bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukemogenesis in infants and young children with trisomy 21
Authors: Roberts Irene 
Published: December 2022

Abstract
Children with Down syndrome (DS) have a greater than 100-fold increased risk of developing acute myeloid leukemia (ML) and an approximately 30-fold increased risk of acute lymphoblastic leukemia (ALL) before their fifth birthday. ML-DS originates in utero and typically presents with a self-limiting, neonatal leukemic syndrome known as transient abnormal myelopoiesis (TAM) that is caused by cooperation between trisomy 21–associated abnormalities of fetal hematopoiesis and somatic N-terminal mutations in the transcription factor GATA1. Around 10% of neonates with DS have clinical signs of TAM, although the frequency of hematologically silent GATA1 mutations in DS neonates is much higher (~25%). While most cases of TAM/silent TAM resolve without treatment within 3 to 4 months, in 10% to 20% of cases transformation to full-blown leukemia occurs within the first 4 years of life when cells harboring GATA1 mutations persist and acquire secondary mutations, most often in cohesin genes. By contrast, DS-ALL, which is almost always B-lineage, presents after the first few months of life and is characterized by a high frequency of rearrangement of the CRLF2 gene (60%), often co-occurring with activating mutations in JAK2 or RAS genes. While treatment of ML-DS achieves long-term survival in approximately 90% of children, the outcome of DS-ALL is inferior to ALL in children without DS. Ongoing studies in primary cells and model systems indicate that the role of trisomy 21 in DS leukemogenesis is complex and cell context dependent but show promise in improving management and the treatment of relapse, in which the outcome of both ML-DS and DS-ALL remains poor.
Cellular therapy for multiple myeloma: what's now and what's next
Authors: Rodriguez-Otero Paula , San-Miguel Jesús F. 
Published: December 2022

Abstract
Despite significant improvement in the treatment of multiple myeloma (MM), a cure remains elusive, and patients failing proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies remain a challenge due to a lack of standard of care treatment and a dismal survival rate. The development of T-cell redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, have transformed the outcome of triple-class exposed relapsed and refractory MM (RRMM). B-cell maturation antigen (BCMA) has proven to be an important target in MM, and BCMA-directed CAR T cells have shown unprecedented efficacy with a prolonged duration of response in a population with advanced RRMM, leading to the approval of 2 different BCMA CAR T-cell products. Still, and in contrast to prior experience in the field of CD19-directed CARs, no plateau has been seen in the survival curves, and relapses continue to occur. Therefore, further improvement is needed. Early use in the course of the disease as well as of next- generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA-directed CAR T-cell therapy in RRMM, as well as potential future developments focused on optimizing patient care and novel CAR designs.
Germline risk factors for second malignant neoplasms after treatment for pediatric hematologic malignancies
Authors: Bhatia Smita 
Published: December 2022

Abstract
Survivors of childhood hematologic malignancies are at a substantially higher risk of developing subsequent neoplasms (SNs) when compared with the general population. SNs commonly observed in this population include basal cell carcinoma, brain tumors, thyroid cancer, breast cancer, bone tumors, and sarcoma. Radiation is the primary therapeutic exposure associated with the development of these SNs. There is emerging evidence of an association between chemotherapeutic exposures (alkylating agents/anthracyclines) and the development of SNs. Despite a strong dose-dependent association between therapeutic exposures and SN risk, there is significant interindividual variability in the risk for SNs for any given dose of therapeutic exposure. This interindividual variability in risk suggests the role of genetic susceptibility. This article describes the clinical and molecular epidemiology of SNs commonly observed in survivors of childhood hematologic malignancies and also highlights some of the work focusing on the development of risk prediction models to facilitate targeted interventions.
Evaluating patients with autoimmune hemolytic anemia in the transfusion service and immunohematology reference laboratory: pretransfusion testing challenges and best transfusion-management strategies
Authors: Johnson Susan T. , Puca Kathleen E. 
Published: December 2022

Abstract
The serologic evaluation of autoimmune hemolytic anemia (AIHA) confirms the clinical diagnosis, helps distinguish the type of AIHA, and identifies whether any underlying alloantibodies are present that might complicate the selection of the safest blood for any needed transfusion. The spectrum of testing is generally dependent on the amount and class (immunoglobulin G or M) of autoantibody as well as the resources and methodologies where testing is performed. The approach may range from routine pretransfusion testing, including the direct antiglobulin test, to advanced techniques such as adsorptions, elution, and red cell genotyping. When transfusion is needed, the selection of the optimal unit of red blood cells is based on urgency and whether time allows for the completion of sophisticated serologic and molecular testing methods. From the start of when AIHA is suspected until the completion of testing, communication among the clinical team and medical laboratory scientists in the transfusion service and immunohematology reference laboratory is critical as testing can take several hours and the need for transfusion may be urgent. The frequent exchange of information including the patient's transfusion history and clinical status, the progress of testing, and any available results is invaluable for timely diagnosis, ongoing management of the patient, and the safety of transfusion if required before testing is complete.
Mitigating the risk of venous thromboembolism in patients with multiple myeloma receiving immunomodulatory-based therapy
Authors: Covut Fahrettin , Sanfilippo Kristen M. 
Published: December 2022

Abstract
Patients with multiple myeloma (MM) have up to a 20-fold increased risk of venous thromboembolism (VTE) compared with the general population, with most events occurring within the first 6 months of diagnosis. Treatment with immunomodulatory drugs (IMiDs) is a strong risk factor for VTE in MM. In a meta-analysis of 2 large, randomized trials comparing anticoagulant thromboprophylaxis vs placebo in ambulatory patients with cancer at high risk of VTE based on a validated risk score, the risk of VTE decreased without increasing the risk of major bleeding. However, few patients with MM participated in these trials (1.1%). Initial guidance for risk-stratifying patients with MM resulted in persistent rates of VTE &gt;10% and highlighted the need for improved VTE risk stratification in patients with MM. Three validated risk scores are now available to quantify risk of VTE in patients with MM: SAVED, IMPEDE VTE, and PRISM scores. Using best available data, thromboprophylaxis should be strongly considered in patients with MM assessed as high risk for VTE, especially newly diagnosed patients receiving IMiD-based combination therapies. However, prospective studies are needed to further validate available models and identify the optimal thromboprophylactic agent for each VTE risk category.
The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study
Authors: Jalnapurkar Isha , Frazier Jean A. , Roth Mark , Cochran David M. , Foley Ann , Merk Taylor , Venuti Lauren , Ronco Lucienne , Raines Shane , Cadavid Diego 
Published: December 2022

Abstract
Background
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP.

Methods
Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules.

Results
There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab.

Conclusion
Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies.
Comparison of apical and basolateral Cu treatment for iron-related gene regulation during deferoxamine induced iron deficiency
Authors: Evcan Ezgi , Gulec Sukru 
Published: December 2022

Abstract
Background
Intestinal copper transporter (Atp7a) mutant-brindled mice with systemic Cu deficiency had elevated Cu levels in enterocyte cells without any perturbation of iron-regulating genes, suggesting that blood Cu level might be important for intestinal iron homeostasis during iron deficiency (ID). We hypothesized that the blood Cu level and polarization (apical and basolateral) of enterocyte cells might be important regulators for the compensatory response on the regulation of genes in enterocyte cells during iron deficiency.

Methods
We grew Caco-2 cells on a bicameral cell culture plate to mimic the human intestine system and on a regular tissue culture plate. Iron deficiency was induced by deferoxamine (DFO). The cells were treated with Cu and Cu with Fe following mRNA expressions of DMT1, FPN, TFR, and ANKRD37 were analyzed.

Results
Our main finding was that basolateral treatment of Cu significantly reduced mRNA expressions of iron-regulated genes, including DMT1, FPN, TFR, and ANKRD37, compared to DFO-treated and DFO with apical Cu-treated groups in both bicameral and regular tissue culture plates.

Conclusions
Cu level in the basolateral side of Caco-2 cells significantly influenced the intracellular gene regulation in DFO-induced iron-deficient condition, and polarization of the cells might be important factor gene regulation in enterocyte cells.
Drug response prediction using graph representation learning and Laplacian feature selection
Authors: Xie Minzhu , Lei Xiaowen , Zhong Jianchen , Ouyang Jianxing , Li Guijing 
Published: December 2022

Abstract
Background
Knowing the responses of a patient to drugs is essential to make personalized medicine practical. Since the current clinical drug response experiments are time-consuming and expensive, utilizing human genomic information and drug molecular characteristics to predict drug responses is of urgent importance. Although a variety of computational drug response prediction methods have been proposed, their effectiveness is still not satisfying.

Results
In this study, we propose a method called LGRDRP (Learning Graph Representation for Drug Response Prediction) to predict cell line-drug responses. At first, LGRDRP constructs a heterogeneous network integrating multiple kinds of information: cell line miRNA expression profiles, drug chemical structure similarity, gene-gene interaction, cell line-gene interaction and known cell line-drug responses. Then, for each cell line, learning graph representation and Laplacian feature selection are combined to obtain network topology features related to the cell line. The learning graph representation method learns network topology structure features, and the Laplacian feature selection method further selects out some most important ones from them. Finally, LGRDRP trains an SVM model to predict drug responses based on the selected features of the known cell line-drug responses. Our five-fold cross-validation results show that LGRDRP is significantly superior to the art-of-the-state methods in the measures of the average area under the receiver operating characteristics curve, the average area under the precision-recall curve and the recall rate of top-k predicted sensitive cell lines.

Conclusions
Our results demonstrated that the usage of multiple types of information about cell lines and drugs, the learning graph representation method, and the Laplacian feature selection is useful to the improvement of performance in predicting drug responses. We believe that such an approach would be easily extended to similar problems such as miRNA-disease relationship inference.
Relationship between red blood cell distribution width-to-albumin ratio and outcome of septic patients with atrial fibrillation: a retrospective cohort study
Authors: Gu You-lan , Yang Duo , Huang Zhi-bin , Chen Yan , Dai Zai-shen 
Published: December 2022

Abstract
Background
This retrospective cohort study aimed to investigate the association between red blood cell distribution width-to-albumin ratio (RAR) and in-hospital mortality in patients with sepsis and atrial fibrillation (AF).

Methods
Data were obtained from the Medical Information Mart for the Intensive Care Database IV database version 1.0. Multivariate Cox regression models, curve-fitting, and Kaplan–Meier analyses were performed to determine the correlation between RAR and in-hospital mortality in patients with sepsis and AF.

Results
This study included 3042 patients with sepsis and AF. Confounding variables were adjusted for in the Multivariable Cox regression analysis models. RAR was independently associated with in-hospital mortality (hazard ratio 1.06; 95% confidence interval 1.03–1.08; p < 0.001). A linear relationship was found between the RAR and in-hospital mortality in patients with sepsis and AF.

Conclusion
Elevated RAR levels are associated with increased in-hospital mortality in patients with sepsis and AF. Further research is required to confirm this association.
Examining the predictors of healthcare facility choice for outpatient care among older adults in India using Andersen’s revised healthcare utilization framework model
Authors: Rahaman Margubur , Chouhan Pradip , Roy Avijit , Rana Md. Juel , Das Kailash Chandra 
Published: December 2022

AbstractBackgroundIn India, the demand for outpatient care is substantially higher than inpatient care among older adults. Therefore, the current study examines the level, patterns, and factors associated with outpatient care use.MethodsThe present research used data from the first wave of the Longitudinal Ageing Study in India (LASI, 2017–18). A total of 34,588 older adults (45 years and above) who accessed outpatient healthcare services in one year prior to the survey were included in this study. A bivariate chi-square test was applied to present the percentage distribution of types of outpatient healthcare utilization by background characteristics and healthcare responsiveness. Multinomial logistic regression analyses were employed to explore the interplay of outpatient healthcare utilization and allied predisposing, enabling, and need factors.ResultsAbout 63.7% of total older adults used a private facility, followed by 22.8% used a public facility, and 13.5% used other facilities. Years of schooling, household wealth status, place of residence, self-rated health, and health insurance were all found to be significant determinants of public or private facility use. In contrast, respondents' sex was found to be a significant determinant of private healthcare use only. The study finds that there was inadequate healthcare reaction to public health facilities.ConclusionThe current study revealed that the use of private facility for outpatient care is noticeably high in India. Older adults' educational attainments, health insurance coverage, and household level economic background were found to be significant factors in healthcare choice. The current study emphasizes the need to strengthen public healthcare services for outpatient care.
Impact of body mass index on in-hospital mortality in older patients hospitalized for bacterial pneumonia with non-dialysis-dependent chronic kidney disease
Authors: Okada Akira , Yamaguchi Satoko , Jo Taisuke , Yokota Isao , Ono Sachiko , Ikeda Kurakawa Kayo , Nangaku Masaomi , Yamauchi Toshimasa , Kadowaki Takashi 
Published: December 2022

Abstract
Background
Low body mass index (BMI) in older individuals with decreased kidney function is important because of its association with poor prognosis and frailty. Herein, we aimed to clarify the association between BMI and in-hospital mortality among older patients with non-dialysis-dependent chronic kidney disease (CKD) stratified by kidney function.

Methods
Using data from the Medical Vision Database, this multicentre cohort study included people aged ≥ 60 years with an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 but without dialysis dependency, hospitalised for bacterial pneumonia during 2014–2019. We compared the risk of in-hospital death between patients with BMI categories based on the quartiles (low, medium–low, medium–high, and high) setting medium–high BMI as a reference. We further assessed the association with BMI using a cubic spline, setting BMI as a nonlinear continuous variable and a BMI of 22 kg/m2 as a reference. We also evaluated the association between BMI and kidney function using a generalised additive model adjusted for interaction terms between nonlinear continuous BMI and kidney function.

Results
We obtained data for 3,952 patients, with 350 (8.9%) in-hospital deaths. When compared with medium–high BMI, low BMI was associated with an increased risk of death and longer hospital stay, whereas the other two categories were comparable. Models using a cubic spline showing an association between BMI and in-hospital death showed an L-shaped curve; BMI < 22.0 kg/m2 was associated with an increased risk for mortality, and at a BMI of 18.5 kg/m2, the odds ratio was 1.43 with a 95% confidence interval of 1.26–1.61 when compared with a BMI of 22.0 kg/m2. Analysis of the interactive effects of kidney function using the generalised additive model showed that a protective association of high BMI tapered along with decreased kidney function.

Conclusions
This cohort study suggests not only that lower BMI and low kidney function are associated with in-hospital mortality independently but also that the protective effects of high BMI weaken as kidney function decreases via the analysis of the interaction terms. This study highlights the necessity for the prevention of underweight and demonstrates the interaction between BMI and kidney function in older patients with non-dialysis-dependent CKD.
Composite hemangioendothelioma in the cervical spine with kaposiform hemangioendothelioma features in an elderly patient: a case report
Authors: Nakamura Shunsuke , Uehara Masashi , Kobayashi Shota , Hasegawa Hiromasa , Tanaka Atsushi , Takahashi Jun 
Published: December 2022

Abstract
Background
Composite hemangioendothelioma (CHE) is an intermediate group of tumors with features between hemangioma and angiosarcoma both histologically and biologically. CHE is predominant in young and middle-aged adults, but very infrequently affects the spine. We describe the case of primary CHE in the cervical spine exhibiting kaposiform hemangioendothelioma (KHE)-like components that was associated with cervical myelopathy with vertebral body destruction in an elderly woman. We retrospectively reviewed the case of a primary cervical spinal tumor, diagnosed as CHE with KHE-like components in pathological findings, associated with cervical myelopathy and cervical vertebral body destruction.

Case presentation
An 80-year-old woman presented with progressive cervical myelopathy caused by a cervical spine tumor. Preoperative cervical MRI revealed a neoplastic lesion invading the cervical spine that strongly compressed the spinal cord, causing right upper-limb paralysis. We performed partial tumor resection along with posterior decompression and fixation. Postoperatively, pathological findings showed that the tumor was CHE with KHE-like features. Following radiotherapy, no recurrences have been observed in 21 months.

Conclusions
This is the first report of CHE with features of KHE in the spine of an elderly patient. Posterior decompression and fusion of the cervical spine and subsequent radiotherapy resulted in a good outcome.
Biofilm infection of a central venous port-catheter caused by Mycobacterium avium complex in an immunocompetent child with cystic fibrosis
Authors: Kavvalou Alexandra , Stehling Florian , Tschiedel Eva , Kehrmann Jan , Walkenfort Bernd , Hasenberg Mike , Olivier Margarete , Steindor Mathis 
Published: December 2022

Abstract
Background
Mycobacterium (M.) chimaera is a non-tuberculous mycobacterium (NTM) that belongs to M. avium complex (MAC). In patients with cystic fibrosis (CF), MAC can cause bronchopulmonary infections that can be prolonged and difficult to treat. MAC infections of sites other than the lungs or central catheters are rare and almost exclusively associated with immunodeficiency.

Case presentation
We present a case of an 8-year-old CF patient (delF508 homozygous) with recurrent pulmonary exacerbations, gradual clinical deterioration, B-symptoms (fever, fatigue, weight loss, night sweat), elevated transaminases and intermittent detection of M. chimaera in the sputum without radiological signs of NTM-associated lung disease with a central venous port-catheter. Next-generation sequencing (NGS) revealed M. chimaera port infection that was also confirmed by mycobacterial culture. The patient recovered within 4 weeks after removal of the catheter and initiation of MAC targeted antimicrobial therapy. Electron microscopy of the catheter illustrated the presence of mycobacteria in a biofilm.

Conclusions
MAC central venous catheter infection needs to be considered in immunocompetent people. NGS is a valuable tool for rapid identification of rare infections. MAC capability of biofilm formation renders catheter removal the central therapeutic intervention for the clearance of the infection.