bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol metabolism in alcohol use disorder: a potential therapeutic target
Authors: Lehner Taylor , Gao Bin , Mackowiak Bryan 
Published: November 2023

Abstract
Ethanol metabolism plays an essential role in how the body perceives and experiences alcohol consumption, and evidence suggests that modulation of ethanol metabolism can alter the risk for alcohol use disorder (AUD). In this review, we explore how ethanol metabolism, mainly via alcohol dehydrogenase and aldehyde dehydrogenase 2 (ALDH2), contributes to drinking behaviors by integrating preclinical and clinical findings. We discuss how alcohol dehydrogenase and ALDH2 polymorphisms change the risk for AUD, and whether we can harness that knowledge to design interventions for AUD that alter ethanol metabolism. We detail the use of disulfiram, RNAi strategies, and kudzu/isoflavones to inhibit ALDH2 and increase acetaldehyde, ideally leading to decreases in drinking behavior. In addition, we cover recent preclinical evidence suggesting that strategies other than increasing acetaldehyde-mediated aversion can decrease ethanol consumption, providing other potential metabolism-centric therapeutic targets. However, modulating ethanol metabolism has inherent risks, and we point out some of the key areas in which more data are needed to mitigate these potential adverse effects. Finally, we present our opinions on the future of treating AUD by the modulation of ethanol metabolism.
Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: pooled data from up to 3 years of treatment in randomized phase III trials
Authors: Gordon Kenneth B , Langley Richard G , Warren Richard B , Okubo Yukari , Rosmarin David , Lebwohl Mark , Peterson Luke , Madden Cynthia , de Cuyper Dirk , Davies Owen , Thaçi Diamant 
Published: November 2023

Abstract

Background
Patients with psoriasis require long-term management; therefore, understanding the long-term safety of new treatments, such as bimekizumab (BKZ), is crucial.

Objectives
To evaluate BKZ’s 3-year safety profile in patients with moderate-to-severe plaque psoriasis.

Methods
Three years of safety data were pooled from three phase III trials (BE VIVID, BE READY and BE SURE) and their ongoing open-label extension (BE BRIGHT). Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY).

Results
In total, 1495 patients received at least one BKZ dose; total BKZ exposure was 3876.4 PY. The overall EAIR of TEAEs was 175.5/100 PY and decreased with longer exposure to BKZ. The most commonly reported TEAEs were nasopharyngitis, oral candidiasis and upper respiratory tract infection (EAIRs of 15.0/100 PY, 10.1/100 PY and 6.5/100 PY, respectively); 99.3% of oral candidiasis events were mild or moderate in severity, none were serious and few led to discontinuation. EAIRs of other TEAEs of interest were low, including serious infections (1.2/100 PY), adjudicated inflammatory bowel disease (0.2/100 PY) and laboratory elevations in aspartate aminotransferase or alanine aminotransferase (&gt; 5 × upper limit of normal: 0.6/100 PY).

Conclusions
In these analyses pooled across 3 years, no new safety signals were observed with longer exposure to BKZ. The vast majority of oral candidiasis events were mild or moderate in severity, as reported previously.
CD3 downregulation identifies high-avidity human CD8 T cells
Authors: Clutton Genevieve T , Weideman Ann Marie K , Mischell Melissa A , Kallon Sallay , Conrad Shayla Z , Shaw Fiona R , Warren Joanna A , Lin Lin , Kuruc JoAnn D , Xu Yinyan , Gay Cynthia M , Armistead Paul M , G. Hudgens Michael , Goonetilleke Nilu P 
Published: November 2023

Abstract
CD8 T cells recognize infected and cancerous cells via their T-cell receptor (TCR), which binds peptide–MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide–MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide–MHC stimulation, the TCR–CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modeling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
Plasma circulating microRNAs associated with blood-based immune markers: a population-based study
Authors: Leonard Samantha , Karabegović Irma , Ikram M Arfan , Ahmad Shahzad , Ghanbari Mohsen 
Published: November 2023

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression and different immune-related pathways. There is a great interest in identifying miRNAs involved in immune cell development and function to elucidate the biological mechanisms underlying the immune system, its regulation, and disease. In this study, we aimed to investigate the association of circulating miRNAs with blood cell compositions and blood-based immune markers. Circulating levels of 2083 miRNAs were measured by RNA-sequencing in plasma samples of 1999 participants from the population-based Rotterdam Study collected between 2002 and 2005. Full blood count measurements were performed for absolute granulocyte, platelet, lymphocyte, monocyte, white, and red blood cell counts. Multivariate analyses were performed to test the association of miRNAs with blood cell compositions and immune markers. We evaluated the overlap between predicted target genes of candidate miRNAs associated with immune markers and genes determining the blood immune response markers. First, principal component regression analysis showed that plasma levels of circulating miRNAs were significantly associated with red blood cell, granulocyte, and lymphocyte counts. Second, the cross-sectional analysis identified 210 miRNAs significantly associated (P &lt; 2.82 × 10−5) with neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index. Further genetic look-ups showed that target genes of seven identified miRNAs (miR-1233-3p, miR-149-3p, miR-150-5p, miR-342-3p, miR-34b-3p, miR-4644, and miR-7106-5p) were also previously linked to NLR and PLR markers. Collectively, our study suggests several circulating miRNAs that regulate the innate and adaptive immune systems, providing insight into the pathogenesis of miRNAs in immune-related diseases and paving the way for future clinical applications.
Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain
Authors: Szczupak Diego , Schaeffer David J , Tian Xiaoguang , Choi Sang-Ho , Fang-Cheng  , Iack Pamela Meneses , Campos Vinicius P , Mayo J Patrick , Patsch Janina , Mitter Christian , Haboosheh Amit , Kwon Ha Seung , Vieira Marcelo A C , Reich Daniel S , Jacobson Steve , Kasprian Gregor , Tovar-Moll Fernanda , Lent Roberto , Silva Afonso C 
Published: November 2023

Abstract
Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.
The Forgotten Rival of Marxism Today: The British Labour Party’s New Socialist and the Business of Political Culture in the Late Twentieth Century
Authors: Murphy Colm 
Published: November 2023

Abstract
In recent years, historians of modern Britain have focused on reconstructing its ‘political culture’, drawing extensively upon print sources. This work routinely highlights the commercial pressures that shape some types of print media—especially popular newspapers—but is less attentive to others. This article argues for closer attention to the business and financial contexts of a broader spectrum of Britain’s political culture in the late twentieth century. Drawing on histories of publishing, it illustrates the importance of business through a case-study of party-political intellectual journals for the 1980s British left. No history of the 1980s is complete without reference to the Communist Party’s glamorous Marxism Today. However, scholars have overlooked one of its significant market competitors. In 1981, the Labour Party founded its own intellectual magazine, the New Socialist. Initially, it was highly successful, recording healthy circulation figures and attracting iconoclastic pieces by leading socialists. Its early commercial success shows that it has been unjustly neglected since. Yet unfavourable political winds and internal editorial divisions fatally overlapped with ruinous business decisions in a worsening financial environment. This precipitated the collapse of New Socialist in the later 1980s—just as its Eurocommunist rival declared the arrival of the ‘New Times’ and wrote itself into history books. Closer attention to business contexts thus returns New Socialist to histories of the left and provides a better map of its ideological debates during a transformative decade. It also situates the travails of the 1980s left within social and cultural trends over the twentieth century.
Is every teacher a teacher of oracy?
Authors: Moorghen Amanda 
Published: November 2023

Abstract
In this article I argue that oracy is disciplinary: it has both generic and subject-specific dimensions that need to be taught explicitly. As such, every educator has a responsibility for teaching students the oracy skills they need in their subject domain; and providing them with the opportunity to practise using them. It cannot be hidden within a single department (e.g. treated as part of ‘English’ only), or treated as an add-on (e.g. ‘academic skills’, taught a-contextually and without relation to subject-experts).
Safety and feasibility of robotic probe steering in echocardiography
Authors: Man J P , Prendergast J M , Schuuring M J , Chamuleau S A J , Bouma B J 
Published: November 2023

Abstract

Introduction
Work related injury is common in medical sonographers. A robotic arm designed to assist in a (transthoracic echocardiography) TTE might be a useful alternative to alleviate the muscle strain of sonographers.

Purpose
In this study the feasibility and safety of a robotic device intended to improve the ergonomics of TTE is tested.

Methods
A CE marked robotic device (LBR iiwa 7 R800, KUKA) mounted with a transthoracic echoprobe and an echo calibration phantom (UltraiQ General Purpose fantoom, Cablon medical) were used to assess the feasibility of robotic assistance. A predefined protocol was used to acquire images of the phantom in 6 standardized viewpoints of the robotically controlled echo probe with respect to the phantom. The probe was moved from a predefined standardized starting point to the first viewpoint, perpendicular to the surface of the phantom. The probe was subsequently rotated 20° and -20° along both its long and short axis, and 90° around its central axis to reach the other 5 viewpoints. Time to and maximum contact force during acquisition was measured. The maximum contact force used during a manual standard TTE acquisition was also measured using the same force sensor. All measurements were performed 3 times.

Results
The average time to reach the 1st viewpoint perpendicular to the surface of the phantom from above the phantom was 4.6s, the maximum contact force was 10.1N. The time used for rotation on the short axis of the probe was 4.1 s, with a maximum force of 11.8N. The time it took to rotate the probe 20° and -20° around its long axis to reach viewpoints 4 and 5 was 4.5s with a maximum force of 9.48N. The average time to rotate the probe 90° around its axis and reach the 6th viewpoint was 5.0 s, the maximum contact force at the rotated axis was 10.3N. The maximum contact force was 11.8N throughout all movements. The reference maximum contact force by manual TTE assessment on a human was 11.5N. The contact forces of the probe controlled by a robot on the phantom did not exceed the predefined maximum force throughout standardized movements used during a TTE assessment.

Conclusion
Robotically assisted TTE scanning was safe in terms of the applied force throughout image acquisition in all viewpoints and comparable with forces used during manual TTE. Imaging at target viewpoints used in a regular TTE assessment was feasible as all images were acquired within a reasonable timeframe. Further studies are needed to evaluate its effectiveness in transthoracic echocardiography in volunteers and patients.
Assessing left atrial size to predict mortality in the overweight and obese population
Authors: Madronio C , Low G , Nundlall N , Strange G , Playford D , Negishi K , Pathan F 
Published: November 2023

Abstract

Background
Left atrial (LA) size provides important prognostic information. A larger LA is associated with a higher risk of death or cardiovascular complications. LA size is generally measured by indexing LA volume to body surface area (BSA). For individuals with a higher BSA, particularly those with obesity, this may lead to an underestimation of true LA size. Alternate indexation methods of measuring LA size have been proposed for this population. There is limited data showing if these indices provide better prognostic value compared to the standard BSA indexation in the overweight and obese population.

Purpose
To determine and compare the performance of various LA size indices in predicting all-cause mortality.

Methods
We obtained data from the National Echocardiography Database of Australia (NEDA), a large, observational registry, capturing routinely acquired echocardiographic data from individuals with potential or established heart disease. Our study outcome was all-cause mortality and LA size was our predictor variable. We evaluated ten indices for LA size: LA volume (obtained at time of scan), and LA volume indexed to BSA, idealised BSA, height(^1, ^2, ^2.7, ^1.83), weight, body mass index (BMI), and estimated lean body mass. From the original NEDA dataset, we excluded observations with: missing values for LA volume, height, weight, and ejection fraction (EF); date of examination is after the census date; and indication of valvular disease. Finally, we selected only the earliest observation for each individual and obtained a sub-population with overweight and obesity for analysis (n = 113,786). We conducted a receiver operating characteristic (ROC) analysis and calculated the summary statistic of the area under the curve (AUC) to compare the accuracy of the ten LA size indices in predicting all-cause mortality.

Results
In the overweight and obese population, all the LA indices had similar predicting accuracy for all-cause mortality (Figure 1). Raw LA volume and LA volume/BMI had slightly lower AUC: AUC [95% confidence interval] values were 0.61 [0.605-0.614] and 0.61 [0.607-0.616], respectively. Other indices, including LA volume/BSA, LA volume/weight and LA volume/height, had equivalent predictive accuracy (0.62∼0.63) for all-cause mortality (Figure 2).

Conclusion
Overall, all LA size indices performed similarly in predicting all-cause mortality in this overweight and obese population, except for LA volume/BMI. Our results found no superior indexation method (including allometric ones) to the current practice (i.e., LA volume/BSA) in this population.ROC curves of indicesAUC, 95% confidence intervals of indices
Treatment with sacubitril/valsartan and improvement of ventricular-arterial coupling in heart failure with reduced ejection fraction
Authors: Stegmann T , Parentin L , Schirmer S H , Hagendorff A , Laufs U , Lavall D 
Published: November 2023

Abstract

Background
Treatment with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) in patients with heart failure and reduced ejection fraction (HFrEF) reduces mortality and heart failure (HF) hospitalizations. The specific hemodynamic mechanisms underlying these beneficial effects are currently unclear.

Purpose
This study aimed to assess the effects of S/V treatment on left ventricular (LV) end-systolic elastance (Ees), effective arterial elastance (Ea), and the ventricular-arterial coupling ratio (Ea/Ees) in patients with HFrEF using non-invasive pressure-volume analysis.

Methods
117 patients with symptomatic HF and LVEF &lt;40% in whom treatment with S/V was initiated were enrolled in this multicenter German prospective study. We used transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements for non-invasive pressure-volume loop analyses. Primary endpoints were changes in Ees, Ea, and Ea/Ees ratio after six months of S/V treatment.

Results
The mean age was 65 (±13) years and 30% were female. In 54.7% of the patients, the etiology of HF was ischemic, and 45.3% was non-ischemic. 58.4% had first HF diagnosis at baseline. 102 patients with complete clinical and echocardiographic data at baseline and after six months of follow-up were analyzed. Among those, 62% were on target dose of S/V. Six months of S/V treatment resulted in a significant increase of Ees (0.66 mmHg/ml, IQR [0.45;0.94] vs. 0.78 mmHg/ml [0.57;1.10], p=0.001) and decrease of Ea (1.76 mmHg/ml [1.48;2.13] vs. 1.62 mmHg/ml [1.36;1.96], p=0.014). Hence, the Ea/Ees ratio significantly improved (2.52 [1.88;4.05] vs. 1.93 [1.50;2.63], p&lt;0.001). In addition, LV volumes and pressure improved significantly with a regression of the LV end-systolic volume (LVESV: 142 ml [115;180] vs. 96 ml [65;124]), end-diastolic volume (LVEDV: 216 ml [179;247] vs. 165 ml [132;200]) and LV end-diastolic pressure (LVEDP: 19.6 mmHg [18.2;22.4] vs. 17.8 mmHg [16.6;19.9]), p&lt;0.001 respectively. The LVEF increased from a median of 33% (27;37) to 43% (36;49), p&lt;0.001.
NT-proBNP level decreased from (median) 1771 pg/ml [838;5211] to 724 pg/ml [300;1575] and mean 6-minute walking distance increased from 371m (±125) to 423 m (±122), p&lt;0.001 respectively.
The percentage of patients with NYHA class III changed from 25.6% to 5.9%.

Conclusion
In a 6-months treatment period, initiation of sacubitril/valsartan in patients with heart failure and reduced ejection fraction was associated with reduction of LV volumes, improved LV function, reduction in afterload and fewer heart failure symptoms. These new data indicate that beyond reverse LV remodeling, improvement of LV contractility and ventricular-arterial coupling may contribute to the favorable clinical outcomes on treatment with sacubitril/valsartan in chronic heart failure.
Association between left atrial coupling index by echocardiography and left ventricular end diastolic pressure by left ventricular catheterization
Authors: Ravnkilde K , Olsen F J , Moegelvang R , Chantal De Knegt M , Galatius S , Pedersen S , Biering-Soerensen T 
Published: November 2023

Abstract

Background
Left atrial volumetric/mechanical coupling index (LACi) is a novel echocardiographic parameter combining important information regarding left atrial size and function in one variable. The association between LACi and invasive pressure measurements of diastolic function has not yet been investigated.

Purpose
We sought to investigate the association between LACi by echocardiography and left ventricular end-diastolic pressure (LVEDP) by left ventricular catheterization.

Methods
Patients suspected of coronary artery disease referred for angiography had simultaneous left heart catheterization performed for invasive pressure measurements and had an echocardiogram performed. LVEDP&gt;12mmHg was considered elevated. LACi was calculated as the index of LAVI (left atrial maximal volume index) and mean peak tissue velocity at late diastole measured using tissue Doppler at the base of the left ventricle.

Results
Forty patients were prospectively included of whom 73% were male and the mean age was 65 years. Median LACi was 2.9 (2.0, 4.1), and a total of 25 (63%) patients had elevated LVEDP. In unadjusted regression analyses, LVEDP increased with 2.3 (0.5-4.0) mmHg per 1.0 increase in LACi (p=0.013) (Figure 1, top panel). This association remained unchanged after adjusting for age and vessel disease (VD). In univariable logistic regression model, a 0.1 increase in LACi was associated with an 8% higher probability of having elevated LVEDP (OR 1.08, 95%CI (1.01-1.15), p=0.021). (Figure 1, bottom panel). These findings were consistent in multivariable analyses. Similar findings were observed in sensitivity analyses restricted to patients with normal LA size (LAVI&lt;34mL, n: 34) (OR 1.10, 95%CI (1.01-1.20), p=0.027, per 0.1 increase in LACi), which also remained unchanged after adjustment for age and VD.

Conclusion
LACi obtained by echocardiography is associated with LVEDP and with elevated LVEDP obtained by left ventricular catheterization. Even in those with normal LA size, higher LACi can indicate elevated filling pressure.