bluuebunny/crossref_metadata_2025 huggingface dataset:
High-efficiency and high-precision identification of transmitting orbital angular momentum modes in atmospheric turbulence based on an improved convolutional neural network
Authors: Zhou Hongping , Pan Zhenzhen , Dedo Maxime Irene , Guo Zhongyi
Published: May 2021

In this paper, we have proposed an improved convolutional neural network model based on the ShuffleNet V2 network for recognizing the orbital angular momentum (OAM) modes for the OAM based free space optical communication systems in the environments of atmospheric turbulence (AT). The network is trained by inputting the intensity images of the Laguerre Gaussian beams, which can effectively finish the training process due to its special designs, and can recognize the OAM modes with high accuracy. Compared with previous works for the single and multiplexing OAM modes, the proposed network model has high-precision and high-efficiency characteristics. Especially for the multiplexing OAM modes, our proposed system can achieve the recognition accuracy of 99.5% under strong AT and long-distance transmission. In addition, in order to prove that our system has good generalization ability and strong robustness, we used the trained model to test several groups of data obtained under untrained AT intensities, and the results showed that our model could still maintain high accuracy under the untrained AT intensities, which is very important to the realization of high-capacity optical communication technologies based on OAM in the future
Line identification of extreme ultraviolet (EUV) spectra from low-Z impurity ions in EAST tokamak plasmas
Authors: LI Lei , ZHANG Ling , XU Zong , MORITA Shigeru , CHENG Yunxin , ZHANG Fengling , ZHANG Wenmin , DUAN Yanmin , ZANG Qing , WANG Shouxin , DAI Shuyu , ZUO Guizhong , SUN Zhen , WANG Liang , DING Xiaobin , QIAN Jinping , LIU Haiqing , HU Liqun
Published: May 2021

Extreme ultraviolet (EUV) spectra emitted from low-Z impurity ions in the wavelength range of 10–500 Å were observed in Experimental Advanced Superconducting Tokamak (EAST) discharges. Several spectral lines from K- and L-shell partially ionized ions were successfully observed with sufficient spectral intensities and resolutions for helium, lithium, boron, carbon, oxygen, neon, silicon and argon using two fast-time-response EUV spectrometers of which the spectral intensities are absolutely calibrated based on the intensity comparison method between visible and EUV bremsstrahlung continua. The wavelength is carefully calibrated using well-known spectra. The lithium, boron and silicon are individually introduced for the wall coating of the EAST vacuum vessel to suppress mainly the hydrogen and oxygen influxes from the vacuum wall, while the carbon and oxygen intrinsically exist in the plasma. The helium is frequently used as the working gas as well as the deuterium. The neon and argon are also often used for the radiation cooling of edge plasma to reduce the heat flux onto the divertor plate. The measured spectra were analyzed mainly based on the database of National Institute of Standards and Technology. As a result, spectral lines of He II, Li II–III, B IV–V, C III–VI, O III–VIII, Ne II–X, Si V–XII, and Ar X–XVI are identified in EAST plasmas of which the central electron temperature and chord-averaged electron density range in T
e0 = 0.6–2.8 keV and n
e = (0.5–6.0) × 1019 m−3, respectively. The wavelengths and transitions of EUV lines identified here are summarized and listed in a table for each impurity species as the database for EUV spectroscopy using fusion plasmas.
Measurement and analysis on failure lifetime of serpentine interconnects for e-textiles under cyclic large deformation
Authors: Koshi Tomoya , Nomura Ken-ichi , Yoshida Manabu
Published: May 2021

Serpentine interconnects are promising for electronic textiles (e-textiles), because they can maintain low electrical resistance even under cyclic large deformation. However, previous studies have not deeply discussed their failure lifetime, and the relationship between the elongation (engineering strain applied to entire structure) and cycle number to failure remains unclear. This clarification will contribute to the lifetime prediction. Therefore, this study investigates the relationship using interconnects having the same conductive material and geometric parameters but with different laminated structures: copper adhered to a polyurethane laminated knit textile (type A); copper adhered directly to a knit textile (type B); and polyethylene-naphthalate-laminated copper adhered to a knit textile only at both ends of the interconnect (type C). An elongation of 7%–70% was applied to the prepared samples with a tensile testing machine. The measurement and analytical calculation show that the type-C interconnects have the highest lifetime, and the relationship between the elongation ϵ
appl and cycle number to failure N
f is given by ϵ
appl = A′N
f
−c/2, where A′ is the coefficient determined by the material properties, geometric parameters, and laminated structures, and c is the fatigue ductility exponent of copper. Moreover, this paper demonstrates the washing durability of an e-textile device using type-C interconnects. A cloth-face-mask-type device that monitors facial skin temperatures was fabricated and repeatedly washed with a washing machine. The demonstration confirms that the temperature variations were stably monitored before and after the first washing, and the multiple failures occurred in the interconnects after ninth washing.
Fundamental formalism of statistical mechanics and thermodynamics of negative kinetic energy systems
Authors: Wang Huai-Yu
Published: May 2021

The solutions of a particle’s Dirac equation contains a negative kinetic energy (NKE) branch. Such an energy spectrum has an upper limit but no lower limit, so that the system with this spectrum, called NKE system, is of negative temperature. Fundamental formulas of statistical mechanics and thermodynamics of NKE systems are presented. All the formulas have the same forms of those of positive kinetic energy (PKE) systems. Almost all thermodynamic quantities, except entropy and specific heat, have a contrary sign compared to those of PKE systems. Specially, pressure is negative and its microscopic mechanism is given. Entropy is always positive and Boltzmann entropy formula remains valid. The three laws of thermodynamics remain valid, as long as the thermodynamic quantities have a negative sign. Negative temperature Carnot engine can work between two negative temperatures. Since the NKE levels need not be fully filled, it is argued that the concept of Dirac’s Fermion Sea can be totally abandoned.
Synoptic and meteorological drivers of regional ozone pollution events in China
Authors: Wei Wenyu , Fang Yuanyuan , Zhou Yuntao
Published: May 2021

Surface ozone (O3) pollution events are becoming more frequent and have recently emerged as a severe air pollution problem in China. However, the spatial–temporal distribution of surface O3, as well as its primary synoptic and meteorological drivers, remains poorly understood. The purpose of this study was to identify the key synoptic and meteorological drivers of O3 pollution in different regions of China. To achieve this goal, this study established meteorology overlaps of regional O3 pollution events in space and time and applied a comprehensive statistical model selection method for optimal synoptic and meteorological models, based on a newly released O3 dataset for 2015–2018. It was observed that extreme regional O3 pollution events (duration >7 d) occurred more frequently and exhibited a high co-occurrence frequency (>50%) with air stagnation (AS). Moreover, the beginning and end of 69% of the regional O3 pollution events coincided with regional daily maximum temperature changes. The intensity of AS is the dominant driver of O3 pollution event intensity across most of the six selected megacity regions. Although other meteorological drivers, such as the intensity of hot days (HD) and meridional wind of 10 m were also important, their impacts varied according to the region. Overall, increase in extreme AS and HD led to the worsening of regional O3 pollution events. These findings imply that mitigating regional O3 pollution should consider changing synoptic and meteorological conditions.
Valuation of fly ash: new horizons for an ecological mortar based on magnetized water application in building materials
Authors: Mghaiouini Redouane , Graich Abderrazzak , El Jouad Zouhair , Mrani Ibrahim , Ghanim Hassan , Monkade Mohamed , EL Bouari Abdeslam
Published: May 2021

Resources natural are limited and run out over time. The building construction sector uses a large number of nature reserves. In previous years, several researchers have attempted to formulate an environmentally friendly mortar from waste materials such as fly ash. In this study, an ecological mortar was developed by replacing some of the cement with fly ash. Various tests were performed to determine the mechanical properties of normal mortar and fly ash (FA) mortars. In this current research, the study was conducted in three different stages. In Phase I, An eco-friendly mortar was manufactured by replacing part of the cement with fly ash powder and replacing tap water (TW) with magnetised water (MW). In Phase II, the Taguchi method and JMP Trial 15 software were used to optimise the design of the mixture. In Phase III, samples of the optimised mixture were cast for testing to confirm the resistance to bending. In addition, the study was extended to analyse the microstructural properties of mortars characterised by SEM. Itwas concluded a 10% replacement of a part of the cement by fly ash powder and replacement of (TW) by (MW) was found to be optimal and can be used appropriately for green mortar design.
Blowup criterion of classical solutions for a parabolic-elliptic system in space dimension 3
Authors: Li Bin , Li Yuxiang
Published: May 2021

This paper is concerned with a parabolic-elliptic system, which was originally proposed to model the evolution of biological transport networks. Recent results show that the corresponding initial-boundary value problem possesses a global weak solution, which, in particular, is also classical in the one and two dimensional cases. In this work, we establish a Serrin-type blowup criterion for classical solutions in the three dimensional setting.
On Sharifi’s conjecture: Exceptional case
Authors: Shih Sheng-Chi , Wang Jun
Published: May 2021

In the present article, we study the conjecture of Sharifi on the surjectivity of the map

ϖ

θ

\varpi _{\theta }

. Here

θ
\theta

is a primitive even Dirichlet character of conductor

N
p

Np

, which is exceptional in the sense of Ohta. After localizing at the prime ideal

p

\mathfrak {p}

of the Iwasawa algebra related to the trivial zero of the Kubota–Leopoldt

p
p

-adic

L
L

-function

L
p

(
s
,

θ

−
1

ω
2

)

L_p(s,\theta ^{-1}\omega ^2)

, we compute the image of

ϖ

θ
,

p

\varpi _{\theta ,\mathfrak {p}}

in a local Galois cohomology group and prove that it is an isomorphism. Also, we prove that the residual Galois representations associated to the cohomology of modular curves are decomposable after taking the same localization.
Optimal stopping of stochastic transport minimizing submartingale costs
Authors: Ghoussoub Nassif , Kim Young-Heon , Palmer Aaron
Published: May 2021

Given a stochastic state process

(

X
t

)
t

(X_t)_t

and a real-valued submartingale cost process

(

S
t

)
t

(S_t)_t

, we characterize optimal stopping times

τ
\tau

that minimize the expectation of

S
τ

S_\tau

while realizing given initial and target distributions

μ
\mu

and

ν
\nu

, i.e.,

X
0

∼
μ

X_0\sim \mu

and

X
τ

∼
ν

X_\tau \sim \nu

. A dual optimization problem is considered and shown to be attained under suitable conditions. The optimal solution of the dual problem then provides a contact set, which characterizes the location where optimal stopping can occur. The optimal stopping time is uniquely determined as the first hitting time of this contact set provided we assume a natural structural assumption on the pair

(

X
t

,

S
t

)
t

(X_t, S_t)_t

, which generalizes the twist condition on the cost in optimal transport theory. This paper extends the Brownian motion settings studied in Ghoussoub, Kim, and Palmer [Calc. Var. Partial Differential Equations 58 (2019), Paper No. 113, 31] and Ghoussoub, Kim, and Palmer [A solution to the Monge transport problem for Brownian martingales, 2019] and deals with more general costs.
Flow Cytometric Evaluation of Surface and Cytoplasmic TRBC1 Expression in the Differential Diagnosis of Immature T-Cell Proliferations
Authors: Horna Pedro , Otteson Gregory E , Shi Min , Jevremovic Dragan , Yuan Ji , Olteanu Horatiu
Published: May 2021

Objectives

Flow cytometric detection of T-cell clonality is challenging, particularly in differential diagnosis of immature T-cell proliferations. Studies have shown utility of TRBC1, in conjunction with other T-cell markers, as reliable means to identify T-cell clonality by flow cytometry. One limitation of surface TRBC1 (sTRBC1) evaluation is it cannot be detected in surface CD3 (sCD3)-negative T cells, such as normal or abnormal immature T-cell precursors. Here, we assess surface and cytoplasmic TRBC1 expression patterns in the differential diagnosis of T-lymphoblastic leukemia/lymphoma (T-ALL) vs normal thymocyte expansions.

Methods

Forty-three samples containing T-ALL, thymoma, normal thymus, and/or indolent T-lymphoblastic proliferation (i-TLBP), were evaluated.

Results

All 24 cases with normal thymocytes or i-TLBPs revealed a characteristic and reproducible sCD3/sTRBC1 expression pattern indicative of polytypic T-cell maturation. In contrast, all 19 T-ALLs lacked this polytypic maturation pattern and were either completely negative for sCD3/sTRBC1 or showed a minor sCD3-positive subset with a monotypic TRBC1 expression pattern. Cytoplasmic TRBC1 evaluation in 9 T-ALLs demonstrated a monotypic intracellular TRBC1-positive (n = 4) or TRBC1-negative (n = 5) expression, indicative of clonality.

Conclusions

Our findings demonstrate flow cytometric evaluation of surface and cytoplasmic TRBC1 expression can aid detection of T-cell clonality and differential diagnosis of immature T-cell proliferations.
Time-Series Analysis of Fentanyl Concentration in the Unregulated Opioid Drug Supply in a Canadian Setting
Authors: Tobias Samuel , Grant Cameron J , Laing Richard , Arredondo Jaime , Lysyshyn Mark , Buxton Jane , Tupper Kenneth W , Wood Evan , Ti Lianping
Published: May 2021

North America has been contending with an unregulated street drug supply in which opioids are often adulterated with illicitly manufactured fentanyl. The unpredictability of composition may result in an increased risk of overdose due to unexpected elevated concentrations of the high-potency drug. Using data from a community-based drug-checking project, we evaluated trends in fentanyl concentration of illicit opioids in the context of an overdose epidemic. Using a quantification model for fentanyl hydrochloride, historical Fourier-transform infrared spectra from opioid drug-checking samples were analyzed to determine fentanyl concentrations. Median monthly fentanyl concentrations were plotted, and polynomial and autoregressive time-series analyses were performed to examine trends over time. A total of 3,621 fentanyl-positive samples were included in the study, spanning November 2017 to December 2019. Monthly median fentanyl concentrations ranged from 4.5% to 10.4%. Time-series analyses indicated that a third-degree polynomial model fit the data well (R2 = 0.639), suggesting a cyclical pattern in median concentration over time. Notably, absolute variance in fentanyl concentration decreased by an average 0.1% per month (P < 0.001). Future research should explore the relationship between fentanyl concentration and overdose to identify potential targeted harm-reduction interventions that can respond to changes in observed fentanyl concentration.
Stability of 5% vancomycin ophthalmic solution prepared using balanced salt solution after freezing for 90 days
Authors: Roura-Turet Judit , Rodriguez-Reyes Montserrat , Guerrero-Molina Laura , Soy-Muner Dolors , López-Cabezas Carmen
Published: May 2021

Purpose

To evaluate the stability of 5% vancomycin ophthalmic solution prepared using balanced salt solution (BSS) and stored at –20°C in polypropylene containers.

Methods

Six batches of vancomycin 50 mg/mL eyedrops were aseptically prepared. One bottle of each batch was analyzed immediately after preparation, and the rest were stored at –20°C and analyzed using high-performance liquid chromatography (HPLC) at 30, 60, and 90 days to test their physicochemical stability and sterility. Thereafter, bottles were removed from the freezer and stored at 5°C for 30 days, with HPLC and other analyses repeated 105 and 120 days after preparation. All samples were analyzed in triplicate. Stability was defined as the absence of particles, color variation, or changes in pH and a remaining vancomycin concentration of 90% to 110% of the initial concentration. The sterility of the ophthalmic solution was evaluated by using soybean-casein digest broth with resins; samples were incubated for 7 days and checked daily for signs of microbial growth.

Results

There was no particle formation or sign of precipitation in any of the solutions throughout the duration of the study, regardless of the storage conditions. No change in color or turbidity was observed. The pH and osmolarity remained unchanged during storage at –20°C and after thawing. The vancomycin concentration remained within 10% of the initial concentration during the 90-day period of storage at –20°C and the subsequent 30 days after thawing. Sterility was preserved in all samples.

Conclusion

A 5% solution of vancomycin prepared using BSS was physicochemically and microbiologically stable when stored at –20°C for 90 days. After thawing, this extemporaneous formulation remained stable when refrigerated at 5°C for 30 days.
Emotional and Non-Emotional Verbal Fluency in Native and Non-Native Speakers
Authors: Lam Boji P W , Marquardt Thomas P
Published: May 2021

Objective

Native speakers frequently outperform non-native speakers on classic semantic verbal fluency tasks that target concrete non-emotional word retrieval. Much less is known about performance differences in retrieval of emotional words, which are abstract and crucial to social–emotional competence. This study compared native and non-native speakers’ verbal productivity on emotional and non-emotional verbal fluency tasks.

Method

Forty-seven native and 37 non-native speakers of English participated in the study. Participants completed seven semantic verbal fluency tasks in English including classic semantic (e.g., “animals”), action (e.g., “things people do”), and emotional variants (e.g., “things that make people happy”). Subjective and objective measures of English proficiency, information about language usage, and cognitive measures (working memory) were obtained for each participant.

Results

Verbal productivity for classic semantic, action, and emotional verbal fluency was lower for non-native speakers. Smaller language-specific vocabulary in non-native speakers did not moderate positivity biases in emotional verbal fluency. Subjective and objective language proficiency measures were less predictive of performance on the emotional than the non-emotional verbal fluency tasks.

Conclusion

Non-native speakers perform more poorly than native speakers on semantic verbal fluency in English for both emotional and non-emotional variants. Positivity biases are not moderated by language proficiency and are reliable features of emotional verbal fluency. Proficiency measures may be less effective in predicting generation of emotional than neutral words.
A Guide to Doppler Ultrasound Analysis of the Face in Cosmetic Medicine. Part 1: Standard Positions
Authors: Velthuis Peter J , Jansen Oscar , Schelke Leonie W , Moon Hyoungjin J , Kadouch Jonathan , Ascher Benjamin , Cotofana Sebastian
Published: May 2021

Interest in Doppler ultrasound (DUS) analysis of the face has grown in cosmetic medicine, in particular for injectable fillers. When dealing with complications, DUS has the advantage of easily visualizing the filler and identifying the problem in relation to the patient’s anatomy. When working with hyaluronic acid filler, ultrasound-guided injections with hyaluronidase can precisely target the problem. In addition, DUS can be used to study the anatomy of a patient, specifically to prevent intravascular injections. We predict that in a few years’ time DUS will become standard equipment in the offices of cosmetic doctors. We discuss the basics of ultrasound imaging of different tissues with the concomitant terminology. With the use of 7 basic DUS probe positions, key anatomic reference points can be easily found. From these, all relevant anatomic structures in the face can be observed and analyzed. With some practice, physicians will ultimately be able to acquire a complete 3-dimensional mental image of a patient’s face.
A Guide to Doppler Ultrasound Analysis of the Face in Cosmetic Medicine. Part 2: Vascular Mapping
Authors: Velthuis Peter J , Jansen Oscar , Schelke Leonie W , Moon Hyoungjin J , Kadouch Jonathan , Ascher Benjamin , Cotofana Sebastian
Published: May 2021

Duplex mode ultrasound imaging can detect the course of the main vascular structures in the face, which are known to be subject to variation. Once duplex mapping has been performed, measures can be taken to prevent injection into an artery, thereby avoiding skin necrosis or, worse, vision loss. For this reason, in particular, we predict that in the coming years sonography will become standard equipment in the offices of cosmetic doctors. We discuss the basics of vascular imaging by Doppler ultrasound, both in normal and pathologic situations. Starting from the 7 basic positions for the ultrasound probe, all facial arteries relevant in cosmetic medicine can be found.
Hierarchical Meta-Storms enables comprehensive and rapid comparison of microbiome functional profiles on a large scale using hierarchical dissimilarity metrics and parallel computing
Authors: Zhang Yufeng , Jing Gongchao , Chen Yuzhu , Li Jinhua , Su Xiaoquan
Published: May 2021

Functional beta-diversity analysis on numerous microbiomes interprets the linkages between metabolic functions and their meta-data. To evaluate the microbiome beta-diversity, widely used distance metrices only count overlapped gene families but omit their inherent relationships, resulting in erroneous distances due to the sparsity of high-dimensional function profiles. Here we propose Hierarchical Meta-Storms (HMS) to tackle such problem. HMS contains two core components: (i) a dissimilarity algorithm that comprehensively measures functional distances among microbiomes using multi-level metabolic hierarchy and (ii) a fast Principal Co-ordinates Analysis (PCoA) implementation that deduces the beta-diversity pattern optimized by parallel computing. Results showed HMS can detect the variations of microbial functions in upper-level metabolic pathways, however, always missed by other methods. In addition, HMS accomplished the pairwise distance matrix and PCoA for 20 000 microbiomes in 3.9 h on a single computing node, which was 23 times faster and 80% less RAM consumption compared to existing methods, enabling the in-depth data mining among microbiomes on a high resolution. HMS takes microbiome functional profiles as input, produces their pairwise distance matrix and PCoA coordinates.

Availability and implementation

It is coded in C/C++ with parallel computing and released in two alternative forms: a standalone software (https://github.com/qdu-bioinfo/hierarchical-meta-storms) and an equivalent R package (https://github.com/qdu-bioinfo/hrms).

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Ecomorphological divergence and lack of gene flow in two sympatric Balkan slow worms (Squamata: Anguidae)
Authors: Thanou Evanthia , Kypraios-Skrekas Vassilis , Kornilios Panagiotis , Giokas Sinos
Published: May 2021

The slow-worm lizards of the genus Anguis show significant morphological, behavioural and ecological uniformity owing to their limbless, elongated bodies and semifossorial lifestyle. This makes the delimitation of species challenging. Five monophyletic, deeply divergent and mostly parapatric mitochondrial lineages are currently recognized, although hybridization occurs along contact zones. In the southern edge of the range of the genus, two endemic Balkan Anguis (Anguis graeca and Anguis cephallonica) share a broad area of co-distribution and intermediate morphological characteristics. Expecting to retrieve hybrids within the overlap in their distributions, we used genome-wide single nucleotide polymorphisms but did not recover any evidence of interspecific gene flow. Within each species, genomic data revealed shallow population structuring influenced by spatial isolation, with the exception of the southernmost population of A. cephallonica from the Mani Peninsula. Species distribution modelling showed a lack of strong niche overlap and specific environmental preferences; both species showed a precipitation dependence, but A. cephallonica was better acclimatized to high temperatures. Finally, geometric morphometrics of the head shape suggested morphological divergence, mostly seen in the elongation of the head of A. cephallonica. All the evidence supports a long and complete reproductive isolation between the two southern slow worms and raises questions about how ecomorphological divergence might have acted to promote their speciation.
The quantitative impact of COVID-19 on surgical training in the United Kingdom
Authors: Clements J M , Burke J R , Hope C , Nally D M , Doleman B , Giwa L , Griffiths G , Lund J N
Published: May 2021

Background

COVID-19 has had a global impact on all aspects of healthcare including surgical training. This study aimed to quantify the impact of COVID-19 on operative case numbers recorded by surgeons in training, and annual review of competency progression (ARCP) outcomes in the UK.

Methods

Anonymized operative logbook numbers were collated from electronic logbook and ARCP outcome data from the Intercollegiate Surgical Curriculum Programme database for trainees in the 10 surgical specialty training specialties.

Operative logbook numbers and awarded ARCP outcomes were compared between predefined dates. Effect sizes are reported as incident rate ratios (IRR) with 95 per cent confidence intervals.

Results

Some 5599 surgical trainees in 2019, and 5310 in surgical specialty training in 2020 were included. The IRR was reduced across all specialties as a result of the COVID-19 pandemic (0.62; 95 per cent c.i. 0.60 to 0.64). Elective surgery (0.53; 95 per cent c.i. 0.50 to 0.56) was affected more than emergency surgery (0.85; 95 per cent c.i. 0.84 to 0.87). Regional variation indicating reduced operative activity was demonstrated across all specialties. More than 1 in 8 trainees in the final year of training have had their training extended and more than a quarter of trainees entering their final year of training are behind their expected training trajectory.

Conclusion

The COVID-19 pandemic has had a major effect on surgical training in the UK. Urgent, coordinated action is required to minimize the impacts from the reduction in training in 2020.
Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy
Authors: Bosanac Todd , Hughes Robert O , Engber Thomas , Devraj Rajesh , Brearley Andrew , Danker Kerstin , Young Kenneth , Kopatz Jens , Hermann Melanie , Berthemy Antoine , Boyce Susan , Bentley Jonathan , Krauss Raul
Published: May 2021

Axonal degeneration is an early and ongoing event that causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of morbidity and the main cause of dose reductions and discontinuations in cancer treatment. Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by sterile alpha and TIR motif containing 1 (SARM1) is responsible for axonopathy in CIPN. SARM1 is the central driver of an evolutionarily conserved programme of axonal degeneration downstream of chemical, inflammatory, mechanical or metabolic insults to the axon. SARM1 contains an intrinsic NADase enzymatic activity essential for its pro-degenerative functions, making it a compelling therapeutic target to treat neurodegeneration characterized by axonopathies of the peripheral and central nervous systems. Small molecule SARM1 inhibitors have the potential to prevent axonal degeneration in peripheral and central axonopathies and to provide a transformational disease-modifying treatment for these disorders.

Using a biochemical assay for SARM1 NADase we identified a novel series of potent and selective irreversible isothiazole inhibitors of SARM1 enzymatic activity that protected rodent and human axons in vitro. In sciatic nerve axotomy, we observed that these irreversible SARM1 inhibitors decreased a rise in nerve cADPR and plasma neurofilament light chain released from injured sciatic nerves in vivo. In a mouse paclitaxel model of CIPN we determined that Sarm1 knockout mice prevented loss of axonal function, assessed by sensory nerve action potential amplitudes of the tail nerve, in a gene-dosage-dependent manner. In that CIPN model, the irreversible SARM1 inhibitors prevented loss of intraepidermal nerve fibres induced by paclitaxel and provided partial protection of axonal function assessed by sensory nerve action potential amplitude and mechanical allodynia.
Nodal Memberships to Communities of Functional Brain Networks Reveal Functional Flexibility and Individualized Connectome
Authors: Zhu Hong , Jin Wen , Zhou Jie , Tong Shanbao , Xu Xiaoke , Sun Junfeng
Published: May 2021

Human brain network is organized as interconnected communities for supporting cognition and behavior. Despite studies on the nonoverlapping communities of brain network, overlapping community structure and its relationship to brain function remain largely unknown. With this consideration, we employed the Bayesian nonnegative matrix factorization to decompose the functional brain networks constructed from resting-state fMRI data into overlapping communities with interdigitated mapping to functional subnetworks. By examining the heterogeneous nodal membership to communities, we classified nodes into three classes: Most nodes in somatomotor and limbic subnetworks were affiliated with one dominant community and classified as unimodule nodes; most nodes in attention and frontoparietal subnetworks were affiliated with more than two communities and classified as multimodule nodes; and the remaining nodes affiliated with two communities were classified as bimodule nodes. This three-class paradigm was highly reproducible across sessions and subjects. Furthermore, the more likely a node was classified as multimodule node, the more flexible it will be engaged in multiple tasks. Finally, the FC feature vector associated with multimodule nodes could serve as connectome “fingerprinting” to gain high subject discriminability. Together, our findings offer new insights on the flexible spatial overlapping communities that related to task-based functional flexibility and individual connectome “fingerprinting.”
Plasma high-density lipoprotein cholesterol and risk of dementia: observational and genetic studies
Authors: Kjeldsen Emilie W , Thomassen Jesper Q , Juul Rasmussen Ida , Nordestgaard Børge G , Tybjærg-Hansen Anne , Frikke-Schmidt Ruth
Published: May 2021

Aims

The association of plasma high-density lipoprotein (HDL) cholesterol with risk of dementia is unclear. We, therefore, tested the hypothesis that high levels of plasma HDL cholesterol are associated with increased risk of dementia and whether a potential association is of a causal nature.

Methods and results

In two prospective population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study (N = 111 984 individuals), we first tested whether high plasma HDL cholesterol is associated with increased risk of any dementia and its subtypes. These analyses in men and women separately were adjusted multifactorially for other risk factors including apolipoprotein E (APOE) genotype. Second, taking advantage of two-sample Mendelian randomization, we tested whether genetically elevated HDL cholesterol was causally associated with Alzheimer’s disease using publicly available consortia data on 643 836 individuals. Observationally, multifactorially adjusted Cox regression restricted cubic spline models showed that both men and women with extreme high HDL cholesterol concentrations had increased risk of any dementia and of Alzheimer’s disease. Men in the 96th–99th and 100th vs. the 41st–60th percentiles of HDL cholesterol had multifactorially including APOE genotype adjusted hazard ratios of 1.66 (95% confidence interval 1.30–2.11) and 2.00 (1.35–2.98) for any dementia and 1.59 (1.16–2.20) and 1.87 (1.11–3.16) for Alzheimer’s disease. Corresponding estimates for women were 0.94 (0.74–1.18) and 1.45 (1.03–2.05) for any dementia and 0.94 (0.70–1.26) and 1.69 (1.13–2.53) for Alzheimer’s disease. Genetically, the two-sample Mendelian randomization odds ratio for Alzheimer’s disease per 1 SD increase in HDL cholesterol was 0.92 (0.74–1.10) in the IGAP2019 consortium and 0.98 (0.95–1.00) in the ADSP/IGAP/PGC-ALZ/UKB consortium. Similar estimates were observed in sex stratified analyses.

Conclusion

High plasma HDL cholesterol was observationally associated with increased risk of any dementia and Alzheimer’s disease, suggesting that HDL cholesterol can be used as an easily accessible plasma biomarker for individual risk assessment.
A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial
Authors: Lansky Alexandra J , Makkar Rajendra , Nazif Tamim , Messé Steven , Forrest John , Sharma Rahul , Schofer Joachim , Linke Axel , Brown David , Dhoble Abhijeet , Horwitz Phillip , Zang Ming , DeMarco Frederico , Rajagopal Vivek , Dwyer Michael G , Zivadinov Robert , Stella Pieter , Rovin Joshua , Parise Helen , Kodali Susheel , Baumbach Andreas , Moses Jeffrey
Published: May 2021

Aims 

The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods and results 

This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2–5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2–5 days. Cumulative scores were compared between treatment groups using the Finkelstein–Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: −5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls.

Conclusion 

REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.
The germline mutational process in rhesus macaque and its implications for phylogenetic dating
Authors: Bergeron Lucie A , Besenbacher Søren , Bakker Jaco , Zheng Jiao , Li Panyi , Pacheco George , Sinding Mikkel-Holger S , Kamilari Maria , Gilbert M Thomas P , Schierup Mikkel H , Zhang Guojie
Published: May 2021

Background

Understanding the rate and pattern of germline mutations is of fundamental importance for understanding evolutionary processes.

Results

Here we analyzed 19 parent-offspring trios of rhesus macaques (Macaca mulatta) at high sequencing coverage of ∼76× per individual and estimated a mean rate of 0.77 × 10−8  de novo mutations per site per generation (95% CI: 0.69 × 10−8 to 0.85 × 10−8). By phasing 50% of the mutations to parental origins, we found that the mutation rate is positively correlated with the paternal age. The paternal lineage contributed a mean of 81% of the de novo mutations, with a trend of an increasing male contribution for older fathers. Approximately 3.5% of de novo mutations were shared between siblings, with no parental bias, suggesting that they arose from early development (postzygotic) stages. Finally, the divergence times between closely related primates calculated on the basis of the yearly mutation rate of rhesus macaque generally reconcile with divergence estimated with molecular clock methods, except for the Cercopithecoidea/Hominoidea molecular divergence dated at 58 Mya using our new estimate of the yearly mutation rate.

Conclusions

When compared to the traditional molecular clock methods, new estimated rates from pedigree samples can provide insights into the evolution of well-studied groups such as primates.
Robust Bayesian estimator for S-wave spectra, using a combined empirical Green’s function
Authors: Törnman W , Martinsson J , Dineva S
Published: May 2021

We propose a new fully automatic and robust Bayesian method to estimate precise and reliable model parameters describing the observed S-wave spectra. All the spectra associated with each event are modelled jointly, using a t-distribution as likelihood function together with informative prior distributions for increased robustness against outliers and extreme values. The model includes the observed noise and a combined empirical Green’s function. It captures source-, receiver-, and path-dependent terms in the description of the observed spectra by combining a physical source and attenuation model with a spatially and event-size dependent empirical compensation. The proposed method propagates estimation uncertainties along the entire processing chain starting from the hypocentre location and delivers reliable uncertainty description of the estimands. The objective is to automatically provide robust and valid descriptions of the observed S-wave spectra generated from an earthquake source in a noisy and heterogeneous environment. The efficiency of the method is tested with synthetic seismograms, and the model is calibrated and cross-validated using 31 640 mining induced seismic events in a iron ore mine (in north of Sweden) with an comprehensive seismic network. The model is evaluated using both posterior predictive checks and residual analysis and we found no evidence that indicates any model deficiencies with respect to central tendency, dispersion, and residual trends.
Development and proposed evaluation of an eHealth learning tool for undergraduate university students in Ireland
Authors: Darker Catherine D , Moore Emma , Flynn Ellen , O’Neill Mary , Doherty Lena , McMahon Jean , McLoughlin Orla , Rouine Eimear , Ivers Jo-Hanna , Allwright Shane , McGrath David , Seery Aidan , McAndrew Martin , Barrett Emer , Tanner Michelle , Bennett Annemarie E , Brennan Sabina , Mullin Martina , Barry Joe M
Published: May 2021

Undergraduate university students are at a critical stage of development in terms of their academic, social, psychological and behavioural health. Patterns established during these formative years can last a lifetime. eHealth tools have the potential to be engaging, convenient and accessible to a wide range of students by providing health information and enhancing the uptake of positive health behaviours. The ‘Healthy Trinity Online Tool’ (H-TOT) was developed in collaboration with students and a transdisciplinary team with decades of experience between them in terms of research, clinical responsibility and service delivery. Developmental steps undertaken included: a literature review to formulate the topic content choices; a survey of students to check the relevance and suitability of topics identified; and, the tacit experience of the development team. This co-design model led to the development of content encompassing academic life, healthy eating, physical activity, mood, financial matters, alcohol, tobacco, drugs and relaxation. Qualitative focus groups were subsequently conducted for in-depth exploration of the usage and functionality of H-TOT. The theoretical underpinnings include the locus of control and social cognitive theory. Evidence-based behavioural change techniques are embedded throughout. During early pre-piloting of H-TOT, the team identified and solved content functionality problems. The tone of the content was also revised to ensure it was non-judgemental. To make the H-TOT as interactive as possible, video scenarios were included and all content was audio-recorded to allow playback for students with visual or learning difficulties. Evaluation plans for the pilot year of H-TOT are outlined.
Prognostic factor analysis for patient outcome of PD-L1 expression in thoracic oesophageal squamous cell carcinoma
Authors: Wu Bo , Gao Jianhua , Ma Muyuan , Wu Yuanyuan , Ye Xiaofeng
Published: May 2021

OBJECTIVES

The purpose of this study was to determine the expression of PD-L1 in oesophageal squamous cell carcinoma (OSCC) and the prognostic factors.

METHODS

PD-L1 expression was investigated by immunohistochemical staining of resected specimens from 50 OSCC patients who were randomly selected from 104 patients with complete follow-up data. The relationships among PD-L1 expression, clinicopathological factors and prognosis were assessed by statistical analysis.

RESULTS

The expression of PD-L1 was positive in 27 (54%, positive cells’ proportion > 25%) and negative in 23 (46%, positive cells proportion ≤25%) of 50 cases, and PD-L1 expression was negative in all pericarcinomatous tissues (P > 0.05). The 5-year survival rate of patients with PD-L1-positive expression was 22.2% (6 of 27), which was less than that of patients with PD-L1-negative expression (47.8%; 11 of 23) (P < 0.05). The results showed significant differences in the depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression (P < 0.05). Multivariable analysis showed that PD-L1 expression was an independent prognostic factor for survival.

CONCLUSIONS

The depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression are important factors affecting the prognosis of patients with thoracic OSCC; in particular, high PD-L1 expression was a significant independent poor prognostic factor in thoracic OSCC patients.
Performance analysis in a stochastic supply chain with reverse flows: a DEA-based approach
Authors: Amirteimoori Alireza , Khoshandam Leila , Kordrostami Sohrab , Jahani Sayyad Noveiri Monireh , Matin Reza Kazemi
Published: May 2021

Traditional efficiency studies on network data envelopment analysis (DEA) consider decision-making units as black boxes that use a set of crisp inputs to produce a set of crisp outputs and that ignore intermediate measures and reverse flows. In real applications, however, we are faced with network systems with reverse flows in an uncertain environment. In this paper, therefore, a chance-constrained multistage DEA model is introduced to analyze the relative performances of supply chains and components in the presence of reverse flows and random factors. A real case in the sugar illustrates the proposed method. The results demonstrate the validity and applicability of the model.
Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity
Authors: Gabrielaite Migle , Bennedbæk Marc , Zucco Adrian G , Ekenberg Christina , Murray Daniel D , Kan Virginia L , Touloumi Giota , Vandekerckhove Linos , Turner Dan , Neaton James , Lane H Clifford , Safo Sandra , Arenas-Pinto Alejandro , Polizzotto Mark N , Günthard Huldrych F , Lundgren Jens D , Marvig Rasmus L
Published: May 2021

Background

Understanding the genetic interplay between human hosts and infectious pathogens is crucial for how we interpret virulence factors. Here, we tested for associations between HIV and host genetics, and interactive genetic effects on viral load (VL) in HIV-positive antiretroviral treatment-naive clinical trial participants.

Methods

HIV genomes were sequenced and the encoded amino acid (AA) variants were associated with VL, human single nucleotide polymorphisms (SNPs), and imputed HLA alleles using generalized linear models with Bonferroni correction.

Results

Human (388 501 SNPs) and HIV (3010 variants) genetic data were available for 2122 persons. Four HIV variants were associated with VL (P < 1.66 × 10–5). Twelve HIV variants were associated with a range of 1–512 human SNPs (P < 4.28 × 10–11). We found 46 associations between HLA alleles and HIV variants (P < 1.29 × 10–7). HIV variants and immunotypes when analyzed separately were associated with lower VL, whereas the opposite was true when analyzed in concert. Epitope binding predictions supported our observations.

Conclusions

Our results show the importance of immunotype specificity on viral antigenic determinants, and the identified genetic interplay emphasizes that viral and human genetics should be studied in the context of each other.

Clinical Trials Registration: NCT00867048.
The application of artificial intelligence and data integration in COVID-19 studies: a scoping review
Authors: Guo Yi , Zhang Yahan , Lyu Tianchen , Prosperi Mattia , Wang Fei , Xu Hua , Bian Jiang
Published: May 2021

Objective

To summarize how artificial intelligence (AI) is being applied in COVID-19 research and determine whether these AI applications integrated heterogenous data from different sources for modeling.

Materials and Methods

We searched 2 major COVID-19 literature databases, the National Institutes of Health’s LitCovid and the World Health Organization’s COVID-19 database on March 9, 2021. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, 2 reviewers independently reviewed all the articles in 2 rounds of screening.

Results

In the 794 studies included in the final qualitative analysis, we identified 7 key COVID-19 research areas in which AI was applied, including disease forecasting, medical imaging-based diagnosis and prognosis, early detection and prognosis (non-imaging), drug repurposing and early drug discovery, social media data analysis, genomic, transcriptomic, and proteomic data analysis, and other COVID-19 research topics. We also found that there was a lack of heterogenous data integration in these AI applications.

Discussion

Risk factors relevant to COVID-19 outcomes exist in heterogeneous data sources, including electronic health records, surveillance systems, sociodemographic datasets, and many more. However, most AI applications in COVID-19 research adopted a single-sourced approach that could omit important risk factors and thus lead to biased algorithms. Integrating heterogeneous data for modeling will help realize the full potential of AI algorithms, improve precision, and reduce bias.

Conclusion

There is a lack of data integration in the AI applications in COVID-19 research and a need for a multilevel AI framework that supports the analysis of heterogeneous data from different sources.