bluuebunny/crossref_metadata_2025_split huggingface dataset:
Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms
Authors: Gotlib Jason 
Published: December 2022

Abstract
The historically poor prognosis of patients with advanced systemic mastocytosis (AdvSM) and primary eosinophilic neoplasms has shifted to increasingly favorable outcomes with the discovery of druggable targets. The multikinase/KIT inhibitor midostaurin and the highly selective KIT D816V inhibitor avapritinib can elicit marked improvements in measures of mast cell (MC) burden as well as reversion of MC-mediated organ damage (C-findings) and disease symptoms. With avapritinib, the achievement of molecular remission of KIT D816V and improved survival compared with historical therapy suggests a potential to affect disease natural history. BLU-263 and bezuclastinib are KIT D816V inhibitors currently being tested in trials of AdvSM. In the new World Health Organization and International Consensus Classifications, the category of “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions” is inclusive of rearrangements involving PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ETV6::ABL1. While the successful outcomes with imatinib in FIP1L1::PDGFRA-positive cases and PDGFRB-rearranged neoplasms have become the “poster children” of these disorders, the responses of the other TK-driven neoplasms to small-molecule inhibitors are more variable. The selective FGFR inhibitor pemigatinib, approved in August 2022, is a promising therapy in aggressive FGFR1-driven diseases and highlights the role of such agents in bridging patients to allogeneic transplantation. This review summarizes the data for these approved and investigational agents and discusses open questions and future priorities regarding the management of these rare diseases.
No crystal stair: supporting fertility care and the pursuit of pregnancy in women with sickle cell disease
Authors: Pecker Lydia H. , Nero Alecia , Christianson Mindy 
Published: December 2022

Abstract
Growing recognition that the ovary is an end organ in sickle cell disease (SCD), advances in SCD treatment and cure, and innovations in assisted reproductive technologies invite progressive challenges in fertility care for women with SCD. The reproductive life span of women with SCD may be reduced because ovarian reserve declines more rapidly in people with SCD compared to unaffected people. Some young women have diminished ovarian reserve, a risk factor for infertility. Referrals for fertility preservation may be offered and anticipatory guidance about when to seek infertility care provided. For a subset of people with SCD, this information is also applicable when pursuing in vitro fertilization with preimplantation genetic testing to avoid implantation of an embryo with SCD. Here we explore the dimensions of SCD-related fertility care illustrated by the case of a 28-year-old woman with hemoglobin SS disease who initially presented for a hematology consultation for preconception counseling. This case highlights the complexity of preconception SCD management and care and the need to partner with patients to help align pregnancy hopes with SCD treatment and the many associated uncertainties.
Genetics of severe congenital neutropenia as a gateway to personalized therapy
Authors: Donadieu Jean , Bellanné-Chantelot Christine 
Published: December 2022

Abstract
Severe congenital neutropenias (SCNs) are rare diseases, and to date about 30 subtypes have been described according to their genetic causes. Standard care aims to prevent infections and limit the risk of leukemic transformation; however, several subtypes may have additional organ dysfunction(s), requiring specialized care. Granulocyte colony-stimulating factor and hematopoietic stem cell transplantation are now the bedrock of standard care. Better understanding of SCN mechanisms now offers the possibility of adapted therapy for some entities. An inhibitor of sodium glucose cotransporter, an antidiabetic drug, may attenuate glycogen storage disease type Ib and glucose-6-phosphatase catalytic subunit 3 neutropenias by clearing 1,5-anhydroglucitol, the precursor of the phosphate ester responsible for these SCNs. Chemokine receptor CXCR4 inhibitors contribute to reversing the leukocyte defect in warts, hypoglobulinemia, infections, and myelokathexis syndrome. All these new approaches use oral drugs, which notably improve quality of life. Additionally, improved research into clonal evolution has highlighted some ways to potentially prevent leukemia, such as stimulating somatic genetic rescue, a physiological process that might limit the risk of leukemic transformation.
Modern management of Fanconi anemia
Authors: Dufour Carlo , Pierri Filomena 
Published: December 2022

Abstract
In this review, we present a clinical case report and discussion to outline the importance of long-term specific Fanconi anemia (FA) monitoring, and we discuss the main aspects of the general management of patients with FA and clinical complications. While several nontransplant treatments are currently under evaluation, hematopoietic stem cell transplantation (HSCT) remains the only therapeutic option for bone marrow failure (BMF). Although HSCT outcomes in patients with FA have remarkably improved over the past 20 years, in addition to the mortality intrinsic to the procedure, HSCT increases the risk and accelerates the appearance of late malignancies. HSCT offers the best outcome when performed in optimal conditions (moderate cytopenia shifting to severe, prior to transfusion dependence and before clonal evolution or myelodysplasia/acute myeloid leukemia); hence, an accurate surveillance program is vital. Haploidentical HSCT offers very good outcomes, although long-term effects on malignancies have not been fully explored. A monitoring plan is also important to identify cancers, particularly head and neck carcinomas, in very early phases. Gene therapy is still experimental and offers the most encouraging results when performed in early phases of BMF by infusing high numbers of corrected cells without genotoxic effects. Patients with FA need comprehensive monitoring and care plans, coordinated by centers with expertise in FA management, that start at diagnosis and continue throughout life. Such long-term follow-up is essential to detect complications related to the disease or treatment in this setting.
Dyskeratosis congenita and telomere biology disorders
Authors: Savage Sharon A. 
Published: December 2022

Abstract
Numerous genetic discoveries and the advent of clinical telomere length testing have led to the recognition of a spectrum of telomere biology disorders (TBDs) beyond the classic dyskeratosis congenita (DC) triad of nail dysplasia, abnormal skin pigmentation, and oral leukoplakia occurring with pediatric bone marrow failure. Patients with DC/TBDs have very short telomeres for their age and are at high risk of bone marrow failure, cancer, pulmonary fibrosis (PF), pulmonary arteriovenous malformations, liver disease, stenosis of the urethra, esophagus, and/or lacrimal ducts, avascular necrosis of the hips and/or shoulders, and other medical problems. However, many patients with TBDs do not develop classic DC features; they may present in middle age and/or with just 1 feature, such as PF or aplastic anemia. TBD-associated clinical manifestations are progressive and attributed to aberrant telomere biology caused by the X-linked recessive, autosomal dominant, autosomal recessive, or de novo occurrence of pathogenic germline variants in at least 18 different genes. This review describes the genetics and clinical manifestations of TBDs and highlights areas in need of additional clinical and basic science research.
New strategies for mismatched unrelated donor (MMUD) hematopoietic cell transplant (HCT)
Authors: Arslan Shukaib , Al Malki Monzr M. 
Published: December 2022

Abstract
With increasing numbers of patients with hematologic malignancies requiring allogeneic hematopoietic cell transplant (HCT), including minority racial and ethnic groups, the limited availability of matched related donors and matched unrelated donors remains a significant obstacle. Hence, the use of alternative donors such as haploidentical and mismatched unrelated donors (MMUDs) is on the rise. Herein, we present case studies to outline a rational and stepwise approach with a focus on the use of MMUD for HCT in patients with hematologic malignancies. We also review novel approaches used to reduce the incidence of severe graft-versus-host disease and improve HCT outcomes in patients undergoing MMUD HCT.
Thrombocytopenia and liver disease: pathophysiology and periprocedural management
Authors: Lim Hana I. , Cuker Adam 
Published: December 2022

AbstractAbnormal bleeding in patients with liver disease may result from elevated portal pressure and varix formation, reduced hepatic synthesis of coagulation proteins, qualitative platelet dysfunction, and/or thrombocytopenia. Major mechanisms of thrombocytopenia in liver disease include splenic sequestration and impaired platelet production due to reduced thrombopoietin production. Alcohol and certain viruses may induce marrow suppression. Immune thrombocytopenia (ITP) may co-occur in patients with liver disease, particularly those with autoimmune liver disease or chronic hepatitis C. Drugs used for the treatment of liver disease or its complications, such as interferon, immunosuppressants, and antibiotics, may cause thrombocytopenia. Periprocedural management of thrombocytopenia of liver disease depends on both individual patient characteristics and the bleeding risk of the procedure. Patients with a platelet count higher than or equal to 50 000/µL and those requiring low-risk procedures rarely require platelet-directed therapy. For those with a platelet count below 50 000/µL who require a high-risk procedure, platelet-directed therapy should be considered, especially if the patient has other risk factors for bleeding, such as abnormal bleeding with past hemostatic challenges. We often target a platelet count higher than or equal to 50 000/µL in such patients. If the procedure is elective, we prefer treatment with a thrombopoietin receptor agonist; if it is urgent, we use platelet transfusion. In high-risk patients who have an inadequate response to or are otherwise unable to receive these therapies, other strategies may be considered, such as a trial of empiric ITP therapy, spleen-directed therapy, or transjugular intrahepatic portosystemic shunt placement.
Risk factors and screening for neurocognitive impacts of therapy
Authors: Krull Kevin R. 
Published: December 2022

Abstract
Long-term survivors of pediatric hematologic malignancies are at elevated risk for neurocognitive impairment. Such impairment manifests in different ways at different times during survivorship, with deficits in processing speed, attention, and memory often appearing before deficits in executive function, intelligence, and academics. Survivors exposed to therapies that directly target the central nervous system (CNS), as is the case in acute lymphoblastic leukemia, may demonstrate subtle deficits during frontline therapy, and these deficits may grow and evolve over time. Survivors who do not receive CNS-directed therapies (eg, Hodgkin lymphoma) are also at elevated risk for neurocognitive impairment, although the influence on brain function is indirect through cancer therapy impact on systemic organ function vital to brain health (eg, cardiopulmonary morbidity). Over the course of the survivor's life span, the presence and impact of neurocognitive deficits will be determined by a complex interaction between premorbid development and environment, cancer therapy and clinical care, and posttreatment recovery and health. The timing and type of these treatment and health events will dictate the approach to screening and monitoring for neurocognitive impairment.
Evidence-Based Minireview: Full dose, modified dose, or no anticoagulation for patients with cancer and acute VTE and thrombocytopenia
Authors: Patell Rushad , Zwicker Jeffrey I. 
Published: December 2022

Abstract
Co-incident venous thromboembolism and thrombocytopenia are frequent in patients with active malignancies. The optimal approach for anticoagulation in patients with cancer and thrombocytopenia is not established. Different strategies are often utilized including dose-reduced anticoagulation dictated by degree of thrombocytopenia or transfusing platelets in order to facilitate therapeutic anticoagulation. This minireview provides an overview of the data and we outline our approach toward anticoagulation in patients with venous thromboembolism and thrombocytopenia in the setting of cancer.
Detecting clusters of transcription factors based on a nonhomogeneous poisson process model
Authors: Wu Xiaowei , Liu Shicheng , Liang Guanying 
Published: December 2022

Abstract
Background
Rapidly growing genome-wide ChIP-seq data have provided unprecedented opportunities to explore transcription factor (TF) binding under various cellular conditions. Despite the rich resources, development of analytical methods for studying the interaction among TFs in gene regulation still lags behind.

Results
In order to address cooperative TF binding and detect TF clusters with coordinative functions, we have developed novel computational methods based on clustering the sample paths of nonhomogeneous Poisson processes. Simulation studies demonstrated the capability of these methods to accurately detect TF clusters and uncover the hierarchy of TF interactions. A further application to the multiple-TF ChIP-seq data in mouse embryonic stem cells (ESCs) showed that our methods identified the cluster of core ESC regulators reported in the literature and provided new insights on functional implications of transcrisptional regulatory modules.

Conclusions
Effective analytical tools are essential for studying protein-DNA relations. Information derived from this research will help us better understand the orchestration of transcription factors in gene regulation processes.
Pro-MAP: a robust pipeline for the pre-processing of single channel protein microarray data
Authors: Mowoe Metoboroghene Oluwaseyi , Garnett Shaun , Lennard Katherine , Talbot Jade , Townsend Paul , Jonas Eduard , Blackburn Jonathan Michael 
Published: December 2022

Abstract
Background
The central role of proteins in diseases has made them increasingly attractive as therapeutic targets and indicators of cellular processes. Protein microarrays are emerging as an important means of characterising protein activity. Their accurate downstream analysis to produce biologically significant conclusions is largely dependent on proper pre-processing of extracted signal intensities. However, existing computational tools are not specifically tailored to the nature of these data and lack unanimity.

Results
Here, we present the single-channel Protein Microarray Analysis Pipeline, a tailored computational tool for analysis of single-channel protein microarrays enabling biomarker identification, implemented in R, and as an interactive web application. We compared four existing background correction and normalization methods as well as three array filtering techniques, applied to four real datasets with two microarray designs, extracted using two software programs. The normexp, cyclic loess, and array weighting methods were most effective for background correction, normalization, and filtering respectively.

Conclusions
Thus, here we provided a versatile and effective pre-processing and differential analysis workflow for single-channel protein microarray data in form of an R script and web application (https://metaomics.uct.ac.za/shinyapps/Pro-MAP/.) for those not well versed in the R programming language.
The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically Ill patients: a retrospective cohort study
Authors: Cao Yongmei , Yao Sijia , Shang Jiawei , Ping Feng , Tan Qin , Tian Zijun , Huang Weifeng , Li Yingchuan 
Published: December 2022

AbstractBackgroundThe mortality rate is high in critically ill patients due to the difficulty of diagnosis and treatment. Thus, it is very important to explore the predictive value of different indicators related to prognosis in critically ill patients.MethodsThis was a retrospective cohort study of patients in the intensive care unit (ICU) of the Sixth People’s Hospital in Shanghai, China. A total of 1465 ICU patients had lactate values > 2.1 mmol/L at least once within 24 h of ICU admission, and arterial blood gas was monitored more than twice during the ICU stay.ResultsThe predictive value of lactate clearance at 24 h was not high, and the sensitivity and specificity were lower. The predictive value of the lactate level at baseline and the APACHE II score was higher than that of lactate clearance at 24 h in critically ill patients. The predictive value of the lactate level at baseline combined with the APACHE II score was higher than that of the lactate level at baseline or the APACHE II score alone. In addition, the predictive value of lactate clearance at 24 h combined with the APACHE II score was also significantly higher than that of lactate clearance at 24 h or the APACHE II score alone. In particular, the area under the ROC curve reached 0.900, the predictive value was markedly higher than that of the ROC alone, and the sensitivity and specificity were better when these three indicators were combined.ConclusionsThe combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically ill patients.
A successful case of electrical storm rescue after acute myocardial infarction
Authors: Liu Bin , Xie Bo , Chen Xun , Zhu Ke , Wang Cheng-Ming , Guo Shu-Hong 
Published: December 2022

Abstract
Background
Electrical storm (ES) is a heterogeneous clinical emergency that can present with malignant ventricular arrhythmias such as ventricular fibrillation (VF), ventricular tachycardia (VT), requiring the need for cardiac defibrillation. ES is a life-threatening condition with a high mortality rate. Successfully managing ES in the setting of acute myocardial infarction (MI) is expected to be known by physicians on call to reduce in-hospital mortality.

Case presentation
A 57-year-old man presenting with acute onset chest pain was found to have an infero-posterior ST-segment elevation myocardial infarction (STEMI) complicated by acute right ventricular MI secondary to total occlusion of the proximal right coronary artery (RCA). The patient developed ES in the form of recurrent VF that was managed successfully with electrical defibrillation, antiarrhythmic therapy with amiodarone and esmolol, endotracheal intubation, sedation, electrolyte replacement, volume resuscitation, comfort care, psychological intervention, and percutaneous coronary intervention (PCI) of the occluded epicardial artery. With these interventions used in quick succession and with the aspiration of a massive RCA thrombus, the patient was reversed to hemodynamic stability, did not have further episodes of VF, and survived the index hospitalization.

Conclusion
ES is a rare but fatal complication of acute MI. Residents on night shifts should be better prepared and equipped to deal with this rare condition. We hope our successful experience can benefit physicians on call who take care of acute MI patients that deteriorate with ES.
Outcome of burn injury and associated factor among patient visited at Addis Ababa burn, emergency and trauma hospital: a two years hospital-based cross-sectional study
Authors: Mulatu Damena , Zewdie Ayalew , Zemede Biruktawit , Terefe Bewuketu , Liyew Bikis 
Published: December 2022

AbstractBackgroundBurn is one of the critical health problems worldwide. Developing countries with sub-Saharan and Asian populations are affected more. Its mortality and non-fatal complications depend on several factors including age, sex, residency, cause, the extent of the burn, and time and level of care given.ObjectiveThe purpose of this study was to assess the outcome of burn injury and its associated factor among patients who visited Addis Ababa burn emergency and trauma hospital.MethodsThe institutional-based, retrospective cross-sectional study design was conducted from April 1, 2019, to March 30, 2021. After checking the data for its consistency the data were entered and analyzed by using SPSS version 25. A total of 241 patients who had visited Addis Ababa burn, emergency and trauma Hospitals after sustained burn injury were recruited through convenience sampling method for final analysis. Model goodness-of-fit was checked by Hosmer and Lemeshow test (0.272). After checking multi-collinearity both the bi-variable and multivariable logistic regression model was fitted and variables having ap-value less than or equal to 0.05 at 95% CI in the multivariable analysis were considered statistically significant.ResultAdults (age 15 to 60 years) are the most affected groups accounting for 55.2% followed by pediatric age groups (age <15 years) (43.6%) and the elderly (age > 60 years) (1.2%). Scald burn was the major cause accounting for 39 % followed by Flame burn (33.6%), Electrical burn (26.6%), and chemical burn (0.8%). The mean TBSA% was 15.49%, ranging from1% to 64%. Adult males are more affected by electrical burns while adult females and the elderly encounter flame burn. 78.4% of patients were discharged without complications, 14.9% were discharged with complications and 6.6% died. The commonest long-term complication is the amputation of the extremity (19, 7.9%). Age greater than 60 years and TBSA% greater than 30% is a strong predictors of mortality with odds of 2.2 at 95% CI of [1.32, 3.69] and 8.7 at 95% CI of [1.33, 57.32] respectively.Conclusion and recommendationThe mortality rate show decrement from previous studies. Overall scald burn is common in all age groups but electrical burns and flame burns affected more adult and elderly age groups. Extremities were by far, the commonest affected body parts. The extent of burn injury and the age of the patient independently predict mortality. Early intervention will reduce mortality and complications.
Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy
Authors: Li Jian-Xu , He Mei-Ling , Qiu Mo-Qin , Yan Liu-Ying , Long Mei-Ying , Zhong Jian-Hong , Zhang Rui-Jun , Liang Chun-Feng , Pang Ya-Dan , He Jun-Kun , Chen Qian-Qian , Weng Jin-Xia , Liang Shi-Xiong , Xiang Bang-De 
Published: December 2022

Abstract
Background
For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction.

Methods
The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram.

Results
The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort.

Conclusions
High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.