bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Costs of Home Monitoring by Telemedicine vs Standard Care for Inflammatory Bowel Diseases—A Danish Register-Based, 5-Year Follow-up Study
Authors: Al-Sheikh Marwah , Ankersen Dorit Vedel , Olsen Jens , Spanggaard Maria , Peters-Lehm Charlotte T , Naimi Rahim M , Bennedsen Mette , Burisch Johan , Munkholm Pia 
Published: August 2024

Abstract

Background and Aims
There are few studies on the cost-effectiveness of telemedicine for inflammatory bowel diseases. We assessed the long-term cost-effectiveness of a telemedicine solution compared to standard care (sCare), as well as its efficacy according to patient-reported outcomes (PROs).

Methods
Between 2015 and 2020, we conducted a retrospective, register-based study among patients with ulcerative colitis and Crohn’s disease. Direct and indirect healthcare costs over a 5-year period were obtained from Danish registers and compared to a control group. Costs were estimated on a yearly basis from 1 year before, until 5 years after, inclusion in the trial. Patients were divided into 2 groups: those not receiving biologics (Cohort 1) and those receiving biologics (Cohort 2).

Results
We recruited 574 patients with inflammatory bowel diseases. In Cohort 1 (61.5%), average total direct costs and total earnings per patient per year were €14 043 and €307 793, respectively, in telemedicine compared to €16 226 and €252 166, respectively, in sCare. In Cohort 2 (38.5%), average total direct costs and total earnings were €73 916 and €215 833, respectively, in telemedicine compared to €41 748 and €203 667, respectively, in sCare. PROs showed improved quality of life, which was higher in Cohort 1 than in Cohort 2. Disease activity among patients with Crohn’s disease increased after Years 3 and 4 in Cohorts 1 and 2, respectively.

Conclusion
Telemedicine is cost-effective for patients not receiving biologics. However, treatment with biologics is more expensive for patients enrolled in telemedicine. Careful attention to PROs in telemedicine improves quality of life and could prolong the time to relapse.
The left ventricular assist device ‘skeleton man’: case report—simple tools for skeletal muscle evaluation and very early aerobic/resistance/inspiratory training in cardiac cachexia
Authors: Laoutaris Ioannis D , Gkouziouta Aggeliki , Bonios Michael J , Katelouzos George , Kogerakis Nektarios , Chamogeorgakis Themistocles , Adamopoulos Stamatis 
Published: August 2024

AbstractBackgroundSkeletal muscle wasting (SMW) is highly prevalent in patients with heart failure (HF) at left ventricular assist device (LVAD) implantation and is associated with morbidity and mortality. At the same time, SMW is clinically under-recognized, while exercise training (ET) studies in weak LVAD patients are lacking.Case summaryA 60-year-old man with advanced HF, SMW, cardiac cachexia, and frailty was confined in bed for 6 months initially supported with intravenous inotropes and subsequently with an intra-aortic balloon pump. His frailty was recognized as an LVAD-responsive frailty, and patient was successfully implanted with a HeartWare (Medtronic). Post-surgery, patient was very weak, unable even to move in bed without assistance. We evaluated skeletal muscle using simple tools such as the Oxford scale, mid-thigh circumference, hand-held dynamometry, and maximum inspiratory pressure. Physical performance was assessed with the sit to stand test, gait speed test, pedal bike timing, and the 6 min walk test. On top of routine physiotherapy, patient underwent an 8-week modified aerobic/resistance/inspiratory (ARIS) ET programme at moderate intensity and showed significant improvements in skeletal muscle mass and strength and physical and functional capacity.DiscussionWe want to emphasize the importance of skeletal muscle evaluation at LVAD implantation and the feasibility and effectiveness of early ARIS training in very weak patients.
Eosinophilic myocarditis: a diagnostic challenge and treatment dilemma—a case report
Authors: Ammouri Zaid , Belkouchia Sami , Rezzouk Ibtissam , Moussaoui Salma , Habbal Rachida 
Published: August 2024

Abstract

Background
Eosinophilic myocarditis, a rare and potentially life-threatening condition, can resemble acute coronary syndrome (ACS) and presents diagnostic difficulties.

Case report
We describe the case of a 32-year-old man initially admitted with ACS-like symptoms, but ultimately diagnosed with eosinophilic myocarditis. The patient presented with intense retrosternal chest pain, significant eosinophilia, and elevated cardiac enzymes. Despite clinical indications suggesting myocardial involvement, an endomyocardial biopsy was not performed due to the patient’s reluctance. Non-invasive imaging and clinical findings led to the presumptive diagnosis of eosinophilic myocarditis. The patient was treated with high-dose corticosteroids and immunosuppressive therapy, resulting in clinical improvement.

Discussion
Our report highlights the importance of considering eosinophilic myocarditis and hypereosinophilic syndrome when evaluating patients with chest pain and hypereosinophilia. It emphasizes the subtleties of diagnosis and the critical need for early identification and appropriate treatment to improve prognosis in cases of eosinophilic myocarditis. This case underscores the diverse clinical manifestations of myocarditis and the essential need for a comprehensive diagnostic approach in the presence of chest pain and hypereosinophilia.
Metabolically healthy obesity in adults with X-linked hypophosphatemia
Authors: Lecoq Anne-Lise , Schilbach Katharina , Rocher Laurence , Trabado Séverine , Briot Karine , Herrou Julia , Forbes Aurélie , Garnier Anthony , Piketty Marie , Bidlingmaier Martin , Rothenbuhler Anya , Linglart Agnès , Carette Claire , Chaumet-Riffaud Philippe , Kamenický Peter 
Published: August 2024

Abstract

Objectives
X-linked hypophosphatemia (XLH) is characterized by increased concentrations of circulating fibroblast growth factor 23 (FGF-23) resulting in phosphate wasting, hypophosphatemia, atypical growth plate and bone matrix mineralization. Epidemiologic studies suggest a relationship between FGF-23, obesity, and metabolic dysfunction. The prevalence of overweight and obesity is high in children with XLH. We aimed to evaluate the prevalence of obesity and metabolic complications in adults with XLH.

Methods
We conducted a prospective cohort study in adult XLH patients from a single tertiary referral center. The proportion of patients with a BMI &gt;25 kg/m2 was the main outcome measure. Body fat mass percentage (FM%) and adipose tissue surfaces were secondary outcome measures. Glucose homeostasis (plasma glucose and insulin concentrations after fasting and 2 hours after an oral glucose tolerance test) was explored in a subgroup of patients and compared with age-, sex-, and BMI-matched healthy controls.

Results
Among 113 evaluated patients, 85 (75%) were female and 110 (97%) carried a PHEX mutation. Sixty-three (56%) patients were overweight or obese, with a median BMI of 25.3 [IQR, 22.7; 29.2] kg/m2. BMI was correlated with FM%, abdominal and thigh subcutaneous and intra-abdominal adipose tissue surfaces. The prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes was not different between XLH patients and matched controls.

Conclusion
The prevalence of overweight and obesity is high among XLH patients and is associated with excess fat mass. However, the prevalence of glucose homeostasis abnormalities is not increased in patients compared to healthy controls, suggesting that metabolically healthy overweight or obesity predominates.
KCNQ1 suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome
Authors: Bains Sahej , Giammarino Lucilla , Nimani Saranda , Alerni Nicolo , Tester David J , Kim C S John , Christoforou Nicolas , Louradour Julien , Horváth András , Beslac Olgica , Barbieri Miriam , Matas Lluis , Hof Thomas S , Lopez Ruben , Perez-Feliz Stefanie , Parodi Chiara , Garcia Casalta Luisana G , Jurgensen Jacqulyn , Barry Michael A , Bego Mariana , Keyes Lisa , Owens Jane , Pinkstaff Jason , Koren Gideon , Zehender Manfred , Brunner Michael , Casoni Daniela , Praz Fabien , Haeberlin Andreas , Brooks Gabriel , Ackerman Michael J , Odening Katja E 
Published: August 2024

Abstract

Background and Aims
Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy.

Methods
KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes.

Results
KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P &lt; .0001, LQT1-SupRep vs. WT, P = ns). Under β-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour.

Conclusions
This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1.
Systematic review and meta-analysis on the impact on outcomes of device algorithms for minimizing right ventricular pacing
Authors: Mei Davide Antonio , Imberti Jacopo Francesco , Vitolo Marco , Bonini Niccolò , Serafini Kevin , Mantovani Marta , Tartaglia Enrico , Birtolo Chiara , Zuin Marco , Bertini Matteo , Boriani Giuseppe 
Published: August 2024

Abstract

Aims
Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD).

Methods and results
We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57–0.97] and CV hospitalization (OR 0.77, 95% CI 0.61–0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78–1.30) or adverse symptoms (OR 1.03, 95% CI 0.81–1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13–20.25), as compared with 45.11% (95% CI 26.64–76.38) of DDD pacing.

Conclusion
Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients.
Genetic mechanisms of axial patterning in Apeltes quadracus
Authors: Herbert Amy L , Lee David , McCoy Matthew J , Behrens Veronica C , Wucherpfennig Julia I , Kingsley David M 
Published: August 2024

Abstract
The genetic mechanisms underlying striking axial patterning changes in wild species are still largely unknown. Previous studies have shown that Apeltes quadracus fish, commonly known as fourspine sticklebacks, have evolved multiple different axial patterns in wild populations. Here, we revisit classic locations in Nova Scotia, Canada, where both high-spined and low-spined morphs are particularly common. Using genetic crosses and quantitative trait locus (QTL) mapping, we examine the genetic architecture of wild differences in several axial patterning traits, including the number and length of prominent dorsal spines, the number of underlying median support bones (pterygiophores), and the number and ratio of abdominal and caudal vertebrae along the anterior–posterior body axis. Our studies identify a highly significant QTL on chromosome 6 that controls a substantial fraction of phenotypic variation in multiple dorsal spine and pterygiophore traits (~15%–30% variance explained). An additional smaller-effect QTL on chromosome 14 contributes to the lengths of both the last dorsal spine and anal spine (~9% variance explained). 1 or no QTL were detected for differences in the numbers of abdominal and caudal vertebrae. The major-effect patterning QTL on chromosome 6 is centered on the HOXDB gene cluster, where sequence changes in a noncoding axial regulatory enhancer have previously been associated with prominent dorsal spine differences in Apeltes. The QTL that have the largest effects on dorsal spine number and length traits map to different chromosomes in Apeltes and Gasterosteus, 2 distantly related stickleback genera. However, in both genera, the major-effect QTL for prominent skeletal changes in wild populations maps to linked clusters of powerful developmental control genes. This study, therefore, bolsters the body of evidence that regulatory changes in developmental gene clusters provide a common genetic mechanism for evolving major morphological changes in natural species.
Single-cell measurement of microbial growth rate with Raman microspectroscopy
Authors: Caro Tristan A , Kashyap Srishti , Brown George , Chen Claudia , Kopf Sebastian H , Templeton Alexis S 
Published: August 2024

Abstract
Rates of microbial growth are fundamental to understanding environmental geochemistry and ecology. However, measuring the heterogeneity of microbial activity at the single-cell level, especially within complex populations and environmental matrices, remains a forefront challenge. Stable isotope probing (SIP) is a method for assessing microbial growth and involves measuring the incorporation of an isotopic label into microbial biomass. Here, we assess Raman microspectroscopy as a SIP technique, specifically focusing on the measurement of deuterium (2H), a tracer of microbial biomass production. We correlatively measured cells grown in varying concentrations of deuterated water with both Raman spectroscopy and nanoscale secondary ion mass spectrometry (nanoSIMS), generating isotopic calibrations of microbial 2H. Relative to Raman, we find that nanoSIMS measurements of 2H are subject to substantial dilution due to rapid exchange of H during sample washing. We apply our Raman-derived calibration to a numerical model of microbial growth, explicitly parameterizing the factors controlling growth rate quantification and demonstrating that Raman–SIP can sensitively measure the growth of microorganisms with doubling times ranging from hours to years. The measurement of single-cell growth with Raman spectroscopy, a rapid, nondestructive technique, represents an important step toward application of single-cell analysis into complex sample matrices or cellular assemblages.
The first high-altitude autotetraploid haplotype-resolved genome assembled (Rhododendron nivale subsp. boreale) provides new insights into mountaintop adaptation
Authors: Lyu Zhen-Yu , Zhou Xiong-Li , Wang Si-Qi , Yang Gao-Ming , Sun Wen-Guang , Zhang Jie-Yu , Zhang Rui , Shen Shi-Kang 
Published: August 2024

Abstract

Background
Rhododendron nivale subsp. boreale Philipson et M. N. Philipson is an alpine woody species with ornamental qualities that serve as the predominant species in mountainous scrub habitats found at an altitude of ∼4,200 m. As a high-altitude woody polyploid, this species may serve as a model to understand how plants adapt to alpine environments. Despite its ecological significance, the lack of genomic resources has hindered a comprehensive understanding of its evolutionary and adaptive characteristics in high-altitude mountainous environments.

Findings
We sequenced and assembled the genome of R. nivale subsp. boreale, an assembly of the first subgenus Rhododendron and the first high-altitude woody flowering tetraploid, contributing an important genomic resource for alpine woody flora. The assembly included 52 pseudochromosomes (scaffold N50 = 42.93 Mb; BUSCO = 98.8%; QV = 45.51; S-AQI = 98.69), which belonged to 4 haplotypes, harboring 127,810 predicted protein-coding genes. Conjoint k-mer analysis, collinearity assessment, and phylogenetic investigation corroborated autotetraploid identity. Comparative genomic analysis revealed that R. nivale subsp. boreale originated as a neopolyploid of R. nivale and underwent 2 rounds of ancient polyploidy events. Transcriptional expression analysis showed that differences in expression between alleles were common and randomly distributed in the genome. We identified extended gene families and signatures of positive selection that are involved not only in adaptation to the mountaintop ecosystem (response to stress and developmental regulation) but also in autotetraploid reproduction (meiotic stabilization). Additionally, the expression levels of the (group VII ethylene response factor transcription factors) ERF VIIs were significantly higher than the mean global gene expression. We suspect that these changes have enabled the success of this species at high altitudes.

Conclusions
We assembled the first high-altitude autopolyploid genome and achieved chromosome-level assembly within the subgenus Rhododendron. In addition, a high-altitude adaptation strategy of R. nivale subsp. boreale was reasonably speculated. This study provides valuable data for the exploration of alpine mountaintop adaptations and the correlation between extreme environments and species polyploidization.
Laboratory constraints on the anisotropic dynamic-to-static ratios for shale's elastic constants: an example from the Duvernay unconventional reservoir
Authors: Shen Luyi , Schmitt Douglas R , Jiao Yu-yong 
Published: August 2024

Summary
Dynamic material constants obtained by wave-based methods are different from their static counterparts. Constraining rock's elastic constants’ dynamic-to-static ratios (Rij) are important for understanding the geomechanical properties of earth's materials, particularly in the context of hydraulic fracturing that requires the knowledge of shale's static elastic constants. Conducting experiments with dynamic and elastic constants’ anisotropy, on top of their pressure dependency, properly accounted for is challenging. Here, we measure suites of dynamic and static elastic constants, with anisotropy fully accounted for, on the shale samples extracted from the Duvernay unconventional reservoir; a comprehensive set of geochemical/petrophysical measurements are obtained too. We observe that the dynamic-to-static ratios are generally not sensitive to the increasing pressures at σ &gt; 50 MPa; we do not find a correlation with the samples’ mineral contents either. However, we find that Rij strongly correlates to the dynamic elastic constants except for the R11. The correlation between Rij, particularly Ri3, and the dynamic elastic constants can be explained by the sedimentary rocks’ compactness and the horizontal void spaces parallel to the rock's laminated bedding planes.
European Commission’s Draft Regulation on SEPs: An IP Finance Assessment
Authors: Borgogno Oscar , Colangelo Giuseppe 
Published: August 2024

Abstract
The European Commission’s proposed Draft Regulation on Standard Essential Patents (SEPs) aims to overhaul the landscape of SEP licensing, addressing transparency deficits and fair, reasonable, and non-discriminatory (FRAND) terms amidst the burgeoning Internet of Things (IoT) market. Emphasizing concerns over hold-up risks, the Draft Regulation introduces mandatory essentiality checks and structured FRAND determinations to mitigate opportunistic behaviours among SEP holders. However, the practical implementation of these measures poses challenges, including the accuracy of essentiality assessments and the potential for increased transaction costs. Moreover, the Draft Regulation fails to consider the financial dimension of technological innovation, namely the potential of SEPs to function as valuable financial assets. By undermining the economic value of SEPs in terms of enforcement and monetisation, there is a risk of watering down their potential to serve as valuable financial collateral and therefore to help innovators access debt financing.
Unlocking the power of tobacco taxation to mitigate the social costs of smoking in Mexico: a microsimulation model
Authors: Saenz-de-Miera Belen , Reynales-Shigematsu Luz Myriam , Palacios Alfredo , Bardach Ariel , Casarini Agustin , Espinola Natalia , Cairoli Federico Rodriguez , Alcaraz Andrea , Augustovski Federico , Pichon-Riviere Andres 
Published: August 2024

Abstract
Despite being the most cost-effective tobacco control policy, tobacco taxation is the least implemented component of the World Health Organization MPOWER package to reduce smoking worldwide. In Mexico, both smoking prevalence and taxation have remained stable for more than a decade. This study aims to provide evidence about the potential effects of taxation to reduce the burden of tobacco-related diseases and the main attributable social costs in Mexico, including informal (unpaid) care costs, which are frequently ignored. We employ a first-order Monte Carlo microsimulation model that follows hypothetical population cohorts considering the risks of an adverse health event and death. First, we estimate tobacco-attributable morbidity and mortality, direct medical costs and indirect costs, such as labour productivity losses and informal care costs. Then, we assess the potential effects of a 50% cigarette price increase through taxation and two alternative scenarios of 25% and 75%. The inputs come from several sources, including national surveys and vital statistics. Each year, 63 000 premature deaths and 427 000 disease events are attributable to tobacco in Mexico, while social costs amount to MX$194.6 billion (US$8.5)—MX$116.2 (US$5.1) direct medical costs and MX$78.5 (US$3.4) indirect costs—representing 0.8% of gross domestic product. Current tobacco tax revenue barely covers 23.3% of these costs. Increasing cigarette prices through taxation by 50% could reduce premature deaths by 49 000 over the next decade, while direct and indirect costs averted would amount to MX$87.9 billion (US$3.8) and MX$67.6 billion (US$2.9), respectively. The benefits would far outweigh any potential loss even in a pessimistic scenario of increased illicit trade. Tobacco use imposes high social costs on the Mexican population, but tobacco taxation is a win-win policy for both gaining population health and reducing tobacco societal costs.