bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary effects of oral ANS-6637, an ALDH2 inhibitor, on cue-induced craving, safety and alcohol consumption among adults with alcohol use disorder: a proof-of-concept, randomized, human laboratory trial
Authors: O’Malley Stephanie S , Miranda Robert , Book Sarah W , Chun Thomas H , Liss Thomas , Malcolm Robert J , Muvvala Srinivas B , Padovano Hayley Treloar , Schacht Joseph P , Blackburn Brent , Diamond Ivan , Ransom Janet , Ryan Megan L , Falk Daniel E , Litten Raye Z 
Published: January 2025

Abstract

Aims
We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD).

Methods
A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200 mg and 600 mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session. Drinking and safety assessments were measured during treatment; other exploratory outcomes were measured 1 week after treatment ended.

Results
The study was terminated following enrollment of 43 of 81 planned participants due to clinically significant, reversible increases in liver enzymes in three women. Adverse events consistent with ALDH2 inhibition in the presence of alcohol (heart rate/palpitations, flushing, nausea) were dose dependent. Group differences in cue-elicited craving were not significant; effect sizes (Cohen’s d) comparing the 200 mg and 600 mg doses to placebo were .71 and .06, respectively. Secondary endpoints did not differ significantly between groups; Cohen’s d ranged from .31 to .57 for the 600 mg dose compared to placebo for continuous drinking outcomes.

Conclusions
Findings of liver toxicity with ANS-6637 led to early termination and reduced power to test hypotheses. Effect size estimates are consistent with the hypothesis that selective ALDH2 inhibition may reduce craving and drinking, however these estimates may be unreliable due to the small sample size. Additional research with non-hepatotoxic selective and reversible ALDH2 inhibitors is needed to evaluate this approach to AUD pharmacotherapy.
Tracking pollen tube and ovule development in vivo reveals rapid responses to pollination in Brassica napus
Authors: Parry Catherine , Turnbull Colin , Gill Richard J 
Published: January 2025

Abstract

Background and Aims
Pollination and subsequent fertilisation in most angiosperms are precursors of seed and fruit development. Thus, understanding the developmental processes can improve management of plant reproductive success and food security. Indeed, the window between ovule fertilisation and seed development is crucial for the accumulation of metabolites which determines ultimate seed quality and yield. Establishing detailed temporal maps of development to describe pollination to early seed development is therefore extremely valuable to provide context for molecular studies, plant breeding, and to refine crop management strategies for optimal seed quality.

Methods
Here, we characterise aspects of post-pollination responses in the globally important crop plant Brassica napus (oilseed rape, canola) with a high-resolution time series of microscope images of the floral organs during the first 48 hours post pollination.

Key results
We demonstrate the rapid response to pollination in B. napus (c.v. Westar), with pollen tubes germinating and traversing the style within just four hours. We also describe markers of early seed formation in response to fertilisation in the synchronous development of ovule area and stigma length.

Conclusions
Our results provide a series of temporal benchmarks for post-pollination floral morphology in B. napus, representing valuable reference points for studying and tracking pollination responses and early seed development.
Acclimation of functional traits leads to biomass increases in leafy green species grown in aquaponics
Authors: Nicholes Victoria , Khan Malik , Lemon Nicholas , Vila Peter , Campany Courtney 
Published: January 2025

Abstract
As human population size continues to increase and climate change effects worsen, future food security has become a primary concern for agricultural industries worldwide. Yields of traditional agricultural methods are commonly limited by water and nutrient availability and many crop yields are predicted to decline. Alternative farming practices like aquaponics, which can alleviate these negative yield pressures, may become critical to reaching food production targets. Aquaponics approaches involve the cyclic joint production of fish and hydroponic plants where the fish efflux provides nutrients to plants that then purify the water to be recycled to the fish tanks. In this study, we investigated the acclimation of physiology and functional traits of plants grown in aquaponics versus soil for three leafy green species. We compared gas exchange, stomatal anatomy, water-use efficiency, and foliar chemistry on newly formed leaves across weekly measurements. Increased photosynthetic rate, driven by higher stomatal conductance and increases in tissue nitrogen, led to higher biomass production in aquaponics for all species. Aquaponics plants adjusted stomatal behavior and to a lesser degree stomatal anatomy to become less water-use efficient than plants grown in soil. Collectively, our findings demonstrate the ability of plants to acclimate quickly to aquaponics growing systems that largely remove water and nutrient limitations to plant growth. The increased biomass production of broccoli, pak choi, and salanova by 185%, 116%, and 362% in aquaponics compared to soil-grown plants demonstrates the potential of small-scale aquaponics systems as an efficient and sustainable alternative farming practice.
Benchmarking 13 tools for mutational signature attribution, including a new and improved algorithm
Authors: Jiang Nanhai , Wu Yang , Rozen Steven G 
Published: January 2025

Abstract
Mutational signatures are characteristic patterns of mutations caused by endogenous mutational processes or by exogenous mutational exposures. There has been little benchmarking of approaches for determining which signatures are present in a sample and estimating the number of mutations due to each signature. This problem is referred to as “signature attribution.” We show that there are often many combinations of signatures that can reconstruct the patterns of mutations in a sample reasonably well, even after encouraging sparse solutions. We benchmarked 13 approaches to signature attribution, including a new approach called Presence Attribute Signature Activity (PASA), on large synthetic data sets (2700 synthetic samples in total). These data sets recapitulated the single-base, insertion–deletion, and doublet-base mutational signature repertoires of nine cancer types. For single-base substitution mutations, PASA and MuSiCal outperformed other approaches on all the cancer types combined. However, the ranking of approaches varied by cancer type. For doublet-base substitutions and small insertions and deletions, while PASA outperformed the other approaches in most of the nine cancer types, the ranking of approaches again varied by cancer type. We believe that this variation reflects inherent difficulties in signature attribution. These difficulties stem from the fact that there are often many attributions that can reasonably explain the pattern of mutations in a sample and from the combinatorial search space due to the need to impose sparsity. Tables herein can provide guidance on the selection of mutational signature attribution approaches that are best suited to particular cancer types and study objectives.
Natural History of Clostridioides difficile–Related Disease Progression in the 2-Step Testing Era
Authors: Turner Nicholas A , Grambow Steven C , Polage Chris , Kuhar David T , Kutty Preeta K , Moehring Rebekah W , Anderson Deverick J 
Published: January 2025

Abstract

Background
The natural history of Clostridioides difficile progression in nucleic acid amplification test (NAAT) positive, toxin enzyme immunoassay–negative patients remains poorly described. Better understanding risk for subsequent disease may improve prevention strategies. We aimed to describe the natural history of C. difficile NAAT+/toxin− adults.

Methods
A cohort of adults (≥18 years) tested for C. difficile within the Duke University Health System between 15 March 2020 and 31 December 2023 were classified as NAAT−, NAAT+/toxin−, or NAAT+/toxin+ and followed up to 90 days. Three time-to-event analyses were conducted. Incidence of toxin+ episodes was assessed by initial test status (analysis 1). Treatment of NAAT+/toxin− adults was described using cumulative incidence curves (analysis 2). Rates of toxin+ episodes and severe disease were compared between treated and untreated NAAT+/toxin− adults (analysis 3).

Results
The cohort included 24 474 tests and 440 toxin+ episodes among 18 337 unique subjects followed for a median 71 days. NAAT+/toxin− status was associated with subsequent toxin positivity (adjusted hazard ratio [aHR], 5.06 [95% confidence interval {CI}, 3.61–7.10]), especially after antibiotic receipt (aHR, 15.71 [95% CI, 9.85–25.06]). Among 2334 NAAT+/toxin− episodes, 33% received presumptive treatment. Just 5% of NAAT+/toxin− subjects progressed to toxin positivity. Presumptive treatment was associated with lower hazard of subsequent toxin positivity (aHR, 0.12 [95% CI, .05–.29]) but not fulminant disease (aHR, 1.93 [95% CI, .50–7.45]).

Conclusions
Clostridioides difficile NAAT+/toxin− status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.
Utility of the radiological report function of an artificial intelligence system in interpreting CBCT images: a technical report
Authors: Feltraco Luciano Tonetto , Rossetto Carolina , Yeung Andy Wai Kan , Soares Mariana Quirino Silveira , Oenning Anne Caroline 
Published: January 2025

Abstract
The aim of this technical report was to assess whether the “Radiological Report” tool within the Artificial Intelligence (AI) software Diagnocat can achieve a satisfactory level of performance comparable to that of experienced dentomaxillofacial radiologists in interpreting cone-beam CT scans. Ten cone-beam CT scans were carefully selected and analysed using the AI tool, and they were also evaluated by two dentomaxillofacial radiologists. Observations related to tooth numeration, alterations in dental crowns, roots, and periodontal tissues were documented and subsequently compared to the AI findings. Kappa statistics, along with their corresponding 95% confidence intervals, were calculated to ascertain the degree of agreement. The agreement between the AI tool and the radiologists ranged from substantial to nearly perfect for identifying teeth, determining the number of roots and canals, assessing crown conditions, and detecting endodontic treatments. However, for tasks such as classifying bone loss, identifying posts, evaluating the quality of fillings, and appraising the situation of periodontal spaces, the agreement was deemed slight. In conclusion, the “radiological report” tool of the Diagnocat demonstrates satisfactory performance in reliably identifying teeth, roots, canals, assessing crown conditions, and detecting endodontic treatment. However, further investigations are needed to evaluate the tool’s effectiveness in diagnosing posts, assessing the condition and quality of fillings, and determining the status of periodontal spaces.
A case report of left ventricular outflow tract obstruction due to early growth of a calcified amorphous tumour despite normal renal function
Authors: Hayashi Misayo , Kato Takayoshi , Fujimoto Keita , Watanabe Takatomo , Okura Hiroyuki 
Published: January 2025

Abstract

Background
Calcified amorphous tumours (CAT) are non-neoplastic cardiac masses that have been the focus of several recent studies. Moreover, CAT is frequently observed in women and in patients undergoing dialysis.

Case summary
A woman in her 70 s with normal renal function was referred to our hospital with a chief complaint of shortness of breath upon effort. Echocardiography and contrast-enhanced CT revealed a cardiac mass with calcification in the intervalvular fibrosa (IVF) of the anterior mitral valve, resulting in left ventricular outflow tract (LVOT) obstruction. One year later, the cardiac mass expanded, and the LVOT obstruction worsened. The patient underwent surgical resection of the mass and double-valve replacement with reconstruction of the IVF (commando operation) and myectomy. Histological examination confirmed that the mass was CAT.

Discussion
We encountered a patient who underwent valve replacement and a commando operation due to rapidly progressive CAT and consequent progression of LVOT obstruction despite normal renal function. In patients with normal renal function, factors other than calcium and phosphate metabolism contribute to the formation of CAT. Understanding the accumulation of CAT is crucial for understanding its pathogenesis.
Transcriptomic response of an algal species (Raphidocelis subcapitata) exposed to 22 per- and polyfluoroalkyl substances
Authors: Flynn Kevin M , Bush Kendra , Cavallin Jenna , Hazemi Monique , Kasparek Alex , Schumann Peter , Villeneuve Daniel L 
Published: January 2025

Abstract
Per- and polyfluoroalkyl substances (PFAS) are a large class of chemicals of concern for both human and environmental health because of their ubiquitous presence in the environment, persistence, and potential toxicological effects. Despite this, ecological hazard data are limited to a small number of PFAS even though there are over 4000 identified PFAS. Traditional toxicity testing will likely be inadequate to generate necessary hazard information for risk assessment. Therefore, the present study investigated the utility of using transcriptomic points of departure (tPODs) for informing PFAS algal toxicity. Raphidocelis subcapitata, a freshwater green algal species, were exposed for 24 hours in 96 well microplates to multiple concentrations of 22 different PFAS. Following exposure, RNA was extracted, and the transcriptome was evaluated by RNA sequencing followed by concentration response modeling to determine a tPOD for each PFAS. PFAS tPODs, based upon measured concentrations, ranged from 0.9 µg/L for perfluorotridecanoic acid to 1 mg/L for perfluorononanoic acid. These values derived from R. subcapitata exposures were compared to published hazard benchmarks from other taxa (larval fathead minnow and Daphnia magna) and in vitro data. While R. subcapitata was generally more sensitive to the tested PFAS than previously tested taxa and in vitro assays, the algal tPODs were, on average, three orders magnitude greater than the maximum concentrations of PFAS detected in Great Lakes tributaries. This high throughput transcriptomics assay with algae is a promising new approach method for an ecologically relevant, tiered hazard evaluation strategy.
A new era of inequality: profound changes to mortality in England, Scotland, and 10 major British cities
Authors: de Haro Moro Maria Teresa , Schofield Lauren , Munoz-Arroyo Rosalia , McCartney Gerry , Walsh David 
Published: January 2025

Abstract
Deeply concerning changes to UK health trends have been noted since the early 2010s, including a widening of mortality inequalities. Given the importance of urban areas to national health outcomes, we sought to address gaps in the evidence by examining trends in intra-city mortality inequalities across Britain, including assessing the impact of the peak COVID-19 pandemic period. Age-standardized mortality rates were calculated (for England, Scotland, and 10 major UK cities) by age (all ages, 0–64 years), sex, year (1981–2020), and country-specific and city-specific area-based quintiles of socio-economic deprivation. Trends in absolute and relative inequalities in mortality by country and city were analysed by means of the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII), respectively. Profound changes to mortality trends and inequalities were observed across both nations and all cities in the decade up to 2020, including increases in death rates among the 20% most deprived populations of almost every city. For deaths at all ages, this was particularly evident in Leeds, Liverpool, Edinburgh, Dundee, and Glasgow. For 0–64 years, Scottish cities stood out. With few exceptions, both absolute and relative inequalities increased in the same time period. COVID-19 further increased death rates and inequalities. The analyses provide a hugely concerning picture of worsening mortality and widening inequalities across England and Scotland. When viewed in the context of the evidence for the impact of UK government austerity policies on population health, they represent a wake-up call for both current and future UK governments.
Emerging Connections Between Inflammatory Bowel Disease Subtypes and Sequential Changes in Total Serum Bilirubin
Authors: Qin Xiaofa 
Published: January 2025

Lay Summary
Building on my long-standing hypothesis that impaired inactivation of digestive proteases by deconjugated bilirubin may be the unifying feature and mechanism of inflammatory bowel disease (IBD), this paper explores potential connections among different subtypes of IBD through sequential changes in total serum bilirubin.
Suspected heparin-induced thrombocytopaenia in pulmonary thromboendarterectomy: retrospective cohort
Authors: Guimbretière Guillaume , Dubost Clément , Issard Justin , Louvain-Quintard Virginie , Jais Xavier , Dolidon Samuel , Stephan François , Ion Daniela-Iolanda , Mercier Olaf , Fadel Elie 
Published: January 2025

Abstract

OBJECTIVES
Heparin is given for anticoagulation during and after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Our objective was to add to the limited data available on the incidence, management and outcomes of suspected heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

METHODS
This retrospective single-centre study included consecutive patients with suspected heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy done in 2005–2018. Confirmed heparin-induced thrombocytopaenia was defined as positive findings from both the antibody test and the platelet aggregation test. Patients with versus without confirmed heparin-induced thrombocytopaenia were compared, as well as patients with versus without heparin replacement therapy within the group with unconfirmed heparin-induced thrombocytopaenia. The platelet counts over time were compared to those in controls without suspected heparin-induced thrombocytopaenia.

RESULTS
Heparin-induced thrombocytopaenia was suspected in 86 (6.3%) of 1360 patients and confirmed in 16 (16/86, 19%), all of whom received heparin replacement therapy and survived to intensive care unit discharge. Of the remaining 70 patients, 28 (40%) received heparin replacement therapy and less often experienced bleeding compared to the other 42 (3.6% vs 21.4%, P = 0.043). Intensive care unit mortality was 17/70 (24.3%) and was lower in the subgroup given heparin replacement therapy (10.7% vs 33.3%; P = 0.046). Confirmed heparin-induced thrombocytopaenia was associated with a sharp platelet-count drop on Day 5. In unconfirmed suspected heparin-induced thrombocytopaenia, the early platelet-count decline was similar to that in the controls without suspected heparin-induced thrombocytopaenia, but the baseline count was lower.

CONCLUSIONS
Clinical features suggesting heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension were associated with excess mortality. Relay heparin replacement therapy was associated with lower mortality and fewer bleeding events.
On Higher Brézin–Gross–Witten Tau Functions
Authors: Alexandrov Alexander , Dhara Saswati 
Published: January 2025

Abstract
In this paper, we consider the higher Brézin–Gross–Witten (BGW) tau functions, given by the matrix integrals. For these tau functions we construct the canonical Kac–Schwarz operators, quantum spectral curves, and $W^{(3)}$-constraints. For the simplest representative we construct the cut-and-join operators, which describe the algebraic version of the topological recursion. We also investigate a one-parametric generalization of the higher BGW tau functions.
The Demise of the `Voluntarist Exclusion Zone?’
Authors: Brodie Douglas 
Published: January 2025

Abstract
In Secretary of State for the Environment v PCSU [2024] UKSC 41the Supreme Court had to consider whether a trade union was entitled to sue on a provision derived from a collective agreement by virtue of the Contracts (Rights of Third Parties) Act 1999.1 The relevance of the presumption in s. 179 of the Trade Union and Labour Relations (Consolidation) Act 1992 to collectively agreed obligations which are incorporated in an employment contract was at the heart of the litigation. The Supreme Court found in favour of the trade union and this well prove beneficial to unions in future cases centring on third party rights. I would suggest that the decision also has significant implications for cases on incorporation of collectively agreed terms. It is also conceivable that the debate as to the merits of direct enforcement of collective agreements will be reopened.
Comprehensive Screening of Per- and Polyfluoroalkyl Substances (PFAS) in Food Contact Materials: Utilizing Combustion Ion Chromatography for Total Organic Fluorine (TOF) Analysis
Authors: Hu Jingli , Cochran Richard E , Grim Cynthia M , Rumachik Neil G 
Published: January 2025

Abstract

Background
Per- and polyfluoroalkyl substances (PFAS) comprise thousands of fluorinated chemicals. They are of growing concern because many PFAS compounds are persistent and toxic. Food contact materials (FCMs) containing PFAS pose multiple exposure pathways to humans, prompting 12 states to enact laws banning FCMs with PFAS levels exceeding 100 ppm total organic fluorine (TOF).

Objective
While LC–MS is often used to measure targeted PFAS compounds, much of the total PFAS content in the sample may be missed. To understand organic fluorine content in samples more comprehensively, we developed a method using combustion ion chromatography (CIC) to measure TOF and extractable organic fluorine (EOF) in FCMs.

Methods
This technology utilizes combustion under an oxygen and argon atmosphere. All gaseous, acidic combustion products are collected in water, with ions separated on an ion-exchange column and detected by conductivity. Total fluorine (TF) was measured by combusting 10–50 mg FCM. Total inorganic fluorine (TIF) was measured by extracting cryo-ground FCM with water followed by direct injection to the ion chromatography (IC) system. TOF was then calculated by subtracting TIF from TF. EOF was determined by CIC after extracting analytes from the ground FCM using methanol-acetonitrile (80 + 20, by volume).

Results
The method detection limit (MDL) for TOF is 0.51 ppm, exceeding the sensitivity requirements of current state regulations. A comparison of EOF to TOF revealed that EOF constitutes less than 15% of the TOF in the FCM samples.

Conclusion
TOF is a critical metric for assessing PFAS contamination in FCMs, as targeted LC–MS approaches may miss much of the PFAS in the samples.

Highlights
We developed a sensitive and automated method to determine TOF and EOF in FCMs. The method can be used to screen for PFAS in FCMs, ensuring compliance with current regulations on PFAS contamination.