bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges with current diagnosis and treatment strategies for precipitated opioid withdrawal in the emergency department and the role of the pharmacist
Authors: Glenn Melody J , Erstad Brian L 
Published: July 2024

Abstract

Purpose
To demonstrate the challenges with current diagnosis and treatment strategies for precipitated opioid withdrawal secondary to naloxone the emergency department (ED) setting and describe the role of the emergency medicine (EM) pharmacist in its management.

Summary
There are no standardized criteria to define precipitated opioid withdrawal syndrome, so the diagnosis is typically based on sentinel signs and symptoms and time course. Complicating factors include a positive urine toxicology screen for nonopioid substances, comorbidities and associated medications prior to admission, medications given in the ED, and a fluctuating patient course during the ED stay that likely involves all these issues. Although buprenorphine is frequently recommended as the primary treatment for precipitated withdrawal, its use can be complicated if patients are on methadone maintenance or other long-acting opioids. The EM pharmacist plays a key role in managing patients with precipitated withdrawal.

Conclusion
Practice changes related to the diagnosis and treatment of opioid use disorder (OUD) with precipitated withdrawal in the ED are needed. EM pharmacists as part of the interprofessional care team have an important role in the management of patients with OUD, including those patients undergoing possible precipitated withdrawal.
ALLSTAR: inference of reliAble causaL ruLes between Somatic muTAtions and canceR phenotypes
Authors: Simionato Dario , Collesei Antonio , Miglietta Federica , Vandin Fabio 
Published: July 2024

Abstract

Motivation
Recent advances in DNA sequencing technologies have allowed the detailed characterization of genomes in large cohorts of tumors, highlighting their extreme heterogeneity, with no two tumors sharing the same complement of somatic mutations. Such heterogeneity hinders our ability to identify somatic mutations important for the disease, including mutations that determine clinically relevant phenotypes (e.g. cancer subtypes). Several tools have been developed to identify somatic mutations related to cancer phenotypes. However, such tools identify correlations between somatic mutations and cancer phenotypes, with no guarantee of highlighting causal relations.

Results
We describe ALLSTAR, a novel tool to infer reliable causal relations between somatic mutations and cancer phenotypes. ALLSTAR identifies reliable causal rules highlighting combinations of somatic mutations with the highest impact in terms of average effect on the phenotype. While we prove that the underlying computational problem is NP-hard, we develop a branch-and-bound approach that employs protein–protein interaction networks and novel bounds for pruning the search space, while properly correcting for multiple hypothesis testing. Our extensive experimental evaluation on synthetic data shows that our tool is able to identify reliable causal relations in large cancer cohorts. Moreover, the reliable causal rules identified by our tool in cancer data show that our approach identifies several somatic mutations known to be relevant for cancer phenotypes as well as novel biologically meaningful relations.

Availability and implementation
Code, data, and scripts to reproduce the experiments available at https://github.com/VandinLab/ALLSTAR.
Brain metabolites are associated with sleep architecture and cognitive functioning in older adults
Authors: Mueller Christina , Nenert Rodolphe , Catiul Corina , Pilkington Jennifer , Szaflarski Jerzy P , Amara Amy W 
Published: July 2024

Abstract
Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging (in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo-inositol; N-acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo-inositol and N-acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo-inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo-inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N-acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood–brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults.
Deoxygenative functionalizations of aromatic dicarbonyls and aldehydes
Authors: Sakihara Moriaki , Shimoyama Shuhei , Kurosawa Miki B , Yamaguchi Junichiro 
Published: July 2024

Abstract
In this study, we developed a method to synthesize deoxygenative functionalized products by reacting aromatic dicarbonyls with DBU, TMSOTf, diphenylphosphine oxide, and a range of nucleophiles. Moreover, we demonstrated that sequential application of phospha-Brook rearrangement and benzylic substitution conditions to aromatic aldehydes affords the deoxygenative functionalized products effectively. With highly nucleophilic reagents, it was possible to proceed with the deoxygenative functionalization without TMSOTf.
How can a regional innovation system meet circular economy challenges? Conceptualization and empirical insights from Germany
Authors: Fromhold-Eisebith Martina 
Published: July 2024

Abstract
Promoting the circular economy (CE) increasingly draws on regional approaches. But in particular the potentially supportive role of regionally provided innovations requires more exploration. This paper suggests an expanded categorization of innovation demands for the regional CE and integrates them into an enriched conceptualization of the challenge-oriented regional innovation system (CORIS). How the proposed framework can guide regional analysis and strategy building is then illustrated by the empirical case study of the German ‘Circular City’ Aachen. Structuring obtained information according to CORIS components reveals which requirements are met, but also which innovation deficiencies should be tackled locally.
Decoy receptors as biomarkers for exploring aetiology and designing new therapies
Authors: Zoccali Carmine , Tripepi Giovanni , Stel Vianda , Fu Edouard L , Mallamaci Francesca , Dekker Friedo , Jager Kitty J 
Published: July 2024

Abstract
Soluble decoy receptors (DR) are circulating proteins that act as molecular traps for ligands that modulate various signalling pathways. These proteins can be exploited as biomarkers and, in some cases, as drugs in various disease contexts. Inflammation is a key area where DRs have shown significant potential. By binding to pro-inflammatory cytokines, inflammatory DRs, such as soluble tumour necrosis factor receptors (sTNFRs), can inhibit downstream inflammatory signalling. This modulation of the inflammatory response holds promise for therapeutic interventions in various inflammatory conditions, including cardiovascular and chronic kidney diseases. Soluble DRs for advanced glycation end products (sRAGE) bind to advanced glycation end products (AGEs), reducing their detrimental effects on vascular function and atherosclerosis. High circulating sRAGE levels are associated with a lower risk for CV events, highlighting the potential of these soluble receptors for assessing the role of AGEs in CV diseases and managing the attendant risk. DRs may serve as biomarkers and therapeutic agents to advance our understanding of disease mechanisms and improve patients' outcomes. Their ability to modulate signalling pathways in a controlled manner opens up new opportunities for therapeutic interventions in various diseases, ranging from inflammation to cardiovascular and renal disorders.
Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study
Authors: Byrne Christina , Kjærgaard Jesper , Møller Jacob E , Biering-Sørensen Tor , Borregaard Britt , Schmidt Henrik , Hassager Christian 
Published: July 2024

Abstract

Aims
To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension.

Methods and results
A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P &lt; 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67).

Conclusion
Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target.
Ticagrelor 60 vs. 90 mg in elderly ACS patients undergoing PCI: a randomized, crossover trial
Authors: Piccolo Raffaele , Simonetti Fiorenzo , Avvedimento Marisa , Cutillo Maria , Canonico Mario Enrico , Conti Valeria , Gargiulo Giuseppe , Paolillo Roberta , Dal Piaz Fabrizio , Filippelli Amelia , Charlier Bruno , Spinelli Alessandra , Cristiano Stefano , Cirillo Plinio , Di Serafino Luigi , Franzone Anna , Esposito Giovanni 
Published: July 2024

Abstract

Aims
Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI).

Methods and results
PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: −4; 95% confidence interval: −16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg.

Conclusion
Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI.
Low-pressure versus standard-pressure pneumoperitoneum in minimally invasive colorectal surgery: a systematic review, meta-analysis, and meta-regression analysis
Authors: Dourado Justin , Rogers Peter , Horesh Nir , Emile Sameh Hany , Aeschbacher Pauline , Wexner Steven D 
Published: July 2024

Abstract

Background
We aimed to assess the efficacy and safety of low-pressure pneumoperitoneum (LPP) in minimally invasive colorectal surgery.

Methods
A PRISMA-compliant systematic review/meta-analysis was conducted, searching PubMed, Scopus, Google Scholar, and clinicaltrials.gov for randomized-controlled trials assessing outcomes of LPP vs standard-pressure pneumoperitoneum (SPP) in colorectal surgery. Efficacy outcomes [pain score in post-anesthesia care unit (PACU), pain score postoperative day 1 (POD1), operative time, and hospital stay] and safety outcomes (blood loss and postoperative complications) were analyzed. Risk of bias2 tool assessed bias risk. The certainty of evidence was graded using GRADE.

Results
Four studies included 537 patients (male 59.8%). LPP was undertaken in 280 (52.1%) patients and associated with lower pain scores in PACU [weighted mean difference: −1.06, 95% confidence interval (CI): −1.65 to −0.47, P = 0.004, I2 = 0%] and POD1 (weighted mean difference: −0.49, 95% CI: −0.91 to −0.07, P = 0.024, I2 = 0%). Meta-regression showed that age [standard error (SE): 0.036, P &lt; 0.001], male sex (SE: 0.006, P &lt; 0.001), and operative time (SE: 0.002, P = 0.027) were significantly associated with increased complications with LPP. In addition, 5.9%–14.5% of surgeons using LLP requested pressure increases to equal the SPP group. The grade of evidence was high for pain score in PACU and on POD1 postoperative complications and major complications, and blood loss, moderate for operative time, low for intraoperative complications, and very low for length of stay.

Conclusions
LPP was associated with lower pain scores in PACU and on POD1 with similar operative times, length of stay, and safety profile compared with SPP in colorectal surgery. Although LPP was not associated with increased complications, older patients, males, patients undergoing laparoscopic surgery, and those with longer operative times may be at risk of increased complications.
Building, Maintaining, and (re-)Deploying Genetic Toolkits during Convergent Evolution
Authors: Oakley Todd H 
Published: July 2024

Synopsis
A surprising insight from the advent of genomic sequencing was that many genes are deeply conserved during evolution. With a particular focus on genes that interact with light in animals, I explore the metaphor of genetic toolkits, which can be operationalized as lists of genes involved in a trait of interest. A fascinating observation is that genes of a toolkit are often used again and again during convergent evolution, sometimes across vast phylogenetic distances. Such a pattern in the evolution of toolkits requires three different stages: (i) origin, (ii) maintenance, and (iii) redeployment of the genes. The functional origins of toolkit genes might often be rooted in interactions with external environments. The origins of light interacting genes in particular may be tied to ancient responses to photo-oxidative stress, inspiring questions about the extent to which the evolution of other toolkits was also impacted by stress. Maintenance of genetic toolkits over long evolutionary timescales requires gene multifunctionality to prevent gene loss when a trait of interest is absent. Finally, the deployment of toolkit genes in convergently evolved traits like eyes sometimes involves the repeated use of similar, ancient genes yet other times involves different genes, specific to each convergent origin. How often a particular gene family is used time and again for the same function may depend on how many possible biological solutions are available. When few solutions exist and the genes are maintained, evolution may be constrained to use the same genes over and over. However, when many different solutions are possible, convergent evolution often takes multiple different paths. Therefore, a focus on genetic toolkits highlights the combination of legacy-plus-innovation that drives the evolution of biological diversity.
Charting the Impact of Maternal Antibodies and Repeat Exposures on Sapovirus Immunity in Early Childhood From a Nicaraguan Birth Cohort
Authors: Bucardo Filemón , Mallory Michael L , González Fredman , Reyes Yaoska , Vielot Nadja A , Yount Boyd L , Sims Amy C , Nguyen Cameron , Cross Kaitlyn , Toval-Ruíz Christian , Gutiérrez Lester , Vinjé Jan , Baric Ralph S , Lindesmith Lisa C , Becker-Dreps Sylvia 
Published: July 2024

Abstract

Background
Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity.

Methods
We measured sapovirus-specific IgG in serum collected between 2017 and 2020 of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n = 112 dyads), using virus-like particles representing 3 sapovirus genotypes (GI.1, GI.2, GV.1).

Results
Of the 112 children, 16 (14.3%) experienced at least 1 sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined by antigenic cartography: newborns share their mothers’ broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections.

Conclusions
By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.
Introducing the UK Antimicrobial Registry (UKAR) study: providing real world data on new antimicrobials to support antimicrobial stewardship and tackle antimicrobial resistance
Authors: Sneddon Jacqueline , Macfarlane Gary J , Jones Gareth T , Moir Laura , Parr Rebecca , Jenkins David , Guise Tracey , Sandoe Jonathan A T , Seaton R Andrew ,   UKAR Steering Committee, Brown Nicholas , Longshaw Christopher , Garraghan Fran 
Published: July 2024

Abstract
The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials.
Comparative analysis of three plasmids from Plesiomonas shigelloides strain MS-17-188 and their role in antimicrobial resistance
Authors: Abdelhamed Hossam , Mannan Shahnewaj Bin , Riman Munshi Mustafiz , Tekedar Hasan C , Lawrence Mark L 
Published: July 2024

Abstract

Background
Plesiomonas shigelloides strain MS-17-188 was isolated from a deceased catfish from East Mississippi and showed resistance to florfenicol, tetracyclines and a sulphonamide. WGS of strain MS-17-188 revealed three plasmids (pPSMS-171881, pPSMS-171882 and pPSMS-171883).

Objectives
To accurately determine the impact of three plasmids found in P. shigelloides strain MS-17-188 on the dissemination of antibiotic resistance genes and to provide insights into the molecular structure of these plasmids.

Methods
The genetic features of these plasmids in terms of genes associated with antimicrobial resistance (AMR), virulence, transfer, maintenance and replication were identified using bioinformatic tools. Additionally, we investigated the in vitro mobilization and stability of plasmid-mediated resistance. The Comprehensive Antibiotic Resistance Database and Virulence Factors Database were used to detect the AMR genes and virulence genes of P. shigelloides plasmids. Moreover, plasmid mobility was evaluated by a filter-mating assay using strain MS-17-188 as a donor and azide-resistant Escherichia coli J53 as a recipient strain. A stability experiment was conducted to explore the persistence of plasmid-mediated antibiotic resistance in strain MS-17-188 in the absence and presence of selection.

Results
pPSMS-171881 harboured multidrug efflux complex (adeF) and two genes responsible for arsenic resistance (arsB and arsC). pPSMS-171882 had a region of 7085 bp encoding type IV secretion system proteins. pPSMS-171883 carried the tetracycline resistance genes tet(A) and tet(R), and a phenicol resistance gene (floR), which were flanked by two transposable elements and mobilization proteins, suggesting that there is a conjugative mechanism by which this plasmid can be mobilized. Results from the stability experiment indicated that pPSMS-171883 is lost over time in the absence of selective pressure. Moreover, pPSMS-171883 is more stable in P. shigelloides at growth temperatures of 30°C and 37°C compared with 40°C and 43°C. After intraperitoneal injection in catfish, P. shigelloides strain MS-17-188 resulted in no mortalities.

Conclusions
This is the first study to report plasmid-mediated AMR in Plesiomonas isolated from cultured fish, which needs continued monitoring. This study will provide an understanding of the genetic mechanisms of AMR and virulence of P. shigelloides.