bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azathioprine Plus Exclusive Enteral Nutrition Versus Azathioprine Monotherapy for the Prevention of Postoperative Recurrence in Patients with Crohn’s Disease: An Open-Label, Single-Centre, Randomized Controlled Trial
Authors: Duan Ming , Lu Mengjie , Diao Yanqing , Cao Lei , Wu Qiong , Liu Yuxiu , Gong Jianfeng , Zhu Weiming , Li Yi 
Published: January 2024

Abstract

Background
Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn’s disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD.

Methods
In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ].

Results
Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively.

Conclusion
In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted.

Trial Number
NCT05214430.
Tritrophic effects mediate host suitability for two parasitoids of the carob moth (Lepidoptera: Pyralidae), infesting pistachio kernels
Authors: Baghery Fatemeh , Michaud J P , Dini Ali 
Published: January 2024

Abstract
The carob moth, Ectomyelois ceratoniae (Zeller) (Lepidoptera: Pyralidae), is an important pest of pistachio causing direct damage to nuts during ripening, and in storage. We examined the tritrophic effects of 5 pistachio cultivars, representing the full range of kernel suitability for E. ceratoniae, on 2 larval parasitoids, Habrobracon hebetor (Say) (Hymenoptera: Braconidae), a gregarious, synovigenic, idiobiont, ectoparasitoid, and Venturia canescens Gravenhorst (Hymenoptera: Ichneumonidae), a solitary, pro-ovigenic, koinobiont, endoparasitoid. The suitability of pistachio cultivars for development and reproduction of the 2 parasitoids was closely correlated, despite their divergent lifestyles and developmental patterns, and paralleled variation in kernel suitability for host larvae. Although kernels of the most resistant cultivar reduced demographic parameters of the parasitoids, the potential impact on numerical responses was minor. Successful biological control of carob moth within the vulnerable period of nut ripening will likely depend on the functional responses of earlier generations of adult parasitoids emerging from other fruit and nut crops, or those released in an augmentation program.
Normal values for left atrial strain, volume, and function derived from 3D echocardiography: the Copenhagen City Heart Study
Authors: Yafasov Marat , Olsen Flemming Javier , Skaarup Kristoffer Grundtvig , Lassen Mats Christian Højbjerg , Johansen Niklas Dyrby , Lindgren Filip Lyng , Jensen Gorm Boje , Schnohr Peter , Møgelvang Rasmus , Søgaard Peter , Biering-Sørensen Tor 
Published: January 2024

Abstract

Aims
3D echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use.

Methods and results
Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were as follows: LA reservoir strain (LASr) 30.8% (18.4–44.2%), LA conduit strain (LAScd) 19.1% (6.8–32.0%), LA contractile strain 11.7% (4.3–22.2%), total LA emptying fraction (LAEF) 61.4% (47.8–71.0%), passive LAEF 37.7% (17.4–53.9%), active LAEF 37.4% (22.2–52.5%), LA minimum volume index (LAVimin) 10.2 (5.9–18.5) mL/m2, and LA maximum volume index (LAVimax) 26.8 (16.5–40.1) mL/m2. All parameters changed significantly with increasing age (P value for all &lt;0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (P for interaction &lt; 0.001), LAScd (P for interaction &lt; 0.001), LAVimin (P for interaction = 0.037), and total LAEF (P for interaction = 0.034) such that these parameters deteriorated faster with age in females than males.

Conclusion
We present age- and sex-specific reference material including limits of normality for LA strain, volume, and function by 3DE.
Early use of intrapartum intra-aortic balloon pump support for haemodynamic stabilization of peripartum and anthracycline-induced cardiomyopathy: a case report
Authors: Chandran Karthic , Quimby Donald , Bezerra Hiram G , Crousillat Daniela 
Published: January 2024

AbstractBackgroundPrior exposure to cardiotoxic cancer therapies has been associated with an increased risk of peripartum cardiomyopathy (PPCM). The management of PPCM in this population remains a clinical challenge. Few studies have explored the use of mechanical circulatory support in PPCM. We present a case of early implementation of intra-aortic balloon pump (IABP) therapy for acute stabilization and intrapartum support of PPCM.Case summaryA 36-year-old G4P2103 (4th pregnancy, two full-term, one premature birth, 0 abortions, and three living children) woman at 26 weeks and 5 days gestation with history of combined peripartum and anthracycline-induced cardiomyopathy [previously left ventricular ejection fraction (LVEF) 10–15% and recently 40–45%] presented with acute decompensated heart failure. Her clinical status deteriorated with a drop in LVEF to 15–20% with a significant increase in pulmonary pressures and worsening mitral regurgitation. A multidisciplinary decision with the cardio-obstetrics team was made to place a pulmonary artery catheter for invasive haemodynamic monitoring and IABP insertion prior to delivery. Intra-aortic balloon pump support had a profound immediate decrease in her systemic and pulmonary vascular resistance allowing for a successful repeat caesarean delivery. Her haemodynamics remained stable after IABP removal and pulmonary pressures improved. She was discharged one week following her delivery on guideline-directed medical therapy.DiscussionOur case highlights the use of prophylactic intrapartum IABP in combined anthracycline-induced and PPCM and begins to explore its safety and efficacy in this high-risk patient population.
Innovation and disruptive science determine the future of cardiothoracic surgery
Authors: Beyersdorf Friedhelm 
Published: January 2024

Summary
One of the currently most asked questions in the field of medicine is how any specialty in the future will evolve to ensure better health for the patients by using current, unparalleled developments in all areas of science. This article will give an overview of new and evolving strategies for cardiothoracic (CT) surgery that are available today and will become available in the future in order to achieve this goal. In the founding era of CT surgery in the 1950s and 1960s, there was tremendous excitement about innovation and disruptive science, which eventually resulted in a completely new medical specialty, i.e. CT surgery. Entirely new treatment strategies were introduced for many cardiovascular diseases that had been considered incurable until then. As expected, alternative techniques have evolved in all fields of science during the last few decades, allowing great improvements in diagnostics and treatment in all medical specialties. The future of CT surgery will be determined by an unrestricted and unconditional investment in innovation, disruptive science and our own transformation using current achievements from many other fields. From the multitude of current and future possibilities, I will highlight 4 in this review: improvements in our current techniques, bringing CT surgery to low- and middle-income countries, revolutionizing the perioperative period and treating as yet untreatable diseases. These developments will allow us a continuation of the previously unheard-of treatment possibilities provided by ingenious innovations based on the fundamentals of CT surgery.
Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma
Authors: Altieri Barbara , Kimpel Otilia , Megerle Felix , Detomas Mario , Chifu Irina , Fuss Carmina Teresa , Quinkler Marcus , Kroiss Matthias , Fassnacht Martin 
Published: January 2024

Abstract

Objective
Mitotane is the standard therapy of adrenocortical carcinoma (ACC) due to its relative selectivity of its cytotoxic effects toward adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. Frequency and characteristics of hypothalamic–pituitary–adrenal axis recovery after discontinuation are ill-defined.

Methods
This was a retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Primary endpoint was adrenal recovery. Cox regression analyses were used to identify predictive factors. Moreover, mitotane plasma elimination rate and hormonal changes after mitotane stop were investigated.

Results
Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8 g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2 mg/L, and the detection limit was 152 days (interquartile range: 114-202), 280 days (192-370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95% confidence interval [CI] = 19.6-32.4). In 4 patients (7.1%), adrenal insufficiency persisted &gt;5 years after discontinuation. Mitotane peak ≥ 27 mg/L significantly correlated with longer time to adrenal recovery (hazard ratio [HR] = 0.2, 95% CI = 0.1-0.8, P = .03). Twenty-seven of 38 patients (71%) followed in reference centers achieved adrenal recovery compared with only 5/18 (28%) followed up in non-reference centers (HR = 4.51, 95% CI = 1.71-11.89, P = .002). Other investigated factors were not associated with adrenal function after discontinuation.

Conclusions
Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long but individually quite variable.
Reference intervals for serum 11-oxygenated androgens in children
Authors: Adriaansen Bas P H , Oude Alink Sandra E , Swinkels Dorine W , Schröder Mariska A M , Span Paul N , Sweep Fred C G J , Claahsen-van der Grinten Hedi L , van Herwaarden Antonius E 
Published: January 2024

Abstract

Objective
Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens.

Design
Reference interval study for serum 11-oxygenated androgens in children.

Methods
We developed and validated a sensitive liquid chromatography-tandem mass spectrometry assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal [n = 133; 94 boys, 39 girls] and pubertal [n = 123; 52 boys, 71 girls]) to compute reference intervals (2.5th-97.5th percentiles).

Results
In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not.

Conclusions
We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism.
Cardiovascular disease risk communication and prevention: a meta-analysis
Authors: Bakhit Mina , Fien Samantha , Abukmail Eman , Jones Mark , Clark Justin , Scott Anna Mae , Glasziou Paul , Cardona Magnolia 
Published: January 2024

Abstract

Background and Aims
Knowledge of quantifiable cardiovascular disease (CVD) risk may improve health outcomes and trigger behavioural change in patients or clinicians. This review aimed to investigate the impact of CVD risk communication on patient-perceived CVD risk and changes in CVD risk factors.

Methods
PubMed, Embase, and PsycINFO databases were searched from inception to 6 June 2023, supplemented by citation analysis. Randomized trials that compared any CVD risk communication strategy versus usual care were included. Paired reviewers independently screened the identified records and extracted the data; disagreements were resolved by a third author. The primary outcome was the accuracy of risk perception. Secondary outcomes were clinician-reported changes in CVD risk, psychological responses, intention to modify lifestyle, and self-reported changes in risk factors and clinician prescribing of preventive medicines.

Results
Sixty-two trials were included. Accuracy of risk perception was higher among intervention participants (odds ratio = 2.31, 95% confidence interval = 1.63 to 3.27). A statistically significant improvement in overall CVD risk scores was found at 6–12 months (mean difference = −0.27, 95% confidence interval = −0.45 to −0.09). For primary prevention, risk communication significantly increased self-reported dietary modification (odds ratio = 1.50, 95% confidence interval = 1.21 to 1.86) with no increase in intention or actual changes in smoking cessation or physical activity. A significant impact on patients’ intention to start preventive medication was found for primary and secondary prevention, with changes at follow-up for the primary prevention group.

Conclusions
In this systematic review and meta-analysis, communicating CVD risk information, regardless of the method, reduced the overall risk factors and enhanced patients’ self-perceived risk. Communication of CVD risk to patients should be considered in routine consultations.
A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting
Authors: Fuat Ahmet , Adlen Ella , Monane Mark , Coll Ruth , Groves Sarah , Little Elizabeth , Wild Jonathan , Kamali Farzan J , Soni Yusuf , Haining Shona , Riding Helen , Riveros-Mckay Fernando , Peneva Iliana , Lachapelle Alexander , Giner-Delgado Carla , Weale Michael E , Plagnol Vincent , Harrison Seamus , Donnelly Peter 
Published: January 2024

Abstract

Aims
The aim of the study was to assess the real-world feasibility, acceptability, and impact of an integrated risk tool for cardiovascular disease (CVD IRT, combining the standard QRISK®2 risk algorithm with a polygenic risk score), implemented within routine primary practice in the UK National Health Service.

Methods and results
The Healthcare Evaluation of Absolute Risk Testing Study (NCT05294419) evaluated participants undergoing primary care health checks. Both QRISK2 and CVD IRT scores were returned to the healthcare providers (HCPs), who then communicated the results to participants. The primary outcome of the study was feasibility of CVD IRT implementation. Secondary outcomes included changes in CVD risk (QRISK2 vs. CVD IRT) and impact of the CVD IRT on clinical decision-making. A total of 832 eligible participants (median age 55 years, 62% females, 97.5% White ethnicity) were enrolled across 12 UK primary care practices. Cardiovascular disease IRT scores were obtained on 100% of the blood samples. Healthcare providers stated that the CVD IRT could be incorporated into routine primary care in a straightforward manner in 90.7% of reports. Participants stated they were ‘likely’ or ‘very likely’ to recommend the use of this test to their family or friends in 86.9% of reports. Participants stated that the test was personally useful (98.8%) and that the results were easy to understand (94.6%). When CVD IRT exceeded QRISK2, HCPs planned changes in management for 108/388 (27.8%) of participants and 47% (62/132) of participants with absolute risk score changes of &gt;2%.

Conclusion
Amongst HCPs and participants who agreed to the trial of genetic data for refinement of clinical risk prediction in primary care, we observed that CVD IRT implementation was feasible and well accepted. The CVD IRT results were associated with planned changes in prevention strategies.
Environmental effects on genetic variance are likely to constrain adaptation in novel environments
Authors: Walter Greg M , Monro Keyne , Terranova Delia , la Spina Enrico , Majorana Maria , Pepe Giuseppe , Clark James , Cozzolino Salvatore , Cristaudo Antonia , Hiscock Simon J , Bridle Jon 
Published: January 2024

Abstract
Adaptive plasticity allows populations to cope with environmental variation but is expected to fail as conditions become unfamiliar. In novel conditions, populations may instead rely on rapid adaptation to increase fitness and avoid extinction. Adaptation should be fastest when both plasticity and selection occur in directions of the multivariate phenotype that contain abundant genetic variation. However, tests of this prediction from field experiments are rare. Here, we quantify how additive genetic variance in a multivariate phenotype changes across an elevational gradient, and test whether plasticity and selection align with genetic variation. We do so using two closely related, but ecologically distinct, sister species of Sicilian daisy (Senecio, Asteraceae) adapted to high and low elevations on Mt. Etna. Using a quantitative genetic breeding design, we generated and then reciprocally planted c. 19,000 seeds of both species, across an elevational gradient spanning each species’ native elevation, and then quantified mortality and five leaf traits of emergent seedlings. We found that genetic variance in leaf traits changed more across elevations than between species. The high-elevation species at novel lower elevations showed changes in the distribution of genetic variance among the leaf traits, which reduced the amount of genetic variance in the directions of selection and the native phenotype. By contrast, the low-elevation species mainly showed changes in the amount of genetic variance at the novel high elevation, and genetic variance was concentrated in the direction of the native phenotype. For both species, leaf trait plasticity across elevations was in a direction of the multivariate phenotype that contained a moderate amount of genetic variance. Together, these data suggest that where plasticity is adaptive, selection on genetic variance for an initially plastic response could promote adaptation. However, large environmental effects on genetic variance are likely to reduce adaptive potential in novel environments.
Characterization of a novel 4-guanidinobutyrase from Candida parapsilosis
Authors: Gaikwad Santoshkumar R , Punekar Narayan S , Pathan Ejaj K 
Published: January 2024

Abstract
Enzymes of the ureohydrolase superfamily are specific in recognizing their substrates. While looking to broaden the substrate specificity of 4-guanidinobutyrase (GBase), we isolated a yeast, typed as Candida parapsilosis (NCIM 3689), that efficiently utilized both 4-guanidinobutyrate (GB) and 3-guanidinopropionate (GP) as a sole source of nitrogen. A putative GBase sequence was identified from its genome upon pBLAST query using the GBase sequence from Aspergillus niger (AnGBase). The C. parapsilosis GBase (CpGBase) ORF was PCR amplified, cloned, and sequenced. Further, the functional CpGBase protein expressed in Saccharomyces cerevisiae functioned as GBase and 3-guanidinopropionase (GPase). S. cerevisiae cannot grow on GB or GP. However, the transformants expressing CpGBase acquired the ability to utilize and grow on both GB and GP. The expressed CpGBase protein was enriched and analyzed for substrate saturation and product inhibition by γ-aminobutyric acid and β-alanine. In contrast to the well-characterized AnGBase, CpGBase from C. parapsilosis is a novel ureohydrolase and showed hyperbolic saturation for GB and GP with comparable efficiency (Vmax/KM values of 3.4 and 2.0, respectively). With the paucity of structural information and limited active site data available on ureohydrolases, CpGBase offers an excellent paradigm to explore this class of enzymes.