bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity, Bayesian thinking, and phenotyping in critical care: A primer
Authors: Jones Timothy W , Hedrick Tanner , Chase Aaron M 
Published: May 2024

Abstract

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.

Summary
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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract

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.