bluuebunny/crossref_metadata_2025 huggingface dataset:
Disciplina et Veritas
Authors: Kumar Vikram
Published: February 2025

In one of his earliest dialogues, the Soliloquia, Augustine identifies the liberal arts (disciplinae) with truth (veritas) and employs this somewhat puzzling identification as a premise in his infamous proof of the immortality of the soul (Sol. 2.24). This contribution examines Augustine’s argument for this peculiar identification. Augustine maintains both that the constituent propositions of the liberal arts are true and that the liberal art of dialectic (disciplina disputandi) is the “truth through which all disciplines are true” (Sol. 2.21). It is argued that Augustine identifies the liberal arts with truth because (1) the constituent propositions of the liberal arts are learned and (2) dialectic’s structure is essential to the liberal arts. The contribution further suggests that the subject matter of each liberal art reflects a distinct segment of intelligible reality, that is, the realm of the intelligible Forms.
Thirty years since Kunda: addressing critiques to reimagine a model of motivated reasoning
Authors: Saucier Camille J , Walter Nathan , Demetriades Stefanie Z
Published: February 2025

Following Kunda’s (1990) defense of the influence of motivations on reasoning, a growing body of communication research has coalesced around the idea that specific motivations can influence decision-making. At the same time, this body of research has been subjected to criticisms highlighting alternative explanations that do not involve motivated processes. The present study contributes to this conversation by reviewing the evidence around motivated reasoning as reflected in empirical communication research over the past 30 years (k = 143), focusing on the framework’s key components: motivation, reasoning, and responses. The findings identify considerable gaps, including a limited focus on distinct motivations, an underemphasis on reasoning, and a concentration on a narrow set of responses. This article concludes by proposing the Motivation-Reasoning-Response Model, which visually summarizes the findings of this review and indicates possible opportunities for future research.
The Occurrence of Health Symptoms in General Practice Before and After the Explantation of Cosmetic Breast Implants
Authors: Lieffering Annemiek S , Mureau Marc A M , Hommes Juliëtte E , Ramerman Lotte , Rakhorst Hinne A , van der Hulst R R W J , Verheij R A
Published: February 2025

Background

Explantation of breast implants is increasingly performed in response to concerns about Breast Implant Illness (BII), an array of various health symptoms. However, the benefits of explantation remain unclear due to methodological limitations in prior studies.

Objectives

To examine the occurrence of health symptoms before and after explantation of cosmetic breast implants.

Methods

Retrospective cohort study linking data from the Dutch Breast Implant Registry and Nivel Primary Care Database. The study included 217 cosmetic explantation patients, and control groups of 228 cosmetic replacement patients, and 433 women without breast implants (non-recipients). BII-related health symptoms presented in general practice were compared between groups one year before and after explantation. Outcomes included any symptom, ≥2 symptoms, ≥3 symptoms, ≥3 consultations, and substantial symptoms (≥3 symptoms with ≥2 consultations for two symptoms).

Results

The likelihood of ≥3 symptoms, ≥3 consultations, and substantial symptoms reduced significantly after explantation (OR ≥3 symptoms 0.26, 95% CI [0.08–0.85]; OR ≥3 consultations 0.56, 95% CI [0.32–0.96]; OR substantial symptoms 0.36, 95% CI [0.14–0.94]). However, compared to non-recipients, explantation patients still had higher odds of any symptom, ≥2 symptoms and ≥3 consultations after explantation. Replacement patients also had a reduced likelihood of any symptom, ≥2 symptoms, and ≥3 consultations from pre- to post-surgery.

Conclusions

Although explantation appears to improve BII-related health symptoms within a year, women still showed an increased likelihood of symptoms compared to non-recipients.
Variants in KLF4 affecting residue Asp441 cause an autosomal dominant syndromic ichthyosis
Authors: Wang Zijuan , Liu Jun , Wechsberg Oded , Liang Lina , Keegan Catherine E , Sloan-Heggen Christina , Mo You , Luo Yangyang , Wang Huijun , Lin Zhimiao
Published: February 2025

Background

Congenital ichthyoses comprise a group of skin scaling diseases with clinical and genetic heterogeneity. They can be subclassified into syndromic and nonsyndromic forms. Syndromic ichthyoses affect organs beyond the skin. An increasing number of causative genes has been identified.

Objectives

To identify the causative gene and the underlying pathogenesis of a previously unreported syndromic ichthyosis.

Methods

Whole-exome sequencing (WES), combined with Sanger sequencing, was utilized to identify the genetic defect. Protein structural modeling and dual-luciferase reporter assays were employed to investigate the effects of the pathogenic variants on KLF4. A human embryonic stem cell-H9 line (hESC-H9) harboring the pathogenic variant was developed into a skin organoid for morphological observation and RNA sequencing analysis. The expression of candidate target genes was further validated in patients’ skin samples using quantitative RT-PCR and immunofluorescence.

Results

We collected four unrelated sporadic patients with a syndromic ichthyosis, predominantly manifesting as ichthyosis, palmoplantar keratoderma, hypotrichosis, periorificial keratosis, nail dystrophy, and varying extracutaneous involvement. WES identified two heterozygous missense variants, c.1322A>G (p.Asp441Gly) and c.1323T>A (p.Asp441Glu), in the KLF4 gene in these patients. Protein modeling predicted that the substitutions of the affected residue, Asp441, were likely to affect the stability of the local α-helix structure. Both variants exhibited reduced transcriptional activity. Skin organoids derived from hESC-H9 cells harboring the heterozygous c.1323T>A variant displayed defects in epithelial morphogenesis and abnormal expression of keratinocyte differentiation-related genes and WNT signaling genes. Decreased expression of KLK7 and WNT10A, which are vital for skin desquamation and multi-organ development, respectively, was detected in the patients’ skin lesions.

Conclusions

Loss-of-function variants affecting residue Asp441 of KLF4 cause an autosomal dominant syndromic ichthyosis with multi-organ involvement. These variants impair KLF4 transcriptional activity, leading to the downregulation of multiple genes, particularly KLK7 and WNT10A. This may disrupt the skin desquamation process and affect multi-organ development in the patients.
PREDICT

ing

P

ost-

E

mbolisation

S

yndrome after uterine fibroid embolisation: The PREDICT-PES study
Authors: Clements Prof Warren , Lukies Matthew W , Coleman Madeleine , Nandurkar Rohan , Mercier Laura Le , Venn Georgina , Koukounaras Jim
Published: February 2025

Objectives

To identify the rate of clinically significant post-embolisation syndrome (csPES) in our cohort of patients after uterine artery embolisation for symptomatic fibroids, and to identify risk factors associated with the development of csPES.

Methods

Retrospective case-control study. All patients that underwent uterine artery embolisation for symptomatic fibroids between the 18-month period of 1 March 2022 and 1 September 2023 were recruited. csPES was defined as maximum pain score on visual analogue scale of > 5 out of 10, plus at least one of: morphine patient-controlled analgesia dose >10mg, fever, or use of 2 or more antiemetics.

Results

69 patients were included, mean age 46.2 years, and median uterine volume 393 mL (range 80-2288 mL). The rate of csPES was 47.8% (33 patients). After adjusting for confounding using multiparametric logistic regression, a positive association was seen between nulliparity and developing csPES (OR 5.51, 95%CI 1.297-23.410, p = 0.021). In addition, a trend was shown between increasing age and a reduced odds of developing csPES (OR 0.87, 95%CI 0.748-1.002, p = 0.054).

Conclusion

The rate of csPES in our cohort was 47.8%, and nulliparity was strongly associated with the development of csPES. We can use this to better counsel our patients regarding the odds of csPES when these risks are present at pre-procedure consultation, and target additional interventions at reducing csPES in this population.

Advances in knowledge

Clinically significant post-embolisation syndrome is common after uterine artery embolisation for symptomatic fibroids. This study showed that nulliparity is a risk factor for developing, previously not known or reported.
Epileptogenic zone characteristics determine effectiveness of electrical transcranial stimulation in epilepsy treatment
Authors: Daoud Maëva , Medina-Villalon Samuel , Garnier Elodie , Bratu Ionuț-Flavius , Damiani Giada , Salvador Ricardo , Wendling Fabrice , Ruffini Giulio , Bénar Christian , Pizzo Francesca , Bartolomei Fabrice
Published: February 2025

Transcranial direct current stimulation shows promise as a non-invasive therapeutic method for patients with focal drug-resistant epilepsy. However, there is considerable variability in individual responses to transcranial direct current stimulation, and the factors influencing treatment effectiveness in targeted regions are not well understood. We aimed to assess how the extent and depth of the epileptogenic zone and associated networks impact patient responses to transcranial direct current stimulation therapy. We conducted a retrospective analysis of stereoelectroencephalography data from 23 patients participating in a personalized multichannel transcranial direct current stimulation protocol. We evaluated the extent and depth of the epileptogenic zone network, propagation zone network, and the combined network of the entire epileptogenic and propagation zones, correlating these factors with clinical response measured by the reduction in seizure frequency following repeated transcranial direct current stimulation sessions. Among the patients, 10 (43.5%) were classified as responders (R), experiencing a significant (>50%) decrease in seizure frequency, while 13 were non-responders, showing minimal improvement or increased seizure frequency. Importantly, we found a significant positive correlation between the extent of the epileptogenic zone network and changes in seizure frequency. A smaller epileptogenic zone network extent was associated with better transcranial direct current stimulation efficacy, with responders demonstrating a significantly smaller epileptogenic and propagation zones compared with non-responders. Additionally, non-responders tended to have a significantly deeper epileptogenic zone network compared with responders. Our results highlight the significant impact of the extent and depth of the epileptogenic zone network on transcranial direct current stimulation efficacy in patients with refractory focal epilepsy. Responders typically exhibited a smaller and shallower epileptogenic zone network compared with non-responders. These findings suggest that utilizing individualized epileptogenic zone network characteristics could help refine patient selection for personalized transcranial direct current stimulation protocols, potentially improving therapeutic outcomes.
Advances of exosomes in diabetic wound healing
Authors: Jin Weixue , Li Yi , Yu Meirong , Ren Danyang , Han Chunmao , Guo Songxue
Published: February 2025

Poor wound healing is a refractory process that places an enormous medical and financial burden on diabetic patients. Exosomes have recently been recognized as crucial players in the healing of diabetic lesions. They have excellent stability, homing effects, biocompatibility, and reduced immunogenicity as novel cell-free therapies. In addition to transporting cargos to target cells to enhance intercellular communication, exosomes are beneficial in nearly every phase of diabetic wound healing. They participate in modulating the inflammatory response, accelerating proliferation and reepithelization, increasing angiogenesis, and regulating extracellular matrix remodeling. Accumulating evidence indicates that hydrogels or dressings in conjunction with exosomes can prolong the duration of exosome residency in diabetic wounds. This review provides an overview of the mechanisms, delivery, clinical application, engineering, and existing challenges of the use of exosomes in diabetic wound repair. We also propose future directions for biomaterials incorporating exosomes: 2D or 3D scaffolds, biomaterials loaded with wound healing-promoting gases, intelligent biomaterials, and the prospect of systematic application of exosomes. These findings may might shed light on future treatments and enlighten some studies to improve quality of life among diabetes patients.
A Novel Approach and Exergy Analysis for a Concentrated Photovoltaic System for Thermoelectric Absorption Cooling
Authors: Al-Tahaineh Hamza
Published: February 2025

A unique and distinctive absorption-thermoelectric cooling system powered by a photovoltaic-thermal unit is presented in this work with a thorough exergy analysis. The photovoltaic module supplied electricity to the thermoelectric cooler, while heat energy fueled the absorption unit. The solar module's efficient cooling enhances electrical output while diminishing the quality of thermal energy. Consequently, the thermoelectric cooler exhibits superior cooling performance compared to the absorption cooler. The primary objectives of the study are the coefficient of performance, exergy efficiency, and cooling capacity of the photovoltaic-thermal absorption system. A mathematical representation of the suggested system is shown. The model is assessed at a local solar irradiance of 1000 W/m² and various operational temperatures. The system coefficient of performance climbed from 0.67 to 0.73, while the exergy efficiency declined from 0.34 to 0.17 as the photovoltaic-thermal temperature rose from 60 to 120 °C, achieving a peak cooling capacity of 6 kW.
Cardiac Troponin I and T Ratio and Risk of Cardiovascular or Non-Cardiovascular Events in a General Population
Authors: de Bakker Marie , Welsh Paul , Sattar Naveed , Lindahl Bertil , Hammarsten Ola , Omland Torbjørn , Campbell Archie , Hayward Caroline , Sudlow Cathie L M , Mills Nicholas L , Kimenai Dorien M , Eggers Kai M
Published: February 2025

Background

Emerging evidence suggests that the ratio between cardiac troponin (cTn) I and T may provide information on the risk of adverse outcomes in individuals with cardiovascular disease. Whether the cTn I/T ratio provides prognostic insights in the general population is unknown.

Methods

The cTn I/T ratio was calculated in 8855 participants (43% female, median age 56 years) from the Generation Scotland Study where both cTnI and cTnT concentrations were above the limit of blank. Multivariable cause-specific Cox proportional hazard models were used to estimate the associations between cTn I/T ratio and the primary outcome of cardiovascular or non-cardiovascular death.

Results

The median cTn I/T ratio was 0.5 (25th–75th percentile, 0.3–0.8) and median follow-up was 11.4 (10.8–12.7) years. Individuals in the highest ratio tertile (≥0.64) were more likely to be male, have a higher body mass index and systolic blood pressure, and a history of cardiovascular disease. Those in the lowest ratio tertile (<0.38) were more likely to be smokers or have diabetes. After adjustment for cardiovascular risk factors, the cTn I/T ratio was positively associated with cardiovascular death (per doubling increase, adjusted hazard ratio [HR] 1.16 [95% CI, 1.05–1.28]), while an inverse association was observed for non-cardiovascular death (HR 0.89 [95% CI, 0.81–0.99]).

Conclusions

The cTn I/T ratio is positively associated with cardiovascular death in the general population, while inversely associated with non-cardiovascular death. Future research is needed to unravel underlying mechanisms and determine whether the cTn I/T ratio provides valuable information regarding risk of cardiovascular and non-cardiovascular mortality to guide further management.
Let me be perfectly unclear: strategic ambiguity in political communication
Authors: Bach Parker , Schmitt Carolyn E , McGregor Shannon C
Published: February 2025

While clarity is often upheld as a core element of successful communication, we argue that a lack of clarity can also benefit a speaker, a concept called strategic ambiguity. This concept has been used across disciplines for decades, but its definitions are often overly context-specific. In this article, we follow Chaffee’s (1991) framework for explication to survey the literature and provide a unified definition of strategic ambiguity as a rhetorical tactic in which a communicator creates a: (1) polysemic message with multiple reasonable interpretations supported by the text, that is: (2) aimed at audiences from varying interpretive communities; and (3) by which polysemy the communicator stands to gain some specific advantage. We offer methodological suggestions on the study of strategic ambiguity, accompanied by two case studies of strategic ambiguity, centering Congressional newsletters and conservative political satire. We close with suggestions for scholarships that could be informed by incorporating strategic ambiguity.
Pregnancy 3 months after inclisiran injection: a unique case report including newborn baby monitoring
Authors: Allevi Massimiliano , Landolfo Matteo , Giulietti Federico , Spannella Francesco , Sarzani Riccardo
Published: February 2025

Background

Data on the safety of inclisiran, a lipid-lowering small interfering RNA (siRNA) inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion, during pregnancy are absent.

Case summary

A 30-year-old woman suffering from heterozygous familial hypercholesterolaemia started treatment with inclisiran 25 weeks before the start of gestation and received a second administration 13 weeks before the start of gestation. As soon as we became aware of the unplanned pregnancy, given the absence of any data regarding the administration of inclisiran during this period, the treatment was discontinued and the pregnancy was closely monitored. After a normal and full-term gestation, birth occurred at 41 + 0 gestational weeks. The baby was female and healthy, with normal anthropometry for her gestational age; her growth and development in the first 8 months of life followed a normal course.

Discussion

Potential harms to the foetus with systemic malformations have been highlighted with the genetically proxied LDL cholesterol lowering through PCSK9. To the best of our knowledge, this is the first case of pregnancy initiated few months after inclisiran administration, without reporting any adverse effect on the patient or the baby. More data are needed on the pharmacodynamics and safety of siRNAs in general, and of inclisiran in particular, to confirm that this drug could be safe even in this specific setting.
Titanium-nitride-oxide-coated vs. drug-eluting stents in acute coronary syndromes: an individual patient data meta-analysis
Authors: Mahendiran Thabo , Bouisset Frederic , Tonino Pim , Pijls Nico H J , Sia Jussi , Kervinen Kari , Rivero-Crespo Fernando , Jüni Peter , Roza da Costa Bruno , Collet Carlos , Mizukami Takuya , Karjalainen Pasi , De Bruyne Bernard
Published: February 2025

Background and Aims

In acute coronary syndromes (ACS), vascular healing at the site of implantation of drug-eluting stents (DES) can be delayed. Titanium-nitride-oxide-coated stents (TiNOS) demonstrate faster strut coverage without the excessive intimal hyperplasia observed with bare metal stents. The 5-year outcomes of patients presenting with ACS, randomized to receive either TiNOS or DES, were compared.

Methods

A systematic review and individual participant data meta-analysis of trials comparing TiNOS with DES for the treatment of ACS was conducted (PROSPERO: CRD42024514342). The primary endpoint was major adverse cardiac events (MACE) at 5 years, a composite of cardiac death (CD), myocardial infarction (MI), and ischaemia-driven target lesion revascularization (TLR). Pre-specified secondary endpoints included CD, MI, TLR, and stent thrombosis. Data were pooled using a mixed-effects Cox regression model with random slope and stratified baseline hazards.

Results

Patient-level data (n = 2743) were obtained from three randomized controlled trials (TiNOS: n = 1620 vs. DES: n = 1123). After a median follow-up of 4.93 years, there was no significant difference in the primary endpoint between TiNOS and DES (12.6% vs. 16.2%; hazard ratio [HR] .82, 95% confidence interval [CI] .67–1.00, P = .051), mainly due to a similar rate of TLR (8.0% vs. 8.1%; HR 1.05, 95% CI .80–1.38, P = .733). However, TiNOS was associated with significantly lower rates of CD (1.5% vs. 3.7%; HR .46, 95% CI .26–.81, P = .007), MI (5.2% vs. 9.6%; HR .56, 95% CI .42–.75, P < .001), and stent thrombosis (1.1% vs. 3.8%; HR .30, 95% CI .17–.53, P < .001).

Conclusions

In ACS patients, TiNOS was associated with similar rates of MACE and TLR as compared with DES but significantly lower rates of CD, MI, and stent thrombosis.
Implantable cardiac monitor in heart failure: just a toy or a useful tool?
Authors: Cicogna Francesco , Canali Emanuele , Lanza Oreste , Jacomelli Ilaria , Panattoni Germana , Fagagnini Alessandro , De Ruvo Ermenegildo , Calò Leonardo
Published: February 2025

The use of implantable cardiac monitors (ICMs) has gradually entered clinical practice in various fields. In addition to the consolidated indications in the study of syncope, cryptogenic stroke and in the management of patients with arrhythmias (suspected or defined), today a possible role for these devices in patients with heart failure (HF) is emerging. The rationale for the use of these devices in HF can be identified in three key areas: (i) identification of silent atrial fibrillation and reduction of the risk of stroke, (ii) stratification of the risk of brady–tachy arrhythmias and consequent reduction of the risk of sudden death, and (iii) identification of patients at risk of imminent exacerbation of HF and their early management with reduction of hospitalizations and episodes of clinical deterioration. For each of these areas, there are conflicting data regarding the real usefulness of ICMs; however, it is reasonable to hypothesize that the use of these devices, under certain conditions, may be useful in patients with HF. The adequate selection of patients to be candidates for this strategy is important. The choice of tools and the availability of an organization that allows the possibility of managing these patients remotely also play an essential role. In any case, case-control studies are needed to establish whether this tool can be truly useful in HF.
From thick walls to clear answers: approaches to diagnosing hypertrophic cardiomyopathy and its mimics
Authors: Angelini Filippo , Bocchino Pier Paolo , Dusi Veronica , Pidello Stefano , De Ferrari Gaetano Maria , Raineri Claudia
Published: February 2025

Hypertrophic cardiomyopathy (HCM) is a genetic condition primarily caused by mutations in sarcomeric proteins, leading to abnormal thickening of the left ventricular wall. Although HCM is the most common genetic cardiovascular disorder, other conditions—such as cardiac amyloidosis, Fabry disease, and mitochondrial myopathies—can mimic its phenotype, complicating diagnosis. Accurate differentiation between HCM and its phenocopies is crucial, as these conditions differ in treatment, prognosis, and inheritance. This paper reviews the clinical, imaging, and laboratory tools essential for diagnosing HCM and its mimics, emphasizing the role of advanced diagnostics like cardiac magnetic resonance, genetic testing, and tissue characterization in guiding personalized management strategies.
Cardiovascular risk assessment in daily clinical practice: when and how to use a risk score
Authors: Panattoni Germana , Desimone Pietro , Toto Federica , Meringolo Federica , Jacomelli Ilaria , Rebecchi Marco , Cicogna Francesco , Calò Leonardo
Published: February 2025

Cardiovascular diseases (CVDs) remain a major cause of morbidity and mortality worldwide. The European Society of Cardiology Guidelines encourage the use of risk prediction models to enhance an adequate management of cardiovascular risk factors and the implementation of healthy behaviours. In primary prevention, estimating CVD risk is used to identify patients at high risk in order to enhance preventive strategies and decrease the incidence of unfavourable events and pre-mature cardiovascular deaths. Risk models integrate information on several conventional risk factors and estimate individual risk over a 10-year period. In addition to conventional risk factors, emerging non-traditional markers should be considered and mentioned in risk stratification. In secondary prevention, optimal management of patients include evaluation of residual CVD risk. The 10-year risk of recurrent events is not the same for all patients. The identification of high-risk patients is mandatory to prevent recurrent events and to allow to engage intensive treatments and follow-up strategies, representing an opportunity for major public health gain. This review provides a guide to evaluate which CVD risk score is appropriate for use in different settings in clinical practice.
Endocardial gaglionated plexi ablation in different vagally-mediated clinical settings: From cardioneuroablation to cardio-neuromodulation
Authors: Rebecchi Marco , De Ruvo Ermenegildo , Sette Antonella , Grieco Domenico , De Luca Lucia , Strano Stefano , Tomaino Marco , Giamundo Domenico , Sasso Stefano , Carabotta Chiara , Desimone Pietro , Fagagnini Alessandro , Crescenzi Cinzia , Martino Annamaria , Panattoni Germana , Romeo Fabiana , Sgueglia Marianna , Barillà Francesco , Brignole Michele , Calò Leonardo
Published: February 2025

Cardioneuroablation (CNA) is now recognized as a safe and effective method in patients with cardioinhibitory neurocardiogenic syncope (CNCS), especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Several investigations have shown beneficial and very satisfactory results with a standard non-extensive endocardial ablation, aimed at identifying high-amplitude fragmented signals in the right and left atria. Despite this, the current scientific debate is focused about a proposal on an ablative method, even more individualized than CNA (at least as a first approach), considering that a standardized approach, especially in the left atrium, could expose CNCS patients with a good prognosis to an excessive risk of complications. These findings, moving from the concept of CNA to a new concept of ‘cardioneuromodulation’, opened a new era, aimed at a non-extensive and individualized treatment of different clinical CNCS scenarios or vagally-mediated atrioventricular block or sinus-atrial node dysfunction.
Cardiac amyloidosis: Innovations in diagnosis and treatment
Authors: Castiglione Vincenzo , Montuoro Sabrina , Orlando Giulia , Aimo Alberto , Vergaro Giuseppe , Emdin Michele
Published: February 2025

Cardiac amyloidosis (CA) is a progressive, underdiagnosed condition caused by the deposition of misfolded proteins in the myocardium, forming amyloid fibrils that impair cardiac structure and function. This review highlights recent advances in the diagnosis and treatment of amyloid light-chain (AL) and transthyretin (ATTR) CA, which globally account for most cases of CA. Novel diagnostic tools, including artificial intelligence-enhanced analysis and advanced imaging modalities like positron emission tomography with amyloid-specific tracers, might improve detection rates and diagnostic accuracy to enable non-invasive subtype differentiation. Furthermore, many innovative treatments are being investigated. For AL-CA, anti-fibril therapies are showing promising results, complementing traditional chemotherapy and autologous stem cell transplantation. In ATTR-CA, gene silencing and anti-fibril therapies are being tested in clinical trials and hold promise of halting disease progression and reducing amyloid deposits, respectively.
Genetics in arrhythmogenic cardiomyopathies: where are we now and where are we heading to?
Authors: Mazzanti Andrea , Kukavica Deni , Trancuccio Alessandro , Scilabra Gabriele G , Coppini Lucia , Pergola Valerio , Tempo Erika , Pili Gianluca , Napolitano Carlo , Priori Silvia G
Published: February 2025

Advances in understanding the genetic architecture and novel imaging techniques have profoundly impacted research on arrhythmogenic right ventricular cardiomyopathy (ARVC). As knowledge of ARVC has evolved, so has its classification: originally termed “arrhythmogenic right ventricular dysplasia”, it was later broadened to “arrhythmogenic cardiomyopathy” (ACM) to include left ventricular forms. However, the 2023 European Society of Cardiology guidelines advocate reintroducing ARVC for fibro-fatty right ventricular disease and adopting “non-dilated left ventricular cardiomyopathy” for left-sided phenotypes previously labelled as ACM variants. Genetic testing has become critical in ARVC diagnosis, particularly for identifying mutations in desmosomal genes (e.g., PKP2, PKP2, PKP2, PKP2, PKP2), which are the primary genetic contributors to ARVC and inform family screening and diagnostic decisions. Recent expert consensus confirmed that only PKP2, PKP2, and PKP2 gene mutations among non-desmosomal genes had sufficient evidence to suggest a causative relationship. While genotype-specific risk assessment models are being developed, at present, genetic background does not represent an independent risk factor for patients with ARVC. Novel gene therapies, particularly AAV-mediated PKP2 gene replacement, have recently been demonstrated to be useful in reversing ARVC phenotypes in preclinical models. FDA-approved trials are currently evaluating PKP2-targeted therapies, and CRISPR/Cas9 methods are being explored for PKP2-R14del mutations. Overall, current evidence supports distinct gene-specific manifestations within ARVC, aligning clinical phenotypes with specific genetic variants. This progress points to a future in which risk stratification and management are personalized through gene- and mutation-specific approaches, advancing the potential for precision medicine in ARVC care.
Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure Results from the SOLVE-CRT Randomised Sub-study
Authors: Montemerlo Elisabetta , Rovaris Giovanni , Singh Jagmeet P , Rinaldi Christopher A , Sanders Prashanthan , Kubo Spencer H , James Simon , Niazi Imran K , Betts Tim R , Aziz Emad , Biffi Mauro , Zaidi Amir , Alison Jeffrey , Auricchio Angelo , Gold Michael R , Lindenfeld JoAnn , Walsh Mary Norine , Butter Christian
Published: February 2025

Background

Despite the well-established role of CRT in heart failure, major limitations of CRT are an occasional incidence of unsuccessful coronary sinus (CS) lead placement, one third non-responders in conventional CRT patients and higher complications risk in CRT upgrade procedures. The WiSE® Wireless Stimulation Endocardial) CRT System is designed to overcome these limitations. Prior non-randomised studies with the WiSE® CRT System have shown high implant success rates and improvement in LV remodeling and heart failure symptoms.

Objectives

Pivotal study to assess the safety and effectiveness of the WiSE® CRT System in an international, randomized, two-arm, double blinded, prospective study (randomized part only).

Method

99 Patients with indication for CRT and previously failed CRT implant, considered as high-risk upgrade to conventional CRT, or non-responders to conventional CRT underwent device implantation and were then randomised into treatment (47 pts, System ON) and control (52 pts System OFF) groups for 6 months. Primary efficacy endpoints were change in LVESV, LVEDV, LVEF and QRS over 6 months in blinded Echo and ECG core lab analysis.

Results

Mean ΔLVESV (%) -14.6 (-19.6, -9.6); mean ΔLVEDV (%) -8.1 (-11.9, -4.3) and mean ΔQRS (ms) -41.9 (-50.1, -33.7) in the treatment group were significantly lower/shorter than mean ΔLVESV (%) -5.2 (-10.7, 0.2); mean ΔLVEDV (%) -3.0 (-7.0, 1.0) and mean ΔQRS (ms) -1.7 (-7.1,3.8) in the control group, p=0.005; p=0.027 and p=0.001, 95% CI. Mean ΔLVEF (%) 5.4 (3.2, 7.7) in the treatment group increased significantly compared to control group ΔLVEF (%) 2.4 (0.2, 4.5), p=0.048. 8 of 99 pts were attempted from WiSE CRT implant.

Conclusion

This randomized sub-study of the pivotal SOLVE-CRT trial demonstrates that leadless, ultrasound-based endocardial pacing for heart failure is feasible and efficacious showing evidence of left ventricular remodelling and electrical response after 6 months.Figure 1WISE® CRT System  Figure 2Efficacy entire randomised population
Magnetic extraction for rapid assessment of low-level Escherichia coli and Salmonella contamination in complex food matrices
Authors: Sharief Saad Asadullah , Caliskan-Aydogan Oznur , Alocilja Evangelyn
Published: February 2025

Foodborne illnesses cause numerous hospitalizations worldwide, making rapid detection of causative pathogens critical for outbreak prevention. Enrichment of pathogens is often required to increase the minimum bacterial count before detection. Traditional magnetic nanoparticle (MNP)-based extraction methods are limited by the costs associated with recognition ligands and cold-storage requirements. This study presents the use of glycan-coated magnetic nanoparticles (gMNPs), synthesized via a simple one-pot method, for the rapid concentration and extraction of Escherichia coli and Salmonella enterica serovar Enteritidis. The efficiency was measured using the concentration factor (CF), which was used to compare the viability of cells cultured with gMNPs with that of the controls. High CF values were achieved in large volumes, with values of 5.2 (±1.0) for E. coli and 3 (±1.3) for S. Enteritidis. Transmission electron microscopy and confocal laser microscopy confirmed gMNPs binding to bacterial cells in buffer solution and food matrices. The gMNPs effectively extracted cells in varied pH environments, indicating their potential for use in different foods. S. Enteritidis and E. coli were successfully extracted from melons, cucumber, raw chicken, and lettuce samples despite the presence of natural microbiota. Among the S. Enteritidis-inoculated food samples, the highest CF was observed in melons (5.57±2.26), followed by cucumbers (2.94±2.02), chicken (2.24±1.05), and lettuce (1.75±0.56). Real-time quantitative polymerase chain reaction (qPCR) confirmed the magnetic extraction, with the gMNP-qPCR system enabling rapid assessment of low pathogen contamination in complex food matrices. The quantification cycle (Cq) ratio, inversely related to the DNA concentration, corroborated the CF results, with the lowest ratio in melons (0.85±0.03), followed by cucumber (0.89±0.07), chicken (0.98±0.01), and lettuce (0.97±0.009). The entire extraction and qPCR detection process can be completed in less than 4 h.
Successful Aging with Innovations in Technology and Housing
Authors: Jenkins Melinda L , Barberio Judith
Published: February 2025

Emphasizing personal autonomy and community support, this paper presents three independent housing models in which older adults may be empowered to age successfully at home and engage in self-care and shared community care with innovations in technologies, financing, and nurse care coordination. Cooperative communities, naturally occurring retirement communities, and virtual villages are described and mapped to the AARP “age friendly” Livability Index, stakeholders, and partners. Helpful neighborhood services are mapped to innovative technologies that will enable them. On-site nurse-led Wellness Hubs are proposed to bridge from self-care in the community to established health care systems. Medicare payment for remote care, care coordination, and transitional care, as well as home-based care for dementia, will support this evolution toward what matters most to the growing population of older Americans.
Recent earthquakes on unmapped faults highlight hidden seismic hazards within the Golden Triangle region of Laos, Thailand, and Myanmar
Authors: Sethanant I , Nissen E , Bergman E , Oliva S J , Pousse-Beltran L , Karasözen E , Pananont P
Published: February 2025

In the past decade, six Mw ≥5.5 earthquakes struck the mountainous Golden Triangle region (Laos, Thailand, Myanmar) of the southeast India-Eurasia collision zone. The largest of them, the 2019 Mw 6.2 Sainyabuli earthquake in western Laos, shook river communities, dams, and a UNESCO World Heritage Site, prompting a need to understand regional earthquake potential. We used Interferometric Synthetic Aperture Radar (InSAR) data and modelling to solve for the 2019 mainshock source parameters, revealing right-lateral strike-slip along a 24 km-long NNW-trending fault which has limited topographic expression and was previously unmapped. InSAR modelling of its largest (Mw 5.5) aftershock in 2021 revealed a 7 km-long splay fault, also previously unrecognized. The 2022 Mw 5.9 Keng Tung earthquake in the northern Golden Triangle also ruptured an unknown, NW-trending right-lateral fault conjugate to longer, NE-trending faults nearby. Collectively, this shows that the region contains faults which are little evident in global digital topography and/or obscured by vegetation but long enough to generate sizeable earthquakes that should be accounted for in seismic hazard assessments. We relocated well-recorded aftershocks and other background seismicity (1978–2023) from across the Golden Triangle using the mloc software. Calibrated hypocenters span focal depths of 5–24 km and are distributed away from the main InSAR-modelled fault traces, another indication of fault structural immaturity. For the three 2019–2022 InSAR-constrained events, we also obtained moment tensor solutions from regional seismic waveform inversion. InSAR-derived peak slip depths and seismological centroid depths are mostly shallow (3–5 km), while focal depths are generally located in areas of low coseismic slip near the bottom of InSAR model faults. More broadly, we estimate a regional seismogenic thickness of ∼17 km (the 90% seismicity cut-off depth), a crucial parameter for seismic hazard calculations and building codes. Our integration of remote-sensing and seismologic analyses could be a blueprint for assessing earthquake potential of other regions with sparse instrumentation and limited topographic fault expression.
Totally endoscopic aortic valve replacement with concomitant septal myectomy
Authors: Kim Sahri , Yoo Jae Suk
Published: February 2025

Left ventricular outflow tract obstruction may become apparent after successful aortic valve replacement for severe aortic stenosis, necessitating both aortic valve replacement and septal myectomy. Despite significant advancements in minimally invasive surgery, the current literature on concurrent minimally invasive cardiac procedures is limited due to the varying optimal exposures required for each procedure. In this context, we present a case of aortic valve replacement with concomitant septal myectomy using a minimally invasive, totally endoscopic approach.
Global profit shifting of multinational companies: Evidence from country-by-country reporting micro data
Authors: Fuest Clemens , Greil Stefan , Hugger Felix , Neumeier Florian
Published: February 2025

We use micro data from country-by-country reports of more than 3 600 multinational companies to analyze global profit shifting to avoid taxes. Unlike other data sets, country-by-country reports provide detailed information about the global economic activities of multinational companies, including those in tax haven countries. We find that these companies reduce their tax burden by €39 billion per year by shifting profits to low-tax countries. Extrapolating our results to the universe of large MNEs indicates a global loss in corporate tax revenues of €162 billion per year (12% of their overall tax payments). We show that taking into account non-linearities in profit shifting and subsidiaries reporting zero profits is key for accurately estimating profit shifting.
Preliminary Validity of a Daily Functional Status Pain Assessment Tool
Authors: Smith Wally R , Qayyum Rehan , Ulbing Alexandra , Guy Margaret S , Sop Daniel M , Zhang Yue May
Published: February 2025

Objectives

Readiness for discharge for a sickle cell disease vaso-occlusive crisis is dictated by factors far beyond pain control, including physical function/activity. We therefore designed and tested a functional status-based pain assessment questionnaire in SCD patients hospitalized with vaso-occlusive crises.

Methods

Sickle cell disease patients on a preselected nursing unit rated 10 draft Functional status-Based Pain Assessment items of activities of daily living on a 5 point Likert scale (0-5) from “very easy” to “very difficult” daily on each day of their admission until discharge, at approximately the same time. Concurrently, they reported Numeric Rating Scale (0-10) pain intensity. For validation, we used exploratory factor analysis, confirmatory factor analysis, and item response theory analysis.

Results and Discussion

We analyzed 503 observations from 175 admissions of 88 patients. Half were female, the mean age was 32.1+/- 11.8 years, and the mean length of stay was 7.1 +/-6.9 days. The mean Numeric Rating Scale (6.8 ± 1.9) was inversely correlated with the mean Functional Status-based Pain Assessment (0-50) score (27 ± 8.0, r= -0.4342, p <.0001). Functional Status-based Pain Assessment item means ranged from 2.1 to 3.3. Cronbach’s alpha was 0.91. Exploratory factor analysis showed that all Functional Status-based Pain Assessment items loaded on a single factor. Confirmatory factor analysis found adequate convergent and discriminant validity and showed strong fit of the model to the data. Item response theory analysis showed item discrimination ranging from 0.56 to 4.1, while difficulty ranged from -2.8 to 7.5.

Conclusion

The Functional Status-based Pain Assessment shows strong correlation with daily Numeric Rating Scale, is multidimensional, and demonstrates strong construct validity. It may improve assessment of sickle cell disease vaso-occlusive crisis pain and may enhance vaso-occlusive crisis discharge discussions.
‘And Then They Will Fast on That Day’ (Mark 2:20): The Absent Bridegroom and the Day of Atonement in Early Christianity
Authors: Botner Max
Published: February 2025

Markan interpreters agree that the fulcrum of the first controversy series (Mark 2:1–3:6) is a logion that underscores Jesus’ absence from the community he founded: ‘The days will come when the bridegroom is taken away from them, and then they will fast on that day’ (2:20). Some conclude that the logion is a post hoc attempt to justify ‘Christian’ fasting practices (e.g. Didache 8:1), while others maintain that it alludes to the nature of the post-crucifixion period. This article (re)introduces into this discussion one of the earliest interpretations of Mark 2:20: Origen’s interpretation of the ‘day’ of the bridegroom’s absence as the eschatological Day of Atonement (Hom. Lev. 9). Second, it explores the extent to which a Yom Kippur typology illuminates Mark’s portrayal of the interstice between the death and resurrection of Jesus, on the one hand, and the parousia of the Son of Man, on the other. My suggestion is that the Markan logion enfolds the disciples into an apocalyptic season of Yom Kippur ‘affliction’ and anticipation.
Clonal expression and structural analysis of polylactic acid degrading enzyme S8SP from Bacillus safensis
Authors: Wang Yujun , Zhang Yuanyi , Li Chunwang , Meng Siqi , Wang Dandan , Zhao Lehui , Wang Zhanyong
Published: February 2025

Polylactic acid (PLA) is one of the most popular biodegradable plastics favored over traditional plastics. However, it is more difficult to degrade than other biodegradable plastics probably due to the low species and number of PLA-degrading microorganisms degrading enzymes in the environment. Therefore, identifying PLA-degrading microorganisms and enzymes is of great significance for the popularization and application of PLA. This study identified a PLA-degrading enzyme, S8 serine peptidase (S8SP), from Bacillus safensis, and the heterologous expression of S8SP was conducted in Escherichia coli. PLA degradation ability of S8SP was investigated using scanning electron microscopy and water contact angle. The surface of S8SP-degraded PLA films showed obvious cracks and pits and exhibited improved hydrophilicity. The molecular weight of S8SP was about 42 kDa, and its optimum temperature and pH were 40 °C and 8.0, respectively. S8SP could maintain high stability in the temperature range of 30-40 °C and pH range of 7.0-9.0. Sodium ions (Na+), potassium ions (K+), Triton X-100, and Tween-80 promoted the enzyme activity of S8SP. S8SP had a high similarity degree to S8 serine peptidase from the genus Bacillus, and had the classical hydrolase-catalyzed triplet structure.
Reduction of the type Ia supernova host galaxy step in the outer regions of galaxies
Authors: Toy M , Wiseman P , Sullivan M , Scolnic D , Vincenzi M , Brout D , Davis T M , Frohmaier C , Galbany L , Lidman C , Lee J , Kelsey L , Kessler R , Möller A , Popovic B , Sánchez B O , Shah P , Smith M , Allam S , Aguena M , Alves O , Bacon D , Brooks D , Burke D L , Rosell A Carnero , Carretero J , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Drlica-Wagner A , Everett S , Ferrero I , Flaugher B , Frieman J , García-Bellido J , Gatti M , Gaztanaga E , Giannini G , Gruendl R A , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Lahav O , Lee S , Marshall J L , Mena-Fernández J , Miquel R , Palmese A , Pieres A , Malagón A A Plazas , Romer A K , Samuroff S , Sanchez E , Cid D Sanchez , Schubnell M , Suchyta E , Swanson M E C , Tarle G , Tucker D L , Vikram V , Walker A R , Weaverdyck N
Published: February 2025

Using 1533 type Ia supernovae (SNe Ia) from the five-year sample of the Dark Energy Survey (DES), we investigate the relationship between the projected galactocentric separation of the SNe and their host galaxies and their light curves and standardization. We show, for the first time, that the difference in SN Ia post-standardization brightnesses between high and low-mass hosts reduces from 0.078 ± 0.011 mag in the full sample to 0.036 ± 0.018 mag for SNe Ia located in the outer regions of their host galaxies, while increasing to 0.100 ± 0.014 mag for SNe in the inner regions. The difference in the size of the mass step between inner and outer regions is 0.064 ± 0.023 mag. In these inner regions, the step can be reduced (but not removed) using a model where the RV of dust along the line-of-sight to the SN changes as a function of galaxy properties. We investigate the remaining difference using the distributions of the SN Ia stretch parameter to test the inferred age of SN progenitors. Comparing red (older) environments only, outer regions have a higher proportion of high-stretch SNe and a more homogeneous stretch distribution. However, this effect cannot explain the reduction in significance of any Hubble residual step in outer regions. We conclude that the standardized distances of SNe Ia located in the outer regions of galaxies are less affected by their global host galaxy properties than those in the inner regions.