (79%) MGUS-like SMM patients were identified where classification of SMM was based on BM findings. Without BM 97 would be classified as low/low-intermediate-risk MGUS and 151 intermediate or high-risk MGUS; 66 had missing information precluding classification. Only three (<1% SMM cohort) were low-risk MGUS without abnormalities in hemoglobin, calcium, and renal function. In patients presenting with low-risk MGUS and normal hemoglobin, calcium, and renal function, the risk of missing a diagnosis of SMM and MM by omitting BM is <1%. BM should be deferred in these patients in preference to clinical and laboratory monitoring.
Innate lymphoid cells control signaling circuits to regulate tissue-specific immunity
Authors: Klose Christoph S. N. , Artis David
Published: May 2020

The multifaceted organization of the immune system involves not only patrolling lymphocytes that constantly monitor antigen-presenting cells in secondary lymphoid organs but also immune cells that establish permanent tissue-residency. The integration in the respective tissue and the adaption to the organ milieu enable tissue-resident cells to establish signaling circuits with parenchymal cells to coordinate immune responses and maintain tissue homeostasis. Innate lymphoid cells (ILCs) are tissue-resident innate immune cells that have a similar functional diversity to T cells including lineage-specifying transcription factors that drive certain effector programs. Since their formal discovery 10 years ago, it has become clear that ILCs are present in almost every tissue but strongly enriched at barrier surfaces, where they regulate immunity to infection, chronic inflammation, and tissue maintenance. In this context, recent research has identified ILCs as key in orchestrating tissue homeostasis through their ability to sustain bidirectional interactions with epithelial cells, neurons, stromal cells, adipocytes, and many other tissue-resident cells. In this review, we provide a comprehensive discussion of recent studies that define the development and heterogeneity of ILC populations and their impact on innate and adaptive immunity. Further, we discuss emerging research on the influence of the nervous system, circadian rhythm, and developmental plasticity on ILC function. Uncovering the signaling circuits that control development and function of ILCs will provide an integrated view on how immune responses in tissues are synchronized with functional relevance far beyond the classical view of the role of the immune system in discrimination between self/non-self and host defense.
Correction to: A universal pipeline for mobile mRNA detection and insights into heterografting advantages under chilling stress
Authors: Wang Ying , Wang Lingping , Xing Nailin , Wu Xiaohua , Wu Xinyi , Wang Baogen , Lu Zhongfu , Xu Pei , Tao Ye , Li Guojing , Wang Yuhong
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The role of calcium in regulating marine phosphorus burial and atmospheric oxygenation
Authors: Zhao Mingyu , Zhang Shuang , Tarhan Lidya G. , Reinhard Christopher T. , Planavsky Noah
Published: May 2020

The marine phosphorus cycle plays a critical role in controlling the extent of global primary productivity and thus atmospheric pO2 on geologic time scales. However, previous attempts to model carbon–phosphorus-oxygen feedbacks have neglected key parameters that could shape the global P cycle. Here we present new diagenetic models to fully parameterize marine P burial. We have also coupled this diagenetic framework to a global carbon cycle model. We find that seawater calcium concentration, by strongly influencing carbonate fluorapatite (CFA) formation, is a key factor controlling global phosphorus cycling, and therefore plays a critical role in shaping the global oxygen cycle. A compilation of Cenozoic deep-sea sedimentary phosphorus speciation data provides empirical support for the idea that CFA formation is strongly influenced by marine Ca concentrations. Therefore, we propose a previously overlooked coupling between Phanerozoic tectonic cycles, the major-element composition of seawater, the marine phosphorus cycle, and atmospheric pO2.
Author Correction: Whole-genome resequencing of 472 Vitis accessions for grapevine diversity and demographic history analyses
Authors: Liang Zhenchang , Duan Shengchang , Sheng Jun , Zhu Shusheng , Ni Xuemei , Shao Jianhui , Liu Chonghuai , Nick Peter , Du Fei , Fan Peige , Mao Ruzhi , Zhu Yifan , Deng Weiping , Yang Min , Huang Huichuan , Liu Yixiang , Ding Yiqing , Liu Xianju , Jiang Jianfu , Zhu Youyong , Li Shaohua , He Xiahong , Chen Wei , Dong Yang
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Bismuthene for highly efficient carbon dioxide electroreduction reaction
Authors: Yang Fa , Elnabawy Ahmed O. , Schimmenti Roberto , Song Ping , Wang Jiawei , Peng Zhangquan , Yao Shuang , Deng Ruiping , Song Shuyan , Lin Yue , Mavrikakis Manos , Xu Weilin
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Symptom-based screening tool for asthma syndrome among young children in Uganda
Authors: Nantanda Rebecca , Siersma Volkert , Ndeezi Grace , Tumwine James K. , Østergaard Marianne S.
Published: May 2020

Under-diagnosis of asthma in ‘under-fives’ may be alleviated by improved inquiry into disease history. We assessed a questionnaire-based screening tool for asthma among 614 ‘under-fives’ with severe respiratory illness in Uganda. The questionnaire responses were compared to post hoc consensus diagnoses by three pediatricians who were guided by study definitions that were based on medical history, physical examination findings, laboratory and radiological tests, and response to bronchodilators. Children with asthma or bronchiolitis were categorized as “asthma syndrome”. Using this approach, 253 (41.2%) had asthma syndrome. History of and present breathing difficulties and present cough and wheezing was the best performing combination of four questionnaire items [sensitivity 80.8% (95% CI 77.6–84.0); specificity 84.7% (95% CI 81.8–87.6)]. The screening tool for asthma syndrome in ‘under-fives’ may provide a simple, cheap and quick method of identifying children with possible asthma. The validity and reliability of this tool in primary care settings should be tested.
The Lipocalin2 Gene is Regulated in Mammary Epithelial Cells by NFκB and C/EBP In Response to Mycoplasma
Authors: Zhao Wei , Bendickson Lee , Nilsen-Hamilton Marit
Published: May 2020

Lcn2 gene expression increases in response to cell stress signals, particularly in cells involved in the innate immune response. Human Lcn2 (NGAL) is increased in the blood and tissues in response to many stressors including microbial infection and in response to LPS in myeloid and epithelial cells. Here we extend the microbial activators of Lcn2 to mycoplasma and describe studies in which the mechanism of Lcn2 gene regulation by MALP-2 and mycoplasma infection was investigated in mouse mammary epithelial cells. As for the LPS response of myeloid cells, Lcn2 expression in epithelial cells is preceded by increased TNFα, IL-6 and IκBζ expression and selective reduction of IκBζ reduces Lcn2 promoter activity. Lcn2 promoter activation remains elevated well beyond the period of exposure to MALP-2 and is persistently elevated in mycoplasma infected cells. Activation of either the human or the mouse Lcn2 promoter requires both NFκB and C/EBP for activation. Thus, Lcn2 is strongly and enduringly activated by mycoplasma components that stimulate the innate immune response with the same basic regulatory mechanism for the human and mouse genes.
Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry
Authors: Tennen Ruth I. , Laskey Sarah B. , Koelsch Bertram L. , McIntyre Matthew H. , Tung Joyce Y.
Published: May 2020

Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) — are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings may help inform the discussion around broader access to BRCA genetic testing.
Deforestation and world population sustainability: a quantitative analysis
Authors: Bologna Mauro , Aquino Gerardo
Published: May 2020

In this paper we afford a quantitative analysis of the sustainability of current world population growth in relation to the parallel deforestation process adopting a statistical point of view. We consider a simplified model based on a stochastic growth process driven by a continuous time random walk, which depicts the technological evolution of human kind, in conjunction with a deterministic generalised logistic model for humans-forest interaction and we evaluate the probability of avoiding the self-destruction of our civilisation. Based on the current resource consumption rates and best estimate of technological rate growth our study shows that we have very low probability, less than 10% in most optimistic estimate, to survive without facing a catastrophic collapse.
Learning physical properties of liquid crystals with deep convolutional neural networks
Authors: Sigaki Higor Y. D. , Lenzi Ervin K. , Zola Rafael S. , Perc Matjaž , Ribeiro Haroldo V.
Published: May 2020

Machine learning algorithms have been available since the 1990s, but it is much more recently that they have come into use also in the physical sciences. While these algorithms have already proven to be useful in uncovering new properties of materials and in simplifying experimental protocols, their usage in liquid crystals research is still limited. This is surprising because optical imaging techniques are often applied in this line of research, and it is precisely with images that machine learning algorithms have achieved major breakthroughs in recent years. Here we use convolutional neural networks to probe several properties of liquid crystals directly from their optical images and without using manual feature engineering. By optimizing simple architectures, we find that convolutional neural networks can predict physical properties of liquid crystals with exceptional accuracy. We show that these deep neural networks identify liquid crystal phases and predict the order parameter of simulated nematic liquid crystals almost perfectly. We also show that convolutional neural networks identify the pitch length of simulated samples of cholesteric liquid crystals and the sample temperature of an experimental liquid crystal with very high precision.
Multilayer Substrate to Use Brittle Materials in Flexible Electronics
Authors: Park Seongmin , Park Hyuk , Seong Suwon , Chung Yoonyoung
Published: May 2020

Flexible materials with sufficient mechanical endurance under bending or folding is essential for flexible electronic devices. Conventional rigid materials such as metals and ceramics are mostly brittle so that their properties can deteriorate under a certain amount of strain. In order to utilize high-performance, but brittle conventional materials in flexible electronics, we propose a novel flexible substrate structure with a low-modulus interlayer. The low-modulus interlayer reduces the surface strain, where active electronic components are placed. The bending results with indium tin oxide (ITO) show that a critical bending radius, where the conductivity starts to deteriorate, can be reduced by more than 80% by utilizing the low-modulus layer. We demonstrate that even rigid electrodes can be used in flexible devices by manipulating the structure of flexible substrate.
Toxicity of ten herbicides to the tropical marine microalgae Rhodomonas salina
Authors: Thomas Marie C. , Flores Florita , Kaserzon Sarit , Fisher Rebecca , Negri Andrew P.
Published: May 2020

Herbicide contamination of nearshore tropical marine ecosystems is widespread and persistent; however, risks posed by most ‘alternative’ herbicides to tropical marine microalgae remain poorly understood. Experimental exposures of the important but understudied microalgae Rhodomonas salina to seven individual Photosystem II (PSII) inhibitor herbicides (diuron, metribuzin, hexazinone, tebuthiuron, bromacil, simazine, propazine) led to inhibition of effective quantum yield (ΔF/Fm′) and subsequent reductions in specific growth rates (SGR). The concentrations which reduced ΔF/Fm′ by 50% (EC50) ranged from 1.71-59.2 µg L−1, while the EC50s for SGR were 4-times higher, ranging from 6.27-188 µg L−1. Inhibition of ΔF/Fm′ indicated reduced photosynthetic capacity, and this correlated linearly with reduced SGR (R2 = 0.89), supporting the application of ∆F/Fm’ inhibition as a robust and sensitive indicator of sub-lethal toxicity of PSII inhibitors for this microalga. The three non-PSII inhibitor herbicides (imazapic, haloxyfop and 2,4-Dichlorophenoxyacetic acid (2,4-D)) caused low or no toxic responses to the function of the PSII or growth at the highest concentrations tested suggesting these herbicides pose little risk to R. salina. This study highlights the suitability of including R. salina in future species sensitivity distributions (SSDs) to support water quality guideline development for the management of herbicide contamination in tropical marine ecosystems.
Production of gold/silver doped carbon nanocomposites for effective photothermal therapy of colon cancer
Authors: Liu Fang , Wang Xiao-di , Du Shi-yu
Published: May 2020

Surgery followed by adjuvant chemotherapy is a reliable therapy for colon cancer, but is associated with side effects and risks. Recent advancements in nanobioengineering in the form of targeted nanoparticles, cubosomes, liposomes, nanosheets, nanorods, quantum dots have generated substantial advancements in theranostics of colon cancer decreasing the cytotoxic drugs’ side effects. We describe a facile mechanism of preparation of hybrid nanocomposite encompassing Au and Ag. Preparation of hybrid nanocomposite is one step process which may be easily escalated. The nanocomposite was characterized using transmission eleactron microscopy, energy dispersive X-Ray spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infra-red spectroscopy, UV-Vis spectroscopy, photoluminescence and cytotoxic studies. In-vivo studies were carried out in Balb/c mice. Photothermal heating experiments in HeLa cells were promising and the characterization studies clearly indicated the formation of hybrid nanocomposite. In-vivo experiments confirmed the efficacy of treatment, along with involvement of epigenetic regulation, which may be helpful in translation from research to clinical applications.
Polarization-sensitive optical coherence tomography for estimating relative melanin content of autologous induced stem-cell derived retinal pigment epithelium
Authors: Matsuzaki Mitsuhiro , Mandai Michiko , Yamanari Masahiro , Totani Kota , Nishida Mitsuhiro , Sugita Sunao , Maeda Tadao , Koide Naoshi , Takagi Seiji , Hirami Yasuhiko , Miyamoto Noriko , Sugiyama Satoshi , Takahashi Masayo , Kurimoto Yasuo
Published: May 2020

Transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithelial (hiPSC-RPE) sheets is a promising therapy for age-related macular degeneration (AMD). As melanin content is a representative feature of healthy RPE, we used polarization-sensitive optical coherence tomography (PS-OCT) to estimate the relative melanin content of RPE in diseased and non-diseased area, and in human iPSC-RPE sheets in vitro and in vivo by evaluating the randomness of polarization (entropy). Two aged Japanese women, one with neovascular AMD that underwent transplantation of an autologous hiPSC-RPE cell sheet and another with binocular dry AMD, were selected for this study. Entropy value was minimal in cells containing no melanin, whereas that of human RPE and hiPSC-RPE sheets was high. En face entropy of the cultured hiPSC-RPE sheet was compared with its grey-scale photo and its values were found to be inversely correlated with the extent of absence of pigmentation in vitro. En face entropy maps were compared to colour fundus photographs, fundus autofluorescence images, and fluorescein angiography images from patients. Entropy values of intact and defective RPEs and of iPSC-RPE transplant areas were determined in vivo using PS-OCT B-scan images. PS-OCT was found to be applicable in the estimation of relative melanin content of cultured and transplanted RPEs in regenerative medicine.
Gigapixel confocal imaging using a massively parallel optical probe array with single directional infinite scanning
Authors: Shin Ryung , Choi Woojae , Kim Taekyung , Kim Donghyun , Han Runjia , Lee Kyungjin , Won Nahyun , Kang Shinill
Published: May 2020

Here we demonstrate high-throughput gigapixel confocal imaging using a massively parallel optical probe array with single directional infinite scanning. For implementation of the single directional infinite scan with high lateral resolution, a parallelogram array micro-objective lens module, composed of two wafer-level microlens arrays, is proposed to generate a massively parallel optical probe array for integration into the confocal imaging system, including an objective-side telecentric relay lens with a low-magnification. To test the feasibility of the proposed system with single directional infinite scanning, we designed and constructed a confocal imaging system using a parallelogram array of multi-optical probes with a massively parallel array size of 200 × 140. The constructed system provides a full width-half maximum lateral resolution of 1.55 μm, as measured by the knife-edge detection method, and a field-of-view width of 28.0 mm with a sampling interval of 1 μm/pixel.
Depletion of Csk preferentially reduces the protein level of LynA in a Cbl-dependent manner in cancer cells
Authors: Kuga Takahisa , Yamane Yuka , Hayashi Soujirou , Taniguchi Masanari , Yamaguchi Naoto , Yamagishi Nobuyuki
Published: May 2020

There are eight human Src-family tyrosine kinases (SFKs). SFK members c-Src, c-Yes, Fyn, and Lyn are expressed in various cancer cells. SFK kinase activity is negatively regulated by Csk tyrosine kinase. Reduced activity of Csk causes aberrant activation of SFKs, which can be degraded by a compensatory mechanism depending on Cbl-family ubiquitin ligases. We herein investigated whether all SFK members are similarly downregulated by Cbl-family ubiquitin ligases in cancer cells lacking Csk activity. We performed Western blotting of multiple cancer cells knocked down for Csk and found that the protein levels of the 56 kDa isoform of Lyn (LynA), 53 kDa isoform of Lyn (LynB), c-Src, and Fyn, but not of c-Yes, were reduced by Csk depletion. Induction of c-Cbl protein levels was also observed in Csk-depleted cells. The reduction of LynA accompanying the depletion of Csk was significantly reversed by the knockdown for Cbls, whereas such significant recovery of LynB, c-Src, and Fyn was not observed. These results suggested that LynA is selectively downregulated by Cbls in cancer cells lacking Csk activity.
Asthma and subsequent school performance at age 15–16 years: A Swedish population-based sibling control study
Authors: Lundholm Cecilia , Brew Bronwyn K. , D’Onofrio Brian M. , Osvald Emma Caffrey , Larsson Henrik , Almqvist Catarina
Published: May 2020

Asthma may negatively affect children’s school performance, such as grades and exam results. Results from previous studies have shown varying results and may have suffered from confounding and other biases. We used a Swedish population-based cohort of 570,595 children with data on asthma (including severity and control) in Grades 7–8 and 9, school performance from Grade 9 (grade point sum, non-eligibility for upper secondary school and national test results) and measured confounders from national registers. We used sibling comparisons to account for unmeasured familial factors. Children with asthma and severe asthma performed slightly better in school than children without asthma when adjusting for measured confounders, but the associations were attenuated in sibling comparisons. In contrast, children with uncontrolled asthma performed slightly worse (e.g. Grade 9: βadj = −9.9; 95% CI −12.8 to −7.0; Cohen’s d = 0.16). This association remained for uncontrolled asthma in Grade 9 in sibling comparisons (Grade 9: β = −7.7 points; 95% CI −12.6 to −2.6; Cohen’s d = 0.12), but not for Grades 7–8. The attenuation of estimates when controlling for familial factors using sibling comparisons suggests that the differences were due to familial factors, rather than being causal. The remaining associations in sibling comparisons between uncontrolled asthma in Grade 9 and school performance are consistent with a causal association.
Chronic Social Defeat Stress Up-Regulates Spexin in the Brain of Nile Tilapia (Oreochromis niloticus)
Authors: Lim Chor Hong , Soga Tomoko , Levavi-Sivan Berta , Parhar Ishwar S.
Published: May 2020

Spexin (SPX), a neuropeptide evolutionarily conserved from fish to mammals, is widely distributed in the brain and peripheral tissues and associated with various physiological functions. Recently SPX has been suggested to be involved in neurological mechanism of stress. The current study investigates the involvement of SPX in chronic social defeat stress, using male teleost, the Nile tilapia (Oreochromis niloticus) as an animal model due to its distinct social hierarchy of dominant and subordinate relationship. The tilapia genome has SPX1a and SPX1b but has no SPX2. In the Nile tilapia, we localized SPX1a and SPX1b in the brain using in-situ hybridization. Next, using qPCR we examined gene expression of SPX1a and SPX1b in chronically stress (socially defeated) fish. SPX1a expressing cells were localized in the semicircular torus of the midbrain region and SPX1b expressing cells in the telencephalon. Chronically stress fish showed elevated plasma cortisol levels; with an upregulation of SPX1a and SPX1b gene expression in the brain compared to non-stress (control) fish. Since social defeat is a source of stress, the upregulated SPX mRNA levels during social defeat suggests SPX as a potentially inhibitory neuropeptide capable of causing detrimental changes in behaviour and physiology.
Alterations in Salience Network Functional Connectivity in Individuals with Restless Legs Syndrome
Authors: Ku Jeonghun , Lee Yeong Seon , Kim Keun Tae , Chang HyukWon , Cho Yong Won
Published: May 2020

Background and purpose: Restless legs syndrome (RLS) is a neurological disorder which is most commonly identified by an urge to move the legs. It often shows alterations in sensory processing which implies the salience network (SN) is experiencing changes. This study investigates the functional connectivity (FC) between the SN and other areas of the brain in RLS patients during the resting state period. Methods: Thirty patients with drug naïve idiopathic RLS and 30 healthy age and gender matched controls were included in this study. Resting state fMRIs were performed in the morning during the asymptomatic period. The SN comparisons were conducted between the two groups. Results: The RLS group showed a reduction in SN FC in the right pyramis, and an increase in SN FC in the bilateral orbitofrontal gyri and right postcentral gyrus. Conclusions: The results of this study give reason to believe that SN FC in RLS patients is altered during asymptomatic periods. This could have an influence on the processing of the saliency of information, particularly sensory information processing and inhibition mechanisms.
Heterozygous loss of Rbm24 in the adult mouse heart increases sarcomere slack length but does not affect function
Authors: de Groot N. E. , van den Hoogenhof M. M. G. , Najafi A. , van der Made I. , van der Velden J. , Beqqali A. , Pinto Y. M. , Creemers E. E.
Published: May 2020

RNA-binding proteins are key regulators of post-transcriptional processes such as alternative splicing and mRNA stabilization. Rbm24 acts as a regulator of alternative splicing in heart and skeletal muscle, and is essential for sarcomere assembly. Homozygous inactivation of Rbm24 in mice disrupts cardiac development and results in embryonic lethality around E12.5. In the present study, we generated somatic Rbm24 knockout (KO) mice and investigated the effects of reduced levels of Rbm24 in the adult heart. Due to the embryonic lethality of Rbm24 KO mice, we examined cardiac structure and function in adult Rbm24 heterozygotes (HETs). Rbm24 protein expression was 40% downregulated in HET hearts compared to WT hearts. Force measurements on isolated membrane-permeabilized myocytes showed increased sarcomere slack length and lower myofilament passive stiffness in adult Rbm24 HET compared to wildtype cardiomyocytes. As a result of the differences in sarcomere slack length, the relations between force development and sarcomere length differed between WT and Rbm24 HET hearts. No differences in sarcomere structure and titin isoform composition were observed. Likewise, in vivo cardiac function and myocardial structure was unaltered in Rbm24 HET mice compared to WT, at baseline and upon pressure overload after transverse aortic constriction. In conclusion, we generated a somatic Rbm24 KO model and recapitulated the previously reported embryonic phenotype. In adult Rbm24 HET cardiomyocytes we observed increased sarcomere slack length, but no difference in sarcomere structure and cardiac function.
Small dense low-density lipoprotein cholesterol is strongly associated with NIHSS score and intracranial arterial calcification in acute ischemic stroke subjects
Authors: Yao Tao , Long Qi , Li Jing , Li Gang , Ding Yanbin , Cui Qin , Liu Zhichao
Published: May 2020

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Small dense low-density lipoprotein cholesterol (sd-LDL-c) was independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether sd-LDL-c is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Serum sd-LDL-c levels and other biochemical parameters were analyzed. Admission NIHSS score and mRS score at discharge were collected. After 60-days 85 patients died during hospitalization and follow-up. Partial correlation analysis showed that serum sd-LDL-c levels were associated with admission NIHSS score and IAC score after adjusted age and gender. Logistic regression analysis showed that serum sd-LDL-c levels independently predicted NIHSS scores (β = 1.537, 95%CI: 0.134-2.878, p = 0.042) and IAC scores (β = 1.355, 95%CI: 0.319-2.446, p = 0.015). The average level of sd-LDL-c in patients who died was also significantly increased compared to survival patients (1.04 ± 0.59 vs 0.88 ± 0.44 mmol/L, p = 0.017). However, multivariate logistic regression analysis showed serum sd-LDL-c levels could not predict all-cause mortality and prognosis in AIS patients. Our study found that sd-LDL-c as a strong atherogenic lipid particle can independently predict admission NIHSS scores and the severity of cerebral artery calcification in AIS patients. However, its prognostic value in AIS patients still needs further study in the future.
Prevalence and pattern of comorbidities in chronic rheumatic and musculoskeletal diseases: the COMORD study
Authors: Ziade Nelly , El Khoury Bernard , Zoghbi Marouan , Merheb Georges , Abi Karam Ghada , Mroue’ Kamel , Messaykeh Jamil
Published: May 2020

Increased risk of comorbidities has been reported in Rheumatic and Musculoskeletal Diseases (RMD). We aimed to evaluate the prevalence and pattern of comorbidities in RMD patients nationwide, to identify multimorbidity clusters and to evaluate the gap between recommendations and real screening. Cross-sectional, multicentric nationwide study. Prevalence of comorbidities was calculated according to six EULAR axes. Latent Class Analysis identified multimorbidity clusters. Comorbidities’ screening was compared to international and local recommendations. In 769 patients (307 RA, 213 OA, 63 SLE, 103 axSpA, and 83 pSA), the most frequent comorbidities were cardiovascular risk factors and diseases (CVRFD) (hypertension 36.5%, hypercholesterolemia 30.7%, obesity 22.7%, smoking 22.1%, diabetes 10.4%, myocardial infarction 6.6%), osteoporosis (20.7%) and depression (18.1%). Three clusters of multimorbidity were identified: OA, RA and axSpA. The most optimal screening was found for CVRF (> = 93%) and osteoporosis (53%). For malignancies, mammograms were the most optimally prescribed (56%) followed by pap smears (32%) and colonoscopy (21%). Optimal influenza and pneumococcus vaccination were found in 22% and 17%, respectively. Comorbidities were prevalent in RMD and followed specific multimorbidity patterns. Optimal screening was adequate for CVRFD but suboptimal for malignant neoplasms, osteoporosis, and vaccination. The current study identified health priorities, serving as a framework for the implementation of future comorbidity management standardized programs, led by the rheumatologist and coordinated by specialized health care professionals.
Deep Learning-based Inaccuracy Compensation in Reconstruction of High Resolution XCT Data
Authors: Topal Emre , Löffler Markus , Zschech Ehrenfried
Published: May 2020

While X-ray computed tomography (XCT) is pushed further into the micro- and nanoscale, the limitations of various tool components and object motion become more apparent. For high-resolution XCT, it is necessary but practically difficult to align these tool components with sub-micron precision. The aim is to develop a novel reconstruction methodology that considers unavoidable misalignment and object motion during the data acquisition in order to obtain high-quality three-dimensional images and that is applicable for data recovery from incomplete datasets. A reconstruction software empowered by sophisticated correction modules that autonomously estimates and compensates artefacts using gradient descent and deep learning algorithms has been developed and applied. For motion estimation, a novel computer vision methodology coupled with a deep convolutional neural network approach provides estimates for the object motion by tracking features throughout the adjacent projections. The model is trained using the forward projections of simulated phantoms that consist of several simple geometrical features such as sphere, triangle and rectangular. The feature maps extracted by a neural network are used to detect and to classify features done by a support vector machine. For missing data recovery, a novel deep convolutional neural network is used to infer high-quality reconstruction data from incomplete sets of projections. The forward and back projections of simulated geometric shapes from a range of angular ranges are used to train the model. The model is able to learn the angular dependency based on a limited angle coverage and to propose a new set of projections to suppress artefacts. High-quality three-dimensional images demonstrate that it is possible to effectively suppress artefacts caused by thermomechanical instability of tool components and objects resulting in motion, by center of rotation misalignment and by inaccuracy in the detector position without additional computational efforts. Data recovery from incomplete sets of projections result in directly corrected projections instead of suppressing artefacts in the final reconstructed images. The proposed methodology has been proven and is demonstrated for a ball bearing sample. The reconstruction results are compared to prior corrections and benchmarked with a commercially available reconstruction software. Compared to conventional approaches in XCT imaging and data analysis, the proposed methodology for the generation of high-quality three-dimensional X-ray images is fully autonomous. The methodology presented here has been proven for high-resolution micro-XCT and nano-XCT, however, is applicable for all length scales.
Pair suppression caused by mosaic-twist defects in superconducting Sr2RuO4 thin-films prepared using pulsed laser deposition
Authors: Garcia Carla Maria Palomares , Di Bernardo Angelo , Kimbell Graham , Vickers Mary E. , Massabuau Fabien C-P. , Komori Sachio , Divitini Giorgio , Yasui Yuuki , Lee Han Gyeol , Kim Jinkwon , Kim Bongju , Blamire Mark G. , Vecchione Antonio , Fittipaldi Rosalba , Maeno Yoshiteru , Noh Tae Won , Robinson Jason W. A.
Published: May 2020

Sr2RuO4 (SRO214) is a prototypical unconventional superconductor. However, since the discovery of its superconductivity a quarter of a century ago, the symmetry of the bulk and surface superconducting states in single crystal SRO214 remains controversial. Solving this problem is massively impeded by the fact that superconducting SRO214 is extremely challenging to achieve in thin-films as structural defects and impurities sensitively annihilate superconductivity. Here we report a protocol for the reliable growth of superconducting SRO214 thin-films by pulsed laser deposition and identify universal materials properties that are destructive to the superconducting state. We demonstrate that careful control of the starting material is essential in order to achieve superconductivity and use a single crystal target of Sr3Ru2O7 (SRO327). By systematically varying the SRO214 film thickness, we identify mosaic twist as the key in-plane defect that suppresses superconductivity. The results are central to the development of unconventional superconductivity.
Integration of aerobic granulation and UV/H2O2 processes in a continuous flow system for the degradation of sulfolane in contaminated water
Authors: Khan Muhammad Faizan , Yu Linlong , Hollman Jordan , Tay Joo Hwa , Achari Gopal
Published: May 2020

Aerobic granulation and UV/H2O2 in a continuous flow-through reactor can effectively degrade emerging contaminates, such as sulfolane.
Many-body effects in an MXene Ti2CO2 monolayer modified by tensile strain: GW-BSE calculations
Authors: Ding Yi-min , Nie Xiaomin , Dong Huilong , Rujisamphan Nopporn , Li Youyong
Published: May 2020

Modified band offset, band gap and optical response of Ti2CO2 monolayer by tensile strain.
‘Template-free’ hierarchical MoS2foam as a sustainable ‘green’ scavenger of heavy metals and bacteria in point of use water purification
Authors: Samantaray Paresh Kumar , Indrakumar Sushma , Chatterjee Kaushik , Agarwal Vipul , Bose Suryasarathi
Published: May 2020

Molybdenum disulfide (MoS2), with its unique optical and electrical properties, has been explored for a variety of applications in the recent past.