bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muttalip green clay and its ultraviolet and infrared absorption and reflection
Authors: Kuru Mutlu Hülya 
Published: December 2022

AbstractThe search for sufficiently high-quality clays for use in the tile industry represents a significant challenge. This study aimed to prepare Muttalip green clay tiles with flexural strengths adhering to the TS EN 1304:2016 standard. Muttalip green clay was subjected to sieving, vacuum pressed, dried and then baked to obtain galette tiles. The tiles were analysed subsequently using optical techniques, including X-ray diffraction, X-ray fluorescence spectrometry and field-emission scanning electron microscopy. The influence of various firing temperatures (900, 950 and 1000°C) on the flexural strength of the tiles was also investigated. The tiles obtained at 950°C exhibited a maximum flexural strength of 153.91 kg cm–2. Fourier-transform infrared spectroscopy revealed that the tiles reflect ultraviolet A radiation and absorb infrared radiation. Muttalip green clay is a suitable material for preparing tiles for roofing applications.
Novel investigational approaches for high-risk genetic subsets of AML: TP53, KMT2A, FLT3
Authors: Sahasrabudhe Kieran D. , Mims Alice S. 
Published: December 2022

Abstract
The treatment landscape in acute myeloid leukemia (AML) is rapidly evolving, with multiple new therapies approved in recent years. However, the prognosis for patients with high-risk genetic subsets of AML remains poor, and the development of more effective treatment options for these patients is ongoing. Three of these high-risk AML patient subsets include TP53-mutated AML, FLT3-internal tandem duplication (ITD)-mutated AML, and AML harboring rearrangements affecting the KMT2A locus (KMT2A-r AML). The prognosis for TP53-mutated AML remains poor with both intensive and targeted regimens, including those incorporating the BCL-2 inhibitor, venetoclax. Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for these patients, but posttransplant relapse rates remain high. Patients with FLT3-ITD-mutated AML continue to have suboptimal outcomes with standard therapies and experience high rates of relapse following transplant. KMT2A-r AML is also associated with poor outcomes with current treatment approaches, and effective standards of care are lacking for patients with relapsed/refractory disease. This article discusses current treatment approaches, along with the investigational agents being explored for the treatment of these 3 AML subsets, focusing primarily on agents that are further along in development.
Treatment of CML in pregnancy
Authors: Robertson Harry F. , Apperley Jane F. 
Published: December 2022

Abstract
Since the introduction of tyrosine kinase inhibitors (TKIs) at the beginning of the millennium, the outlook for patients with chronic myeloid leukemia (CML) has improved remarkably. As such, the question of life expectancy and survival has become less problematic while quality of life and family planning have become more so. While TKIs are the cornerstone of CML management, their teratogenicity renders them contraindicated during pregnancy. In recent years, patients who satisfy standardized criteria can stop TKI therapy altogether, and indeed, in eligible patients who wish to become pregnant, these objectives overlap. However, not all patients satisfy these criteria. Some pregnancies are unplanned, and a number of patients are pregnant when diagnosed with CML. In these patients the way forward is less clear, and there remains a paucity of good evidence available to guide treatment. In this article, we summarize the relevant literature and provide a framework for clinicians faced with the challenge of managing CML and pregnancy.
Ph+ ALL in 2022: is there an optimal approach?
Authors: Wieduwilt Matthew J. 
Published: December 2022

Abstract
Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) carried a very poor prognosis prior to the advent of tyrosine kinase inhibitors (TKIs) that block the activity of the BCR-ABL1 oncoprotein. With improvements in TKI efficacy and allogeneic hematopoietic cell transplantation (HCT), survival has improved over the past 3 decades, and the role of chemotherapy and allogeneic HCT is now changing. Better risk stratification, the application of the third-generation TKI ponatinib, and the use of immunotherapy with the CD19-CD3 bifunctional T-cell engaging antibody blinatumomab in place of chemotherapy has made therapy for Ph+ ALL more tolerable and arguably more efficacious, especially for older patients who comprise most patients with Ph+ ALL.
Novel therapies and combinations in CLL refractory to BTK inhibitors and venetoclax
Authors: Scarfò Lydia 
Published: December 2022

Abstract
Patients with chronic lymphocytic leukemia (CLL) refractory to covalent BTK and BCL2 inhibitors have a new unmet clinical need. Standard treatment options are able to obtain only limited and short-lasting disease control associated with reduced overall survival, and thus these patients have become ideal candidates for enrollment in clinical trials. Favorable results have been obtained with the use of noncovalent BTK inhibitors (roughly 70% overall response rate regardless of the actual resistance or intolerance to previous covalent BTK inhibitors) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (with complete responses in up to 45% of cases and an undetectable measurable residual disease rate of 65% in the bone marrow). These 2 approaches should be considered valid options in this setting, although not yet approved. For young fit patients achieving remissions with salvage treatments, the option of allogeneic stem cell transplantation should be discussed as the outcome appears to be unaffected by number and type of previous targeted agents. Novel treatment strategies interfering with different mechanisms of CLL cell survival and proliferation are warranted, including small molecules with novel targets (eg, CDK9, MCL1, ERK inhibitors), CAR T cells targeting different antigens, CAR natural killer cells, or bispecific antibodies.
High or low? Assessing disease risk in multiple myeloma
Authors: Schmidt Timothy Martin 
Published: December 2022

Abstract
Based upon the development of highly effective therapies such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that target plasma cell biology, a dramatic improvement in overall survival has been observed for most patients with multiple myeloma (MM) over the past 2 decades. Although it is now commonplace for many patients with myeloma to live in excess of 10 years after diagnosis, unfortunately a large subset of patients continues to experience an aggressive disease course marked by substantial morbidity and early mortality. Many clinical biomarkers and staging systems in use today can help with prognostication, but accurate risk assessment can be difficult due to the presence of many different biomarkers with variable prognostic value. Furthermore, with the implementation of novel therapies and unprecedented rates of deep and durable responses, it is becoming apparent that risk assessment is best envisioned as a dynamic process that requires ongoing reevaluation. As risk and response-adapted approaches are becoming more commonplace, it is essential that clinicians understand the biological and prognostic implications of clinical, genomic, and response-based biomarkers in order to promote management strategies that will help improve both survival and quality of life for patients across the risk spectrum.
Risk stratifying MDS in the time of precision medicine
Authors: Cazzola Mario 
Published: December 2022

AbstractMyelodysplastic syndromes (MDS) are myeloid neoplasms characterized by morphologic dysplasia, persistent cytopenia, and a variable risk of evolution to acute myeloid leukemia (AML). Risk stratification is crucial in a patient-centered approach to the treatment of MDS. Based on hematologic parameters and cytogenetic abnormalities, the Revised International Prognostic Scoring System is currently used for this purpose. In the past years, the use of massively parallel DNA sequencing has clarified the genetic basis of MDS and has enabled development of novel diagnostic and prognostic approaches. When conventional cytogenetics is combined with gene sequencing, more than 90% of patients are found to carry a somatic genetic lesion. In addition, a portion of patients has germline variants that predispose them to myeloid neoplasms. The recently developed International Consensus Classification of MDS includes new entities that are molecularly defined—namely, SF3B1-mutant and TP53-mutant MDS. The International Working Group for Prognosis in MDS has just developed the International Prognostic Scoring System–Molecular (IPSS-M) for MDS, which considers hematologic parameters, cytogenetic abnormalities, and somatic gene mutations. The IPSS-M score is personalized and can be obtained using a web-based calculator that returns not only the individual score but also the expected leukemia-free survival, overall survival, and risk of AML transformation. Providing an efficient risk stratification of patients with MDS, the IPSS-M represents a valuable tool for individual risk assessment and treatment decisions.
Targeting inflammation in lower-risk MDS
Authors: Gonzalez-Lugo Jesus D. , Verma Amit 
Published: December 2022

Abstract
The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant hematopoietic stem cell disorders characterized by ineffective growth and differentiation of hematopoietic progenitors leading to peripheral blood cytopenias, dysplasia, and a variable risk of transformation to acute myelogenous leukemia. As most patients present with lower-risk disease, understanding the pathogenesis of ineffective hematopoiesis is important for developing therapies that will increase blood counts in patients with MDS. Various inflammatory cytokines are elevated in MDS and contribute to dysplastic differentiation. Inflammatory pathways mediated by interleukin (IL) 1b, IL-6, IL-1RAP, IL-8, and others lead to growth of aberrant MDS stem and progenitors while inhibiting healthy hematopoiesis. Spliceosome mutations can lead to missplicing of genes such as IRAK4, CASP8, and MAP3K, which lead to activation of proinflammatory nuclear factor κB–driven pathways. Therapeutically, targeting of ligands of the transforming growth factor β (TGF-β) pathway has led to approval of luspatercept in transfusion-dependent patients with MDS. Presently, various clinical trials are evaluating inhibitors of cytokines and their receptors in low-risk MDS. Taken together, an inflammatory microenvironment can support the pathogenesis of clonal hematopoiesis and low-risk MDS, and clinical trials are evaluating anti-inflammatory strategies in these diseases.
Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy
Authors: Kotecha Rishi S. 
Published: December 2022

Abstract
Outcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival. We have now entered an era of immunotherapy with integration of agents, such as blinatumomab or chimeric antigen receptor T-cell therapy, into the standard chemotherapy backbone, showing significant promise for improving the dismal outcomes for this disease. There remains much optimism for the future as a wealth of preclinical studies have identified additional novel targeted agents, such as venetoclax or menin inhibitors, ready for incorporation into treatment, providing further ammunition to combat this aggressive disease. In contrast, infants with KMT2A-germline ALL have demonstrated excellent survival outcomes with current therapy, but there remains a high burden of treatment-related morbidity. Greater understanding of the underlying blast genetics for infants with KMT2A-germline ALL and incorporation of immunotherapeutic approaches may enable a reduction in the intensity of chemotherapy while maintaining the excellent outcomes.
Management of marginal zone lymphomas
Authors: Merli Michele , Arcaini Luca 
Published: December 2022

Abstract
Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes—namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed tomography was not initially recommended, recent data have reassessed its role in the routine staging of MZL, especially when only localized treatment is planned or there is a suspicion of histologic transformation. Recent findings have improved the risk stratification of MZL patients, highlighting the association of early progression after frontline therapy with worse overall survival. A significant fraction of MZL cases may be related to specific bacterial (ie, Helicobacter pylori in gastric EMZL) or viral infections (hepatis C virus), and in the earlier phases of disease, a variable percentage of patients may respond to anti-infective therapy. Involved-site radiotherapy has a central role in the management of localized EMZL not amenable to or not responding to anti-infective therapy. Although rituximab-based treatments (bendamustine- rituximab in advanced EMZL or rituximab monotherapy in SMZL) have demonstrated favorable results, the current therapeutic scenario is predicted to rapidly change as emerging novel agents, especially Bruton's tyrosine kinase inhibitors, have demonstrated promising efficacy and safety profiles, leading to their approval in the relapsed setting. Moreover, a large variety of novel agents (phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cells, bispecific antibodies) are being tested in MZL patients with encouraging preliminary results.
Long-term health outcomes following curative therapies for sickle cell disease
Authors: Chakravarthy Rohini , Friedman Debra L. 
Published: December 2022

Abstract
Treatment options for patients with sickle cell disease (SCD) continue to rapidly expand and evolve. The goal of therapies such as an allogeneic hematopoietic stem cell transplant (HSCT), gene therapy, and gene editing is to cure rather than control SCD. The benefits of these therapies must be accompanied by minimizing long-term adverse health outcomes from SCD and its treatment. SCD can have adverse effects on a variety of organ systems, including the heart, lung, kidney, and reproductive system, leading to high disease burden, morbidity, and premature mortality in both pediatric and adult patients. While curative therapies are being increasingly used, there remains a paucity of data on the long-term health outcomes associated with these treatments in children and adults with SCD. There are data available regarding the effects of HSCT performed largely for malignant diseases, from which data on SCD outcomes may be extrapolated. However, given the significant differences between these 2 populations of patients who undergo HSCT, such extrapolation is imprecise at best. Furthermore, there are currently no published data on long-term health outcomes following gene therapy for SCD due to current short follow-up times. We summarize the limited data reported on health outcomes following HSCT for SCD and emphasize the need for more research within this area.
Thrombopoietin receptor agonists for chemotherapy-induced thrombocytopenia: a new solution for an old problem
Authors: Al-Samkari Hanny 
Published: December 2022

Abstract
Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which can negatively affect oncologic outcomes. The only agent approved by the US Food and Drug Administration to manage CIT (oprelvekin) was voluntarily withdrawn from the market by the manufacturer, leaving few options for patients. Therefore, patients experiencing CIT present a significant clinical challenge in daily practice. The availability of thrombopoietin receptor agonists has led to formal clinical trials describing efficacy in CIT as well as a rather extensive body of published observational data from off-label use in this setting but no formal regulatory indications for CIT to date. The accumulated data, however, have affected National Comprehensive Cancer Network guidelines, which now recommend consideration of TPO-RA clinical trials as well as off-label use of romiplostim. This review article details the evidence to date for the management of CIT with thrombopoietin receptor agonists (TPO-RAs), discussing the efficacy data, the specific circumstances when treatment is warranted (and when it is generally unnecessary), and safety considerations. Specific recommendations regarding patient selection, initiation, dosing, titration, and discontinuation for TPO-RA therapy in CIT are given, based on published data and expert opinion where evidence is lacking.
Evidence-based management of pregnant women with sickle cell disease in high-income countries
Authors: Oteng-Ntim Eugene , Shangaris Panicos 
Published: December 2022

Abstract
Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).
Epidemiology and treatment of priapism in sickle cell disease
Authors: Idris Ibrahim M. , Burnett Arthur L. , DeBaun Michael R. 
Published: December 2022

Abstract
Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.
Thrombosis and anticoagulation: clinical issues of special importance to hematologists who practice in Asia
Authors: Boonyawat Kochawan , Angchaisuksiri Pantep 
Published: December 2022

Abstract
There are clinical issues of special importance and practice variation in the management of venous thromboembolism (VTE) and in the use of anticoagulants among hematologists who practice in Asia. In Asian-inherited thrombophilia, coagulation is disturbed due to loss-of-function mutations of protein S and protein C causing protein S and protein C deficiencies, whereas the gain-of-function factor V Leiden and prothrombin G20210A mutations are almost absent. Thrombophilia screening is not recommended in patients with VTE patients who have major provoking factors. However, it can be considered in unprovoked young patients with VTE who have a strong family history of VTE. Cancer is the most important acquired risk factor for VTE in Asians. Limited cancer screening at the initial presentation of unprovoked VTE is appropriate, especially in the elderly. Direct oral anticoagulants have been shown to have similar efficacy and reduce risk of major bleeding, including intracranial hemorrhage and bleeding requiring hospitalization, compared with warfarin. Most clinical trials evaluating therapies for treatment and prevention of VTE have included small numbers of Asian patients. Despite this lack of evidence, direct oral anticoagulants have been increasingly used in Asia for cancer-associated thrombosis. Individualized assessment of thrombotic and bleeding risks should be used for all hospitalized Asian patients when deciding on pharmacologic thromboprophylaxis. More research is needed to understand the factors that contribute to risks of VTE and anticoagulant-associated bleeding in Asian patients as these may differ from Western populations.
Anticoagulant therapy for women: implications for menstruation, pregnancy, and lactation
Authors: DeLoughery Emma , Bannow Bethany Samuelson 
Published: December 2022

Abstract
Estrogen exposure, in the setting of pregnancy, the postpartum state, combined hormonal contraceptives (CHCs), or hormone therapy use, has been clearly associated with increased rates of venous thromboembolism (VTE). Although recurrence rates are low in these settings, up to 70% of anticoagulated menstruating individuals experience abnormal or heavy menstrual bleeding (HMB), which commonly results in iron deficiency with or without anemia. Patients taking rivaroxaban appear to experience higher rates of HMB compared with those on apixaban, dabigatran, or warfarin. HMB can often be diagnosed in a single visit with a good menstrual history assessing for factors with a known association with increased or heavy bleeding, such as changing pads or tampons more often than every 2 hours, clots larger than a quarter, and iron deficiency (ferritin &lt;50  ng/mL). HMB can be managed with hormonal therapies, including those associated with VTE risk, such as CHCs and depot-medroxyprogesterone acetate (DMPA). In many cases, continuing CHCs or DMPA while a patient is therapeutically anticoagulated is reasonable, so long as the therapy is discontinued before anticoagulation is stopped. Modification of the anticoagulation regimen, such as decreasing to a prophylactic dose in the acute treatment period, is not currently recommended. For patients who are currently pregnant, low-molecular-weight heparin (LMWH) is still standard of care during pregnancy; routine monitoring of anti–factor Xa levels is not currently recommended. Warfarin or LMWH may be considered in the postpartum setting, but direct-acting oral anticoagulants are currently not recommended for lactating patients.