bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical spike amplitude weighting and neuromimetic rate coding using a joint VCSEL-MRR neuromorphic photonic system
Authors: Hejda Matěj , Doris Eli A , Bilodeau Simon , Robertson Joshua , Owen-Newns Dafydd , Shastri Bhavin J , Prucnal Paul R , Hurtado Antonio
Published: May 2024

Spiking neurons and neural networks constitute a fundamental building block for brain-inspired computing, which is poised to benefit significantly from photonic hardware implementations. In this work, we experimentally investigate an interconnected optical neuromorphic system based on an ultrafast spiking vertical cavity surface emitting laser (VCSEL) neuron and a silicon photonics (SiPh) integrated micro-ring resonator (MRR). We experimentally demonstrate two different functional arrangements of these devices: first, we show that MRR weight banks can be used in conjunction with the spiking VCSEL-neurons to perform amplitude weighting of sub-ns optical spiking signals. Second, we show that a continuously firing VCSEL-neuron can be directly modulated using a locking signal propagated through a single weighting MRR, and we utilise this functionality to perform optical spike firing rate-coding via thermal tuning of the MRR. Given the significant track record of both integrated weight banks and photonic VCSEL-neurons, we believe these results demonstrate the viability of combining these two classes of devices for use in functional neuromorphic photonic systems.
Error bounds for Gauss–Jacobi quadrature of analytic functions on an ellipse
Authors: Sugiura Hiroshi , Hasegawa Takemitsu
Published: May 2024

For the Gauss–Jacobi quadrature on

[
−
1
,
1
]

[-1,1]

, the location is estimated where the kernel of the error functional for functions analytic on an ellipse and its interior in the complex plane attains its maximum modulus. For the Jacobi weight

(
1
−
t

)
α

(
1
+
t

)
β

(1-t)^\alpha (1+t)^\beta

(

α
>
−
1

\alpha >-1

,

β
>
−
1

\beta >-1

) except for the Gegenbauer weight (

α
=
β

\alpha =\beta

), the location is the intersection point of the ellipse with the real axis in the complex plane. For the Gegenbauer weight, it is the intersection point(s) with either the real or the imaginary axis or other axes with angle

1
4

π

\tfrac {1}{4}\pi

and

3
4

π

\tfrac {3}{4}\pi

. Our results support the empirical results provided by Gautschi and Varga [SIAM J. Numer. Anal, 20 (1983), pp. 1170–1186] for the Jacobi weight, the Gegenbauer weight and the Legendre weight. The results obtained are also illustrated numerically.
Müntz Legendre polynomials: Approximation properties and applications
Authors: Cui Tengteng , Xu Chuanju
Published: May 2024

The Müntz Legendre polynomials are a family of generalized orthogonal polynomials, defined by contour integral associated with a complex sequence

Λ
=
{

λ

0

,

λ

1

,

λ

2

,
⋯
}

\Lambda =\{\lambda _{0},\lambda _{1},\lambda _{2},\cdots \}

. In this paper, we are interested in two subclasses of the Müntz Legendre polynomials. Precisely, we theoretically and numerically investigate the basic approximation properties of the Müntz Legendre polynomials for two sets of

Λ
\Lambda

sequences:

λ

k

=
λ

\lambda _{k}=\lambda

, and

λ
k

=
k
λ
+
q

\lambda _k=k\lambda +q

for some

λ
\lambda

and

q
q

. First, the projection and interpolation errors are analyzed and numerically tested for each of the two subclasses of polynomials, and some error estimates are derived for functions in non-uniformly weighted Sobolev spaces. Then, in order to demonstrate the applicability of the Müntz polynomials, a Galerkin spectral method based on the Müntz Legendre polynomials is proposed to solve the time-space fractional differential equation. The obtained numerical results show that the proposed method leads to an exponential convergence rate even if the exact solutions are not smooth. This is opposed to low order algebraic convergence if traditional orthogonal polynomials are used.
Yosida distance and existence of invariant manifolds in the infinite-dimensional dynamical systems
Authors: Bui Xuan-Quang , Minh Nguyen Van
Published: May 2024

We consider the existence of invariant manifolds to evolution equations

u
′

(
t
)
=
A
u
(
t
)

u’(t)=Au(t)

,

A
:
D
(
A
)
⊂

X

→

X

A:D(A)\subset \mathbb {X}\to \mathbb {X}

near its equilibrium

A
(
0
)
=
0

A(0)=0

under the assumption that its proto-derivative

∂
A
(
x
)

\partial A(x)

exists and is continuous in

x
∈
D
(
A
)

x\in D(A)

in the sense of Yosida distance. Yosida distance between two (unbounded) linear operators

U
U

and

V
V

in a Banach space

X

\mathbb {X}

is defined as

d
Y

(
U
,
V
)
≔

lim sup

μ
→
+
∞

‖

U
μ

−

V
μ

‖

d_Y(U,V)≔\limsup _{\mu \to +\infty } \| U_\mu -V_\mu \|

, where

U
μ

U_\mu

and

V
μ

V_\mu

are the Yosida approximations of

U
U

and

V
V

, respectively. We show that the above-mentioned equation has local stable and unstable invariant manifolds near an exponentially dichotomous equilibrium if the proto-derivative of

∂
A

\partial A

is continuous in the sense of Yosida distance. The Yosida distance approach allows us to generalize the well-known results with possible applications to larger classes of partial differential equations and functional differential equations. The obtained results seem to be new.
Formal vs. Informal Voluntary Disclosure Policies
Authors: Noked Noam , Wöhrer Viktoria , Lai Pierce
Published: May 2024

Tax administrations have long grappled with the question of how noncompliant taxpayers should be allowed to correct their tax affairs voluntarily. While many jurisdictions have adopted various voluntary disclosure programs, several countries—including some of the world’s largest economies—have not done so. This Article examines the voluntary disclosure practices in twenty-five countries that do not have voluntary disclosure programs. It finds that the tax authorities in these jurisdictions frequently follow informal voluntary disclosure practices that operate as de facto substitutes for formal policies. In some countries, informal voluntary disclosure practices coexist alongside formal schemes. In light of these findings, this Article explores the tax policy considerations concerning the choice between formal and informal voluntary disclosure policies, and shows that formal schemes have several advantages over informal practices.
Tennessee hospital noncompliance with price transparency legislation for 8 common laboratory tests
Authors: Hart Stephanie A , Khan Ayesha , Booth Garrett S , Wiencek Joesph R
Published: May 2024

Objectives

The goal of this study was to assess hospital compliance with federal price transparency mandates and barriers to pricing information in Tennessee.

Methods

All hospitals websites were queried for gross, cash, and BlueCross BlueShield of Tennessee prices for 8 high-frequency laboratory tests in 2 Centers for Medicare & Medicaid Services–mandated pricing sources: (1) a machine-readable file of all available services and (2) a consumer-friendly display of 300 shoppable services. Barriers, including click counts, data availability, and intrahospital price discrepancies, were noted.

Results

Of the 145 Tennessee hospitals assessed, 97.2% were noncompliant with the Centers for Medicare & Medicaid Services final rule. Subanalysis of available machine-readable files, price estimators, and shoppable services files demonstrated 49.6%, 95.1%, and 78.6% noncompliance, respectively. Barriers to pricing information included requiring protected health information (55.9%), missing at least 1 pricing source (7.6%), having no pricing sources available (6.2%), and involving more than 3 clicks to access the cash price in machine-readable files (54.1%) and price estimators (68.6%.) Average intrahospital discrepancy for basic metabolic panel cash prices across pricing sources was $101.30 (range, $0-1012.40).

Conclusions

Our study showed high levels of noncompliance with price transparency laws, inconsistent and inaccessible pricing, and continued challenges facing patients in Tennessee.
Predicted 25-hydroxyvitamin D over the adult lifetime and the risk of ovarian cancer
Authors: Ritonja Jennifer A , Danieli Coraline , Pana Magnoudewa Priscille , Palmer Michael J , L’Espérance Kevin , Ho Vikki , Abrahamowicz Michal , Koushik Anita
Published: May 2024

The evidence from previous studies of serum 25-hydroxyvitamin D (25(OH)D) and ovarian cancer risk is not conclusive. However, the 25(OH)D levels were generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (n = 490 cases and 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for average predicted 25(OH)D over the adult lifetime and ovarian cancer risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20-nmol/L increase in average predicted 25(OH)D over the adult lifetime, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20-nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D levels in adulthood and ovarian cancer risk.

This article is part of a Special Collection on Gynecological Cancers.
Defining the “ideal state”: A primer on critical care pharmacy practice models
Authors: Smith Susan E , Nei Andrea M
Published: May 2024

Purpose

Critical care pharmacists (CCPs) have been clearly established as value-added members of the interprofessional team, and their contributions positively impact patient outcomes in the intensive care unit (ICU). Despite this, not every critically ill patient in the US receives care from a CCP and the model through which CCPs practice is variable, which has important implications. The purpose of this primer is to review current CCP models and discuss elements of the optimal CCP practice model.

Current CCP practice models are defined, including the drug processing and dispensing model, clinical pharmacy specialist model, integrated pharmacy generalist model, and hybrid model, as well as unit-based vs service-based models. The optimal CCP practice model considers the Triple Domain of CCP workload, which includes direct patient care, indirect patient care, and professional service. Elements of the ideal CCP practice model including 24/7/365 CCP services, unit- vs service-based models, prescriptive authority, operational support, and CCP-to-patient ratio are discussed. Other vital elements include dedicated offline time, use of appropriate workload metrics, development of career ladders, opportunities for professional development, and providing wellness resources. The ideal CCP practice model must also be considered through the lens of the patient and medical team, the CCP, the institution, and professional organizations. Strategies for optimizing current CCP practice models are provided, and application of optimal CCP practice model elements is explored through 5 case studies.

Conclusion

The optimal CCP practice model includes multiple elements and incorporates the viewpoints of patients, providers, CCPs, institutions, and professional organizations; this model will increase access of all ICU patients to CCPs, enhance the scope of CCP cognitive services, and ensure the economic sustainability of CCP practice while establishing CCP involvement in activities outside of patient care and in professional service.
Heterogeneity, Bayesian thinking, and phenotyping in critical care: A primer
Authors: Jones Timothy W , Hedrick Tanner , Chase Aaron M
Published: May 2024

Purpose

To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect.

The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field’s research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research.

Conclusion

The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice.
Sex differences in neuronal activation in the cortex and midbrain during quinine-adulterated alcohol intake
Authors: Arnold Miranda E , Schank Jesse R
Published: May 2024

Aims

Continued alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This is modeled in mice by pairing negative stimuli with alcohol, such as adulterating alcohol solution with quinine. Mice consuming alcohol under these conditions are considered to be engaging in aversion-resistant intake. Previously, we have observed sex differences in this behavior, with females more readily expressing aversion-resistant consumption. We also identified three brain regions that exhibited sex differences in neuronal activation during quinine-alcohol drinking: ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA). Specifically, male mice showed increased activation in vmPFC and PIC, while females exhibited increased activation in VTA. In this study, we aimed to identify what specific type of neurons are activated in these regions during quinine-alcohol drinking.

Method

We assessed quinine-adulterated alcohol intake using the two-bottle choice procedure. We also utilized RNAscope in situ hybridization in the three brain regions that previously exhibited a sex difference to examine colocalization of Fos, glutamate, GABA, and dopamine.

Result

Females showed increased aversion-resistant alcohol consumption compared to males. We also found that males had higher colocalization of glutamate and Fos in vmPFC and PIC, while females had greater dopamine and Fos colocalization in the VTA.

Conclusions

Collectively, these experiments suggest that glutamatergic output from the vmPFC and PIC may have a role in suppressing, and dopaminergic activity in the VTA may promote, aversion-resistant alcohol consumption. Future experiments will examine neuronal circuits that contribute to sex differences in aversion resistant consumption.
High freezing sensitivity of legumes relative to other herbaceous species in northern temperate plant communities
Authors: Rycroft Samuel L , Henry Hugh A L
Published: May 2024

Background and Aims

Reduced snow cover and increased air temperature variability are predicted to expose overwintering herbaceous plants to more severe freezing in some northern temperate regions. Legumes are a key functional group that may exhibit lower freezing tolerance than other species in these regions, but this trend has been observed only for non-native legumes. Our aim was to confirm if this trend is restricted to non-native legumes or whether native legumes in these regions also exhibit low freezing tolerance.

Methods

First, we transplanted legumes (five non-native species and four native species) into either an old field (non-native) or a prairie (native) and used snow removal to expose the plots to increased soil freezing. Second, we grew plants in mesocosms (old field) and pots (prairie species) and exposed them in controlled environment chambers to a range of freezing treatments (control, 0, −5 or −10 °C) in winter or spring. We assessed freezing responses by comparing differences in biomass, cover and nodulation between freezing (or snow removal) treatments and controls.

Key Results

Among legume species, lower freezing tolerance was positively correlated with a lower proportion of nodulated plants and active nodules, and under controlled conditions, freezing-induced reductions in above-ground biomass were lower on average in native legumes than in non-native legumes. Nevertheless, both non-native and native legumes (except Desmodium canadense) exhibited greater reductions in biomass in response to increased freezing than their non-leguminous neighbours, both in controlled environments and in the field.

Conclusions

These results demonstrate that both native and non-native legumes exhibit low freezing tolerance relative to other herbaceous species in northern temperate plant communities. By reducing legume biomass and nodulation, increased soil freezing could reduce nitrogen inputs into these systems.
Trade secrets at risk—the protection against expropriation of a trade secret
Authors: Ferguson Alexander
Published: May 2024

An investor exploiting their trade secret in a foreign territory puts it at risk of disclosure, use, or regulation by the host State. If the risk materializes, a foreign investor may seek to mitigate the impacts with the protections afforded by an investment treaty. As investors in the Czech Republic, Kenya, Pakistan, and Venezuela have sought to do. While the protection of trade secrets has been noted by commentators, a detailed analysis of the protection of trade secrets under international investment law is yet to be offered. In this article, I outline how trade secrets amount to an ‘investment’, the types of risks to a trade secret, and how the protection against expropriation can mitigate four risks for a foreign investor.
Imaging and therapy in prostate cancer using prostate specific membrane antigen radioligands
Authors: Naik Mitesh , Khan Sairah R , Lewington Valerie , Challapalli Amarnath , Eccles Amy , Barwick Tara D
Published: May 2024

Prostate specific membrane antigen (PSMA) directed PET imaging has rapidly transformed prostate cancer workup over the past decade and paved the way for a theranostic approach using 177Lu-labelled PSMA radioligand therapy (RLT). This review gives an overview of the underlying principles behind PSMA as a target; the current use of PSMA PET in prostate cancer imaging and benefits compared to conventional imaging; and therapeutic applications including optimisation of patient selection. It also explores the evidence base of PSMA PET for other indications not in routine clinical use and the future of PSMA-directed RLT.
Blood–CSF barrier integrity in amyotrophic lateral sclerosis
Authors: Klose Veronika , Jesse Sarah , Lewerenz Jan , Kassubek Jan , Dorst Johannes , Rosenbohm Angela , Nagel Gabriele , Wernecke Deborah , Roselli Francesco , Tumani Hayrettin , Ludolph Albert C
Published: May 2024

The integrity of the blood–CSF barrier plays a major role in inflammation, but also in shielding the CNS from external and systemic—potentially toxic—factors. Here we report results of measurements of the albumin quotient—which is thought to mirror the integrity of the blood-CSF barrier—in 1059 patients with amyotrophic lateral sclerosis. The results were compared with groups of patients suffering from Alzheimer’s disease, facial palsy and tension headache.

The albumin quotient, an accepted measure of the blood-CSF barrier integrity, was not significantly different from control populations. In addition, we found that the albumin quotient correlated with survival of the patients; this effect was mainly driven by male patients and influenced by age, body mass index and diabetes mellitus.

We conclude that the blood-CSF barrier is intact in this large cohort of patients with amyotrophic lateral sclerosis and that the albumin quotient correlates with survival. Whether this is important for the pathogenesis of the disease, requires mechanistic studies.
High frequency oscillations in human memory and cognition: a neurophysiological substrate of engrams?
Authors: Kucewicz Michal T , Cimbalnik Jan , Garcia-Salinas Jesus S , Brazdil Milan , Worrell Gregory A
Published: May 2024

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes.

High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60–150 Hz), ripple (80–250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing.

Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.
Metal-desorption and selective metal-trapping properties of an organized molecular film of azacalixarene-containing copolymer with spherulite-forming ability
Authors: Terui Ryoma , Otsuki Yuto , Shibasaki Yuji , Fujimori Atsuhiro
Published: May 2024

The metal-trapping and metal-desorption abilities and selective metal-scavenging properties of an interfacial molecular film of a highly ordered copolymer that exhibits spherulite-forming ability in the bulk state, despite having bulky azacalixarene rings, were investigated. The synthesized copolymer contained an azacalixarene ring and a crystalline polyethylene-glycol-chain-based repeating unit. The monolayer on the water surface of this copolymer was able to collect various metal ions from the subphase and trap monovalent ions; this was not possible with other derivatives. As the metal cations were incorporated via weak interactions with the applied electric field inside the azacalixarene ring, they could be desorbed or recovered by using simple ultrasonic treatment. The valences and ionic radii of the captured cations strongly influenced the desorption behavior. In addition, characteristic selectivity was confirmed by evaluating the ability to capture metals from the subphase containing multiple metal cations. The preference for the trapping ion was strongly correlated with the difficulty of desorption from the azacalixarene ring.
Organocatalyzed asymmetric Mannich reaction of α-aminomaleimides with N-Boc imines
Authors: Suzuki Shun , Kimura Kodai , Han Wei , Oriyama Takeshi
Published: May 2024

The first asymmetric Mannich reaction of α-aminomaleimides with N-Boc imines was successfully performed using 5 mol% of a urea-type organocatalyst derived from quinine to afford the corresponding Mannich adducts in high yields with high enantioselectivities. This protocol has a simple experimental procedure, good functional group tolerance, broad substrate scope, and high enantioselectivities.
Loss-of-function FLG mutations are associated with reduced history of acne vulgaris in a cohort of patients with atopic eczema of Bangladeshi ancestry in East London
Authors: Hughes Aaron J , Barbosa Elsa , Cernova Jeva , Thomas Bjorn R , O’Shaughnessy Ryan F L , O’Toole Edel A
Published: May 2024

Background

Acne vulgaris (AV) is the eighth most common nonfatal disease globally. Previous work identified an association between AV and increased filaggrin (FLG) protein expression in the follicular epidermis, but further work did not find a clear link between loss-of-function (LoF) FLG gene mutations and protection from AV.

Objectives

To explore any association between AV and FLG LoF mutations in a cohort of genotyped patients of Bangladeshi ancestry with atopic eczema (AE) in East London.

Methods

A retrospective notes review was performed on 245 patients who had been genotyped for FLG LoF mutations and undergone ­clinical assessment. A χ2-test or Fisher’s exact test was used to determine differences in AV history between FLG LoF genotype groups.

Results

We found a significant reduction in history of AV in patients with AE with FLG LoF mutations (19 of 82) relative to those without FLG mutations (47 of 129) (23% vs. 36.4%; P = 0.02). We showed a nonsignificant reduction in AV diagnosis in patients with impaired barrier function (measured by transepidermal water loss) and palmar hyperlinearity. We found that patients with severe AE were less likely to have a history of AV only if they had an existing FLG LoF mutation (P = 0.02).

Conclusions

In the context of AE, our work suggests that FLG LoF mutations protect patients from developing AV.
Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records
Authors: Matthewman Julian , Mulick Amy , Dand Nick , Major-Smith Daniel , Henderson Alasdair , Pearce Neil , Denaxas Spiros , Iskandar Rita , Roberts Amanda , Cornish Rosie P , Brown Sara J , Paternoster Lavinia , Langan Sinéad M
Published: May 2024

Background

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on the presence and severity of symptoms reported in questionnaires (severe–frequent, moderate–frequent, moderate–declining, mild–intermittent, unaffected–rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inference of subtypes from EHRs alone, which would enable their study in large primary care databases.

Objectives

Firstly, to explore whether the presence and number of AD records in EHRs agree with AD symptom and severity reports from ALSPAC. Secondly, to explore whether EHRs agree with ALSPAC-derived AD subtypes. Thirdly, to construct models to classify ALSPAC-derived AD subtypes using EHRs.

Methods

We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991–2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g. diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models, tuning hyperparameters and evaluating performance in the testing set [receiver operating characteristic (ROC) area under the curve (AUC), accuracy, sensitivity and specificity].

Results

Overall, 8828 individuals out of a total 13 898 had been assigned an AD subtype and also had linked EHRs. The number of AD-related codes in EHRs generally increased with the severity of the AD subtype. However, not all patients with the severe–frequent subtype had AD in EHRs, and many with the unaffected–rare subtype did have AD in EHRs. When predicting the ALSPAC AD subtype using EHRs, the best tuned model had an ROC AUC of 0.65, a sensitivity of 0.29 and a specificity of 0.83 (both macro-averaged). When different sets of predictors were used, individuals with missing EHR coverage were excluded, and subtypes were combined, sensitivity was not considerably improved.

Conclusions

ALSPAC and EHRs disagreed not only on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered to have AD in one source may not be considered to have AD in another.
Aberrant effort-based reward dynamics in anhedonia
Authors: Wen Hailing , Wu Menglin , Wang Zhao , Gao Bo , Zheng Ya
Published: May 2024

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost–benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.
Exploring intricate connectivity patterns for cognitive functioning and neurological disorders: incorporating frequency-domain NC method into fMRI analysis
Authors: Wang Bocheng ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

This study extends the application of the frequency-domain new causality method to functional magnetic resonance imaging analysis. Strong causality, weak causality, balanced causality, cyclic causality, and transitivity causality were constructed to simulate varying degrees of causal associations among multivariate functional-magnetic-resonance-imaging blood-oxygen-level-dependent signals. Data from 1,252 groups of individuals with different degrees of cognitive impairment were collected. The frequency-domain new causality method was employed to construct directed efficient connectivity networks of the brain, analyze the statistical characteristics of topological variations in brain regions related to cognitive impairment, and utilize these characteristics as features for training a deep learning model. The results demonstrated that the frequency-domain new causality method accurately detected causal associations among simulated signals of different degrees. The deep learning tests also confirmed the superior performance of new causality, surpassing the other three methods in terms of accuracy, precision, and recall rates. Furthermore, consistent significant differences were observed in the brain efficiency networks, where several subregions defined by the multimodal parcellation method of Human Connectome Project simultaneously appeared in the topological statistical results of different patient groups. This suggests a significant association between these fine-grained cortical subregions, driven by multimodal data segmentation, and human cognitive function, making them potential biomarkers for further analysis of Alzheimer’s disease.
Lowering the Acquisition of Multidrug-Resistant Organisms (MDROs) With Pulsed-xenon (LAMP) Study: A Cluster-Randomized, Controlled, Double-Blinded, Interventional Crossover Trial
Authors: Dhar Sorabh , Jinadatha Chetan , Kilgore Paul E , Henig Oryan , Divine George W , Todter Erika N , Coppin John D , Carter Marissa J , Chopra Teena , Egbert Steve , Carling Philip C , Kaye Keith S
Published: May 2024

Background

Environmental disinfection is essential for reducing spread of healthcare-associated infections (HAIs). Previous studies report conflicting results regarding the effects of ultraviolet (UV) light in reducing infections. This trial evaluated the impact of adding pulsed-xenon UV (PX-UV) to standard terminal cleaning in reducing environmentally implicated HAIs (eiHAIs).

Methods

The Lowering the Acquisition of MDROs with Pulsed-xenon (LAMP) trial was conducted in 2 hospitals (15 inpatient wards) utilizing a cluster-randomized, controlled, double-blinded, interventional crossover trial comparing standard terminal cleaning followed by either PX-UV (intervention arm) or sham (control arm) disinfection. The primary outcome was incidence of eiHAIs from clinical microbiology tests on the fourth day of stay or later or within 3 days after discharge from the study unit. EiHAIs included clinical cultures positive for vancomycin-resistant enterococci, extended-spectrum beta-lactamase–producing Escherichia coli or Klebsiella pneumonia, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii, and stool polymerase chain reaction (PCR) positive for Clostridiodes difficile.

Results

Between 18 May 2017 and 7 January 2020, 25 732 patients were included, with an incidence of 601 eiHAIs and 180 954 patient-days. There was no difference in the rate of eiHAIs in the intervention and sham arms (3.49 vs 3.17 infections/1000 patient-days, respectively; RR, 1.10; 95% CI, .94–1.29; P = .23). Study results were similar when stratified by eiHAI type, hospital, and unit type.

Conclusions

The LAMP study failed to demonstrate an effect of the addition of UV light disinfection following terminal cleaning on reductions in rates of eiHAIs. Further investigations targeting hospital environmental surfaces and the role of no-touch technology to reduce HAIs are needed.

Clinical Trials Registration.  ClinicalTrials.gov identifier: NCT03349268; R01HS024709.
Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy
Authors: Xia Wen , Deng Jiayi , Zhuang Lulu , Xu Feng , Jin Ying , Zhou Houan , Zhang Ti , Liu Zhengzhao , Zhang Haitao , Zeng Caihong , Liu Zhihong , Hu Weixin
Published: May 2024

Background

Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analysed the clinicopathological features and risk factors for AKI and relapse in lupus podocytopathy patients.

Methods

The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022 and was divided into the mild glomerular lesion (MGL) and focal segmental glomerulosclerosis (FSGS) groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regressions were employed to identify the risk factors for AKI and relapse, respectively.

Results

Among 6052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in the CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared with the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and haematuria; in addition, they had higher Systemic Lupus Erythematosus Disease Activity Index 2000, ATI and CTI scores but a significantly lower CRR rate. Urinary protein ≥7.0 g/24 h and serum C3 ≤0.750 g/l were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for kidney relapse.

Conclusions

In this study, histological subtypes of lupus podocytopathy were found to be associated with clinical features and treatment response. In addition, several risk factors associated with AKI occurrence and kidney relapse were identified.
Harnessing the potential of monocytes/macrophages to regenerate tissue-engineered vascular grafts
Authors: Das Arundhati , Smith Randall J , Andreadis Stelios T
Published: May 2024

Cell-free tissue-engineered vascular grafts provide a promising alternative to treat cardiovascular disease, but timely endothelialization is essential for ensuring patency and proper functioning post-implantation. Recent studies from our lab showed that blood cells like monocytes (MCs) and macrophages (Mϕ) may contribute directly to cellularization and regeneration of bioengineered arteries in small and large animal models. While MCs and Mϕ are leucocytes that are part of the innate immune response, they share common developmental origins with endothelial cells (ECs) and are known to play crucial roles during vessel formation (angiogenesis) and vessel repair after inflammation/injury. They are highly plastic cells that polarize into pro-inflammatory and anti-inflammatory phenotypes upon exposure to cytokines and differentiate into other cell types, including EC-like cells, in the presence of appropriate chemical and mechanical stimuli. This review focuses on the developmental origins of MCs and ECs; the role of MCs and Mϕ in vessel repair/regeneration during inflammation/injury; and the role of chemical signalling and mechanical forces in Mϕ inflammation that mediates vascular graft regeneration. We postulate that comprehensive understanding of these mechanisms will better inform the development of strategies to coax MCs/Mϕ into endothelializing the lumen and regenerate the smooth muscle layers of cell-free bioengineered arteries and veins that are designed to treat cardiovascular diseases and perhaps the native vasculature as well.
Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis
Authors: Paolucci Luca , Mangiacapra Fabio , Sergio Sara , Nusca Annunziata , Briguori Carlo , Barbato Emanuele , Ussia Gian Paolo , Grigioni Francesco
Published: May 2024

Background and Aims

Conflicting data are available regarding the association between periprocedural myocardial infarction (PMI) and mortality following percutaneous coronary intervention. The purpose of this study was to evaluate the incidence and prognostic implication of PMI according to the Universal Definition of Myocardial Infarction (UDMI), the Academic Research Consortium (ARC)-2 definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition.

Methods

Studies reporting adjusted effect estimates were systematically searched. The primary outcome was all-cause death, while cardiac death was included as a secondary outcome. Studies defining PMI according to biomarker elevation without further evidence of myocardial ischaemia (‘ancillary criteria’) were included and reported as ‘definition-like’. Data were pooled in a random-effect model.

Results

A total of 19 studies and 109 568 patients were included. The incidence of PMI was progressively lower across the UDMI, ARC-2, and SCAI definitions. All PMI definitions were independently associated with all-cause mortality [UDMI: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.32–1.97; I2 34%; ARC-2: HR 2.07, 95% CI 1.40–3.08, I2 0%; SCAI: HR 3.24, 95% CI 2.36–4.44, I2 78%]. Including ancillary criteria in the PMI definitions were associated with an increased prognostic performance in the UDMI but not in the SCAI definition. Data were consistent after evaluation of major sources of heterogeneity.

Conclusions

All currently available international definitions of PMI are associated with an increased risk of all-cause death after percutaneous coronary intervention. The magnitude of this latter association varies according to the sensitivity and prognostic relevance of each definition.
Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi
Authors: Linnenbrink Miriam , Breton Gwenna , Misra Pallavi , Pfeifle Christine , Dutheil Julien Y , Tautz Diethard
Published: May 2024

De novo evolved genes emerge from random parts of noncoding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which has been implicated to have a role in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment's demography, we could estimate a selection coefficient ranging between 0.21 and 0.61 for the wildtype allele compared to the ko allele in males, under various models. This implies a relatively strong selective advantage, which would fix the new gene in less than hundred generations after its emergence.
Deleterious mutation/epimutation–selection balance with and without inbreeding: a population (epi)genetics model
Authors: Chernomas Gregory , Griswold Cortland K
Published: May 2024

Epigenetics in the form of DNA methylation and other processes is an established property of genotypes and a focus of empirical research. Yet, there remain fundamental gaps in the evolutionary theory of epigenetics. To support a comprehensive understanding of epigenetics, this paper investigates theoretically the combined effects of deleterious mutation and epimutation with and without inbreeding. Both spontaneous epimutation and paramutation are considered to cover a broader range of epigenetic phenomena. We find that inbreeding generally reduces the amount of segregating deleterious genetic and epigenetic variation at equilibrium, although interestingly inbreeding can also increase the amount of deleterious genetic or epigenetic variation. Furthermore, we also demonstrate that epimutation indirectly can cause increased or decreased deleterious genetic variation at equilibrium relative to classic expectations, which is particularly evident when paramutation is occurring. With the addition of deleterious epimutation, there may be significantly increased purging of deleterious variation in more inbred populations and a significantly increased amount of segregating deleterious variation in more outbred populations, with notable exceptions.
Physical Activity Fragmentation and Falls in Older Adults: Findings From the National Health and Aging Trends Study
Authors: Popelsky Braden K , Pettee Gabriel Kelley , Dooley Erin E , Ylitalo Kelly R
Published: May 2024

Background

Physical activity (PA) may be an important fall prevention strategy. Current PA guidelines emphasize total PA dose, but daily patterning of PA is underappreciated. With aging, PA bouts become less frequent and shorter in duration (ie, more fragmented). PA fragmentation may be an indicator of fall risk, but the relationship is not well understood. This study examined daily PA accumulation and patterns with fall risk in older adults.

Methods

Participants (n = 685, 54.3% women, 61.5% aged 70–79 years) from the National Health and Aging Trends Study with wrist-worn accelerometry PA data from Round 11 (baseline) and sample person interviews with fall data from Round 12 (follow-up) were included. PA variables were categorized into tertiles and incident falls were defined as ≥1 self-reported fall in the year following the PA assessment between baseline and follow-up. A modified Poisson approach was used to estimate the relative risk of both PA accumulation and fragmentation with falls.

Results

Overall, 40.0% reported an incident fall. After adjustment for sociodemographic and health characteristics, those in the highest tertile of total PA accumulation had lower fall risk (aRR = 0.74, 95% CI: 0.57, 0.95) and those in the highest tertile of PA fragmentation had increased fall risk (aRR = 1.33, 95% CI: 1.03, 1.73). Models were attenuated after adjustment for physical functioning.

Conclusions

PA fragmentation may identify fall risk in older adults. Longitudinal studies are needed to disentangle the temporal sequencing of the complex relationship between PA and physical functioning across the life course.
Separating the Effects of Transitions Into and Out of Social Isolation and Loneliness on Cognitive Function in Later Life
Authors: Kim Jinho , Hwang Sungsik
Published: May 2024

Objectives

This study investigates the effects of social isolation and loneliness on cognitive function, distinguishing between the effects of transitioning into and out of these states.

Methods

This study analyzed data from 6,663 adults aged 65 or older collected over the course of 7 waves (12 years) of the Korean Longitudinal Study of Aging from 2006 to 2018. A novel asymmetric fixed effects model was utilized to separately estimate the effects of transitions into and out of social isolation or loneliness.

Results

The association of transitions into social isolation due to a lack of informal social contact or loneliness with cognitive function (b = −1.387, p < .001 and b = −0.601, p < .001, respectively) was stronger than the association of transitions out of these states (b = 0.345, p < .05 and b = 0.353, p < .001, respectively). The magnitude of the negative and positive coefficients was statistically different (F-statistic = 45.29, p < .001 and F-statistic = 5.12, p < .05, respectively). In contrast, no such asymmetric effects were observed for social isolation due to a lack of formal activity (F-statistic = 0.06, p = .800).

Discussion

The detrimental effects of transitioning into social isolation due to a lack of informal social contact (but not formal activity) or loneliness on cognitive function outweigh the beneficial effects of transitioning out of these states. Preventing the onset of social disconnection should be prioritized as an intervention to improve the cognitive function of older adults.