bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&gt;G (p.Asp441Gly) and c.1323T&gt;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&gt;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.
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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

Abstract

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 &gt; 5 out of 10, plus at least one of: morphine patient-controlled analgesia dose &gt;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

Abstract
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 (&gt;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

Abstract
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

Abstract
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

Abstract

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 (&lt;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

Abstract
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

Abstract

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

Abstract

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 &lt; .001), and stent thrombosis (1.1% vs. 3.8%; HR .30, 95% CI .17–.53, P &lt; .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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.