bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML
Authors: Murdock H. Moses , Kim Haesook T. , Denlinger Nathan , Vachhani Pankit , Hambley Bryan , Manning Bryan S. , Gier Shannon , Cho Christina , Tsai Harrison K. , McCurdy Shannon , Ho Vincent T. , Koreth John , Soiffer Robert J. , Ritz Jerome , Carroll Martin P. , Vasu Sumithira , Perales Miguel-Angel , Wang Eunice S. , Gondek Lukasz P. , Devine Steven , Alyea Edwin P. , Lindsley R. Coleman , Gibson Christopher J. 
Published: March 2022

Abstract
Older patients with acute myeloid leukemia (AML) have high relapse risk and poor survival after allogeneic hematopoietic cell transplantation (HCT). Younger patients may receive myeloablative conditioning to mitigate relapse risk associated with high-risk genetics or measurable residual disease (MRD), but older adults typically receive reduced-intensity conditioning (RIC) to limit toxicity. To identify factors that drive HCT outcomes in older patients, we performed targeted mutational analysis (variant allele fraction ≥2%) on diagnostic samples from 295 patients with AML aged ≥60 years who underwent HCT in first complete remission, 91% of whom received RIC, and targeted duplex sequencing at remission in a subset comprising 192 patients. In a multivariable model for leukemia-free survival (LFS) including baseline genetic and clinical variables, we defined patients with low (3-year LFS, 85%), intermediate (55%), high (35%), and very high (7%) risk. Before HCT, 79.7% of patients had persistent baseline mutations, including 18.3% with only DNMT3A or TET2 (DT) mutations and 61.4% with other mutations (MRD positive). In univariable analysis, MRD positivity was associated with increased relapse and inferior LFS, compared with DT and MRD-negative mutations. However, in a multivariable model accounting for baseline risk, MRD positivity had no independent impact on LFS, most likely because of its significant association with diagnostic genetic characteristics, including MDS-associated gene mutations, TP53 mutations, and high-risk karyotype. In summary, molecular associations with MRD positivity and transplant outcomes in older patients with AML are driven primarily by baseline genetics, not by mutations present in remission. In this group of patients, where high-intensity conditioning carries substantial risk of toxicity, alternative approaches to mitigating MRD-associated relapse risk are needed.
Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice
Authors: Lundgren Taran S. , Denning Gabriela , Stowell Sean R. , Spencer H. Trent , Doering Christopher B. 
Published: March 2022

Abstract
Advances in the development of novel treatment options for hemophilia A are prevalent. However, the anti–factor VIII (FVIII) neutralizing antibody (inhibitor) response to existing FVIII products remains a major treatment challenge. Although some novel products are designed to function in the presence of inhibitors, they do not specific address the immunogenicity risk or mechanistic causes of inhibitor development, which remain unclear. Furthermore, most preclinical studies supporting clinical gene therapy programs have reported immunogenicity signals in animal models, especially at higher vector doses and sometimes using multiple vector designs. In these settings, immunogenicity risk factor determination, comparative immunogenicity of competing vector designs, and the potential for obtaining meaningful prognostic data remain relatively unexplored. Additionally, there remains the opportunity to investigate clinical gene therapy as an alternative to standard immune tolerance induction therapy. The current study was designed to address these issues through longitudinal dose-response evaluation of 4 adeno-associated viral (AAV) vector candidates encoding 2 different FVIII transgenes in a murine model of hemophilia A. Plasma FVIII activity and anti-FVIII antibody data were used to generate a pharmacokinetic model that (1) identifies initial AAV-FVIII product expression kinetics as the dominant risk factor for inhibitor development, (2) predicts a therapeutic window where immune tolerance is achieved, and (3) demonstrates evidence of gene therapy–based immune tolerance induction. Although there are known limitations to the predictive value of preclinical immunogenicity testing, these studies can uncover or support the development of design principles that can guide the development of safe and effective genetic medicines.
Donor-recipient sex is associated with transfusion-related outcomes in critically ill patients
Authors: Alshalani Abdulrahman , Uhel Fabrice , Cremer Olaf L. , Schultz Marcus J. , de Vooght Karen M. K. , van Bruggen Robin , Acker Jason P. , Juffermans Nicole P. 
Published: March 2022

Abstract
Transfusion of red blood cells (RBCs) from female donors has been associated with increased risk of mortality. This study aims to investigate the associations between donor-recipient sex and posttransfusion mortality and morbidity in critically ill patients who received RBC transfusions from either male-only donors or from female-only donors (unisex-transfusion cases). Survival analysis was used to compare 4 groups: female-to-female, female-to-male, male-to-female, and male-to-male transfusion. Multivariate logistic model was used to evaluate the association between donor sex and intensive care unit (ICU) mortality. Associations between transfusion and acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and nosocomial infections were assessed. Of the 6992 patients included in the original cohort study, 403 patients received unisex-transfusion. Survival analysis and the logistic model showed that transfusion of female RBCs to male patients was associated with an increased ICU mortality compared with transfusion of female RBCs to female patients (odds ratio, 2.43; 95% confidence interval, 1.02-5.77; P &lt; .05). There was a trend toward increased ARDS in patients receiving RBC from female donors compared with those receiving blood from males (P = .06), whereas AKI was higher in donor-recipient sex-matched transfusion groups compared with sex-mismatched groups (P = .05). This was an exploratory study with potential uncontrolled confounders that limits broad generalization of the findings. Results warrant further studies investigating biological mechanisms underlying the association between donor sex with adverse outcomes as well as studies on the benefit of matching of blood between donor and recipient.
CEACAM1 is a novel culture-compatible surface marker of expanded long-term reconstituting hematopoietic stem cells
Authors: Ansari Unain , Tomellini Elisa , Chagraoui Jalila , Lehnertz Bernhard , Mayotte Nadine , Bordeleau Marie-Eve , Roux Philippe P. , Sauvageau Guy 
Published: March 2022

Key Points
CEACAM1 is a novel cell surface marker of ex vivo expanded LT-HSCs. Sorting umbilical cord blood cells based on CEACAM1 and known HSC marker expression allows purification of LT-HSCs with improved purity.
Evaluation of the right atrial phasic functions in patients with anterior ST-elevation myocardial infarction: a 2D speckle-tracking echocardiography study
Authors: Eisvand Mokhtar , Mohseni-Badalabadi Reza , Hosseinsabet Ali 
Published: March 2022

Abstract
Background
Evidence suggests that changes in left ventricular systolic and diastolic functions may affect right atrial (RA) phasic functions. We aimed to evaluate RA phasic functions in the presence of anterior ST-elevation myocardial infarction (ASTEMI) as an acute event and to compare the findings with those in a control group.

Methods
We recruited 92 consecutive ASTEMI patients without accompanying significant stenosis in the proximal and middle parts of the right coronary artery and 31 control subjects, matched for age, sex, diabetes, and hypertension. RA phasic functions were evaluated concerning their longitudinal 2D speckle-tracking echocardiography-derived markers. The ASTEMI group was followed up for all-cause mortality or reinfarction.

Results
In the ASTEMI group, RA strain was reduced during the reservoir (33.2% ± 4.3% vs 30.5% ± 8.1%; P = 0.021) and conduit (16% [12–18%] vs 14% [9–17%]; P = 0.048) phases. The other longitudinal 2D speckle-tracking echocardiography-derived markers of RA phasic functions were not different between the 2 groups. RA strain and strain rate during the contraction phase were predictive of all-cause mortality or reinfarction (hazard ratio = 0.80; P = 0.024 and hazard ratio = 0.39; P = 0.026, respectively).

Conclusions
Based on 2D speckle-tracking echocardiography, in the ASTEMI group, compared with the control group, RA reservoir and conduit functions were reduced, while RA contraction function was preserved. RA contraction function was predictive of all-cause mortality or reinfarction during the follow-up period.
Metabolically healthy versus unhealthy obese phenotypes in relation to hypertension incidence; a prospective cohort study
Authors: Hamzeh Behrooz , Pasdar Yahya , Moradi Shima , Darbandi Mitra , Rahmani Negin , Shakiba Ebrahim , Najafi Farid 
Published: March 2022

Abstract
Background
Although obesity increases the risk of hypertension, the effect of obesity based on metabolic status on the incidence of hypertension is not known. This study aimed to determine the association between obesity phenotypes including metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) and the risk of hypertension incidence.

Methods
We conducted a prospective cohort study on 6747 adults aged 35–65 from Ravansar non-communicable diseases (RaNCD) study. Obesity was defined as body mass index above 30 kg/m2 and metabolically unhealthy was considered at least two metabolic disorders based on the International Diabetes Federation criteria. Obesity phenotypes were categorized into four groups including MUO, MHO, metabolically unhealthy non obesity (MUNO), and metabolically healthy non obesity (MHNO). Cox proportional hazards regression models were applied to analyze associations with hypertension incidence.

Results
The MHO (HR: 1.37; 95% CI: 1.03–1.86) and MUO phenotypes (HR: 2.44; 95% CI: 1.81–3.29) were associated with higher hypertension risk compared to MHNO. In addition, MUNO phenotype was significantly associated with risk of hypertension incidence (HR: 1.65; 95% CI: 1.29–2.14).

Conclusions
Both metabolically healthy and unhealthy obesity increased the risk of hypertension incidence. However, the increase in metabolically unhealthy phenotype was higher.
Early fluid management affects short-term mortality in patients with end-stage kidney disease undergoing chronic hemodialysis and requiring continuous renal replacement therapy
Authors: Kim Kyun Young , Ryu Jung-Hwa , Kang Duk-Hee , Kim Seung-Jung , Choi Kyu Bok , Lee Shina 
Published: March 2022

Abstract
Background
Early fluid management is considered a key element affecting mortality in critically ill patients requiring continuous renal replacement therapy (CRRT). Most studies have primarily focused on patients with intrinsic acute kidney injury requiring CRRT, although end-stage kidney disease (ESKD) patients generally exhibit greater vulnerability. We investigated the association between fluid balance and short-term mortality outcomes in ESKD patients undergoing chronic hemodialysis and requiring CRRT.

Methods
This retrospective study included 110 chronic hemodialysis patients who received CRRT between 2017 and 2019 at Ewha Womans University Mokdong Hospital. The amounts of daily input and output, and cumulative 3-day and 7-day input and output, were assessed from the initiation of CRRT. The participants were classified into two groups based on 7-day and 14-day mortalities. Cox regression analyses were carried out on the basis of the amounts of daily input and output, cumulative input and output, and cumulative fluid balance.

Results
During follow-up, 7-day and 14-day mortalities were observed in 24 (21.8%) and 34 (30.9%) patients. The patients were stratified into two groups (14-day survivors vs. non-survivors), and there were no significant differences in demographic characteristics between the two groups. However, diabetes mellitus was more common among survivors than among non-survivors. Univariate analyses showed that the amounts of daily output at 48, and 72 h, and 3-day cumulative input and output, were significantly associated with 7-day mortality risk regardless of the cumulative fluid balance (HR: 0.28, 95% CI: 0.12–0.70, p = 0.01 for daily output at 48 h; HR: 0.34, 95% CI: 0.13–0.85, p = 0.02 for daily output at 72 h.; HR: 0.72, 95% CI: 0.61–0.86, p = 0.01 for 3-day cumulative input; HR: 0.65, 95% CI: 0.41–0.90, p = 0.01 for 3-day cumulative output). Adjusted multivariate analyses showed that the lower 3-day cumulative output is an independent risk factor for 7-day and 14-day mortality.

Conclusions
In our study, increased cumulative output were significantly associated with reduced short-term mortality risk in chronic hemodialysis patients undergoing CRRT regardless of cumulative fluid balance. Further prospective studies to investigate the association between fluid balance and mortality in ESRD patients requiring CRRT are warranted.
Late effects of high-dose methotrexate treatment in childhood cancer survivors—a systematic review
Authors: Daetwyler Eveline , Bargetzi Mario , Otth Maria , Scheinemann Katrin 
Published: March 2022

Abstract
Background
High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking.

Method
We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262).

Results
We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision.

Conclusions
CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.
Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma
Authors: Guo Yusheng , Ren Yanqiao , Chen Lei , Sun Tao , Zhang Weihua , Sun Bo , Zhu Licheng , Xiong Fu , Zheng Chuansheng 
Published: March 2022

Abstract
Purpose
To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection.

Patients and methods
R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events.

Results
Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs.

Conclusion
Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.
Carotid artery dissection in Hutchinson-Gilford Progeria: a case report
Authors: González-Maestro Víctor , Monteagudo-Vilavedra Einés , Rodríguez-Antuña Jorge , Lendoiro-Fuentes Marta , Gómez María Soledad Brage , Miño Elena Maside 
Published: March 2022

Abstract
Background
Strokes in the paediatric age group have their own epidemiology and aetiology and are frequently misdiagnosed. As in the adult population, they present some risk factors that must be identified. Cerebral arteriopathies as a cause of paediatric ischaemic stroke present a very diverse aetiology and morphology.
In this article we report a paediatric stroke in a patient who was diagnosed during his first months of life of Hutchinson-Gilford´s Progeria (HGP). This is a rare genetic condition caused by mutations in the LMNA gene, producing an aberrant lamin A protein. The disease leads to premature aging, and cardiovascular complications are the first cause of morbidity and mortality in these patients.

Case presentation
We report the case of a 5-year-old patient with HGP (missense mutation—de novo—c.1822G > A in heterozygosis, LMNA gene). The patient was diagnosed during his first year of life and presented distinct phenotypical features. No other relevant comorbidities were present.
He was admitted to the emergency department for right hemiparesis with at least 4 h of evolution, with inability to open the hand and slight decrease in the level of consciousness (pedNIHSS 5–6). Cranial-CT and angio-CT showed findings indicative of left carotid dissection. Consensus was reached on conservative medical management with anticoagulation and antiplatelet therapy. In the first few days, the patient had a favourable evolution with resolution of the right lower limb hemiparesis and, one month after discharge, of the hand paresis.

Conclusions
The clinical manifestations, the vascular phenotype of the genetic mutation and the location of the radiological signs on a specific vascular morphology are indicative of carotid dissection. Spontaneous dissections occur under a predisposing risk factor or disease and are an exceptional finding in patients with HGP.
Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults
Authors: Wang Zuxing , Chen Lili , Xiao Jun , Jiang Fugui , Min Wenjiao , Liu Shuyun , Wang Yunqiong , Qi Mengsha 
Published: March 2022

Abstract
Background
The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior.

Methods
A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis.

Results
Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594–0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor.

Conclusion
Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.