bluuebunny/crossref_metadata_2025 huggingface dataset:
The contemporary role of genetics in cardiovascular medicine: from phenotypes to precision diagnoses
Authors: Urtis Mario , Tagliani Marilena , Bondavalli Davide , Paganini Chiara , Cavaliere Claudia , Vilardo Viviana , Buccieri Edward , Tescari Antonio , Ferrari Michela , Arbustini Eloisa
Published: February 2025

The diagnostic work-up of cardiovascular genetic diseases is emerging as a reference model for precision (cause and phenotype) and personalized medicine (tailored individual management). This approach is expanding across all areas of cardiovascular medicine, ranging from monogenic diseases to multifactorial disorders where ‘risk factors’ such as familial hypercholesterolaemia may play a role in the risk profile. In this context, cardiomyopathies provide an ideal reference because they are monogenic yet genetically heterogeneous diseases, much like many other cardiovascular genetic disorders. In this model, the genetic path starts with deep phenotyping of the patient and relatives and progresses with genetic testing including extensive multigene panels, up to whole-exome sequencing and whole-genome sequencing. Although genetic work-ups are increasingly successful, several unresolved challenges and limitations remain. These include the interpretation and reinterpretation of variants, as many pre-American College of Medical Genetics variants previously classified as likely pathogenic or pathogenic are now recognized as variants of uncertain significance or benign/likely benign; pathogenic variants missed with short-read next generation sequencing (NGS) technologies (e.g. deep intronic variants or Copy Number Variations); gene-specific issues such as pseudogenes and pseudo-exons; and differing interpretations of pathogenicity for the same gene defects by commercial pipelines. Despite widespread NGS-based testing, about half of suspected Mendelian conditions still lack a precise molecular diagnosis. New organizational models are needed to integrate emerging knowledge and innovations incorporating both clinical and genetic data into intelligent platforms that may support shared management pathways.
Global Prevalence of Myocardial Fibrosis among Individuals with Cardiometabolic Conditions: A Systematic Review and Meta-Analysis
Authors: Yeo Tin Mei , Chin Woon Loong Calvin , Seah Chuen Wei Alvin , Cheng Ling Jie , Lin Weiqin , Dalakoti Mayank , Foo Sik Yin Roger , Wang Wenru
Published: February 2025

Background

Cardiometabolic conditions including hypertension, diabetes, hyperlipidaemia and obesity are significant risk factors for cardiovascular diseases. Myocardial fibrosis (MF) is a complication and final common pathway of these conditions, potentially leading to heart failure, arrhythmias and sudden death. Existing reviews explored pathophysiological changes and treatment of MF, but the global prevalence of MF among individuals with cardiometabolic conditions remain limited.

Objectives

To evaluate the global prevalence of MF in individuals with cardiometabolic conditions and explore factors influencing its rate.

Methods

CINAHL, Cochrane Library, Embase, PubMed, ProQuest Theses and Dissertations, Scopus, and Web of Science were systematically reviewed until January 2024. Studies included individuals with hypertension, type 2 diabetes mellitus, hyperlipidaemia, and obesity, with MF prevalence assessed via biopsy or Late Gadolinium Enhancement-Cardiac Magnetic Resonance (LGE-CMR). Meta-analysis was conducted using jamovi and factors associated with MF were synthesised narratively. This review is registered on PROSPERO, CRD42024544632.

Results

The meta-analysis included 52 articles involving 5,921 individuals. 32.7% of individuals with cardiometabolic conditions developed MF, with hypertension demonstrating the highest prevalence [35.2%(95%CI:25.5-45.0)]. Biopsy-based studies reported a higher prevalence [75.6%(95%CI:53.6-97.6)] compared to LGE-CMR studies [26.8%(95%CI:20.6-33.0)]. Key factors associated with MF included increased LV mass/LV hypertrophy, reduced LV function, and myocardial stiffness.

Conclusions

This first global review estimates that one-third of individuals with cardiometabolic conditions develop MF, with the rate expected to rise. Standardized CMR measures cut-offs are needed to address prevalence inconsistencies. Future research should explore MF prevalence using diverse samples, combined CMR measures, considering socio-demographic and clinical factors for more accurate estimates.
Outdoor Environmental Risk Factors for Falls and Fear of Falling: A Systematic Review
Authors: Dunlap Pamela M , Fan Erica K , Hubbard Zachary L , VonVille Helena M , Strotmeyer Elsa S , Rosso Andrea L
Published: February 2025

Background and Objectives

The objective of this systematic review was to determine the outdoor environmental factors that are associated with increased risk of falls and fear of falling in middle-aged and older adults.

Research Design and Methods

PubMed, Medline, EMBASE, APA Psych INFO, and CINAHL electronic databases were searched through August 2024 for studies that included participants 45 years or older, falls or fear of falling as an outcome, and measure the outdoor environment (i.e., uneven sidewalks, neighborhood disorder). Title and abstract screenings, full text screenings, and critical appraisal assessments were independently reviewed.

Results

The search retrieved 7474 records, 627 full texts were reviewed, and 51 unique studies met the inclusion/exclusion criteria. The number of participants ranged from 12 to 6,720,937. There were 41 studies that included fall outcomes, 5 studies that included fear of falling outcomes, and 5 studies that included both outcomes. Micro-walkability (e.g., sidewalk quality) were the most frequently studied outdoor environmental characteristics and many studies found associations with falls and fear of falling. Macro-walkability (e.g., land use), crime and safety, socioeconomic, greenspace, terrain, physical disorder, and social features were studied to a lesser extent and had mixed findings.

Discussion and Implications

The most consistent associations were found between micro-walkability features of the outdoor environment with falls whereas other environmental domains and fear of falling were studied to a lesser extent. Environmental contributors to falls should be considered in future research, policy implementation, and clinical interventions to reduce falls and their negative outcomes for older adults.
The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting lectin microarray data
Authors: Tateno Hiroaki , Mahal Lara K , Feizi Ten , Kettner Carsten , Paulson James C
Published: February 2025

The MIRAGE (Minimum Information Required for a Glycomics Experiment) project has been established by experts in glycobiology, glycoanalytics, and glycoinformatics under the auspieces of the Beilstein-Institut. The working group aims to develop guidelines for reporting results from various experiments and analyses conducted in structural and functional studies of glycans in the scientific literature. Previous guidelines have been established for glycomic analytics, including mass spectrometry and glycan microarrays. Lectin microarrays are used worldwide for glycan profiling of various biological samples, but there are often insufficient reports on information about experimental methods such as sample preparation and fluorescence labeling. Here, we propose guidelines specifically designed to improve the standards for reporting data from lectin microarray analyses. For each of the seven areas in the workflow of a lectin microarray experiment, we provide recommendations for the minimum information that should be included when reporting results. When adopted by the scientific community the MIRAGE lectin microarray guidelines are expected to enhance data interpretation, facilitate comparison of data between laboratories and encourage the deposition of lectin microarray data in international databases.
Intellectual community in Saint Victor: 1108–c.1200
Authors: Hopper Joseph
Published: February 2025

This article examines the community of Saint Victor in the twelfth century and argues the dangers of considering intellectual life and communal life as two distinct things. It responds critically to the tendency to separate the two by canalizing intellectual activities into the model of a ‘school’. This article suggests instead the importance of thinking of Saint Victor as an ‘intellectual community’. The immediate significance for Victorine studies lies in thinking more imaginatively about the relationship between the ‘ideas’ which are rightly famous and the community which remains strangely anonymous. Beyond Saint Victor, this approach disrupts a much broader historiographical landscape of ‘cathedral schools’, ‘the university’ and twelfth-and-thirteenth-century Paris. What emerges is a city that played host to experimentation, both in ideas and the ways that communal life could be organized to facilitate their exchange and development.
Performance Validation of the IEH Laboratories Multiplex PCR Listeria Detection System for Environmental Samples in Comparison to Health Canada Reference Method (MFHPB-30) for Listeria Detection
Authors: Themeli Eni , Mai Tam , Forghani Fereidoun , Samadpour Mansour
Published: February 2025

Background

Laboratory detection methods are commonly tested against gold standards and corresponding reference methods to confirm their suitability and efficiency.

Objective

The IEH Listeria Test System (multiplex PCR) was tested against Health Canada’s reference method (MFHPB-30) for the simultaneous detection of Listeria spp. and Listeria monocytogenes, on three different surfaces: plastic (PL), sealed concrete (SC) and stainless steel (SS).

Methods

The R2 medium was used for pre-enrichment of the samples at 35 °C for 24 h, followed by the IEH Listeria multiplex PCR. Each individual surface coupon (PL, SC, SS) was inoculated with either Listeria innocua, L. monocytogenes, or L. welshimeri along with two non-target microorganisms of concern and subjected to candidate (IEH Listeria multiplex PCR) and reference method (MFHPB-30) testing in an unpaired manner, and included culture confirmation for IEH method.

Results

The candidate method demonstrated 0% false negative, 0% false positive, 100% sensitivity, and 100% specificity after only 24 h enrichment followed by Multiplex PCR.

Conclusion

Evaluating the differences between the candidate and reference method detection probabilities across all three surface types revealed that the candidate method was equivalent to MFHPB-30, while requiring significant less time for detection.
Identification and characterization of a novel hemolytic and hemagglutinating bifunctional lectin from the coral Acropora millepora
Authors: Takahashi Yuki , Kamimura Ryosuke , Toyama Ryo , Kita Shun , Ushijima Yuki , Taniyama Shigeto , Unno Hideaki , Hatakeyama Tomomitsu , Goda Shuichiro
Published: February 2025

Two genes, AML-I and AML-II, have been reported to exhibit increased expression during the development of the coral Acropora millepora. They show amino acid sequence homology with CEL-III, a hemolytic lectin found in the sea cucumber Cucumaria echinata. CEL-III binds to carbohydrate chains on the surface of erythrocytes, forming heptameric pores in their membranes. To clarify the role of these proteins in coral, we identified and elucidated their functions. The carbohydrate binding domains of them showed similar carbohydrate-binding specificity as that of CEL-III. AML-I showed hemagglutinating activity in erythrocytes, whereas AML-II can only be prepared as an aggregate and its function could not yet be determined. AML-IΔC and AML-IIΔC mutants were generated through deletion of the C-terminal extended amino acid residues of them relative to CEL-III. AML-IΔC showed hemolytic activity toward erythrocytes, whereas AML-IIΔC showed no activity. A tobacco etch virus (TEV) protease recognition site was inserted into the C-terminus of AML-I to regulate these activities. The hemagglutinating activity of AML-I was converted into hemolytic activity after TEV protease treatment. As a result, TEV protease could control the hemolytic and hemagglutinating activity of the lectin, which could be useful as an anticancer or antiviral drug because of its cytotoxic activity.
A Critical Interpretive Literature Review of Phronesis in Medicine
Authors: Jameel Sabena Yasmin
Published: February 2025

This article presents the results of a rigorous critical interpretive review that maps the current literature on phronesis in medicine. The literature in this area involves varied disciplines, centuries, and conceptions and is extensive, but through a focused review, this study seeks to clarify definitions and key distinctions. It thereby aims to elucidate a depth of meaning and understanding regarding phronesis in medicine to inform future work on the topic. Specifically, 12 themes are inductively identified and analyzed from the literature, and organized into three chronological categories of past, present, and future. A narrative summation of the literature to date is then offered, assessing the varied conceptual applications of phronesis to medical practice, the emerging literature on its applicability to organizations, prospects for empirical work on the concept, and its application in medical education.
The impact of cigarette package tar yield displays, tar warning statement, and plain packaging on low-tar cigarette misperceptions among South Koreans who smoke
Authors: Lee Stella Juhyun
Published: February 2025

Introduction

This study examined whether different cigarette package features such as tar yield display, tar warning statement, and plain packaging affect beliefs about tar intake, smoothness, and safety of low-tar cigarettes among South Koreans who smoke.

Methods

An online randomized between-subjects experiment was carried out (n = 500) on a panel of South Koreans who smoke. Participants were exposed to either a mock cigarette package that 1) displayed tar yield; 2) did not display tar yield; 3) showed a tar warning statement; or 4) was plain packaged. Beliefs about tar intake, smoothness, and safety were measured post-exposure. Beliefs were compared across conditions, and mediation analysis was conducted.

Results

Participants exposed to the tar warning statement believed the mock cigarette would deliver lesser tar compared to those only exposed to the package that displayed tar yield. Those who viewed the cigarette package with no tar yield number were less likely to agree that the cigarette would be smoother compared to those who viewed the package with a visible tar yield number. The effect of viewing the tar warning statement on safety beliefs was fully mediated by tar intake beliefs. The effect of exposure to tar yield display on safety beliefs was fully mediated by smoothness beliefs.

Conclusion

Study results indicate that the current tar warning statement could increase misperceptions. Removing tar yield numbers may reduce smoothness beliefs about low-tar cigarettes. Health communication efforts should address beliefs about tar intake and smoothness when trying to correct low-tar cigarette misperceptions about safety.

Implications

Previous research has found that tar yield numbers displayed on the front of South Korean low-tar cigarette packages may mislead people to perceive lesser harm. However, studies have not yet examined whether other package elements such as the current tar warning statement or plain packaging could reduce misperceptions. Study results indicated that viewing the current tar warning statement backfires by increasing belief in lesser tar intake. Viewing tar yield numbers also led to increased perception that the cigarette will feel smoother. Plain packaging did not exert any effects on beliefs about tar intake, safety or smoothness. Findings can inform tobacco packaging policies and health communication efforts to reduce misperceptions about low-tar cigarettes.
Solvent dependent structural, electronic, and optical properties of ureidopeptidomimetics: a DFT and TD-DFT study on the effects of donor and acceptor functional groups
Authors: Pavani Y , Aravind S , Padmavathi K V , Subba Rao M , Babu Nambury S
Published: February 2025

This study provides a comprehensive examination of the structural, electronic, optical, and reactivity properties of ureidopeptidomimetics (UPMs) featuring various donor and acceptor functional groups using density functional theory (DFT) and time-dependent DFT (TD-DFT). To systematically explore their effects on charge transfer, HOMO-LUMO energy gaps, and molecular stability, the molecular models were intentionally designed with both electron-donating groups (-CH3, -OCH3, -OH, -NH2) and electron-accepting groups (-SH, -COCl, -CF3). A detailed analysis of the bond lengths confirmed the electron-rich nature of the substituents, revealing that the introduction of electron-donating groups at the ureido and carboxylate terminals of the UPMs decreased the C-O and C-N bond lengths by 0.005 Å and 0.0003 Å, respectively, compared to the unsubstituted UPM. Polar solvents, notably water and DMSO, enhance the stabilization of HOMO and LUMO energy levels, thus improving the electronic stability and reactivity of UPM molecules, as demonstrated by DFT and TD-DFT calculations. In the case of UPM, the molecular orbitals (HOMO: -6.8646 eV to -6.9027 eV, LUMO: -0.3957 eV to -0.4248 eV) experienced slight stabilization as it transitioned from the gas phase to the aqueous phase. This transition increased the chemical potential (χ) and global hardness (η), signifying enhanced electronic stability. UV-Vis experiments revealed that UPM's λmax values remained around 218.6 nm across various solvents, with polar solvents, particularly water, exhibiting more robust oscillators. In water, λmax decreased to 207.58 nm for D2-UPM-A2 and shifted to 227.86 nm for D1-UPM-A1. For D3-UPM-A3, λmax in water exhibited a redshift to 249.28 nm along with reduced absorption. Specifically, for A1-UPM-D1 and A2-UPM-D2, the polarity of the solvent influenced transitions and increased transition probabilities, indicating their potential in optoelectronic applications.
Extreme Crustal Fractionation in a Proterozoic Chemical Hotspot
Authors: Liebmann J , Ware B , Kirkland C L , Mole D R , Fraser G , Mahan B , Wainwright A N , Maas R
Published: February 2025

The distribution of mineral systems is heterogeneous over space and time, reflecting transient element enrichment within Earth’s evolving crust. Australian Proterozoic rocks host some of the world’s largest ore deposits, including the Broken Hill Pb-Zn-Ag deposit within the Curnamona Province, and the Olympic Dam Cu-U-Au-Ag super-deposit, within the Gawler Craton, offering key insights into crustal preconditioning for mineralization. New feldspar and whole-rock Pb isotopic data, and complementary apatite geochronology, support a common source for Mesoproterozoic magmatism in the Curnamona Province and Gawler Craton and hence a genetic link between their world-class ore deposits. Exceptionally radiogenic Pb isotope ratios in the Curnamona Province indicate extreme crustal fractionation, likely driven by a positive feedback scenario where crustal anatexis produced melts strongly enriched in heat-producing, incompatible elements, which in turn prolonged anatectic conditions through radiogenic heat production. The resulting granitic rocks may have acted as important metal sources for certain ore deposits, while more generally fostering metal enrichment by providing a persistent heat source for hydrothermal systems. This chemical hotspot may have been triggered by the combination of insulating thickened crust and gravitational destabilization following the assembly of the Nuna supercontinent.
The Effects of Intersphincteric Space Dissection Approaches on Low Rectal Cancer Outcomes: A Multicenter Retrospective Study in China
Authors: Zang Yiwen , Zhang Bin , Liu Xing , Chen Baoxiang , Gao Linfeng , Zhou Minwei , Gu Xiaodong , Li Zhenyang , Zhou Yiming , Tang Bo , Jiang Congqing , Guan Guoxian , Ding Jianhua , Xiang Jianbin
Published: February 2025

Objective:

To evaluate the effects of 2 intersphincteric space (ISS) dissection approaches for intersphincteric resection (ISR) on perioperative safety, oncological prognosis, and anal function.

Background:

The dissection of ISS is a crucial aspect of ISR, yet the outcomes associated with various ISS dissection approaches remain uncertain.

Methods:

Data were retrospectively collected from 314 patients with rectal cancer who underwent ISR at 5 Chinese tertiary referral medical institutions from January 2015 to December 2020. ISS dissection was performed using 1 of the 2 avenues: the complete transabdominal approach (CTA) and the transabdominal-perineal transanal approach (TPTA). The primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) rates. The secondary endpoints were postoperative anal function assessed by questionnaires. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to match the clinicopathological characteristics of patients from both cohorts.

Results:

After PSM, 140 patients were successfully matched in the CTA and TPTA groups. There were no statistically significant differences between the groups in terms of perioperative complication rates, 3-year OS/DFS, and Wexner incontinence scores within 3 years after ileostomy reversal surgery (P > 0.05). However, the CTA group demonstrated less surgical time and superior low anterior resection syndrome (LARS) scores compared with the TPTA group (P < 0.05). Similar outcomes were observed after conducting IPTW adjustment.

Conclusions:

CTA and TPTA showed similar efficacy regarding perioperative safety and oncological outcomes. However, the CTA approach demonstrated a clear superiority in the LARS score.
Public health implications of diagnosing and treating acute HIV
Authors: Rutstein Sarah E. , Limarzi-Klyn Laura , Miller William C. , Powers Kimberly A.
Published: February 2025

Purpose of review

The earliest months of HIV infection are characterized by high viral loads and elevated transmissibility, particularly during the acute (preseroconversion) phase. Transmission prevention during early HIV requires diagnostic tools that narrow the window between viral acquisition and reactive test, followed by rapid linkage to effective antiretroviral therapy (ART). Here, we review recent advances related to diagnosing and treating persons during early HIV, with a particular focus on acute HIV infection (AHI).

Recent findings

Point-of-care (POC) fourth-generation antigen/antibody tests have mixed performance, often dependent on the pretest probability of early infection within the screened population. Risk score algorithms demonstrate the potential for prioritizing resource-intensive tests, such as POC HIV RNA, to those most likely to have AHI, but their predictive performance varies across populations, complicating implementation. Emerging and re-emerging infections, including SARS-CoV-2 and mpox, present opportunities for and challenges to symptom-driven AHI screening. Daily oral ART with standard first-line regimens quickly suppresses viremia during AHI, but long-acting injectable drugs are yet to be explored for this indication.

Few practice-changing results related to diagnosing or treating persons with early HIV have been released in the last 18 months. Accurate POC HIV RNA tests could leapfrog fourth-generation POC assays, but they remain unavailable for routine use. Implementation science approaches are needed to guide use of evidence-based strategies for early HIV screening, and additional research on same-day ART linkage, including injectable ART, could produce dramatic impacts on forward transmission during this period.
The effect of Psilocybe cubensis alkaloids on depressive-like behavior in mice exposed to maternal separation with respect to hippocampal gene expression and DNA methylation of Slc6a4 and Nr3c1
Authors: Jasemi Eghbal , Razmi Ali , Vaseghi Salar , Amiri Shayan , Najafi S. Mahmoud A.
Published: February 2025

Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis extract (PCE) on depressive-like and anxiety-like behaviors, and locomotor activity in mice exposed to early maternal separation. Also, we assessed the expression and methylation level of Slc6a4 and Nr3c1 in the hippocampus. Maternal separation was done in postnatal days (PNDs) 2–18. PCE was intraperitoneally injected at the dose of 20 mg/kg at PND 60, and our tests were done at days 1, 3, and 10, of administration. The results showed that maternal separation significantly induced depressive-like behavior in the forced swim test and anxiety-like behavior in the open field test (OFT). Also, maternal separation decreased locomotor activity in the OFT. In addition, maternal separation decreased the expression and increased the methylation level of both Slc6a4 and Nr3c1 in the hippocampus. However, PCE significantly reversed all these effects. In conclusion, it seems that P. cubensis affects serotonergic signaling via altering Slc6a4 expression and methylation level in the hippocampus of mice. The effect of P. cubensis on Nr3c1 expression and methylation level may also lead to alter the function of the hypothalamus-pituitary-adrenal axis and the stress response in mice exposed to maternal separation.
Monlunabant suppresses appetite through a central mechanism
Authors: Mullassaril Priya , Brodkin Lucy , Brodkin Jesse
Published: February 2025

This study aimed to determine whether the second-generation cannabinoid receptor subtype 1 (CB1) antagonist, monlunabant – designed to treat obesity by targeting peripheral receptors – might actually exert its effects through CB1 receptors in the central nervous system. In adult male mice, both monlunabant and rimonabant reduced appetite and antagonized CB1 agonist-induced hypothermia. Monlunabant was consistently less potent than rimonabant in both appetite suppression and blocking hypothermia. The cannabinoid agonist HU-210 produced profound hypothermia, which was significantly attenuated by 10 mg/kg of either drug and by 3 mg/kg of rimonabant. Similarly, both drugs reduced appetite in food-deprived mice with limited access to preferred food at the same doses that were effective in the hypothermia assay. Lower doses of monlunabant, which likely saturated peripheral receptors, had no effect on appetite. These findings suggest that monlunabant suppresses appetite mainly through antagonism of central CB1 receptors. Consequently, monlunabant and other second-generation CB1 antagonists being developed for obesity may carry a similar risk of adverse psychiatric effects, as previously observed with rimonabant.
C/EBPβ transcription factor promotes alcohol-induced liver fibrosis in males via HDL remodeling
Authors: Schonfeld Michael , Nataraj Kruti , Weinman Steven , Tikhanovich Irina
Published: February 2025

Background:

Alcohol-associated liver disease (ALD) is the main cause of alcohol-associated mortality. However, the mechanism of ALD development is poorly understood. Epigenetic changes are thought to play an important role in ALD. We aimed to define the epigenetic changes induced by alcohol and predict drivers of these changes.

Methods:

Mice were fed high-fat diet with or without 20% of alcohol in the drinking water for 20 weeks (WDA model). scATAC-seq data set was analyzed using Signac R package. To test the role of C/EBPβ, Cebpb-floxed mice were treated with AAV8-TBG-Cre or AAV8-control.

Results:

We analyzed differentially accessible regions in livers from control and alcohol-fed mice and found that activity of C/EBPβ transcription factor was associated with alcohol-induced epigenetic changes in hepatocytes. C/EBPβ protein levels were significantly upregulated in multiple models of ALD and human ALD samples. Using hepatocyte-specific Cebpb knockout mice we found that Cebpb loss protected male mice from alcohol-induced fibrosis development. We found no protection in female mice, suggesting that this mechanism is specific to male ALD. In vitro studies suggested that the protective effect of Cebpb loss was mediated by altered hepatocyte—macrophage cross talk. Cebpb knockout in hepatocytes reduced a profibrotic and promoted a pro-resolving phenotype in macrophages, thus modulating ALD development. We further identified the mediators of the cross talk. Cebpb knockout altered the expression of several HDL protein components, increasing APOA1 and apolipoprotein M and reducing apolipoprotein E and SAA levels in male mice. HDL secreted by Cebpb knockout hepatocytes was sufficient to confer anti-inflammatory and antifibrotic changes to macrophages.

Conclusions:

Taken together, alcohol-induced C/EBPβ activation is a key driver of ALD fibrosis in males via C/EBPβ-dependent HDL remodeling.
Safety and efficacy of a defined bacterial consortium, VE303, to treat HE
Authors: Bloom Patricia P. , Bassis Christine M. , Crossette Emily , Silber Jeffrey L. , Norman Jason M. , Young Vincent B. , Lok Anna S.F.
Published: February 2025

Background:

Novel therapies are needed to treat HE, and microbiome modulation is a promising target. VE303 is a defined consortium of 8 purified, clonal bacterial strains, known to produce metabolites that may be beneficial in HE. We evaluated the safety and efficacy of VE303 to treat HE.

Methods:

We performed a single-center, randomized, placebo-controlled trial of VE303 in adult patients with a history of overt HE (NCT04899115). Eligible patients were taking lactulose and rifaximin, had no recent systemic antibiotics, and had MELD ≤20. All patients received 5 days of oral vancomycin followed by randomization to 14 days of VE303 or placebo (2:1). The primary endpoints were incidence of serious adverse events and change in psychometric HE score (PHES) from baseline to 4 weeks after treatment. Stool samples underwent metagenomic sequencing and metabolite quantification.

Results:

Eighteen patients completed the trial, 56% men, with a mean age of 59 years and a mean MELD of 11. Patients who received VE303 had a mean change in PHES of +1.5 versus −1.0 in those who received a placebo (p=0.20). Two of the 12 patients who received VE303 had at least 1 serious adverse event (all overt HE hospitalizations), compared with 0/6 patients who received a placebo. In the patients who received VE303, 2 of 8 strains engrafted in >50% of patients. Both VE303 strain engraftment and increased stool butyrate production had a trend toward improved PHES.

Conclusions:

VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.
Health-related quality of life is impaired in people with autoimmune hepatitis: Results of a multicentre cross-sectional study within the European Reference Network
Authors: Snijders Romée J.A.L.M. , Janik Maciej K. , Mund Meike , Uhlenbusch Natalie , Raszeja-Wyszomirska Joanna , Gerussi Alessio , Bolis Francesca , Cristoferi Laura , Invernizzi Pietro , Kovats Patricia , Papp Mária , Grønbæk Lisbet , Grønbæk Henning , Tjwa Eric T.T.L. , Aamann Luise , Ytting Henriette , Ronca Vincenzo , Olsen Kathryn , Oo Ye H. , van der Meer Adriaan J. , Madaleno João , Canhão Bernardo , Engel Bastian , Campos-Murguia Alejandro , Taubert Richard , Koc Özgür M. , Kramer Matthijs , Willemse José A. , Löwe Bernd , Lohse Ansgar W. , Drenth Joost P.H. , Schramm Christoph , Milkiewicz Piotr , Gevers Tom J.
Published: February 2025

Background:

Impaired health-related quality of life (HRQoL) contributes to the overall disease burden in autoimmune hepatitis (AIH). This study aimed to evaluate HRQoL in people with AIH and to identify potentially modifiable factors associated with impaired HRQoL using validated patient-reported outcome measures.

Methods:

Adult AIH patients diagnosed at 12 European centers were enrolled in this prospective, cross-sectional study from July 2020-June 2023. HRQoL was assessed using the Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-item Short Form Health Survey (SF-12), and the European Quality-of-life 5-Dimension 5-Level (EQ-5D-5L) utility index (UI) score. Mixed-model regression analyses identified factors associated with HRQoL and somatic symptom severity. Controls were recruited from the general population in five European countries.

Results:

A total of 882 patients with AIH (mean age: 51.0 y [SD 17.0]; 76.4% female) and 178 controls were included. Physical but not mental HRQoL was impaired in the AIH group compared with the control group (PCS: 46.3 vs. 51.9, p<0.001; EQ-5D UI: 0.87 vs. 0.95, p<0.001). HRQoL was associated with severe somatic symptoms (PCS β=−4.26, p<0.001), fatigue (PCS β=−0.25, p<0.001; MCS β=−0.25, p<0.001), and depression/anxiety (PCS β=−3.37, p<0.001; MCS β=−6.79, p<0.001). A complete biochemical response was associated with a lower somatic symptom severity (odds ratio 0.69, p<0.05).

Conclusions:

People with AIH had impaired HRQoL compared with controls, particularly in terms of physical well-being. HRQoL scores are associated with symptom burden, encompassing both somatic and psychosocial dimensions.
Epidermal Transient Receptor Potential Vanilloid 1 innervation is increased in patients with painful diabetic polyneuropathy experiencing ongoing burning pain
Authors: Galosi Eleonora , Falco Pietro , Di Pietro Giuseppe , Esposito Nicoletta , De Stefano Gianfranco , Evangelisti Enrico , Leone Caterina , Litewczuk Daniel , Tramontana Lorenzo , Di Stefano Giulia , Truini Andrea
Published: February 2025

Preclinical studies suggested that Transient Receptor Potential Vanilloid 1 (TRPV1) channels contribute to neuropathic pain in animal models of diabetic polyneuropathy. Patients with painful diabetic polyneuropathy commonly experience ongoing burning pain. This study aimed at evaluating the association between this specific type of pain and TRPV1 intraepidermal nerve fibers in patients with painful diabetic polyneuropathy. We consecutively enrolled 70 patients with diabetic polyneuropathy. Each patient completed the Neuropathic Pain Symptom Inventory (NPSI) to identify the various types of neuropathic pain. All patients underwent a distal leg skin biopsy, with immunostaining of skin nerve fibers using antibodies for the pan-axonal marker Protein Gene Product 9.5 (PGP9.5), TRPV1, Calcitonin Gene-Related Peptide (CGRP), and Substance P. We found that 57% of patients (n = 40) had neuropathic pain symptoms, with ongoing burning pain being the most frequently reported type of pain at the NPSI (70% of patients with pain, n = 28). Patients with ongoing burning pain had higher TRPV1 intraepidermal nerve fiber density and TRPV1/PGP9.5 ratio compared with those with painless polyneuropathy (P = 0.014, P = 0.013) and painful polyneuropathy with other types of pain (P < 0.0001, P = 0.024); they also had increased CGRP dermal nerve fiber density compared with patients with painless polyneuropathy (P = 0.005). Our study showed that ongoing burning pain is associated with an increased expression of intraepidermal TRPV1 fibers, as well as an increased dermal representation of CGRP fibers. These findings suggest that TRPV1 contributes to ongoing burning pain, possibly in conjunction with elevated CGRP expression, highlighting its significance as a therapeutic target for patients with painful diabetic polyneuropathy.
Early opioid administration and pain-related patient-reported outcomes on the first postoperative day: an analysis of data from 111,693 patients in 392 surgical wards in Germany
Authors: Baumbach Philipp , Zaslansky Ruth , Dreiling Johannes , Komann Marcus , Arnold Christin , Stamer Ulrike M. , Weinmann Claudia , Meissner Winfried
Published: February 2025

The risk-benefit ratio of perioperative opioid analgesia is controversial. Few studies have analyzed the effectiveness of opioids in the early postoperative period. To analyze the effectiveness of early opioid administration in this period in a large number of surgeries in routine care, we compared pain-related outcomes between patients treated on wards with different rates of early opioid administration. In this observational study, we analyzed data from 111,693 patients in 392 surgical wards between 2010 and 2022 within the German Quality Improvement in Postoperative Pain Management registry. We defined early opioid administration at the ward-level as the percentage of patients who received at least 1 opioid dose between the end of surgery and data collection on the first postoperative day, including recovery room and ward. To identify different patterns of early opioid administration, we considered these percentages in patients with mild, moderate, and severe pain and applied k-means clustering. We performed mixed regression analyses to assess associations between clusters and patient-reported outcomes on the first postoperative day. At the ward-level, the median percentage of early opioid administration was 79.5% (first-third quartile: 64.5%-92.0%), and 2 clusters of wards were identified. In clusters 1 and 2, an opioid was administered in 58.5% and 89.0% of patients, respectively. Patients in cluster 2 reported better outcomes for pain intensity and pain-related interference but worse outcomes for nausea. However, the effect sizes were small. Patients treated on surgical wards with a higher rate of early opioid administration reported slightly better pain-related outcomes on the first postoperative day.
Pharmacist-Led Population Health Initiative to Address Statin Care Gaps: A Quality Improvement Project
Authors: Raymer Danielle , Everhart Anna , Baker Danielle
Published: February 2025

Background:

Evidence-based guidelines recommend statins as first-line therapy to reduce the risk of cardiovascular events in patients with cardiovascular disease and/or diabetes. The Centers for Medicare and Medicaid Services assess compliance with these guidelines through performance and process quality measures.

Purpose:

To describe innovative practices to address statin use care gaps, to identify successes and challenges of a pharmacist-led statin initiative, and share quality improvement opportunities related to statin quality metrics.

Methods:

A retrospective review was conducted in 2023 of patients enrolled in Medicare Advantage value-based care contracts in a large health system. The primary outcome measures were the percentage of patients identified with statin care gaps who met the criteria for statin treatment and the percentage of patients who accepted pharmacist-led recommendations to initiate statin therapy. Outcomes were analyzed using descriptive statistics.

Results:

Among those with statin care gaps, 42% met criteria for pharmacist-led statin initiation. Of those who met criteria, 22% accepted pharmacist's recommendation to initiate statin therapy.

Conclusions:

Pharmacist-led statin initiation is effective; however, systematic barriers remain to improve statin quality performance. These results can help others adopt innovative practices that target statin care gaps and assess opportunities for quality improvement.
A Biophysics-Based Mathematical Model of Shear-Induced Platelet Activation and Receptor Shedding: Re-Examining Previous Experimental Data
Authors: Han Dong , Tarafder Anik , Griffith Bartley P. , Wu Zhongjun J.
Published: February 2025

The power-law model, originally developed for shear-induced hemolysis, has been used to predict shear-induced platelet activation and receptor shedding. However, its empirical nature lacks mechanistic explanations and violates physical reality by not imposing an upper limit, often leading to inaccuracies. Recent studies suggest that the mechanical pulling of platelet GPIb-IX complex triggers the unfolding of its mechanosensitive domain, a crucial process to platelet activation, which can be explained by Bell’s model of bond unbinding under force. Motivated by these findings, we propose a novel mathematical model for shear-induced platelet activation (P-selectin) and shear-induced platelet receptor (glycoprotein Ibα [GPIbα], GPVI, and GPIIb/IIIa) shedding based on the principle of bond unbinding. The model was examined using experimental data from previous studies in which blood samples were exposed to different combinations of constant shear stress and exposure time. The new model demonstrated an excellent fit with experimental data with an overall coefficient of determination R
2 >0.8, mapping the trends in platelet activation and receptor shedding (except for GPIIb/IIIa) across a range of shear conditions. This new model not only addresses the intrinsic upper bound error in the power-law model but also provides a theoretical foundation into blood damage under shear stress.
Pro- and anti-inflammatory immune biomarkers as predictors of neurodevelopment in young children exposed to HIV
Authors: Li Wei , Egler Ashley , Oyungu Eren , Yang Ziyi , Xu Huiping , Jang Jeong Hoon , McHenry Megan S. , Yu Qigui , Khaitan Alka
Published: February 2025

Objective:

Higher inflammation and lower neurodevelopmental outcomes (ND) have been reported in children exposed to HIV but uninfected (CHEU) compared to children unexposed to HIV (CHU) during infancy, but whether these differences persist in early childhood is unclear. We assessed pro- and anti-inflammatory biomarkers and their associations with ND in CHEU and CHU aged 18–36 months.

Design:

Cross-sectional study of 45 CHEU and 36 CHU aged 18–36 months enrolled in Eldoret, Kenya.

Methods:

Plasma levels of 65 cytokines, chemokines, growth factors, and soluble receptors, and 16 soluble immune checkpoints (ICPs) were quantified using multiplex immunoassays. Monocyte activation (sCD14, sCD163) and endothelial activation (CD146, ICAM-1, VCAM-1) plasma levels were measured by ELISAs. ND was assessed using the culturally adapted developmental assessment of cognition, language, and motor function. Predictors of ND were assessed using Bayesian Model Averaging of the linear regression model.

Results:

CHEU exhibited lower levels of several chemokine and growth factors and four inflammatory cytokines compared to CHU: APRIL (p = 0.03), IL-12p70 (p < 0.001), MIF (p = 0.002), and Tweak (p = 0.003). Conversely, two soluble ICPs, CD40 (p = 0.02) and TIM3 (p = 0.001), were higher in CHEU compared to CHU. IL-22 and SDF-1α emerged as the strongest predictors of neurodevelopment in CHEU and CHU, respectively.

Conclusion:

In early childhood, CHEU exhibited an immunosuppressive rather than inflammatory biomarker profile. Immune biomarkers more frequently predicted ND than social and demographic factors, and the predictors of cognitive, motor, and language outcomes differed between CHU and CHEU. Further research is necessary to explore the connection between childhood neurodevelopment and immune biomarkers.
Enhancing Viability of Internal Mammary Artery Perforator Flaps Using Delay Phenomenon
Authors: Alsheshi Mohammad , El-Maaytah Khalid , Abu Ashour Mohammed , Ritter Edmond , El-Qawaqzeh Khaled
Published: February 2025

The introduction of perforator flaps in 1989 opened new possibilities for reconstruction, allowing for primary closure of the donor site and providing superior functional and cosmetic outcomes. This case details the successful application of the delay phenomenon to internal mammary artery perforator flap reconstruction in a left posterior neck third-degree burn victim. This technique enabled us to 1) reliably harvest a long internal mammary artery perforator flap on a single vessel without congestion and 2) maximize aesthetics.
Health Insurance Instability Following Firearm Injury
Authors: Karandinos George , Giuriato Mia , Masiakos Peter T. , Sacks Chana A. , Song Zirui
Published: February 2025

Objective:

To estimate the risk of insurance instability following firearm injury.

Background:

Health insurance instability is associated with negative clinical outcomes. After nonfatal firearm injury, continuity of health care is particularly important given substantially increased physical, mental, and rehabilitative needs and related healthcare spending.

Methods:

Using 2007-2022 commercial insurance claims data, we studied 3,653 survivors and 17,422 matched controls to investigate the risk of health insurance instability associated with firearm injury. Participants were matched on age, Diagnostic Cost Group risk score, year, month, plan type, drug coverage, sex, metropolitan statistical area, state, and enrollee category.

Results:

The mean age of survivors was 30.5 years, 83.7% were male, 39.2% were primary enrollees, with observable characteristics closely balanced between exposed and control groups after matching. Within 1 year of injury, 36.1% of survivors experienced insurance instability compared with 28.1% of matched controls—an attributable risk of 8.0 (95% CI: 5.8, 10.1) and adjusted hazard ratio of 1.34 (95% CI: 1.26, 1.42). For survivors with more severe injuries, 37.3% experienced insurance instability compared with 27.6% of matched controls—an attributable risk of 9.8 (95% CI: 6.7, 12.9) and adjusted hazard ratio of 1.43 (95% CI: 1.31, 1.56). On average, firearm-injured primary enrollees experiencing insurance instability provided coverage for 0.84 dependents (spouses and children) at the time of their insurance status change.

Conclusions:

Firearm injury was followed by increased insurance instability among survivors, with increased risk following more severe injuries. Insurance instability may disrupt care and shift costs to the public through public insurance enrollment and uncompensated care for the uninsured.
The Impact of Psychological Prehabilitation on Surgical Outcomes
Authors: Hall Anne E. , Nguyen Nghiem H. , Cascavita Catherine T. , Shariati Kaavian , Patel Archi K. , Chen Wei , Kang Youngnam , Ren Xiaoyan , Tseng Chi-Hong , Hidalgo Marco A. , Lee Justine C.
Published: February 2025

Objective:

To investigate the efficacy of psychological prehabilitation in improving surgical outcomes.

Summary Background Data:

Prehabilitation aims to improve surgical outcomes through prevention. While most prehabilitation protocols have focused on improving patient knowledge and physical function, mental health has started to receive greater attention due to its effects on postoperative recovery, including persistent opioid use. However, the efficacy of psychological prehabilitation remains unclear due to the heterogeneity of psychological modalities, intervention characteristics, and surgical contexts.

Methods:

A systematic review, meta-analysis, and meta-regression of randomized controlled trials (RCTs) from 2004–2024 were conducted per PRISMA guidelines to assess the effect of psychotherapy on four postoperative outcomes: length of stay (LOS), pain, anxiety, and depression. RCTs were retrieved from MEDLINE, EMBASE, CENTRAL, and Google Scholar databases (March 2024). Studies with >50 adult surgical patients were included. Random-effects meta-analyses estimated pooled effect sizes, with meta-regression analyzing intervention and surgery types.

Results:

Twenty articles comprising 2,376 patients were included. Psychological prehabilitation interventions included cognitive behavioral therapy (70%), supportive psychotherapy (25%), and acceptance and commitment therapy (5%). Pooled analysis revealed greater reductions in LOS (Mean Difference (MD)=−1.62 days, 95%CI: −2.899,−0.349, P=0.012), pain (MD=−3.52, 95%CI: −2.642,−4.401, P<0.001), anxiety (standard mean difference (SMD)=−1.51, 95%CI: −0.634,−2.385, P<0.001) and depression (SMD=−1.48, 95%CI: −0.578,−2.382, P=0.001). Psychotherapy modality and surgery type showed no significant effects, except for anxiety.

Conclusion:

Psychological prehabilitation reduces LOS, pain, anxiety, and depression after surgery. Further studies are necessary to compare different types, duration, and delivery methods of psychotherapy for specific postoperative outcomes of interest.