bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early outcomes of aortic valve replacement with Perceval PLUS sutureless valve: results of the prospective multicentric MANTRA study
Authors: Micovic Slobodan , Nobre Angelo , Choi Jae Woong , Solinas Marco , Shehada Sharaf-Eldin , Torella Michele , Baeza Cristian , Parrino Eugene , Pollari Francesco , Troise Giovanni , Kappert Utz , Mellert Friedrich , Je Hyung Gon , Argano Vincenzo , Lam Ka Yan , Rinaldi Mauro , Gutermann Herbert , Meuris Bart ,   the MANTRA Investigators
Published: June 2024

Abstract
Background
The aim of this study is to report the preliminary real-word clinical and hemodynamic performance from the MANTRA study in patients undergoing aortic valve replacement with Perceval PLUS sutureless valve.

Methods
MANTRA is an ongoing “umbrella” prospective, multi-center, international post-market study to collect real-life safety and performance data on Corcym devices (Corcym S.r.l, Saluggia, Italy). Clinical and echocardiographic outcomes were collected preoperatively, at discharge and at each follow up. KCCQ-12 and EQ-5D-5L quality of life questionnaires were collected preoperatively and at 30-days.

Results
A total of 328 patients underwent aortic valve replacement with Perceval PLUS in 29 International institutions. Patients were enrolled from July 2021 to October 2023 and enrollment is still ongoing. Mean age was 71.9 ± 6.4 years, mean EuroSCORE II was 2.9 ± 3.9. Minimally invasive approach was performed in 44.2% (145/328) of patients; concomitant procedures were done in 40.8% (134/328) of cases. Thirty-day mortality was 1.8% (6/328) and no re-interventions were reported. Pacemaker implant was required in 4.0% (13/328) of the patients.
The assessment of the functional status demonstrated marked and stable improvement in NYHA class in most patients at 30-day follow-up, with significant increase of KCCQ-12 summary score (from 58.8 ± 23.0 to 71.8 ± 22.1, p < 0.0001) and EQ-5D-5L VAS score (from 64.5 ± 20.4 to 72.6 ± 17.5, p < 0.0001). Mean pressure gradient decreased from 46.2 ± 17.3 mmHg to 10.1 ± 4.7 mmHg at 30-day follow-up. Low or no incidence of moderate-to-severe paravalvular or central leak was reported.

Conclusions
Preliminary results demonstrate good clinical outcomes and significant improvement of Quality of Life at 30-days, excellent early hemodynamic performance within patient implanted with Perceval PLUS.

Trial Registration
The MANTRA study has been registered in ClinicalTrials.gov (NCT05002543, Initial release 26 July 2021).
Thirty-three-year follow-up of pseudoaneurysm of the mitral-aortic intervalvular fibrosa without surgical treatment: a case report and literature review
Authors: Mirhosseini Seyed Mohsen , Soltanipur Masood , Yarmohammadi Hossein , Rezaei Mahdi , Fattah Eisa , Bayat Fariba 
Published: June 2024

Abstract
Background
Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (PMAIF) is a rare complication of infective endocarditis or aortic valve surgery. Surgical treatment is suggested, but the long-term follow-up of conservative management remains unclear.

Case presentation
A 33-year follow-up of a patient who developed PMAIF six years after aortic valve replacement is reported. The patient presented to our center with dyspnea, and the echocardiography revealed an ejection fraction of 20% and a PMAIF measuring 7 × 10 mm. Despite being advised to undergo surgery, the patient declined due to fear of surgical outcomes. Consequently, conservative treatment with close observation but without surgery was initiated. During the 33-year follow-up period, the patient did not experience any adverse health effects.

Conclusion
Surgical intervention should be considered whenever the PMAIF is diagnosed. However, in any case that the surgery was not applicable, conservative management might lead to long-term survival, based on this and similar case reports in the literature.
Thymic Rosai-Dorfmann disease: a case report
Authors: Liu Gaohua , Jing Min , Wang Juan 
Published: June 2024

Abstract
Background
Rosai-Dorfman disease (RDD), known as sinus histiocytosis with massive lymphadenopathy, commonly involves lymph nodes in the neck or mediastinum, although extranodal involvement is observed in approximately 40% of RDD patients. RDD involving only the thymus has rarely been reported. Here, we report a case of RDD originating in the thymus. The lesion was surgically removed, and a cure was finally achieved. There was no recurrence after telephone follow-up for 3 years.

Case presentation
A 52-year-old male was accidentally found to have a 7 × 6 cm anterior mediastinum lump by chest computed tomography (CT). The mediastinal lesion was resected by surgery, and postoperative pathology revealed RDD originating from the thymus. Regular telephone follow-up after surgery lasted 3 years and showed that the patient remained in good condition without any relevant symptoms.

Conclusions
RDD originating in the thymus cannot be characterized from CT images and is easily misdiagnosed as a traditional mediastinal tumor. This is mainly because there is so little disease in this area that physicians are not aware of it. We report this case with the hope that clinicians will have a better understanding of this disease. According to our follow-up results, surgery is an effective means of treatment.
Trends in hospitalizations of children with respiratory syncytial virus aged less than 1 year in Italy, from 2015 to 2019
Authors: Cutrera Renato , d’Angela Daniela , Orso Massimiliano , Guadagni Liliana , Vittucci Anna Chiara , Bertoldi Ilaria , Polistena Barbara , Spandonaro Federico , Carrieri Ciro , Montuori Eva Agostina , Iantomasi Raffaella , Orfeo Luigi 
Published: June 2024

Abstract
Background
Respiratory syncytial virus (RSV) affects 60–80% of children below 1 year and it’s the first cause of acute bronchiolitis. The aim of this study was to assess the trend and characteristics of hospitalizations for RSV infections in Italy.

Methods
This is a retrospective study based on the Italian Hospital Discharge Record (HDR) database. We analysed HDRs from June 2015 to May 2019, considering two groups of infants: Group 1 had a confirmed diagnosis of RSV; Group 2 had a diagnosis of acute bronchiolitis not RSV-coded.

Results
There were 67,746 overall hospitalizations (40.1% Group 1, and 59.9% Group 2). Hospitalization rate increased for Group 1 from 125 to 178 per 10,000 infants (+ 42.4%), and for Group 2 from 210 to 234 per 10,000 (+ 11.4%). The mean hospitalization length was 6.3 days in Group 1, longer than Group 2 (+ 1.0 day). A further analysis revealed that infants with heart disease or born premature had longer mean hospital stay compared to infants without risk factors (10.7 days versus 6.1 days, p < 0.0001; 34.0 days versus 6.1 days, p < 0.0001, respectively). Group 1 required more critical care (oxygen therapy and/or mechanical ventilation) than Group 2. We found that, in proportion to hospital admissions in pediatric and general hospitals, RSV was more frequently diagnosed in the first ones. The mean hospitalization cost increased for Group 1 (from € 2,483 to € 2,617) and Group 2 (from € 2,007 to € 2,180).

Conclusions
Our results confirmed that RSV pulmonary disease in infants is seasonal and often requires hospitalization. Our study suggested that RSV is responsible for an increasing hospitalization rate and related costs during the study period.
The effect of exercise rehabilitation with exergames combined with ice therapy in the treatment of obese patients with gout: protocol for a clinical trial
Authors: Cao Manting , Yusof Hazwani Ahmad , Chen Jianer , Jalil Mohd Faizal , Rahim Siti Khairizan , Abdullah Mohamad Zulfadhli 
Published: June 2024

Abstract
Background
Gout remains a leading cause of inflammatory arthritis worldwide, and the main risk factor for gout is persistent hyperuricemia. The clinical management of gout is mostly drug-based, and other treatment options are often ignored. This research proposal will explore whether exergames combined with ice therapy can help patients with gout to lose weight, relieve pain, improve the range of movement, improve quality of life, decrease uric acid level, decrease kinesiophobia and improve mental health of patients with gout.

Methods
This experiment will use a two-arm randomized controlled design. The study setting is at the Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM). Obese patients with gout (N = 30) will be randomly assigned to the control group (receive an exergames intervention) and intervention group (receive an exergames intervention combined with ice therapy). The outcomes measurement will be conducted before (baseline) and after intervention (4 weeks). Then, it will be followed up at 12 weeks.

Discussion
To our knowledge, no study has investigated the effect of exergames and ice therapy among gout patients. This study is expected to demonstrate that exercise rehabilitation facilitated by exergames with ice therapy is more effective in gout management compared to a conventional rehabilitation intervention.

Trial registration
Chinese Clinical Trial Registry (ChiCTR2300070029). Registered on 31 March 2023.
Outcome improvement for anaemia and iron deficiency in ERAS hip and knee arthroplasty: a descriptive analysis
Authors: Jørgensen Christoffer Calov , Kehlet Henrik ,   The Center for Fast-track Hip, Knee Replacement Collaborative Group, Hansen Torben B. , Gromov Kirill , Jakobsen Thomas , Varnum Claus , Overgaard Soren , Rathsach Mikkel , Lindberg-Larsen Martin , Bieder Manuel Josef 
Published: June 2024

Abstract
Background and purpose
Preoperative anaemia including iron deficiency anaemia (IDA) is a well-established perioperative risk factor. However, most studies on iron therapy to treat IDA have been negative and few have been conducted within an enhanced recovery after surgery (ERAS) protocol. Furthermore, patients with IDA often have comorbidities not necessarily influenced by iron, but potentially influencing traditional study endpoints such as length of stay (LOS), morbidity, etc. The aim of this paper is to discuss patient-related challenges when planning outcome studies on the potential benefits of iron therapy in patients with IDA, based upon a large detailed prospective database in ERAS total hip (THA) and knee arthroplasty (TKA).

Methods
A prospective observational cohort study in ERAS THA and TKA from 2022 to 2023. Detailed complete follow-up through questionnaires and electronic medical records.

Results
Of 3655 included patients, 276 (7.6%) had IDA defined as a haemoglobin (Hb) of < 13.0 g/dL and transferrin saturation of 0.20, while 3379 had a Hb of ≥ 13.0. Patients with IDA were a median 5 years older than non-anaemics, with an increased fraction living alone (38.4% vs. 28.8%), using walking aids (54.3% vs 26.4%) and receiving home care (16.2% vs 4.7%). Fewer IDA patients were working (12.7% vs. 29.6%) and a median number of prescribed drugs was higher (10 vs. 6).
Median LOS was 1 day in both IDA and non-anaemic patients, but a LOS of > 2 days occurred in 11.6% of patients with IDA vs. 4.3% in non-anaemics. The proportion with 30- or 90-day readmissions was 6.5% vs. 4.1% and. 13.4% vs6.0%, in patients with IDA and non-anaemics, respectively. However, potentially anaemia or iron deficiency-related causes of LOS > 2 days or 90-day readmissions were only 5.4% and 2.2% in patients with IDA and 1.9% and 1.0% in non-anaemics.

Conclusion
Conventional randomised trials with single or composite “hard” endpoints are at risk of being inconclusive or underpowered due to a considerable burden of other patient-related risk factors and with postoperative complications which may not be modifiable by correction of IDA per se. We will propose to gain further insights from detailed observational and mechanistic studies prior to initiating extensive randomised studies.
Exploring the interplay of emotional intelligence, psychological resilience, perceived stress, and life satisfaction: A cross-sectional study in the Turkish context
Authors: Kartol Aslı , Üztemur Servet , Griffiths Mark D. , Şahin Derya 
Published: June 2024

Abstract
Background
Emotional intelligence and life satisfaction are essential components for good psychological well-being. Studies examining the elements contributing to emotional intelligence and its relationships with different psychological constructs are likely to positively contribute to mental health. Therefore, the present study examined the mediating roles of perceived stress and psychological resilience in the relationship between emotional intelligence and life satisfaction.

Methods
The study sample comprised 780 university students (62.3% females) studying at universities in different regions of Türkiye. An online survey included the Emotional Intelligence Scale, Satisfaction with Life Scale, Psychological Resilience Scale, and Perceived Stress Scale. A multifactorial complex predictive correlational design was used.

Results
The results showed that emotional intelligence was (i) positively correlated with life satisfaction and psychological resilience, and (ii) negatively correlated with perceived stress. In the final model, perceived stress and psychological resilience played a mediating role in the relationship between emotional intelligence and life satisfaction. The findings suggest that higher emotional intelligence may lower perceived stress and appears to have a positive effect in relation to life satisfaction and psychological resilience.

Conclusion
Individuals working in the field of mental health need to help individuals increase their level of EI, which may help reduce the level of perceived stress and increase psychological resilience and life satisfaction.
Autocrine insulin-like growth factor 2 signaling as a potential target in the associated development of pulmonary emphysema and cancer in smokers
Authors: Boo Hye-Jin , Min Hye-Young , Lim Heung-Bin , Lee Euni , Lee Ho-Young 
Published: June 2024

Abstract
Background
Tobacco smoking causes pulmonary inflammation, resulting in emphysema, an independent risk factor for lung cancer. Induction of insulin-like growth factor 2 (IGF2) in response to lung injury by tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and polycyclic aromatic hydrocarbon benzo[a]pyrene in combination (NB), is critical for the proliferation of alveolar type 2 cells (AT2s) for lung repair. However, persistent IGF2 overexpression during NB-induced severe injury results in hyperproliferation of AT2s without coordinated AT2-to-AT1 differentiation, disrupting alveolar repair, which leads to the concurrent development of emphysema and lung cancer. The current study aims to verify the role of IGF2 signaling in the associated development of emphysema and cancer and develop effective pharmaceuticals for the diseases using animal models that recapitulate the characteristics of these chronic diseases.

Methods
The pathogenesis of pulmonary emphysema and cancer was analyzed by lung function testing, histological evaluation, in situ zymography, dihydroethidium staining, and immunofluorescence and immunohistochemistry analyses utilizing mouse models of emphysema and cancer established by moderate exposure to NB for up to seven months.

Results
Moderate NB exposure induced IGF2 expression in AT2s during the development of pulmonary emphysema and lung cancer in mice. Using AT2-specific insulin receptor knockout mice, we verified the causative role of sustained IGF2 signaling activation in AT2s in emphysema development. IGF2-targeting strategies, including voltage-dependent calcium channel blocker (CCB) and a neutralizing antibody, significantly suppressed the NB-induced development of emphysema and lung cancer. A publicly available database revealed an inverse correlation between the use of calcium channel blockers and a COPD diagnosis.

Conclusions
Our work confirms sustained IGF2 signaling activation in AT2s couples impaired lung repair to the concurrent development of emphysema and cancer in mice. Additionally, CCB and IGF2-specific neutralizing antibodies are effective pharmaceuticals for the two diseases.
Germline Mutational Landscape and Novel Targetable RAD51D Variant in Chinese Patients With Ovarian Cancer
Authors: Feng Zheng , Chen Siyu , An Na , Xiu Zhihui , Ju Xingzhu , Chen Xiaojun , Bi Rui , Wang Jie , Zhu Shida , Wu Xiaohua , Wen Hao 
Published: June 2024

PURPOSE Genetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant. METHODS Between 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2, other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays. RESULTS Overall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin. CONCLUSION Our study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.
Impact of colorectal liver metastases (CRLM) in patients with metastatic colorectal cancer (mCRC) receiving trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BEV) in the phase 3 SUNLIGHT trial.
Authors: Tabernero Josep , Prager Gerald W. , Taieb Julien , Calleja Elizabeth Martine , Liu Mei , Amellal Nadia , Fakih Marwan 
Published: June 2024

3584 Background: Many patients with CRC develop CRLM during their disease, which are associated with poor prognosis. In the phase 3 SUNLIGHT trial, the addition of BEV to FTD/TPI significantly improved overall survival (OS) compared with FTD/TPI alone in patients with refractory mCRC, irrespective of mutational status, tumor sidedness, and other factors associated with poor prognosis. Here, we assessed the impact of baseline CRLM on efficacy outcomes among patients treated in SUNLIGHT. Methods: In this post hoc analysis, OS, progression-free survival (PFS), and disease control rate (DCR) were assessed in patients with and without CRLM. Differences in survival between FTD/TPI + BEV and FTD/TPI alone were assessed in each subgroup. The Kaplan-Meier method and log-rank test were used to compare differences in OS and PFS; DCRs were compared using Fisher's exact tests. The hazard ratios (HRs) for OS and PFS were estimated using a Cox proportional hazards model. Results: Of the 492 patients enrolled in SUNLIGHT, 382 (77.6%) had CLRM, comprising 194 randomized to FTD/TPI + BEV and 188 randomized to FTD/TPI alone. Among patients randomized to FTD/TPI + BEV (n=246), median OS (95% confidence interval [CI]) was 10.4 (8.6, 11.0) months and not estimable (NE) (11.1–NE) for patients with and without CRLM, respectively (HR: 1.88; P=0.005). For patients randomized to FTD/TPI alone (n=246), median OS (95% CI) was 6.5 (5.9, 8.0) months and 10.9 (9.0, 13.8) months for patients with and without CRLM, respectively (HR: 1.75; P=0.002). Similar trends were observed for PFS and DCR. When comparing treatment effects across arms, FTD/TPI + BEV resulted in longer OS and PFS compared with FTD/TPI alone in patients with and without CRLM. In patients with CRLM, the HRs for OS and PFS were 0.61 (95% CI: 0.48, 0.77; P<0.001) and 0.44 (95% CI: 0.35, 0.55; P<0.001), respectively. In patients without CRLM, the HRs for OS and PFS were 0.60 (95% CI: 0.35, 1.0; P=0.052) and 0.38 (95% CI: 0.24, 0.58; P<0.001), respectively. The DCR was also higher in patients treated with FTD/TPI + BEV compared with FTD/TPI alone (68.6% vs 38.3% in patients with CRLM and 73.1% vs 53.5% in patients without CRLM). Conclusions: The results of this analysis show that patients treated with the combination of FTD/TPI + BEV had numerically longer OS and PFS and a higher DCR than those treated with FTD/TPI alone, irrespective of whether or not patients had CRLM at baseline. Owing to the imbalance in numbers of patients with and without CRLM, the data need to be interpreted with caution. Clinical trial information: NCT04737187 .
Real-world ctDNA testing patterns, associated biomarkers and sites of metastasis in early stage colorectal cancer.
Authors: Fidyk Erin , Kalesinskas Laurynas , Krismer Konstantin , Blarre Auriane , Bouzit Lilia , Ritten John James , Gao Jessica , Marinescu Anca , Kelly Jonathan , Harrison Katherine , Cohen Aaron B. 
Published: June 2024

3610 Background: There is a growing body of evidence to support the prognostic and predictive relevance of ctDNA in patients (pts) with early stage colorectal cancer (CRC). Relatively little is known about the real-world (rw) utilization of tumor-informed, personalized ctDNA assays in this population. We described the uptake of ctDNA testing over time as well as how results correlate with other biomarkers and the development of specific sites of metastasis (SOM). Methods: Pts with stage I-III CRC diagnosed after 1/1/2018 and a commercial ctDNA test in the early stage setting were selected using machine learning models from the Flatiron Health nationwide EHR-derived, de-identified database with a data cutoff of 10/31/23. Pts were considered ctDNA positive (ctDNA+) if they had at least one positive test. Odds ratios (OR) were calculated using logistic regression, adjusting for age, race, stage, practice type, insurance, and adjuvant treatment. Median time to metastasis (mets) for the ctDNA+ cohort (indexed to first positive test) was estimated using the Kaplan Meier estimator. Differences in minimal residual disease (MRD) in MTM/mL were compared using a Wilcox rank-sum test using maximum MRD. Results: In a cohort of 78,046 pts with stage I-III disease, 17,209 ctDNA tests were performed in 5,005 pts (median 3 per pt) with the majority in stage III pts (54.2%). 11% of pts (1652 / 14803) diagnosed between 1/1/21 and 4/1/22 received ctDNA testing compared to 14% of pts (1610 / 11412) diagnosed between 4/1/22 and 4/1/23. Among tested pts, 1,729 (34.5%) had at least one positive test. Pts with ctDNA+ tests were more likely to have tumor mutations in TP53 (OR: 1.69 [95% CI: 1.37, 2.08]) and KRAS (OR: 1.78 [95% CI: 1.10, 1.72]) than pts with ctDNA- tests. No differences were found in NRAS, BRAF or HER2. Progression to metastatic disease was observed in 365 (21.1%) pts with ctDNA+ tests vs 93 (2.8%) pts with ctDNA- tests (OR: 8.84 [95% CI: 6.95, 11.26]). The median time from first ctDNA+ to mets was 24.2 [95% CI: 21.7, NR] months. In those who developed mets, pts with ctDNA+ tests were significantly more likely to have liver mets compared to pts with ctDNA- tests (OR: 1.89 [95% CI: 1.12, 3.19]). Pts with liver mets had higher levels of MRD compared to non-liver SOM. (p <0.001). Conclusions: This is the largest study to date of early stage CRC ctDNA testing in routine practice. Results suggest that pairing ctDNA and NGS testing has the potential to predict risk for liver mets and other pt outcomes. Future work is needed to translate these findings into clinically actionable insights and treatment strategies. [Table: see text]