bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of artificial ground freezing in construction of cross passages under Suez Canal
Authors: Phillips Mina , Fadhel Haider , Raafat Ibrahim , El‐Kelesh Adel
Published: June 2021

The Artificial Ground Freezing (AGF) has demonstrated its versatility as an effective approach for both temporary ground stabilization and ground water control in almost all types of saturated soils. This paper describes the use of a closed circuit freezing system in the construction of four cross passages. The passages connect 4.8 km long twin road tunnels that have recently been constructed at depths of up to 60 m under Suez Canal in Ismailia, Egypt. The paper starts by describing the ground conditions at the locations of the cross passages and by presenting the results of laboratory tests conducted on unfrozen, frozen and thawed soil specimens. The main design criteria considered in designing the freezing works are discussed and the freezing and cross passages construction works are described. The frozen body was carefully monitored during the freezing process and construction of passages. Records of the adopted monitoring program are presented and discussed. Significant observations that contribute to effective planning of future freezing works are also presented.
Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma
Authors: Beltramini Giada A. , Belloni Laura M. , Fusco Nicola , Sacconi Andrea , Muti Paola , Baj Alessandro , Bolzoni Alessandro R. , Giannì Aldo B.
Published: June 2021

Background

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition.

Methods

One hundred and forty‐two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease‐free survival (DFS) was evaluated.

Results

Fifty‐seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p = 0.02). Instead N classification was not significantly predictive of OS (p = 0.10). High LNRs resulted in decreases in OS of approximately 40% within 6 months after surgery.

Conclusions

The LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.
The influence of extracellular tissue on neutrophil function and its possible linkage to inflammatory diseases
Authors: Kraus Richard F. , Gruber Michael A. , Kieninger Martin
Published: June 2021

Background: Migration, production of reactive oxygen species (ROS), release of myeloperoxidase (MPO), and NETosis are functional immunological reactions of elementary importance for polymorphonuclear neutrophils (PMN).

Unregulated inflammatory response of PMN within tissues plays a key role in the pathophysiology of several diseases. However, little is known about the behavior of PMN after migration through blood vessel walls. Therefore, we investigated the influence of the extracellular matrix (ECM) on PMN function.

Materials and Methods: We established an in vitro chemotaxis model of type I and III collagen, fibrin, and herbal agarose tissues using µ‐slide chemotaxis devices and N‐formylmethionine‐leucyl‐phenylalanine (fMLP). PMN within the matrices were assessed with a fluorescent time‐lapse microscope for live‐cell imaging.

Results: PMN function was obviously influenced by the ECM. Type III collagen had an inhibitory effect on PMN migration regarding track length, direction, and targeting. Type III collagen also had an accelerating effect on neutrophil ROS production. Agarose had an inhibitory effect on MPO release and fibrin a retarding effect on NETosis.

Conclusion: Because of the high abundance of type III collagen in lung and skin matrices, the interaction of PMN with the respective matrix could be an important mechanism in the pathophysiology of acute respiratory distress syndrome and pyoderma gangrenosum.
To sell the cow and drink the milk: How could China harmonize its growth and risk?
Authors: Chen Ku‐Hsieh , Chen Pei‐Hua , Lin Yen‐Ju , Chi Ching‐Fang
Published: June 2021

Facing the challenge of the new normal, mainstream public opinion advises China to adopt a conservative strategy of “slowing down the growth and lowering the leverage.” This paper proposes an alternative compatible idea of “stabilizing the growth and lowering the leverage.” For this purpose, the study first describes the investment and credit‐led mode as well as the dilemma confronted by China with an identity equation to deliberate the harmonic role played by the efficiency of aggregate social financing increments. The empirical work uses data from 31 regions in China from the first quarter of 2014 to the first quarter of 2018 as observations. The outcome shows that, if the aggregate social financing increment reaches full efficiency, the rate of output growth could provide a chance to stabilize in the short term up to around 10%, while the surging leverage and debt ratio could become moderate. There should also be an opportunity to eliminate the threat of financial risks in the medium term if combined with the deployment and implementation of ongoing supporting measures. This paper recommends a three‐step strategy of promoting efficiency, easing the risks and optimizing the structure. The expectation of “stabilizing the growth and lowering the leverage” would not be unachievable.
A novel machine learning‐based analytical framework for automatic detection of COVID‐19 using chest X‐ray images
Authors: Johri Shikhar , Goyal Mehendi , Jain Sahil , Baranwal Manoj , Kumar Vinay , Upadhyay Rahul
Published: June 2021

Considering the prevailing scenario of COVID‐19 pandemic, early detection of the disease is an important and crucial step in disease management. Early detection and correct treatment may limit disease progression to severe levels and prevent deaths. In addition, early isolation of infected patients will lead to control transmission rate and will possibly reduce the stress on the present healthcare system. Currently, the most common and reliable testing method available for COVID‐19 diagnosis is real‐time reverse transcription‐polymerase chain reaction (rRT‐PCR) test. However, the chest radiological (X‐ray) imaging can be used as an alternate method to rRT‐PCR test, and early COVID‐19 symptoms can be investigated by critical examination of patient's chest scans. In the present work, a novel machine learning (ML)‐based analytical framework is developed for automatic detection of COVID‐19 using chest X‐ray (CXR) images of plausible patients. The framework is designed, trained, and validated to identify four classes of CXR images namely, healthy, bacterial pneumonia, viral pneumonia, and COVID‐19. The experimental results pose the proposed framework as a potential candidate for COVID‐19 disease diagnosis using CXR images, with training, validation, and testing accuracy of 92.4%, 88.24%, and 87.13%, respectively, in four‐class classification. The comparative analysis demonstrates the better capabilities of the proposed framework COVID‐19 detection along with other types of pneumonia.
The evaluation of a multiphasic 3D‐bioplotted scaffold seeded with adipose derived stem cells to repair osteochondral defects in a porcine model
Authors: Nordberg Rachel C. , Huebner Pedro , Schuchard Karl G. , Mellor Liliana F. , Shirwaiker Rohan A. , Loboa Elizabeth G. , Spang Jeffery T.
Published: June 2021

There is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D‐bioplotted osteochondral scaffold design that can drive site‐specific tissue formation when seeded with adipose‐derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC‐seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold‐facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.
Unrecognized tax benefit and its impact on firms’ financial activities: A longitudinal analysis
Authors: Ren Yi , Hsieh Chialing
Published: June 2021

Our study investigates the unrecognized tax benefit (UTB) across firms and its impact on the firm's financial activities using the generalized estimating equations (GEEs). We find the UTB variation across firms is largely related to the firms’ operation characteristics and firms with higher UTB balances are more likely to overstate their uncertain tax positions (UTPs). Also, we find that UTB balances are positively associated with firms’ cash holding and employee stock compensation expenses. Our results provide evidence that UTB has become an important financial disclosure and have affected firms’ financial operations.
Notes from the youth mental health field: Using movement towards goals as a potential indicator of service change and quality improvement
Authors: Jacob Jenna , Edbrooke‐Childs Julian , Costa da Silva Luís , Law Duncan
Published: June 2021

The aim of this paper is to report our notes from the field on using movement toward goals at an aggregate level as an inference of service effectiveness. Analysis of routinely collected data from UK youth mental health services was conducted (N = 8,172, age M = 13.8, 67% female, 32% male) to explore the impact of including goal‐based outcome data in combined calculations of standardized measures based on the principles of reliable change (“measurable change”). Due to the broad nature of standardized measures, inferred validity becomes diluted in any team or service level aggregate analysis. To make inferences that are closer to the person's interpretation of their difficulties, we argue that Idiographic Patient Reported Outcome Measures (I‐PROMs) counterbalance these limitations. This is supported by our findings. The measurable change metric is the first step towards enabling national analysis of aggregated I‐PROMs. I‐PROMs, supplemented by standardized measures should be used to consider service evaluation.
Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression
Authors: McCormack Nikki M. , Villalón Eric , Viollet Coralie , Soltis Anthony R. , Dalgard Clifton L. , Lorson Christian L. , Burnett Barrington G.
Published: June 2021

Background

Spinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. While timing of treatment is important, it remains unclear why SMN restoration is insufficient to fully restore muscle size and function. We and others have shown that SMN‐deficient muscle precursor cells fail to efficiently fuse into myotubes. However, the role of SMN in myoblast fusion is not known.

Methods

In this study, we show that SMN‐deficient myoblasts readily fuse with wild‐type myoblasts, demonstrating fusion competency. Conditioned media from wild type differentiating myoblasts do not rescue the fusion deficit of SMN‐deficient cells, suggesting that compromised fusion may primarily be a result of altered membrane dynamics at the cell surface. Transcriptome profiling of skeletal muscle from SMN‐deficient mice revealed altered expression of cell surface fusion molecules. Finally, using cell and mouse models, we investigate if myoblast fusion can be rescued in SMN‐deficient myoblast and improve the muscle pathology in SMA mice.

Results

We found reduced expression of the muscle fusion proteins myomaker (P = 0.0060) and myomixer (P = 0.0051) in the muscle of SMA mice. Suppressing SMN expression in C2C12 myoblast cells reduces expression of myomaker (35% reduction; P < 0.0001) and myomixer, also known as myomerger and minion, (30% reduction; P < 0.0001) and restoring SMN levels only partially restores myomaker and myomixer expression. Ectopic expression of myomixer improves myofibre number (55% increase; P = 0.0006) and motor function (35% decrease in righting time; P = 0.0089) in SMA model mice and enhances motor function (82% decrease in righting time; P < 0.0001) and extends survival (28% increase; P < 0.01) when administered in combination with an antisense oligonucleotide that increases SMN protein levels.

Conclusions

Here, we identified reduced expression of muscle fusion proteins as a key factor in the fusion deficits of SMN‐deficient myoblasts. This discovery provides a novel target to improve SMA muscle pathology and motor function, which in combination with SMN increasing therapy could enhance clinical outcomes for SMA patients.
Impact of the apelin/APJ axis in the pathogenesis of Parkinson’s disease with therapeutic potential
Authors: Angelopoulou Efthalia , Paudel Yam Nath , Bougea Anastasia , Piperi Christina
Published: June 2021

The pathogenesis of Parkinson's disease (PD) remains elusive. There is still no available disease‐modifying strategy against PD, whose management is mainly symptomatic. A growing amount of preclinical evidence shows that a complex interplay between autophagy dysregulation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, and excessive neuroinflammation underlies PD pathogenesis. Identifying key molecules linking these pathological cellular processes may substantially aid in our deeper understanding of PD pathophysiology and the development of novel effective therapeutic approaches. Emerging preclinical evidence indicates that apelin, an endogenous neuropeptide acting as a ligand of the orphan G protein‐coupled receptor APJ, may play a key neuroprotective role in PD pathogenesis, via inhibition of apoptosis and dopaminergic neuronal loss, autophagy enhancement, antioxidant effects, endoplasmic reticulum stress suppression, as well as prevention of synaptic dysregulation in the striatum, excessive neuroinflammation, and glutamate‐induced excitotoxicity. Underlying signaling pathways involve phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin, extracellular signal‐regulated kinase 1/2, and inositol requiring kinase 1α/XBP1/C/EBP homologous protein. Herein, we discuss the role of apelin/APJ axis and associated molecular mechanisms on the pathogenesis of PD in vitro and in vivo and provide evidence for its challenging therapeutic potential.
Should nutrition therapy be modified to account for mitochondrial dysfunction in critical illness?
Authors: Flower Luke , Page Alexandria , Puthucheary Zudin
Published: June 2021

Metabolic dysfunction, and its associated muscle atrophy, remains the most common complication of critical care. At the center of this is mitochondrial dysfunction, secondary to hypoxia and systemic inflammation. This leads to a bioenergetic crisis, with decreased intramuscular adenosine triphosphate content and a reduction in the highly energy‐dependent process of protein synthesis. Numerous methods have been studied to try and reduce these effects, with only limited success. Trials investigating the use of increased energy and protein administration have instead found a decrease in relative lean body mass and a potential increase in morbidity and mortality. Ketone bodies have been proposed as alternative substrates for metabolism in critical illness, with promising results seen in animal models. They are currently being investigated in critical care patients in the Alternative Substrates in the Critically Ill Subjects trial (ASICS). The evidence to date suggests that individualized feeding regimens may be key in the nutrition approach to critical illness. Consideration of individual patient factors will need to be combined with personalized protein content, total energy load received, and the timing of such feeds. This review covers mitochondrial dysfunction in critical illness, how it contributes to muscle wasting and the resultant morbidity and mortality, and the scientific basis of why current nutrition approaches to date have not been successful in negating this effect. These two factors underpin the need for consideration of alternative nutrition strategies in the critically ill patient.
Low‐Molecular‐Weight Polymer with CO2‐Switchable Surface Activity
Authors: Zhu Zhuoyan , Huang Xiaoling , Hou Qingfeng , Sun Zhitao , Su Xin , Quan Hongping
Published: June 2021

The introduction of external CO2 could reversibly convert tertiary amines into quaternary ammonium salts, enabling demulsification/emulsification switching of emulsions or latexes. However, CO2‐switchable oligomeric or low‐molecular‐weight polymeric surfactants are rarely researched. In this study, 2‐(dimethylamino)ethyl methacrylate and stearyl methacrylate are chosen to synthesize a switchable oligomeric surfactant (OS). The conductivity of OS aqueous solution (0.2 wt%) increased from 14.0 to 329 μS cm−1 by adding and removing CO2, which proved a good performance of OS in response to the CO2 stimulus. The most important finding was that the crude oil emulsion containing OS was reversibly degraded and re‐formed by the alternate CO2 and N2 treatment. In contrast to that, the investigated PS latex system underwent apparent stratification after the N2 bubbling, but it regained a homogeneous phase upon the N2 bubbling. The particle size of PS latex varied between 245 nm and 130 μm, and zeta potential changed from −43.2 to −5.8 mV, which demonstrated that the PS latex stability might break and recover by addition and removal of CO2. This work is expected to open a new window for the CO2‐stimulated reversible emulsification of emulsions or polymer latexes.
Sleep Quality Improvements After MDMA‐Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder
Authors: Ponte Linnae , Jerome Lisa , Hamilton Scott , Mithoefer Michael C. , Yazar‐Klosinski Berra B. , Vermetten Eric , Feduccia Allison A.
Published: June 2021

Sleep disturbances (SDs) are among the most distressing and commonly reported symptoms in posttraumatic stress disorder (PTSD). Despite increased attention on sleep in clinical PTSD research, SDs remain difficult to treat. In Phase 2 trials, 3,4‐methylenedioxymethamphetamine (MDMA)–assisted psychotherapy has been shown to greatly improve PTSD symptoms. We hypothesized that MDMA‐assisted psychotherapy would improve self‐reported sleep quality (SQ) in individuals with PTSD and be associated with declining PTSD symptoms. Participants in four studies (n = 63) were randomized to receive 2–3 sessions of active MDMA (75–125 mg; n = 47) or placebo/control MDMA (0–40 mg, n = 16) during all‐day psychotherapy sessions. The PSQI was used to assess change in SQ from baseline to the primary endpoint, 1–2 months after the blinded sessions. Additionally, PSQI scores were measured at treatment exit (TE) and 12‐month follow‐up. Symptoms of PTSD were measured using the CAPS‐IV. At the primary endpoint, CAPS‐IV total severity scores dropped more after active MDMA than after placebo/control (−34.0 vs. −12.4), p = .003. Participants in the active dose group showed more improvement in SQ compared to those in the control group (PSQI total score ΔM = −3.5 vs. 0.6), p = .003. Compared to baseline, SQ had improved at TE, p < .001, with further significant gains reported at 12‐month follow‐up (TE to 12‐months ΔM = −1.0), p = .030. Data from these randomized controlled double‐blind studies provide evidence for the beneficial effects of MDMA‐assisted psychotherapy in treating SDs in individuals with PTSD.
Snapshot Space–Time Holographic 3D Particle Tracking Velocimetry
Authors: Chen Ni , Wang Congli , Heidrich Wolfgang
Published: June 2021

Digital inline holography is an amazingly simple and effective approach for 3D imaging, to which particle tracking velocimetry is of particular interest. Conventional digital holographic particle tracking velocimetry techniques are computationally separated in particle and flow reconstruction, plus the expensive computations. Usually, the particle volumes are recovered first, from which fluid flows are computed. Without iterative reconstructions, This sequential space–time process lacks accuracy. This paper presents a joint optimization framework for digital holographic particle tracking velocimetry: particle volumes and fluid flows are reconstructed jointly in a higher space–time dimension, enabling faster convergence and better reconstruction quality of both fluid flow and particle volumes within a few minutes on modern GPUs. Synthetic and experimental results are presented to show the efficiency of the proposed technique.
Thermal Healing of Copolyacrylate Elastomer Based on Catalyst‐Free Transketalization
Authors: Zhao Dan , Peng Jiayu , Jian Guodong , Liu Chang , Chen Hongxiang , Zhou Yu , Zhou Yang
Published: June 2021

Copolyacrylate can heal via dynamic covalent bonds when it is exposed to external stimuli, such as pH value, ionic strength, humidity, and light, but the incorporation of dynamic covalent bonds will result in a decrease in the thermal stability of materials. It is still a great challenge to design a healable copolyacrylate with high thermal stability. The transketalization is confirmed by the reaction of model compounds including acetophenone glycerol ketal (AGK) and ethylene glycol (EG) in the absence of catalyst. The copolyacrylate elastomers are prepared by copolymerization of methyl methacrylate (MMA), butyl acrylate (BA), 2,3‐dihydroxypropyl methacrylate (DHPMA), and ketal‐containing diacrylate as a cross‐linking agent. The results show that the ketal‐containing copolyacrylate (KCPA) can achieve a 96% of healing efficiency at 120 °C, meanwhile, it has high thermal stability. The healing of copolyacrylate elastomers originates from the transketalization between ketal and o‐dihydroxyl groups, which is confirmed by comparison with those of the ketal‐free control samples. The study will expand the scope of self‐healing polymers based on dynamic covalent bonds.
Toward an Efficient Process for the Cu(0)‐Mediated Synthesis and Chain Extension of Poly(methyl acrylate) Macroinitiator Using PMDETA as Ligand
Authors: Cooze Morgan J. , Barr Nathaniel R. , Hutchinson Robin A.
Published: June 2021

Me6TREN (tris[2‐(dimethylamino)ethyl]amine) is commonly used in Cu(0)‐mediated polymerization of acrylates due to its ability to promote high reaction rates while maintaining excellent control of chain growth. However, its cost presents a significant barrier to commercialization. Thus, the use of PMDETA (N,N,Nʹ,Nʹʹ,Nʹʹ‐pentamethyldiethylenetriamine), a ligand that is significantly less expensive than Me6TREN but is known to reduce the polymerization rate as well as control, is explored. The continuous production of low molecular weight (MW) poly(methyl acrylate) using PMDETA ligand in a copper tubular reactor is demonstrated, with conversions >70% achieved with a residence time of 32 min at 70 °C. The resulting macroinitiator solution can be stored and chain extended with methyl acrylate (MA) to high conversion in a semibatch reactor using either PMDETA or Me6TREN as additional ligand, increasing the versatility of a newly developed process to efficiently produce block copolymers using either ligand, or a combination of the two. First results suggest that the two‐step process can also be used to chain extend the macroinitiator with methacrylates, thus extending the range of materials that can be produced.
A Skin‐Inspired Triboelectric Nanogenerator with an Interpenetrating Structure for Motion Sensing and Energy Harvesting
Authors: You Aimei , Zhang Xieli , Peng Xiao , Dong Kai , Lu Yuyuan , Zhang Qiang
Published: June 2021

Rapid advancements in wearable electronics impose the challenge on power supply devices. Herein, a flexible single‐electrode triboelectric nanogenerator (SE‐TENG) that enables both human motion sensing and biomechanical energy harvesting is reported. The SE‐TENG is fabricated by interpenetrating Ag‐coated polyethylene terephthalate (PET) nanofibers within a polydimethylsiloxane (PDMS) elastomer. The Ag coating and PDMS are performed as the electrode and dielectric material for the SE‐TENG, respectively. The Ag‐coated PET nanofibers enlarge the electrode surface area, which is beneficial to increase sensing sensitivity. The flexible SE‐TENG sensor shows the capability of outputting alternating electrical signals with an open‐circuit voltage up to 50 V and a short‐circuit current up to 200 nA in response to externally applied pressure. It is used to sense various types of human motions and harvest electric energy from body motion. The harvested energy can successfully power wearable electronics, such as an electronic watch and light‐emitting diode. Therefore, the as‐prepared SE‐TENG sensor with a pressure response and self‐powered capability provides potential applications in wearable sensors or flexible electronics for personal healthcare and human–machine interfaces.
3D Printing of Flexible Composites via Magnetophoresis: Toward Medical Application Based on Low‐Frequency Induction Heating Effect
Authors: Xiang Ziyin , Nguyen Van‐Cuong , Ducharne Benjamin , Della Schiava Nellie , Capsal Jean‐Fabien , Cottinet Pierre‐Jean , Le Minh‐Quyen
Published: June 2021

In this work, a commercial extrusion 3D printer is used to process magnetic pastes into desired 3D structures. The magnetic pastes prepared in the authors' laboratory are mixtures of Fe3O4 (iron oxide), microparticles, and PDMS (polydimethylsiloxane) polymer. After multiple composition tests, they produced pastes compatible with the 3D printer that can be additively manufactured into flexible ferromagnetic samples. The design optimization, together with the characterizations of composites, are investigated. Magnetic particles do not simply mix with the polymer but formed a chain‐like structure under the influence of a magnetic field during the printing process. The chain‐like structure induces magnetic and thermal anisotropies. The relative permeability and the low‐frequency induction heating (LFIH) effect are improved. The authors' development is highly relevant in healthcare applications, especially endovascular ablation for varicose treatment.
CD40LG mutations in Vietnamese patients with X‐linked hyper‐IgM syndrome; catastrophic anti‐phospholipid syndrome as a new complication
Authors: Phan Anh Nguyen Lien , Pham Thuy Thi Thanh , Phan Xinh Thi , Huynh Nghia , Nguyen Tuan Minh , Cao Cuc Tran Thu , Nguyen Duong Thuy , Luong Khanh Thi Xuan , Nguyen Tam Thi Minh , Tran Anh Ngoc Kim , Pham Linh Thi Truc , Nguyen Vy Vuong Thao , Swagemakers Sigrid , Bui Chi‐Bao , Van Hagen Petrus Martinus
Published: June 2021

Background

X‐linked hyper‐IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects.

Methods

We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole‐exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features.

Results

Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti‐phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non‐frameshift deletion c.436_438delTAC, stop‐gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis.

Conclusion

This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.
Probabilistic shaping communication system aided by neural network distribution matcher in data center optical network
Authors: Jing Zexuan , Tian Qinghua , Xin Xiangjun , Wang Yongjun , Guo Dong , Sheng Xia , Yu Chao
Published: June 2021

A neural network (NN)‐assisted probabilistic shaping (PS) distribution matcher is proposed, in which the model is simplified by a structured optimization method. The NN algorithm can encode the information sequence, making the signal obey the Gaussian distribution, and can directly restore the received signal. In addition, the algorithm uses the novel training method at both ends of the transmitter and receiver so that the system performance is significantly improved. PS system verification experiments have been carried out under 16QAM‐DMT modulation format. Under the hard decision forward error correction (FEC) threshold of 3.8*10−3 BER, the proposed system achieves 1.1 dB improvement compared to the traditional 16QAM‐DMT system.
Temporal clustering, tissue composition, and total variation for mapping oxygen extraction fraction using QSM and quantitative BOLD
Authors: Cho Junghun , Spincemaille Pascal , Nguyen Thanh D. , Gupta Ajay , Wang Yi
Published: June 2021

Purpose

To improve the accuracy of quantitative susceptibility mapping plus quantitative blood oxygen level‐dependent magnitude (QSM+qBOLD or QQ) based mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) using temporal clustering, tissue composition, and total variation (CCTV).

Methods

Three‐dimensional multi‐echo gradient echo and arterial spin labeling images were acquired from 11 healthy subjects and 33 ischemic stroke patients. Diffusion‐weighted imaging (DWI) was also obtained from patients. The CCTV mapping was developed for incorporating tissue‐type information into clustering of the previous cluster analysis of time evolution (CAT) and applying total variation (TV). The QQ‐based OEF and CMRO2 were reconstructed with CAT, CAT+TV (CATV), and the proposed CCTV, and results were compared using region‐of‐interest analysis, Kruskal‐Wallis test, and post hoc Wilcoxson rank sum test.

Results

In simulation, CCTV provided more accurate and precise OEF than CAT or CATV. In healthy subjects, QQ‐based OEF was less noisy and more uniform with CCTV than CAT. In subacute stroke patients, OEF with CCTV had a greater contrast‐to‐noise ratio between DWI‐defined lesions and the unaffected contralateral side than with CAT or CATV: 1.9 ± 1.3 versus 1.1 ± 0.7 (P = .01) versus 0.7 ± 0.5 (P < .001).

Conclusion

The CCTV mapping significantly improves the robustness of QQ‐based OEF against noise.
Humanitarian INGO governance arrangements and forms of coordination
Authors: Beagles Jonathan E.
Published: June 2021

As international humanitarian nongovernmental organizations (INGOs) continue to adapt their global governance arrangements in response to changes in the external environment, these changes are creating new challenges for internal coordination. However, we know little about the relationship between these governance arrangements and the forms of internal coordination INGOs adopt. This paper provides a comparative analysis of 40 INGO families with diverse backgrounds and approaches to humanitarian and development work. It examines the relationship between their global governance arrangements in terms of decision‐making, integration, and membership; and the forms of internal coordination they adopt. The finding is that different forms of coordination are associated withmembership sizeandresource disparity, combined with the varyingneeds for group‐level capacitythat comes with different forms of decision‐making and integration.
Staging childhood cancers in Europe: Application of the Toronto stage principles for neuroblastoma and Wilms tumour. The JARC pilot study
Authors: Gatta Gemma , Botta Laura , Capocaccia Riccardo , Cañete Adela , Pritchard‐Jones Kathy ,   JARC Pilot Study Toronto Guidelines Working Group
Published: June 2021

Background

The ‘Toronto consensus principles and guidelines’ (TG) provided paediatric‐specific staging system affordable by population‐based cancer registries (CRs). Within the European Rare Cancers Joint Action, a pilot study of the application of TG for childhood cancer (CC) was conducted to test the ability of CRs to reconstruct stage, describe stage across countries and assess survival by stage.

Procedure

Twenty‐five CRs representing 15 countries contributed data on a representative sample of patients with neuroblastoma (NB) and Wilms tumour (WT) <15 years, diagnosed between 2000 and 2016. Outcome was calculated by Kaplan–Meier method and by Cox regression model.

Results

Stage was reconstructed for 95% of cases. Around half of the children had localised or locoregional disease at diagnosis. The proportion of metastatic cases was 38% for NB and 13% for WT. Three‐year survival was >90% for locoregional cases both of NB and WT, 58% for NB M‐stage and 77% for WT stage‐IV. Older age was associated with more advanced stage.

Conclusions

European CRs were able to reconstruct stage according to the TG. Stage should be included in the routine collection of variables. Stage information had clear prognostic value and should be used to investigate survival variations between countries or over time.
Impact of universal health coverage on childhood cancer outcomes in Indonesia
Authors: Indraswari Braghmandita Widya , Kelling Emil , Vassileva Sofi M. , Sitaresmi Mei Neni , Danardono Danardono , Mulatsih Sri , Supriyadi Eddy , Widjajanto Pudjo Hagung , Sutaryo Sutaryo , Kaspers Gertjan L. , Mostert Saskia
Published: June 2021

Background

Starting from 2014, the Indonesian government has implemented Universal Health Coverage (UHC) with the aim to make healthcare services accessible and affordable to all Indonesian citizens. A major reason for childhood cancer treatment failure in low‐ and middle‐income countries, particularly among families with low socioeconomic status (SES), is abandonment of expensive cancer treatment. Our study compared childhood cancer treatment outcomes of the overall, low, and high SES population before and after introduction of UHC at a large Indonesian academic hospital.

Methods

Medical records of 1040 patients diagnosed with childhood cancer before (2011‐2013, n = 506) and after (2014‐2016, n = 534) introduction of UHC were abstracted retrospectively. Data on treatment outcome, SES, and health‐insurance status at diagnosis were obtained.

Findings

After introduction of UHC, the number of insured patients increased from 38% to 82% (P < 0.001). Among low SES population, insurance coverage increased from 40% to 85% (P < 0.001), and among high SES population from 33% to 77% (P < 0.001). In the overall population, treatment abandonment decreased from 36% to 22% (P < 0.001). Event‐free survival estimates at four years after diagnosis of overall population improved from 16% to 22% (P < 0.001). Hazard ratio for treatment failure was 1.26 (CI: 1.07‐1.48, P = 0.006) for uninsured versus insured patients. In the low SES population, treatment abandonment decreased from 36% to 19% (P < 0.001). Event‐free survival estimates at four years after diagnosis of low SES population improved from 14% to 22% (P < 0.001).

Interpretation

Introduction of UHC in Indonesia contributed significantly to better treatment outcome and event‐free survival of children with cancer from low SES families.
Recent advances in protein modifications techniques for the targeting N‐terminal cysteine
Authors: Asiimwe Nicholas , Al Mazid Mohammad Faysal , Murale Dhiraj P. , Kim Yun Kyung , Lee Jun‐Seok
Published: June 2021

N‐terminal modifications of proteins have garnered the attention of chemical biologists because of their critical roles in numerous cellular processes, including protein translocation, protein structural and metabolic stability, and the regulation of the half‐life of proteins by a process known as “N‐end rule pathway.” In addition, other posttranslational modification processes also depend on the N‐terminal signal sequences. Chemical probes are powerful tools that can be used to investigate N‐terminal modifications, to gain structural and functional insights into protein modification, protein‐protein interactions, protein localization, and protein dynamics. Most modifications target cysteine and lysine residues because of their high nucleophilicity. However, due to multiple occurrences of these residues in a protein at a given time, regioselective labeling can be quite difficult to accomplish. N‐terminal cysteine presents itself as a unique practical option to overcome regioselectivity and site‐specificity challenges. This review provides an overview of N‐terminal cysteine labeling tools, including N‐terminal cysteine condensation with aldehydes, cyanobenzothiazoles, cyclopropenones, and trans‐thioesterification. The review also highlights the technical challenges of each of the techniques, which need to be addressed to broaden the scope of these approaches.
Colloidal Analysis of Particles Extracted from Microalloyed Steels
Authors: Hegetschweiler Andreas , Jochem Aljosha‐Rakim , Zimmermann Anna , Walter Johannes , Staudt Thorsten , Kraus Tobias
Published: June 2021

Different colloidal particle characterization methods are examined for their suitability to determine the particle size distribution of particles extracted from steels. Microalloyed steels are dissolved to extract niobium and titanium carbonitride particles that are important for the mechanical properties of these steels. Such particles have sizes ranging from several nanometers to hundreds of nanometers depending on the precipitation stage during the thermomechanically controlled rolling process. The size distribution of the particles is analyzed by dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and hollow fiber flow field‐flow fractionation (HF5) and compared to data obtained for reference particles as well as data from electron microscopy, the standard sizing technique used in metallurgy today. AUC and HF5 provide high‐quality size distributions, average over large particle numbers that enables statistical analysis, and yield useful insights for alloy design; however, DLS fails due to a lack of resolution. Important aspects in the conversion and comparison of size distributions obtained for broadly distributed particle systems with different measurement principles and the role of surfactants used in sample preparation are discussed.
PEG Modificated Bubble‐Like Carbon Spherical‐W18O49 Using for In Vitro Chemotherapy‐Photothermal Synergistic Reverse Cancer Cells
Authors: Yang Pengfei , Zhao Zhihuan , Yang Shasha , Lin Jianying , Fan Jimin , Zhang Bing
Published: June 2021

In this study, a chemotherapy‐photothermal synergistic anti‐tumor system is constructed. Both W18O49@R‐C and PEG‐W18O49@R‐C synthesized by hydrothermal method show the potential of photothermal therapy (PTT). The structure of reflux‐carbon is bubble‐like spherical and W18O49@R‐C obtained by hydrothermal synthesis will cause bubble collapse due to the formation of crystal W18O49; thus, the particle size decreases sharply. Furthermore, the photothermal stability of PEG‐W18O49@R‐C is higher than that of W18O49@R‐C, and ζ‐potential measurement indicates that PEG‐W18O49@R‐C has excellent dispersion characteristics. The test of drug loading and drug release performance show that PEG‐modified W18O49@R‐C has superior performance on drug loading amount and release capacity. In the synergistic anti‐tumor process, the cancer cell viability after co‐incubating with PEG‐W18O49@R‐C+DOX.HCl (with 808nm) is only 16.6%. These results indicate that PEG‐W18O49@R‐C has potential in the treatment of cancer by a combination of PTT and chemotherapy.
Resveratrol and endoplasmic reticulum stress: A review of the potential protective mechanisms of the polyphenol
Authors: Ahmadi Ali , Hayes A. Wallace , Karimi Gholamreza
Published: June 2021

The endoplasmic reticulum (ER) is an organelle that performs a set of essential functions in cellular biology. These include synthesis of lipids, homeostasis of calcium, and controlling the folding of proteins. Inflammation and oxidative stress are two important reasons behind the accumulation of misfolded or unfolded proteins in the ER. In such circumstances, a series of measures are undertaken in the cell which are collectively called unfolded protein response (UPR). The aim of UPR is to reduce the burden of protein aggregates and promote survival. However, extended and unrestricted ER stress (ERS) can induce further inflammation and apoptosis. ERS and the UPR are involved in different diseases such as neurodegenerative and cardiovascular diseases. Resveratrol (RSV), a natural polyphenol, has well‐documented evidence supporting its numerous biological properties including antioxidant, antiinflammatory, antiobesity, antidiabetic, and antiischemic activities. The compound is also known for its potential beneficial effects on cognitive function and liver, kidney, and lung health. In this review, the role of ERS in several pathological conditions and the potential protective effects of RSV are discussed. However, the scarcity of clinical data means that more research needs to be conducted to gain a lucid understanding of RSV's effects on endoplasmic reticulum stress (ERS) in humans.
Distinguishing between isomeric neoxanthin and violaxanthin esters in yellow flower petals using liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry and tandem mass spectrometry
Authors: Watanabe Takehiro , Yamagaki Tohru , Azuma Toshiaki , Horikawa Manabu
Published: June 2021

Rationale

Liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry (LC/PDA‐APCI‐MS) is used for the analysis of various carotenoid pigments in plants. Among them, it is difficult to distinguish between the isomeric violaxanthin/neoxanthin esters.

Methods

The yellow pigments of tomato petals were extracted with acetone, and the extracts were kept at −30°C to allow the contaminating triacylglycerols to settle out physically. The supernatants were analyzed using LC/PDA‐APCI‐MS with a high‐resolution orbitrap mass spectrometer for their exact masses. The expected carotenoid esters were calculated with the combination of carotenoids and fatty acids, and they were matched with the experimental exact masses. The fatty acid structures in the carotenoid esters were also identified using collision‐induced dissociation (CID) tandem mass spectrometry (MS/MS). The isomeric violaxanthin/neoxanthin esters were distinguished using CID MS/MS from their in‐source dehydrated product ions as pseudoprecursor ions.

Results

The in‐source dehydrated ions [M − H2O + H]+ of neoxanthin diesters predominated over their protonated molecules [M + H]+ in LC/MS. By contrast, the protonated molecules of violaxanthin diesters predominated. The 92 u loss product ions [M − H2O − C7H8 + H]+ were observed from the dehydrated violaxanthin diesters, but they were not generated from the dehydrated neoxanthin diesters in the CID MS/MS of their dehydrated pseudoprecursor ion [M − H2O + H]+.

Conclusions

The allene allyl carbocation in neoxanthin diesters was generated from dehydration after preferential protonation at the hydroxy group. The epoxide group of violaxanthin diesters opens easily after protonation; however, the dehydration did not proceed at this stage. The 92 u loss of C7H8 was explained by an intramolecular [2 + 2] cycloaddition, which proceeded preferentially in dehydrated violaxanthin diesters because the carbocations in the dehydrated species were conjugated to the polyene and those double bonds were depolarized during CID MS/MS. Therefore, the isomeric neoxanthin/violaxanthin diesters were distinguished using LC/PDA‐APCI‐MS and MS/MS. This method was a practical and useful method of profiling the carotenoid esters of the yellow petals.
Integrated multiple mediation analysis: A robustness‐specificity trade‐off in causal structure
Authors: Tai An‐Shun , Lin Sheng‐Hsuan
Published: June 2021

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two‐way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path‐specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when crossworld exchangeability is invalid. Consequently, this study yields a robustness‐specificity trade‐off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer dataset from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality.
Preparation and Electrochemical Behavior of Quinoxaline‐Bridged Diphenylamines
Authors: Hayashi Hideki , Tsuda Erika , Koizumi Take‐aki
Published: June 2021

N‐Phenylindroquinoxalines (PhIQs), which have a bridged diphenylamine structure, were synthesized and their physical and chemical properties were investigated. Syntheses of the materials were carried out by dehydration condensation between 4,5‐disubstituted‐1,2‐phenylenediamine derivatives and N‐phenylisatin. PhIQs showed fluorescent solvatochromism. PhIQs contain a diphenylamine moiety, but exhibit n‐type properties due to the introduction of an electronegative quinoxaline unit. Introduction of substituents at the 2‐ and 3‐positions of PhIQ can regulate the reduction‐oxidation potentials of the compound. The first reduction potential and fluorescent λmax vs. Hammett's σp value has a good linear correlation.