bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of older Hodgkin lymphoma patients
Authors: Evens Andrew M. , Carter Jordan , Loh Kah Poh , David Kevin A. 
Published: December 2019

AbstractHodgkin lymphoma (HL) in older patients, commonly defined as ≥60 years of age, is a disease for which survival rates have historically been significantly lower compared with younger patients. Older HL patients appear to have different disease biology compared with younger patients, including increased incidence of mixed cellularity histology, Epstein-Barr virus–related, and advanced-stage disease. For prognostication, several studies have documented the significance of comorbidities and functional status in older HL patients, as well as the importance of achieving initial complete remission. Collectively, selection of therapy for older HL patients should be based in part on functional status, including pretreatment assessment of activities of daily living (ADL), comorbidities, and other geriatric measures (eg, cognition, social support). Treatment of fit older HL patients should be given with curative intent, regardless of disease stage. However, attention should be paid to serious treatment-related toxicities, including risk of treatment-related mortality. Although inclusion of anthracycline therapy is important, bleomycin-containing regimens (eg, doxorubicin, bleomycin, vinblastine, dacarbazine) may lead to prohibitive pulmonary toxicity, and intensive therapies (eg, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are too toxic. Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, and dacarbazine to fit, untreated advanced-stage older HL patients was recently shown to be tolerable and highly effective. Therapy for patients who are unfit or frail because of comorbidities and/or ADL loss is less clear and should be individualized with consideration of lower-intensity therapy, such as brentuximab vedotin with or without dacarbazine. Altogether, therapy for older HL patients should be tailored based upon a geriatric assessment, and novel targeted agents should continue to be integrated into treatment paradigms.
Integrating patient-centered factors in the risk assessment of MDS
Authors: Buckstein Rena J. 
Published: December 2019

AbstractMyelodysplastic syndromes are clonal myeloid neoplasms that primarily present in older adults. Although leukemia develops in approximately 25% to 30% of individuals, the significantly shortened survival in this population is attributed more commonly to nonleukemic causes. The current prognostic scoring systems for leukemia and overall survival based on disease characteristics are becoming increasingly sophisticated and accurate with the incorporation of molecular data. The addition of patient-related factors such as comorbidity, disability, frailty, and fatigue to these new models may improve their predictive power for overall survival, treatment toxicity, and health care costs. To improve the generalizability of clinical trial results to the real world, geriatric assessment testing should become a standard of care in MDS clinical trials.
Inflammatory bone marrow microenvironment
Authors: Leimkühler Nils B. , Schneider Rebekka K. 
Published: December 2019

Abstract
Self-renewing hematopoietic stem cells and their progeny, lineage-specific downstream progenitors, maintain steady-state hematopoiesis in the bone marrow (BM). Accumulating evidence over the last few years indicates that not only primitive hematopoietic stem and progenitor cells (HSPCs), but also cells defining the microenvironment of the BM (BM niche), sense hematopoietic stress signals. They respond by directing and orchestrating hematopoiesis via not only cell-intrinsic but also cell-extrinsic mechanisms. Inflammation has many beneficial roles by activating the immune system in tissue repair and as a defense mechanism. However, chronic inflammation can have detrimental effects by stressing HSPCs, leading to cell (DNA) damage resulting in BM failure or even to leukemia. Emerging data have demonstrated that the BM microenvironment plays a significant role in the pathogenesis of hematopoietic malignancies, in particular, through disrupted inflammatory signaling, specifically in niche (microenvironmental) cells. Clonal selection in the context of microenvironmental alterations can occur in the context of toxic insults (eg, chemotherapy), not only aging but also inflammation. In this review, we summarize mechanisms that lead to an inflammatory BM microenvironment and discuss how this affects normal hematopoiesis. We pay particular attention to the process of aging, which is known to involve low-grade inflammation and is also associated with age-related clonal hematopoiesis and potentially malignant transformation.
Optimizing cord blood selection
Authors: Ruggeri Annalisa 
Published: December 2019

Abstract
Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched unrelated donor, an unrelated donor for umbilical cord blood transplantation (UCBT), or a haploidentical donor depends not only on the availability of the donor but also on patient-, disease-, and center-related factors. This paper summarizes the recent criteria in the selection of cord blood unit, including the cell dose requirement and the HLA typing for the optimal donor choice. The main strategies to optimize the results of UCBT, the conditioning regimens, and the use of antithymocyte globulin and the other platforms of graft-versus-host disease prophylaxis are discussed. The paper describes the results of UCBT in children and adults with malignant and nonmalignant diseases and the comparative analysis with other donor type and stem cell sources. Emerging strategies, focusing on the different platforms of ex vivo expansion and the new applications using cord blood stem cell, are also examined.
The growing landscape of FLT3 inhibition in AML
Authors: Smith Catherine C. 
Published: December 2019

Abstract
Midostaurin and gilteritinib are FLT3 inhibitors that have been recently approved for use in FLT3-mutant acute myeloid leukemia (AML). These approved drugs represent a new standard of care for patients with FLT3 mutations in both the first-line and salvage settings. The success of midostaurin used in combination with induction chemotherapy has prompted exploration of newer, more potent and targeted inhibitors (including gilteritinib) in the first-line setting in combination with chemotherapy. At the same time, the success of gilteritinib and other newer FLT3 inhibitors as monotherapy in the salvage setting has been tempered by the development of resistance because of diverse mechanisms. Investigational strategies that incorporate FLT3 inhibitors in combination with hypomethylating agents and as maintenance therapy after allogeneic stem cell transplantation have shown promise. Other novel combination strategies are also undergoing clinical investigation. In this article, we review the current landscape of approved and investigational FLT3 inhibitors in AML, including the current standard of care and investigational strategies.
Myeloma: next generation immunotherapy
Authors: Cohen Adam D. 
Published: December 2019

Abstract
The course of multiple myeloma (MM) from initial diagnosis to a relapsed/refractory state is characterized by acquisition of drug resistance as well as progressive immunologic dysfunction. Despite this, however, a number of novel therapies that work in part or solely via immune stimulation are in development for MM, with promising early clinical results. Several new whole-cell or multiepitope vaccine approaches are demonstrating immunologic efficacy in smoldering MM or as posttherapy consolidation, with trials ongoing to see whether this translates into delayed progression or elimination of minimal residual disease. Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibition in combination with immunomodulatory drugs demonstrated excessive toxicity in randomized trials; however, antibodies targeting PD-1/PD-L1 and other checkpoint molecules continue to be explored in combination with tumor-targeted antibodies and other T cell–directed therapies. B-cell maturation antigen (BCMA) has emerged as the next big antigen target, with multiple BCMA-specific antibody-drug conjugates (ADCs) and T cell–directed bispecific antibodies/bispecific therapeutic engagers (BiTEs) entering the clinic. In initial trials, the ADC GSK2857916 and the BiTE AMG 420 have demonstrated high response rates in relapsed/refractory patients, with depth and durability of responses that may end up rivaling chimeric antigen receptor T-cell therapies. These agents have unique toxicities that require close monitoring, but they are moving forward in larger registration studies and in combination with standard MM agents. Additional ADCs and bispecific antibodies targeting BCMA and other surface antigens (eg, CD38, CD46, CD48, FcRH5, and G protein–coupled receptor, class C group 5 member D) are moving forward in phase 1 trials and may provide even more options for MM patients.
Evidence-Based Minireview: Mortality and thrombosis in patients receiving prothrombin complex concentrates or andexanet alfa for the management of direct oral factor Xa inhibitor–associated major bleeding
Authors: Kimpton Miriam , Siegal Deborah M. 
Published: December 2019

Abstract
A 77-year-old man with atrial fibrillation and a CHA2DS2Vasc score of 6 for hypertension, age, diabetes, and previous stroke is brought to the emergency department with decreased level of consciousness. He is anticoagulated with rivaroxaban (a direct oral factor Xa inhibitor [FXaI]) and received his last dose about 4 hours before presentation. Urgent computed tomography of the head shows intracerebral hemorrhage. Because of his previous stroke, the patient’s family is concerned about treating the bleed with pharmacological agents that may increase the risk of stroke. What are the risks of thrombosis and mortality related to the use of prothrombin complex concentrates (PCCs) and andexanet alfa for patients with direct oral FXaI-associated major bleeding?
Clonal dynamics in chronic lymphocytic leukemia
Authors: Gutierrez Catherine , Wu Catherine J. 
Published: December 2019

Abstract
Chronic lymphocytic leukemia has a highly variable disease course across patients, thought to be driven by the vast inter- and intrapatient molecular heterogeneity described in several large-scale DNA-sequencing studies conducted over the past decade. Although the last 5 years have seen a dramatic shift in the therapeutic landscape for chronic lymphocytic leukemia, including the regulatory approval of several potent targeted agents (ie, idelalisib, ibrutinib, venetoclax), the vast majority of patients still inevitably experience disease recurrence or persistence. Recent genome-wide sequencing approaches have helped to identify subclonal populations within tumors that demonstrate a broad spectrum of somatic mutations, diverse levels of response to therapy, patterns of repopulation, and growth kinetics. Understanding the impact of genetic, epigenetic, and transcriptomic features on clonal growth dynamics and drug response will be an important step toward the selection and timing of therapy.
Delivering intensive therapies to older adults with hematologic malignancies: strategies to personalize care
Authors: Olin Rebecca L. 
Published: December 2019

AbstractIntensive therapies are often medically indicated for older adults with hematologic malignancies. These may include induction chemotherapy for acute myeloid leukemia (AML), as well as autologous hematopoietic cell transplant (autoHCT) and allogeneic hematopoietic cell transplant (alloHCT). However, it is not always clear how to best deliver these therapies, in terms of determining treatment eligibility, as well as adjusting or adding supportive measures to the treatment plan to maximize successful outcomes. Beyond performance status and presence of comorbidities, comprehensive geriatric assessment and individual geriatric metrics have increasingly been used to prognosticate in these settings and may offer the best approach to personalizing therapy. In the setting of AML induction, evidence supports the use of measures of physical function as independent predictors of survival. For patients undergoing alloHCT, functional status, as measured by instrumental activities of daily living (IADL) and gait speed, may be an important pretransplant assessment. IADL has also been associated with post-autoHCT morbidity and mortality. Current best practice includes assessment of relevant geriatric metrics prior to intensive therapy, and work is ongoing to develop complementary interventions.
Serum amyloid a protein as a potential biomarker in predicting acute onset and association with in-hospital death in acute aortic dissection
Authors: He Yuchen , Ma Changcheng , Xing Jia , Wang Shiyue , Ji Chao , Han Yanshuo , Zhang Jian 
Published: December 2019

AbstractBackgroundAcute aortic dissection (AAD) is a life-threatening disorder in vascular surgery with a high early mortality. Serum amyloid A (SAA) is a kind of acute-phase protein with a rapid diagnostic value in other diseases. However, the researches on the performance of SAA for the diagnosis of AAD is still lacking. This retrospective study aimed to evaluate the SAA levels and further explore its potential diagnostic role in AAD patients.MethodsSAA levels were measured by enzyme-linked immunosorbent assay (ELISA) in 63 controls and 87 AAD patients. Laboratory examinations were also performed. And relative clinical information was collected from participants included in this study.ResultsSAA levels were significantly higher in AAD patients than those in healthy controls. SAA levels were independently associated with the risk of AAD. There was a positive significant correlation between SAA and C reactive protein (R = 0.442, andP = 0.001). Based on receiver-operating characteristic (ROC) analysis, the area under the curve (AUC) of SAA for the diagnosis of AAD were 0.942 with optimal cut-off points of 0.427 mg/L. For in-hospital mortality, the AUC of SAA were 0.732 with optimal cut-off points of 0.500 mg/L. According to logistic regression analysis, higher SAA levels represent a higher risk of in-hospital mortality (OR = 1.25; 95%CI: 1.07–1.47;P = 0.005).ConclusionOur findings demonstrated that SAA levels were significantly enhanced in AAD. SAA was closely correlated with inflammatory parameters and coagulation-related parameters in AAD. Furthermore, SAA could be a potential bio-marker for identifying AAD in the early diagnosis. Finally, SAA > 5.0 mg/L are independently related to AAD in-hospital mortality.
Existence of positive ground state solutions of Schrödinger–Poisson system involving negative nonlocal term and critical exponent on bounded domain
Authors: Zheng Wenxuan , Gan Wenbin , Liu Shibo 
Published: December 2019

AbstractIn this paper, we prove the existence of positive ground state solutions of the Schrödinger–Poisson system involving a negative nonlocal term and critical exponent on a bounded domain. The main tools are the mountain pass theorem and the concentration compactness principle.
On the existence of positive solutions for generalized fractional boundary value problems
Authors: Seemab Arjumand , Ur Rehman Mujeeb , Alzabut Jehad , Hamdi Abdelouahed 
Published: December 2019

AbstractThe existence of positive solutions is established for boundary value problems defined within generalized Riemann–Liouville and Caputo fractional operators. Our approach is based on utilizing the technique of fixed point theorems. For the sake of converting the proposed problems into integral equations, we construct Green functions and study their properties for three different types of boundary value problems. Examples are presented to demonstrate the validity of theoretical findings.
Urinary Phytoestrogens and Relationship to Menstrual Cycle Length and Variability Among Healthy, Eumenorrheic Women
Authors: Levine Lindsay D , Kim Keewan , Purdue-Smithe Alexandra , Sundaram Rajeshwari , Schisterman Enrique F , Connell Matthew , Devilbiss Elizabeth A , Alkhalaf Zeina , Radoc Jeannie G , Buck Louis Germaine M , Mumford Sunni L 
Published: December 2019

Abstract

Context
Phytoestrogens may influence fecundability, although biological mechanisms remain elusive. Since it is hypothesized that phytoestrogens may act through influencing hormone levels, we investigated associations between phytoestrogens and menstrual cycle length, a proxy for the hormonal milieu, in healthy women attempting pregnancy.

Design
A population-based prospective cohort of 326 women ages 18 to 40 with self-reported cycles of 21 to 42 days were followed until pregnancy or for 12 months of attempting pregnancy.

Methods
Urinary genistein, daidzein, O-desmethylangolensin, equol, enterodiol, and enterolactone were measured upon enrollment. Cycle length was determined from fertility monitors and daily journals. Linear mixed models assessed associations with continuous cycle length and were weighted by the inverse number of observed cycles. Logistic regression models assessed menstrual regularity (standard deviation &gt; 75th vs ≤ 75th percentile). Models were adjusted for age, body mass index, race, creatinine, exercise, supplements, lipids, lead, cadmium, cotinine, parity, alcohol, and other phytoestrogens.

Results
Individual phytoestrogens were not associated with cycle length, although total phytoestrogens were associated with shorter cycles (−0.042 days; 95% confidence interval [CI], −0.080 to −0.003, per 10% increase). Each 1 nmol/L increase in enterolactone (odds ratio [OR] 0.88; 95% CI, 0.79-0.97) and total lignans (OR 0.85; 95% CI, 0.76-0.95) was associated with reduced irregularity, and each 1 nmol/L increase in genistein with irregularity (OR 1.19; 95% CI, 1.02-1.38).

Conclusion
Phytoestrogens were not meaningfully associated with cycle length but may be associated with menstrual regularity, among women with self-reported regular cycles. These results highlight differences between isoflavones and lignans and are reassuring for women attempting pregnancy.
Acute Apnea Does Not Improve 3-km Cycling Time Trial Performance
Authors: BOUTEN JANNE , COLOSIO ALESSANDRO L. , BOURGOIS GIL , LOOTENS LEEN , VAN EENOO PETER , BOURGOIS JAN G. , BOONE JAN 
Published: December 2019

ABSTRACT

Purpose
Intense exercise evokes a spleen contraction releasing red blood cells into blood circulation. The same mechanism is found after acute apnea, increasing hemoglobin concentration ([Hb]) by 2% to 5%. The aim of this study was twofold: [1] to identify the optimal apnea modalities to acutely increase [Hb] and [2] use these modalities to examine whether prerace apnea can improve a 3-km time trial (TT).

Methods
In part 1, 11 male subjects performed 12 different apnea protocols based on three modalities: mode, frequency, and intensity. Venous blood samples for [Hb] were collected before, immediately, and 5 min after each protocol. In part 2, 12 recreationally active subjects performed 3-km cycling TT in three different conditions: apnea, control, and placebo, after a 10-min warm-up. Power output, HR, and oxygen uptake (V˙O2) were continuously measured. Venous [Hb] was sampled at baseline, after warm-up, and before TT. Additionally, these subjects performed constant cycling at Δ25 (25% between gas exchange threshold and V˙O2 max) in two conditions (control and apnea) to determine V˙O2 kinetics.

Results
Although including one single apnea in the warming up evoked a positive change in [Hb] pattern (P = 0.049) and one single apnea seemed to improve V˙O2 kinetics in constant submaximal cycling (τ: P = 0.060, mean response time: P = 0.064), performance during the 3-km TT did not differ between conditions (P = 0.840; apnea, 264.8 ± 14.1 s; control, 263.9 ± 12.9 s, placebo, 264.0 ± 15.8 s). Average normalized power output (P = 0.584) and V˙O2, HR, and lactate did not differ either (P > 0.05).

Conclusions
These results suggest that potential effects of apnea, that is, speeding of V˙O2 kinetics through a transient increase in [Hb], are overruled by a warming-up protocol.
O LAZER: UM ASPECTO A SER CONSIDERADO NA QUALIDADE DE VIDA NO TRABALHO
Authors: Araújo Pessoa Raimundo Wellington , Do Nascimento Eandra Fernandes 
Published: December 2019

Este artigo analisa as contribuições do lazer na
vida individual e organizacional dos docentes e
para a instituição Cefet/CE. O objetivo foi proporcionar
uma discussão política na instituição sobre
a temática – o lazer e o trabalho. Contou-se com
a participação de 63 docentes da instituição
mencionada, utilizando-se o software Sphinx para
a tabulação, apresentação e discussão dos
principais resultados do estudo. Segundo os docentes,
o lazer nas organizações é capaz de contribuir
significativamente para a qualidade de vida
do indivíduo no trabalho, além de beneficiar diretamente
a própria organização.
Palavras-chave: qualidade de vida no trabalho
– QVT, lazer, responsabilidade social empresarial
– RSE, tecnologia, organização.
QUALIDADE DE VIDA E RESILIÊNCIA EM PACIENTES PÓS-OPERATÓRIO DE CIRURGIA CARDÍACA
Authors: Giaretta Davisson Gonçalves , Vigueras Evelyn Soledad Reyes , Ruschel Patricia Pereira , Souza Camila 
Published: December 2019

Em âmbito mundial, as doenças crônicas não transmissíveis são responsáveis pelas principais causas de morte e incapacidade. Entre essas, encontram-se as de maior importância para a saúde pública, as doenças cardiovasculares. Tendo em vista que a capacidade de resiliência e a Qualidade de Vida são construtos relevantes a serem considerados em pacientes internados em ambiente hospitalar, o presente estudo objetiva verificar como se apresentam esses conceitos em indivíduos que realizaram cirurgia de revascularização do miocárdio e/ou cirurgia de válvula em uma instituição hospitalar. Para tanto, foi realizada uma pesquisa transversal na qual foram aplicados um questionário sociodemográfico, o questionário de qualidade de vida SF-12 e uma escala de resiliência. Participaram desse estudo 37 pacientes, maioria do sexo masculino, submetidos à primeira intervenção cirúrgica. Observou-se uma média de 37,3 pontos (dp ±4,4) e 43,3 (dp±7,6) nos componentes físico e mental da escala de Qualidade de Vida SF-12, respectivamente. Já a escala de Resiliência aplicada revelou média de 131 (dp±31). Verificou-se uma correlação direta fraca entre o componente físico da qualidade de vida com o escore de resiliência (r=0,386, p=0,02), o que sugere tendência positiva entre tais conceitos.