bluuebunny/crossref_metadata_2025 huggingface dataset:
An attention-based deep learning approach for the classification of subjective cognitive decline and mild cognitive impairment using resting-state EEG
Authors: Sibilano Elena , Brunetti Antonio , Buongiorno Domenico , Lassi Michael , Grippo Antonello , Bessi Valentina , Micera Silvestro , Mazzoni Alberto , Bevilacqua Vitoantonio
Published: February 2023

Objective. This study aims to design and implement the first deep learning (DL) model to classify subjects in the prodromic states of Alzheimer’s disease (AD) based on resting-state electroencephalographic (EEG) signals. Approach. EEG recordings of 17 healthy controls (HCs), 56 subjective cognitive decline (SCD) and 45 mild cognitive impairment (MCI) subjects were acquired at resting state. After preprocessing, we selected sections corresponding to eyes-closed condition. Five different datasets were created by extracting delta, theta, alpha, beta and delta-to-theta frequency bands using bandpass filters. To classify SCD vs MCI and HC vs SCD vs MCI, we propose a framework based on the transformer architecture, which uses multi-head attention to focus on the most relevant parts of the input signals. We trained and validated the model on each dataset with a leave-one-subject-out cross-validation approach, splitting the signals into 10 s epochs. Subjects were assigned to the same class as the majority of their epochs. Classification performances of the transformer were assessed for both epochs and subjects and compared with other DL models. Main results. Results showed that the delta dataset allowed our model to achieve the best performances for the discrimination of SCD and MCI, reaching an Area Under the ROC Curve (AUC) of 0.807, while the highest results for the HC vs SCD vs MCI classification were obtained on alpha and theta with a micro-AUC higher than 0.74. Significance. We demonstrated that DL approaches can support the adoption of non-invasive and economic techniques as EEG to stratify patients in the clinical population at risk for AD. This result was achieved since the attention mechanism was able to learn temporal dependencies of the signal, focusing on the most discriminative patterns, achieving state-of-the-art results by using a deep model of reduced complexity. Our results were consistent with clinical evidence that changes in brain activity are progressive when considering early stages of AD.
Assembling global and local spatial-temporal filters to extract discriminant information of EEG in RSVP task
Authors: Li Bowen , Zhang Shangen , Hu Yijun , Lin Yanfei , Gao Xiaorong
Published: February 2023

Objective. Brain–computer interface (BCI) system has developed rapidly in the past decade. And rapid serial visual presentation (RSVP) is an important BCI paradigm to detect the targets in high-speed image streams. For decoding electroencephalography (EEG) in RSVP task, the ensemble-model methods have better performance than the single-model ones. Approach. This study proposed a method based on ensemble learning to extract discriminant information of EEG. An extreme gradient boosting framework was utilized to sequentially generate the sub models, including one global spatial-temporal filter and a group of local ones. EEG was reshaped into a three-dimensional form by remapping the electrode dimension into a 2D array to learn the spatial-temporal features from real local space. Main results. A benchmark RSVP EEG dataset was utilized to evaluate the performance of the proposed method, where EEG data of 63 subjects were analyzed. Compared with several state-of-the-art methods, the spatial-temporal patterns of proposed method were more consistent with P300, and the proposed method can provide significantly better classification performance. Significance. The ensemble model in this study was end-to-end optimized, which can avoid error accumulation. The sub models optimized by gradient boosting theory can extract discriminant information complementarily and non-redundantly.
Cu-BTC derived CuO and CuO/Cu2O composite: an efficient adsorption material to iodide ions
Authors: Wang Peng , Gong Chun-Hui , Tang An-Yu , Gu Ao-Tian , Chen Kai-Wei , Yi Yang
Published: February 2023

The copper benzene tricarboxylic acid (Cu-BTC) cannot be used as an adsorbent in water due to hydrophilicity. However, the calcination process can destroy the benzene ring structure to lose hydrophilicity and retains carbon structure skeleton. The CuO composite and CuO/Cu2O composite based on cubical Cu-BTC (C-Cu-BTC) and dodecahedral Cu-BTC (D-Cu-BTC) are successfully manufactured to absorb radioactive iodine ion from water. Before and after calcination, the SEM and XRD were used to characterize the changes of morphology and material structure. The adsorption experiment for iodine ion showed that their saturated adsorption capacities can reach 28.64 mg g−1 (for C–CuO), 49.63 mg g−1 (for D-CuO), 49.84 mg g−1 (for C–CuO/Cu2O) and 91.91 mg g−1 (for D-CuO/Cu2O), respectively. The iodine ion adsorption of adsorbent is an exothermic reaction as shown thermodynamic curves. Through results of adsorption kinetics it is proved that the iodide ion adsorption of CuO composite is physical adsorption and the iodide ion adsorption of CuO/Cu2O composite is chemical adsorption. Compared with CuO composite, CuO/Cu2O composite had better absorption capacity for iodide ions. Furthermore, the interference of common ion on iodide absorption has also been studied. The different types of ion, such as Cl−, SO4
2− and CO3
2−, have effects on the iodine ions absorption capacity for two types of adsorbent. These ions have a slightly effect on iodine ions adsorption of CuO composite. However, these ions have greater influences on iodine ions absorption capacity of the CuO/Cu2O composite. The biggest influence is CO3
2−, and the CO3
2− reduces the adsorption capacity by 44% iodine ion absorption capacity for the CuO/Cu2O composite.
Influence of incommensurate structure on the elastic constants of crystalline Bi2Sr2CaCu2O8+δ
by Brillouin light scattering spectroscopy
Authors: McNiven B D E , LeBlanc J P F , Andrews G T
Published: February 2023

Brillouin light scattering spectroscopy was used to probe the room-temperature elasticity of crystalline high-T

c
superconductor Bi2Sr2CaCu2O8+δ
. A complete set of best-estimate elastic constants was obtained using established relationships between acoustic phonon velocities and elastic constants along with a simple expression relating crystal elastic constant C
22 to the corresponding constants of the constituent incommensurate sublattices. This latter relationship, which was derived and validated in the present work, has important implications for those studying incommensurate systems as it appears that it may be applied in its general form to any composite incommensurate crystal. The results obtained in this work are also consistent with sublattice assignments of Bi2Sr2O4 and CaCu2O4 reported in a previous Brillouin scattering study.
Precision of neuronal localization in 2D cell cultures by using high-performance electropolymerized microelectrode arrays correlated with optical imaging
Authors: Ghazal Mahdi , Scholaert Corentin , Dumortier Corentin , Lefebvre Camille , Barois Nicolas , Janel Sebastien , Tarhan Mehmet Cagatay , Colin Morvane , Buée Luc , Halliez Sophie , Pecqueur Sebastien , Coffinier Yannick , Alibart Fabien , Yger Pierre
Published: February 2023

Recently, the development of electronic devices to extracellularly record the simultaneous electrical activities of numerous neurons has been blooming, opening new possibilities to interface and decode neuronal activity. In this work, we tested how the use of EDOT electropolymerization to tune post-fabrication materials could optimize the cell/electrode interface of such devices. Our results showed an improved signal-to-noise ratio, better biocompatibility, and a higher number of neurons detected in comparison with gold electrodes. Then, using such enhanced recordings with 2D neuronal cultures combined with fluorescent optical imaging, we checked the extent to which the positions of the recorded neurons could be estimated solely via their extracellular signatures. Our results showed that assuming neurons behave as monopoles, positions could be estimated with a precision of approximately tens of micrometers.
Optimized EEG based mood detection with signal processing and deep neural networks for brain-computer interface
Authors: Adhikary Subhrangshu , Jain Kushal , Saha Biswajit , Chowdhury Deepraj
Published: February 2023

Electroencephalogram (EEG) is a very promising and widely implemented procedure to study brain signals and activities by amplifying and measuring the post-synaptical potential arising from electrical impulses produced by neurons and detected by specialized electrodes attached to specific points in the scalp. It can be studied for detecting brain abnormalities, headaches, and other conditions. However, there are limited studies performed to establish a smart decision-making model to identify EEG’s relation with the mood of the subject. In this experiment, EEG signals of 28 healthy human subjects have been observed with consent and attempts have been made to study and recognise moods. Savitzky-Golay band-pass filtering and Independent Component Analysis have been used for data filtration.Different neural network algorithms have been implemented to analyze and classify the EEG data based on the mood of the subject. The model is further optimised by the usage of Blackman window-based Fourier Transformation and extracting the most significant frequencies for each electrode. Using these techniques, up to 96.01% detection accuracy has been obtained.
Detailed analysis and simulation verification for reconstruction of plasma optical boundary with spectrometric technique on HL-2M tokamak
Authors: SU Zhihao , GAO Jinming , GAO Zhe
Published: February 2023

The plasma optical boundary reconstruction technique based on Hommen’s theory is promising for future tokamaks with high parameters. In this work, we conduct detailed analysis and simulation verification to estimate the ‘logic loophole’ of this technique. The finite-width effect and unpredictable errors reduce the technique’s reliability, which leads to this loophole. Based on imaging theory, the photos of a virtual camera are simulated by integrating the assumed luminous intensity of plasma. Based on Hommen’s theory, the plasma optical boundary is reconstructed from the photos. Comparing the reconstructed boundary with the one assumed, the logic loophole and its two effects are quantitatively estimated. The finite-width effect is related to the equivalent thickness of the luminous layer, which is generally about 2‒4 cm but sometimes larger. The level of unpredictable errors is around 0.65 cm. The technique based on Hommen’s theory is generally reliable, but finite-width effect and unpredictable errors have to be taken into consideration in some scenarios. The parameters of HL-2M are applied in this work.
Perspective on quantum bubbles in microgravity
Authors: Lundblad Nathan , Aveline David C , Balaž Antun , Bentine Elliot , Bigelow Nicholas P , Boegel Patrick , Efremov Maxim A , Gaaloul Naceur , Meister Matthias , Olshanii Maxim , Sá de Melo Carlos A R , Tononi Andrea , Vishveshwara Smitha , White Angela C , Wolf Alexander , Garraway Barry M
Published: February 2023

Progress in understanding quantum systems has been driven by the exploration of the geometry, topology, and dimensionality of ultracold atomic systems. The NASA Cold Atom Laboratory (CAL) aboard the International Space Station has enabled the study of ultracold atomic bubbles, a terrestrially-inaccessible topology. Proof-of-principle bubble experiments have been performed on CAL with an radiofrequency-dressing technique; an alternate technique (dual-species interaction-driven bubbles) has also been proposed. Both techniques can drive discovery in the next decade of fundamental physics research in microgravity.
Polarons in perovskite solar cells: effects on photovoltaic performance and stability
Authors: Zhang Hui , Park Nam-Gyu
Published: February 2023

Organic–inorganic hybrid perovskites manifest unique photophysical properties in terms of their long carrier lifetime, low recombination rate, and high defect tolerance, enabling them to be promising candidates in optoelectronic devices. However, such advanced properties are unexpected in perovskite materials with moderate charge mobility. Recent investigations have revealed that these appealing properties were endowed due to the formation of large polarons in the perovskite crystals, resulting from the coupling of photogenerated carriers and a polarized crystal lattice, which largely affected the carrier-transport dynamics and structural stability of perovskite solar cells (PSCs). In this review, first the crystal structure of the perovskite lattice and the formation mechanism of polarons are elucidated. Then, the modulation of polaron states in PSCs, including large polaron stabilization, polaron-facilitated charge transport, hot-carrier solar cells, and polaron-related stability issues such as polaron-induced metastable defects, polaronic strain, and photostriction are systematically investigated. Finally, the prospect of further understanding and manipulating polaron-related phenomena, working toward highly efficient and stable PSCs, is suggested.
Lidstone interpolation III. Several variables
Authors: Waldschmidt Michel
Published: February 2023

A polynomial in a single variable is uniquely determined by its derivatives of even order at 0 and 1. More precisely, such an univariate polynomial can be written and a finite sum of

f

(
2
n
)

(
0
)

Λ
n

(
1
−
z
)

f^{(2n)}(0) \Lambda _n(1-z)

and

f

(
2
n
)

(
1
)

Λ
n

(
z
)

f^{(2n)}(1) \Lambda _n(z)

, (

n
≥
0

n\ge 0

), where the

Λ
n

(
z
)

\Lambda _n(z)

are the Lidstone polynomials defined by the conditions
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis StartFraction normal d Over normal d z EndFraction right-parenthesis Superscript 2 k Baseline normal upper Lamda Subscript n Baseline left-parenthesis 0 right-parenthesis equals 0 and left-parenthesis StartFraction normal d Over normal d z EndFraction right-parenthesis Superscript 2 k Baseline normal upper Lamda Subscript n Baseline left-parenthesis 1 right-parenthesis equals delta Subscript k comma n Baseline comma k greater-than-or-equal-to 0 comma n greater-than-or-equal-to 0 period">

(

d

d

z

)

2
k

Λ
n

(
0
)
=
0
 and 

(

d

d

z

)

2
k

Λ
n

(
1
)
=

δ

k
,
n

,

k
≥
0
,

n
≥
0.

\begin{equation*} \left (\frac {\mathrm {d}}{\mathrm {d}z}\right )^{2k} \Lambda _n(0)=0\text { and } \left (\frac {\mathrm {d}}{\mathrm {d}z}\right )^{2k} \Lambda _n(1)=\delta _{k,n},\quad k\ge 0, \; n\ge 0. \end{equation*}

We generalize this theory to

n
n

variables, replacing the two points

0
0

,

1
1

in

C

\mathbb {C}

with

n
+
1

n+1

points

e
_

0

,

e
_

1

,
…
,

e
_

n

{\underline {e}}_0,{\underline {e}}_1,\dots ,{\underline {e}}_n

in

C

n

\mathbb {C}^n

, where

e
_

0

{\underline {e}}_0

is the origin of

C

n

\mathbb {C}^n

and

e
_

1

,
…
,

e
_

n

{\underline {e}}_1,\dots ,{\underline {e}}_n

the canonical basis of

C

n

\mathbb {C}^n

. By selecting a suitable subset of even order derivatives at these

n
+
1

n+1

points, we show that any polynomial in

n
n

variables has a unique expansion. We obtain generating series for these sequences of polynomials and we deduce an expansion for entire functions in

C

n

\mathbb {C}^n

of exponential type

>
π

>\pi

. We extend to several variables results due to Lidstone [Proceedings Edinburgh Math. Soc., II. Ser. (2)2, 16-19 (1930)], Poritsky [Trans. Amer. Math. Soc. 34 (1932), pp. 274–331], Whittaker [Proc. London Math. Soc. (2) 36 (1934), pp. 451–469], Schoenberg [Bull. Amer. Math. Soc. 42 (1936), pp. 284–288], Buck [Proc. Amer. Math. Soc. 6 (1955), pp. 793–796]. We also show that our results are, to a certain extent, best possible.
Pain in People Experiencing Homelessness: A Scoping Review
Authors: Anastas Tracy M , Stewart Jesse C , Rand Kevin L , Hirsh Adam T
Published: February 2023

Background

Prior work suggests that people experiencing homelessness (PEH) are at heightened risk for developing pain and have a uniquely burdensome pain experience.

Purpose

The aim of this scoping review was to map the current peer-reviewed, published literature on the pain experience of PEH.

Methods

In accordance with the US Annual Homeless Assessment Report, we defined homelessness as lacking shelter or a fixed address within the last year. We conceptualized the pain experience via a modified version of the Social Communication Model of Pain, which considers patient, provider, and contextual factors. Published articles were identified with CINHAL, Embase, PubMed, PsycINFO, and Web of Science databases.

Results

Sixty-nine studies met inclusion criteria. Studies revealed that PEH have high rates of pain and experience high levels of pain intensity and interference. Substantially fewer studies examined other factors relevant to the pain experience, such as self-management, treatment-seeking behaviors, and pain management within healthcare settings. Nonetheless, initial evidence suggests that pain is undermanaged in PEH.

Conclusions

Future research directions to understand pain and homelessness are discussed, including factors contributing to the under-management of pain. This scoping review may inform future work to develop interventions to address the specific pain care needs of PEH.
Affective Response to Exercise and Affective Judgments as Predictors of Physical Activity Intention and Behavior among New Mothers in their first 6-Months Postpartum
Authors: Rhodes Ryan E , Blanchard Chris M , Hartson Kimberly R , Symons Downs Danielle , Warburton Darren E R , Beauchamp Mark R
Published: February 2023

Background

Understanding the predictors of moderate to vigorous physical activity (MVPA) during early postpartum is important to improve promotion efforts. Affect-related constructs are key predictors of MVPA but have limited research in mothers during the postpartum period.

Purpose

To examine two affect-related constructs (affective response to exercise and affective judgments) as predictors of MVPA intention and behavior across three months, among a sample of new mothers.

Methods

Participants were 105 mothers (M age = 30.64 years; SD = 3.93) who completed measures during postpartum at 2-months post-birth of their first child. The affective response to exercise (assessed at baseline [2-months postpartum] during a submaximal treadmill test), affective judgments and intention (baseline, 6-weeks after baseline), and MVPA (baseline, 6- and 12-weeks after baseline) were assessed via self-report.

Results

Path analysis, using ordinary least squares regression, showed that the affective response during exercise was a significant predictor of intention (baseline, 6-weeks), as well as change in intention from baseline to 6-weeks. By contrast, affective judgments predicted intention at 6-weeks, but not at baseline or in the change model. Past MVPA did not moderate these findings, although the affective response during exercise also had a significant indirect effect on MVPA through intention at 6-weeks and 12-weeks.

Conclusions

Interventions targeting women’s affective response during exercise may be important during postpartum, perhaps through self-paced physical activity guidance. Affective judgments may not be predictive of MVPA, in part due to unanticipated changes during early postpartum leading to inaccurate expectations of the physical activity experience.
Comparative effectiveness of non-pharmacological interventions for frailty: a systematic review and network meta-analysis
Authors: Sun Xuemei , Liu Wenqi , Gao Yinyan , Qin Lang , Feng Hui , Tan Hongzhuan , Chen Qiong , Peng Linlin , Wu Irene X Y
Published: February 2023

Background

Frailty endangers the health of older adults. Furthermore, the prevalence of frailty continues to increase as the global population ageing.

Objective

To update evidence on the effectiveness of non-pharmacological interventions for frailty by conducting a network meta-analysis (NMA) of randomised controlled trials (RCTs).

Methods

Eight databases were searched from January 1, 2000, until September 24, 2021. RCTs of interventions for frailty among participants aged ≥60 years were considered eligible. The primary outcome was frailty. Pairwise meta-analysis and NMA were performed, with the pooled standardised mean difference (SMD) and 95% confidence interval (CI) being reported.

Results

A total of 69 RCTs were included after screening 16,058 retrieved citations. There were seven types of interventions (11 interventions) for frailty among the included RCTs. Physical activity (PA) (pooled SMD = 0.43, 95% CI: 0.34–0.51), multicomponent intervention (pooled SMD = 0.34, 95% CI: 0.23–0.45) and nutrition intervention (pooled SMD = 0.21, 95% CI: 0.06–0.35) were associated with reducing frailty compared to control, of which PA was the most effective type of intervention. In terms of specific types of PA, resistance training (pooled SMD = 0.58, 95% CI: 0.33–0.83), mind–body exercise (pooled SMD = 0.57, 95% CI: 0.24–0.90), mixed physical training (pooled SMD = 0.47, 95% CI: 0.37–0.57) and aerobic training (pooled SMD = 0.36, 95% CI: 0.09–0.62) were associated with a reduction in frailty compared to usual care. Resistance training was the most effective PA intervention.

Conclusion

Resistance training has the best potential to reduce frailty in older adults. This finding might be useful to clinicians in selecting interventions for older adults with frailty.
Evaluating the effects of a global pandemic on the operation of an investigational drug service
Authors: Coulter Carolyn , Thorne Andrew , Amerine Lindsey
Published: February 2023

Purpose

This study is an analysis of the changes to workload and operations of UNC Health’s investigational drug service (IDS) brought about by the coronavirus disease 2019 (COVID-19) pandemic.

Methods

Workload statistics were collected and analyzed for trend changes to illustrate operational changes necessitated by the COVID-19 pandemic within the IDS pharmacy at UNC Health.

Results

Multiple workload metrics declined at the beginning of the COVID-19 pandemic, followed by an increase in the metrics for many categories as the pandemic continued. Notably, monthly inventory added initially decreased by 37.5%, later leveling off but showing increased variability. Fills dispensed and monitoring visits both decreased by 34.5% from the first quarter (Q1) to Q2 of 2020. Both metrics returned to or slightly exceeded prepandemic levels by the end of the study period in March 2021. Patient enrollment decreased 76% from February to May 2020 before dramatically increasing in Q3 of 2020 and Q1 of 2021 with the initiation of COVID-19 vaccine studies. The average time to study startup increased for trials not related to COVID-19 and decreased for COVID-19–related trials. There has been no major impact on the number of open protocols throughout the course of the pandemic.

Conclusion

Despite initial decreases in workload following the start of the COVID-19 pandemic, IDS operations returned to and, in some cases, exceeded prepandemic levels.
Potential Effects of Repetitive Panfacial Filler Injections on Facelift Surgery and Surgical Outcomes: Survey Results of the Members of The Aesthetic Society
Authors: Sweis Iliana , DeRoss Lance , Raman Shreya , Patel Pravin
Published: February 2023

Background

Facial soft-tissue filler injections are being performed in the United States with increasing popularity.

Objectives

This study aimed to characterize the observations of The Aesthetic Society members regarding the potential impact of repetitive panfacial fillers on the outcomes of subsequent facelift surgery.

Methods

A survey containing closed and open-ended questions was sent to The Aesthetic Society members through email.

Results

The response rate was 3.7%. The majority of the respondents (80.8%) believed that less than 60% of their facelift patients had previous repetitive panfacial filler injections. One half (51.9%) reported that a history of panfacial filler injections increased the difficulty of performing facelifts. A large subset (39.7%) of respondents believed that a history of panfacial fillers increased postoperative complication rates, while the remaining either disagreed (28.9%) or were unsure (31.4%). The most common complications following the facelift surgery included undesirable palpability or visibility of filler (32.7%), compromised flap vascularity (15.4%), and decreased longevity of the lifting effect (9.6%).

Conclusions

This study identified a potential association with repetitive panfacial filler injections and outcomes following facelift surgery, although the exact effect on postoperative outcomes remains unclear. Large prospectively designed studies are needed to capture objective data comparing facelift patients with a history of repetitive panfacial fillers with those facelift patients who have never had injectables. Given the results of The Aesthetic Society members’ survey, the authors encourage careful history-taking to elicit an accurate filler injection record including complications after filler injections, as well as engaging patients in a thorough preoperative discussion regarding the potential of panfacial fillers on the facelift procedure and postoperative outcomes.

Level of Evidence: 5
AD-Syn-Net: systematic identification of Alzheimer’s disease-associated mutation and co-mutation vulnerabilities via deep learning
Authors: Pan Xingxin , Coban Akdemir Zeynep H , Gao Ruixuan , Jiang Xiaoqian , Sheynkman Gloria M , Wu Erxi , Huang Jason H , Sahni Nidhi , Yi S Stephen
Published: February 2023

Alzheimer’s disease (AD) is one of the most challenging neurodegenerative diseases because of its complicated and progressive mechanisms, and multiple risk factors. Increasing research evidence demonstrates that genetics may be a key factor responsible for the occurrence of the disease. Although previous reports identified quite a few AD-associated genes, they were mostly limited owing to patient sample size and selection bias. There is a lack of comprehensive research aimed to identify AD-associated risk mutations systematically. To address this challenge, we hereby construct a large-scale AD mutation and co-mutation framework (‘AD-Syn-Net’), and propose deep learning models named Deep-SMCI and Deep-CMCI configured with fully connected layers that are capable of predicting cognitive impairment of subjects effectively based on genetic mutation and co-mutation profiles. Next, we apply the customized frameworks to data sets to evaluate the importance scores of the mutations and identified mutation effectors and co-mutation combination vulnerabilities contributing to cognitive impairment. Furthermore, we evaluate the influence of mutation pairs on the network architecture to dissect the genetic organization of AD and identify novel co-mutations that could be responsible for dementia, laying a solid foundation for proposing future targeted therapy for AD precision medicine. Our deep learning model codes are available open access here: https://github.com/Pan-Bio/AD-mutation-effectors.
A noise-robust deep clustering of biomolecular ions improves interpretability of mass spectrometric images
Authors: Guo Dan , Föll Melanie Christine , Bemis Kylie Ariel , Vitek Olga
Published: February 2023

Motivation

Mass Spectrometry Imaging (MSI) analyzes complex biological samples such as tissues. It simultaneously characterizes the ions present in the tissue in the form of mass spectra, and the spatial distribution of the ions across the tissue in the form of ion images. Unsupervised clustering of ion images facilitates the interpretation in the spectral domain, by identifying groups of ions with similar spatial distributions. Unfortunately, many current methods for clustering ion images ignore the spatial features of the images, and are therefore unable to learn these features for clustering purposes. Alternative methods extract spatial features using deep neural networks pre-trained on natural image tasks; however, this is often inadequate since ion images are substantially noisier than natural images.

Results

We contribute a deep clustering approach for ion images that accounts for both spatial contextual features and noise. In evaluations on a simulated dataset and on four experimental datasets of different tissue types, the proposed method grouped ions from the same source into a same cluster more frequently than existing methods. We further demonstrated that using ion image clustering as a pre-processing step facilitated the interpretation of a subsequent spatial segmentation as compared to using either all the ions or one ion at a time. As a result, the proposed approach facilitated the interpretability of MSI data in both the spectral domain and the spatial domain.

Availabilityand implementation

The data and code are available at https://github.com/DanGuo1223/mzClustering.

Supplementary information

Supplementary data are available at Bioinformatics online.
Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study
Authors: Okuda Darin T , Kantor Daniel , Jaros Mark , deVries Tina , Hunter Samuel
Published: February 2023

Baclofen, a racemic γ-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis–related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the γ-aminobutyric acid B receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12 h and have shown a favourable safety and efficacy profile in early clinical development. A 12-week, randomized, placebo-controlled Phase 3 trial in adults with multiple sclerosis–related spasticity demonstrated that arbaclofen extended-release 40 mg/day significantly reduced spasticity symptoms compared with placebo and was safe and well tolerated. The current study is an open-label extension of the Phase 3 trial designed to evaluate the long-term safety and efficacy of arbaclofen extended-release. In a 52-week, open-label, multicentre study, adults with a Total Numeric-transformed Modified Ashworth Scale score ≥2 in the most affected limb received oral arbaclofen extended-release titrated over 9 days up to 80 mg/day based on tolerability. The primary objective was assessment of arbaclofen extended-release safety and tolerability. Secondary objectives included an assessment of efficacy using the Total Numeric-transformed Modified Ashworth Scale-most affected limb, the Patient Global Impression of Change and Expanded Disability Status Scale. Of 323 patients enrolled, 218 (67.5%) completed 1 year of treatment. Most patients (74.0%) achieved an arbaclofen extended-release maintenance dose of 80 mg/day. At least one treatment-emergent adverse event was reported by 278 patients (86.1%). The most common adverse events were [n patients (%)]: urinary tract disorder [112 (34.7)], muscle weakness [77 (23.8)], asthenia [61 (18.9)], nausea [70 (21.7)], dizziness [52 (16.1)], somnolence [41 (12.7)], vomiting [29 (9.0)], headache [24 (7.4)] and gait disturbance [20 (6.2)]. Most adverse events were of mild–moderate severity. Twenty-eight serious adverse events were reported. One death occurred during the study, a myocardial infarction that was considered by investigators as unlikely to be related to treatment. Overall, 14.9% of patients discontinued due to adverse events, primarily muscle weakness, multiple sclerosis relapse, asthenia and nausea. Evidence of improvement in multiple sclerosis–related spasticity was observed across arbaclofen extended-release dosages. Arbaclofen extended-release treatment (up to 80 mg/day) was well tolerated and reduced symptoms of spasticity in adult patients with multiple sclerosis for 1 year.

Clinical Trial Identifier: ClinicalTrials.gov, NCT03319732
Nonalcoholic Fatty Liver Disease Is a Risk Factor for Thiopurine Hepatotoxicity in Crohn’s Disease
Authors: George Alvin T , Glover Matthew , Alayo Quazim , Zulfiqar Maria , Ludwig Daniel R , Ciorba Matthew A , McHenry Scott , Deepak Parakkal
Published: February 2023

Background

Patients with Crohn’s disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

Methods

In this prospective cohort analysis, CD patients at a single center were recruited 6/2017–5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a Cox-proportional hazards model.

Results

Of the 311 CD patients studied, 116 (37%) were treated with thiopurines, 54 (47%) of which were found to have NAFLD. At follow-up, there were 44 total cases of elevated liver enzymes in those treated with thiopurines. Multivariable analysis demonstrated that NAFLD was a predictor of elevated liver enzymes in patients with CD treated with thiopurines (HR 3.0, 95% CI 1.2–7.3, P = .018) independent of age, body mass index, hypertension, and type 2 diabetes. Steatosis severity by PDFF positively correlated with peak alanine aminotransferase (ALT) at follow-up. Kaplan–Meier analysis demonstrated poorer complication-free survival (log-rank 13.1, P < .001).

Conclusions

NAFLD at baseline is a risk factor for thiopurine-induced hepatotoxicity in patients with CD. The degree of liver fat positively correlated with the degree of ALT elevation. These data suggest that evaluation for hepatic steatosis be considered in patients with liver enzyme elevations with thiopurine therapy.
Are There Edge Effects on the Genetic Diversity of the Trap-Jaw Ant Odontomachus chelifer (Formicidae: Ponerinae) in a Neotropical Savanna Fragment? A First Assessment
Authors: Azevedo-Silva Marianne , Lemos Alessandra S M , Gonçalves-Neto Salatiel , Salles Luís F P , Pereyra Mariana , Christianini Alexander V , Souza Anete P , Oliveira Paulo S
Published: February 2023

Habitat fragmentation is considered an important threat to biodiversity, increasing species exposure to edge effects. The Brazilian Cerrado savanna is considered a biodiversity hotspot and has been converted to small, isolated fragments due to human activities. Ant communities and colony survivorship are known to be affected by edge effects in Cerrado, but to date there is no information on the genetic diversity of ant colonies at the edge of fragmented areas. Here, we investigate if colony genetic diversity and structure of Odontomachus chelifer (Latreille) ants (Hymenoptera: Formicidae) are subject to edge effects in a Cerrado reserve in southeast Brazil. Using microsatellites, we evaluated the number of breeders (queens and males) and the genetic diversity in O. chelifer colonies located in the interior versus edge of a Cerrado fragment. All O. chelifer nests had multiple queens, which presented a low mating frequency. The number of breeders and most estimates of genetic diversity did not differ between colonies at the edge versus interior of the fragment. Genetic structure was not influenced by nest location as well. However, we detected a small and positive increase in the observed heterozygosity in colonies located at fragment edges. High heterozygosity is thought to be particularly important in fast-changing environments, such as edges, providing an advantage for genetic diversity. Further investigation is needed to assess in greater detail how habitat loss affects O. chelifer biology. Our study is a first step toward elucidating edge effects on genetic diversity of ant colonies, a topic still poorly explored in tropical environments.
Hydrodynamicex vivoanalysis of valve-sparing techniques: assessment and comparison
Authors: Di Leonardo Sofia , Vella Danila , Grillo Carmelo Savio , Martorana Carla , Torre Salvatore , Argano Vincenzo , Burriesci Gaetano
Published: February 2023

OBJECTIVES

Valve-sparing procedures are surgical techniques allowing to restore adequate function of the native aortic valve by replacing the dysfunctional ascending aorta with a prosthetic conduit. A number of techniques are currently used, such as Yacoub’s remodelling and David’s reimplantation, based on a regular straight conduit. More recently, the De Paulis proposed the use of bulging conduits to reconstruct the shape of the Valsalva sinuses. This work investigates the impact of the valve-sparing technique on the aortic valve function.

METHODS

The performance of 3 porcine aortic roots (Medtronic Freestyle™) was assessed in a cardiovascular pulse duplicator before and after performing 3 alternative valve-sparing procedures: David’s reimplantation, Yacoub’s remodelling and De Paulis’ reimplantation.

RESULTS

The porcine aortic roots, representative of the healthy native configuration, were characterized by the highest efficiency, with a mean energetic dissipation under normal operating conditions of 26 mJ. David’s and Yacoub’s techniques resulted in significantly lower performance (with mean energetic loss of about 70 mJ for both cases). The De Paulis’ procedure exhibited intermediate behaviour, with superior systolic performance and valve dynamics similar to the native case, and a mean energetic loss of 38 mJ.

CONCLUSIONS

The dynamics and performance after valve-sparing strongly depend on the adopted technique, with the use of conduits replicating the presence of Valsalva sinuses restoring more physiological conditions.
Functional tug of war between kinases, phosphatases, and the Gcn5 acetyltransferase in chromatin and cell cycle checkpoint controls
Authors: Liu Qihao , Pillus Lorraine , Petty Emily L
Published: February 2023

Covalent modifications of chromatin regulate genomic structure and accessibility in diverse biological processes such as transcriptional regulation, cell cycle progression, and DNA damage repair. Many histone modifications have been characterized, yet understanding the interactions between these and their combinatorial effects remains an active area of investigation, including dissecting functional interactions between enzymes mediating these modifications. In budding yeast, the histone acetyltransferase Gcn5 interacts with Rts1, a regulatory subunit of protein phosphatase 2A (PP2A). Implicated in the interaction is the potential for the dynamic phosphorylation of conserved residues on histone H2B and the Cse4 centromere-specific histone H3 variant. To probe these dynamics, we sought to identify kinases which contribute to the phosphorylated state. In a directed screen beginning with in silico analysis of the 127 members of yeast kinome, we have now identified 16 kinases with genetic interactions with GCN5 and specifically found distinct roles for the Hog1 stress-activated protein kinase. Deletion of HOG1 (hog1Δ) rescues gcn5Δ sensitivity to the microtubule poison nocodazole and the lethality of the gcn5Δ rts1Δ double mutant. The Hog1–Gcn5 interaction requires the conserved H2B-T91 residue, which is phosphorylated in vertebrate species. Furthermore, deletion of HOG1 decreases aneuploidy and apoptotic populations in gcn5Δ cells. Together, these results introduce Hog1 as a kinase that functionally opposes Gcn5 and Rts1 in the context of the spindle assembly checkpoint and suggest further kinases may also influence GCN5's functions.
Epigenetic and Genetic Population Structure is Coupled in a Marine Invertebrate
Authors: Silliman Katherine , Spencer Laura H , White Samuel J , Roberts Steven B
Published: February 2023

Delineating the relative influence of genotype and the environment on DNA methylation is critical for characterizing the spectrum of organism fitness as driven by adaptation and phenotypic plasticity. In this study, we integrated genomic and DNA methylation data for two distinct Olympia oyster (Ostrea lurida) populations while controlling for within-generation environmental influences. In addition to providing the first characterization of genome-wide DNA methylation patterns in the oyster genus Ostrea, we identified 3,963 differentially methylated loci between populations. Our results show a clear coupling between genetic and epigenetic patterns of variation, with 27% of variation in interindividual methylation differences explained by genotype. Underlying this association are both direct genetic changes in CpGs (CpG-SNPs) and genetic variation with indirect influence on methylation (mQTLs). When comparing measures of genetic and epigenetic population divergence at specific genomic regions this relationship surprisingly breaks down, which has implications for the methods commonly used to study epigenetic and genetic coupling in marine invertebrates.
Age and Cognitive Ability Predict Emotion Regulation Strategy Use
Authors: Growney Claire M , English Tammy
Published: February 2023

Objectives

This study examines how age and cognitive ability predict use of different emotion regulation strategies in a laboratory task eliciting emotions varying in valence and arousal.

Methods

Participants (N = 287) aged 25–85 completed the NIH Toolbox Cognitive Battery and an emotion regulation task in a laboratory setting. They watched a series of emotional clips (disgust, sadness, amusement, and contentment) under instructions to increase positive emotions or decrease negative emotions. After each clip, they rated the extent to which they used emotion regulation strategies that involve different types of engagement with emotional stimuli and disengagement from emotional stimuli.

Results

Older age was predictive of greater use of immersive-engagement strategies (e.g., perspective taking) and less use of disengagement strategies (e.g., distraction). Fluid cognitive ability was positively associated with immersive-engagement strategy use, particularly for high-arousal clips. For older adults, fluid cognitive ability was also associated with using positive-engagement strategies (e.g., positive reappraisal) to a greater extent to regulate negative emotions.

Discussion

Patterns of emotion regulation strategy use varied by age, even when accounting for differences in reactivity. Findings suggest that older adults may not necessarily prefer strategies that are lower in cognitive demands or that focus on enhancing positivity. Results support the idea that strategy preferences are driven by a combination of characteristics of the regulator and the regulation context. The relevance of cognitive resources likely varies across situations, perhaps being most consequential for deeper processing of high-arousal stimuli and for older adults’ engagement with positive aspects of an otherwise negative situation.
Independencia, transparencia y rendición de cuentas: experiencia de la India con la designación de entidades reguladoras
Authors: Vakil Raeesa
Published: February 2023

Regulatory governance requires multiple, complex channels of accountability, especially when agencies are located at the conjunction of judicial, executive, and legislative powers. In this paper, I evaluate appointments to independent regulators in India, focusing on eight key bodies. A study of how they staff and manage their appointments, in the Indian context, demonstrates a significant reliance on judicial review as a mechanism of control, to the near exclusion of any other method of accountability. A limited effort to define certain regulators as judicial bodies, based on their decision-making functions, has enabled some accountability, but in other cases, judges struggle to find ways to constrain executive power outside the confines of judicial ­activity. As with other states that have active courts engaged in monitoring regulatory ­activity, the Indian case, as this paper argues, demonstrates that accountability is better achieved by supplementing judicial review with participatory governance and legislative frameworks.
The switch: The Israel High Court of Justice’s transition from occupation law to human rights law
Authors: Cohen Amichai , Shany Yuval
Published: February 2023

It has been suggested that the jurisprudence of the High Court of Justice (HCJ) relating to the territories occupied by Israeli in 1967 had effectively legitimized the occupation. Recent decisions by the HCJ suggest, however, that the legal paradigm it applies has shifted from Israeli administrative law to Israeli constitutional law, and from the international law of belligerent occupation to domestic human rights law. The Silwad judgment—a landmark decision from June 2020 in which the HCJ struck down the Regularization Law of 2017—illustrates this switch. Furthermore, it reflects the challenge confronting the HCJ when striving to facilitate structural change in the situation in the occupied territories. Contrary to some of the literature which criticized the switch to human rights norms for diluting the rights of Palestinians residing in the occupied territories, we submit that it potentially constitutes an important step in the direction of confronting the systematic discrimination of Palestinians which that belligerent occupation law paradigm failed to prevent.
Constitutional interpretation and legal consciousness: Out of the courts and onto the ground
Authors: Chua Lynette J
Published: February 2023

This article examines the relevance of the study of legal consciousness, particularly that of ordinary people, to constitutional interpretation. It draws on sociolegal scholarship to explain how empirically informed, ground-up research on legal consciousness can make important contributions to the study of constitutional law away from elite actors and formal political institutions. Statutes, regulations, and court opinions that restrict the exercise of constitutional rights, and political discourse that is averse or friendly to activism and rights claims are conditions that shape the legal consciousness of ordinary people—their willingness and ability to make constitutional claims of their own in the courts, as well as their self-perceptions, social interactions, and relationships. Constitutional interpretation by ordinary people—their legal consciousness—in turn influences the development of constitutional law as it is interpreted by courts and other branches of government. By studying the words, thoughts, feelings, and (non)actions of citizens as a means of revealing how they perceive, think, and behave toward the constitution, scholars can produce a different type of study about constitutional interpretation—one that emerges from the ground up. Adopting the approach of legal consciousness research can contribute much-needed empirical insights into typically normative debates in legal scholarship about constitutional legitimacy and developments.
Pluralizing constitutional interpretation: An introduction
Authors: De Visser Maartje , Neo Jaclyn L
Published: February 2023

The purpose of the symposium on pluralizing constitutional interpretation was to reflect upon the multiple sites at which interpretative activities take place, their real-world significance, and the methodological implications of expanding our scholarly lens beyond court rulings and beyond legal materials for a more complete understanding of how constitutions are engaged with. In this introductory article, we propose at least three directions for diversification. The first is the pluralization of actors beyond the courts, attention being drawn to the diverse range of institutions, entities, and individuals involved in giving meaning to the constitution. The second is methodological and disciplinary in nature; it addresses the manner in which this plurality of interpreters relates to nonlegal methods and sources, as compared to classic legal methods and sources. The third is about orientation and entails a shift from the study of doctrines, precedents, and conceptional analysis to a more dynamic approach to interpretation, as defined by intersecting viewpoints, coinciding sites of interpretation, and a shifting of institutional and disciplinary boundaries. Taken together, these directions hold out the promise of arriving at a more complete understanding of how constitutional law is engaged with as a lived reality.