bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Task that Exceeded the Technology: Early Applications of the Computer to the Lunar Three-body Problem
Authors: Olley Allan 
Published: October 2019

Abstract
The lunar Three-Body problem is a famously intractable problem of Newtonian mechanics. The demand for accurate predictions of lunar motion led to practical approximate solutions of great complexity, constituted by trigonometric series with hundreds of terms. Such considerations meant there was demand for high speed machine computation from astronomers during the earliest stages of computer development. One early innovator in this regard was Wallace J. Eckert, a Columbia University professor of astronomer and IBM researcher. His work illustrates some interesting features of the interaction between computers and astronomy.
Structural biology of the TGFβ family
Authors: Goebel Erich J , Hart Kaitlin N , McCoy Jason C , Thompson Thomas B 
Published: October 2019

The transforming growth factor beta (TGFβ) signaling pathway orchestrates a wide breadth of biological processes, ranging from bone development to reproduction. Given this, there has been a surge of interest from the drug development industry to modulate the pathway – at several points. This review discusses and provides additional context for several layers of the TGFβ signaling pathway from a structural biology viewpoint. The combination of structural techniques coupled with biophysical studies has provided a foundational knowledge of the molecular mechanisms governing this high impact, ubiquitous pathway, underlying many of the current therapeutic pursuits. This work seeks to consolidate TGFβ-related structural knowledge and educate other researchers of the apparent gaps that still prove elusive. We aim to highlight the importance of these structures and provide the contextual information to understand the contribution to the field, with the hope of advancing the discussion and exploration of the TGFβ signaling pathway. Impact statement The transforming growth factor beta (TGFβ) signaling pathway is a multifacetted and highly regulated pathway, forming the underpinnings of a large range of biological processes. Here, we review and consolidate the key steps in TGFβ signaling using literature rooted in structural and biophysical techniques, with a focus on molecular mechanisms and gaps in knowledge. From extracellular regulation to ligand–receptor interactions and intracellular activation cascades, we hope to provide an introductory base for understanding the TGFβ pathway as a whole.
Managing Indolent Lymphomas in Relapse
Authors: Cabanillas Fernando , Horning Sandra , Kaminski Mark , Champlin Richard 
Published: October 2019

Abstract
The front-line management of stage IV indolent non-Hodgkin's lymphoma has ranged from the watch-and-wait approach to intensive experimental regimens such as high-dose chemotherapy and bone marrow transplant. With this broad spectrum of regimens to choose from the decision has become a challenging exercise for both patients and oncologists. With the recent introduction of new agents such as rituximab, fludarabine, and combinations based on these, the management of relapsed cases can be similarly confusing. More aggressive approaches such as high-dose chemotherapy with autologous bone marrow transplant and more recently allogeneic bone marrow transplant have also been used. Recently the technique of “mini-allo transplants” has been introduced. It utilizes a less myelosuppressive conditioning chemotherapy regimen based on fludarabine which is immunosuppressive enough to allow engraftment of the donor marrow. Since it is less myelotoxic it is better tolerated, and this has allowed us to significantly extend the age cut-off for allogeneic transplants. All these advances provide us with a more extensive armamentarium, but at the same time they confront physicians with new challenges in choosing from a large and continuously growing therapeutic menu.
In this review of the alternative therapies a panel of three expert hemato-oncologists each discuss their approach to the management of a 49-year-old patient with a relapsed indolent follicular lymphoma. Dr. Horning discusses the traditional alternatives available for this patient such as standard chemotherapy combinations or the watch-and-wait approach in Section I. In Section II, Dr. Kaminski reviews the different therapeutic monoclonal antibody options such as rituximab, Bexxar (Iodine-labeled anti-CD20) and Ytrium-labeled anti-CD20 antibody. Allogeneic transplants are increasingly more popular for the treatment of indolent lymphomas because they can provide an immune-mediated graft-versus-lymphoma effect. In Section III, Dr. Richard Champlin reviews various transplant options including autologous, allogeneic and mini-allogeneic transplants.
Viral Disease in Hematology
Authors: Franchini Genoveffa , Ambinder Richard F. , Barry Michèle 
Published: October 2019

AbstractAs part of the international outreach of the American Society of Hematology, this review addresses some aspects of the genetics, biology, epidemiology, and clinical relevance of viruses that cause a variety of hematopoietic disorders in human populations. The viruses described here have a different pattern of geographical distribution, and the disease manifestations may vary according to environmental and/or genetic characteristics of the host. Epstein-Barr virus, a linear double-stranded DNA virus (herpesvirus), and the human T-cell leukemia virus, a retrovirus with a single-stranded diploid RNA genome, are associated among other diseases with lymphoma and leukemia/lymphoma, respectively. Both viruses cause a lifelong infection, but only a small percentage of infected individuals develop hematopoietic neoplasms. Epidemiological data suggest that the time of infection may be important in determining disease outcome in both HTLV-I and EBV infection. The pathogenic mechanisms used by these viruses are of most interest since they may recapitulate growth dysregulation steps also occurring in other hematopoietic malignancies.In Section I Dr. Franchini reviews the biology, genetics and diseases associated with HTLV-I and HTLV-II. In Section II, Dr. Ambinder reviews the biology of EBV infection and its relationship to the pathogenesis of Hodgkin's disease and other malignancies.In Section III, Dr. Barry reviews the viral hemorrhagic fevers caused by RNA viruses such as Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae, which can lead to acute syndromes that can be fatal. However, prompt diagnosis is key for patient management as well as for limiting their spread to others. These syndromes have become the focus of public concern and represent not only a clinical challenge, since in most cases no specific antiviral treatment is available, but also a challenge for future basic research on their biology and pathogenesis since little is known at present.
Ham-Wasserman Lecture
Authors: Wang Zhen-yi 
Published: October 2019

Abstract
Conventional treatment of acute leukemia involves the use of cytotoxic agents (chemotherapy), but other strategies have been explored. All-trans retinoic acid (ATRA) and arsenic have clearly been effective in the treatment of acute promyelocytic leukemia (APL), which creates the possibility that other types of acute leukemia can be conquered by selectively inducing differentiation and/or apoptosis. A great number of investigations have been performed to elucidate the mechanisms and search for effective agents in the treatment of other types of acute leukemia by these new strategies. Progress at the molecular level has been achieved in explaining the mechanisms of action of ATRA and arsenic compounds, and several new agents have emerged, although their clinical effectiveness remains to be confirmed. Mechanism-/gene-based targeted therapy and a combination of different strategies will improve the treatment of acute leukemia.
Comprehensive Management of the CLL Patient: A Holistic Approach
Authors: Shanafelt Tait D. , Kay Neil E. 
Published: October 2019

Abstract
The current management of B-chronic lymphocytic leukemia (CLL) is no longer straightforward for the practicing hematologist. Rapid advances in diagnostic precision, methods of predicting prognosis, understanding of natural history of CLL, recognition of clinical complications, clarification of the quality of life (QOL) issues facing the CLL patient, and the exciting array of novel treatment approaches have made the care of the CLL patient more demanding. This review is focused on summarizing these advances in order to provide a framework for integrating this knowledge into routine hematologic practice.
Monitoring after successful therapy for chronic myeloid leukemia
Authors: Branford Susan 
Published: October 2019

Abstract
Monitoring response to therapy for patients with chronic myeloid leukemia using an effective strategy is fundamental for achieving optimal patient outcomes. It will allow the initiation of timely therapeutic intervention for patients with a suboptimal response or kinase inhibitor therapy failure. Evidence is mounting that reaching molecular targets early in therapy is as important as the initial hematologic and cytogenetic response for the identification of patients who may have a poorer outcome. When the molecular target of a major molecular response is achieved at 18 months, patients reach a safe haven where loss of response is rare. However, this benefit is dependent on continuous drug adherence in most patients. As some patients reach their second decade of successful imatinib therapy, how long will frequent response monitoring be necessary? Assuming that very late relapse will be extremely rare for responding patients remaining on kinase inhibitor therapy, there are reasons for maintaining a regular molecular monitoring frequency, including monitoring adherence assessment and confirming sustained undetectable BCR-ABL1 for those considering a discontinuation trial and for late molecular recurrence in patients who maintain response after treatment discontinuation.
Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy
Authors: Meyer Ralph M. , Hoppe Richard T. 
Published: October 2019

Abstract
The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.
Immunoconjugates and new molecular targets in hairy cell leukemia
Authors: Kreitman Robert J. 
Published: October 2019

Abstract
Hairy cell leukemia (HCL) is a B-cell malignancy that in its classic form is exquisitely sensitive to single-agent purine analog therapy, but that is associated in many patients with late relapse and eventual purine analog resistance. Minimal residual disease, which is present in most patients achieving complete remission with purine analogs, retains Ags that are ideal for targeted therapy. Rituximab, which targets CD20, is active as a single agent, particularly if combined with purine analogs. Recombinant immunotoxins targeting either CD25 or CD22 and containing truncated Pseudomonas exotoxin have achieved major responses in relapsed/refractory HCL. Moxetumomab pasudotox in phase 1 testing achieved responses in 86% of such patients (complete in 46%) without dose limiting toxicity and often without MRD. Soluble CD22 has been used for improved detection and monitoring of HCL, particularly the poor-prognosis variant that lacks CD25. Ig rearrangements unique for each HCL patient have been cloned, sequenced, and followed by real-time quantitative PCR using sequence-specific reagents. Analysis of these rearrangements has identified an unmutated IGVH4-34–expressing poor-prognosis variant with immunophenotypic characteristics of either classic or variant HCL. The BRAF V600E mutation, reported in 50% of melanomas, is present in > 85% of HCL cases that are both classic and express rearrangements other than IGVH4-34, making HCL a potential target for specific inhibitors of BRAF V600E. Additional targets are being defined in both classic and variant HCL, which should improve both detection and therapy.
THE VALUE OF PENICILLIN IN THE TREATMENT OF AGRANULOCYTOSIS CAUSED BY THIOURACIL
Authors: TYSON MARY CATHERINE , VOGEL PETER , ROSENTHAL NATHAN 
Published: October 2019

Abstract
Thiouracil has been found to be an effective drug in the treatment of hyperthyroidism. Agranulocytosis following its use occurred in nine cases, four of which terminated fatally. In five others a complete and rapid recovery took place following penicillin therapy. The latter drug is believed to be ideal for all cases of agranulocytosis, and especially those in which chemotherapy has been used and may have been responsible for the condition. Thus far we have not seen any report of any untoward effect on the hemopoietic system from the use of penicillin.
The use of antibacterial agents for the treatment of agranulocytosis was suggested by Dameshek and Wolfson21 in 1942. It was believed by these authors that patients with agranulocytosis died not of the leukopenia per se but of the sepsis which developed secondarily to the lack of granulocytes. Two very severe cases of aminopyrine agranulocytosis treated with sulfathiazole made complete recoveries. For the treatment of sulfonamide agranulocytosis, it was suggested that a preparation differing from that which had already been used be given. With the discovery of penicillin, and its complete lack of possible deleterious effect on the bone marrow, its use was suggested by Dameshek17 (1944). A report on the beneficial effects of this medication in a case of sulfonamide agranulocytosis was later reported by Dameshek and Knowlton18 and similar cases by Sprague and Ferguson19 and by Meredith and Fink.20
Since sulfonamides may cause further toxic effect on the bone marrow, we feel that their use should be avoided in the treatment of agranulocytosis, especially where a history of previous use is obtained. We do not agree with others21, 22 who continue the use of sulfonamides in the treatment of leukopenia or agranulocytosis where these very drugs may have been responsible for the condition. It would seem better judgment to use penicillin, which by combating the bacterial invasion of the body and the consequent toxemia enables the patient to survive until the bone marrow cells regenerate.
ANTI-ANEMIC PROPERTIES OF THYMINE
Authors: SPIES TOM D. , FROMMEYER WALTER B. , VILTER CARL F. , ENGLISH ANN 
Published: October 2019

Abstract
Three patients with Addisonian pernicious anemia were selected, hospitalized and given a diet devoid of meat and meat products. After baseline hematological studies were made and checked repeatedly, daily large doses of thymine were given orally.
The clinical and hematological improvement in these three patients was in every way similar to that which follows the administration of folic acid to patients with pernicious anemia in relapse. The exact mode of action of thymine is obscure, but it is possible that folic acid may act as an enzyme or co-enzyme in the synthesis of thymine or a thymine-like compound. Such synthesis may take place in the gastro-intestinal tract. The present findings indicate that thymine has anti-anemic properties and a profound effect on the general metabolism of patients with Addisonian pernicious anemia in relapse.
Histochemical and Quantitative Studies of the In Vitro Dehydrogenase Activity of Spleen in Hypersplenism
Authors: BLACK MAURICE M. , PRESTON JOSEPH A. , SPEER FRANCIS D. , BRENOWITZ PHYLLIS 
Published: October 2019

Abstract
Tetrazolium chloride was used to visualize the in vitro dehydrogenase activity of splenic tissues from cases with and without hypersplenism. In addition, quantitative measurements of such activity were made in the presence and absence of fluoride, malonate and azide. The data indicate that spleen slices from cases of hypersplenism differed from the controls and were characterized by (a) increased endogenous dehydrogenase activity of the lymphocytes, particularly around the follicles, (b) a decreased azide stimulation in those cases having an initial thrombocytopenia which responded to splenectomy, and (c) a decreased fluoride stimulation in those cases having an initial leukopenia which responded to splenectomy.
Routine histological studies confirmed other reports that a constant structural feature of the spleen in hypersplenism is a perifollicular lymphocytic rimming.
Myeloblastic Leukemia Preceded by Prolonged Hematologic Disorder
Authors: WILLIAMS MARJORIE J. 
Published: October 2019

Abstract
A case with a prolonged period of blood disorder preceding the terminal development of myeloblastic leukemia is reported in some detail. The preleukemic period was characterized by anemia, neutropenia and thrombocytopenia. It extended over a period of almost nine years but was punctuated by a period of remission lasting four and one half years. In the initial phase, the marrow was hypoplastic but during the later stages, it was hyperplastic.
Brief reference is made to somewhat similar cases that have been recorded and to the ideas expressed by the authors of these reports.
It is suggested that further investigation is needed to determine whether the initial blood disease occurring in such cases is irrevocably linked to the subsequent leukemia.
Constitutional Anemia (Fanconi’s Syndrome) and Leukemia in Two Brothers
Authors: COWDELL R. H. , PHIZACKERLEY P. J. R. , PYKE D. A. 
Published: October 2019

Abstract
Two brothers physically very alike became ill in their third decade, one with severe bone marrow hypoplasia and the other with acute leukemia. Both died and the autopsy findings are described.
The two shared certain congenital defects, notably short stature with small heads, cutaneous pigmentation, pituitary and genital hypoplasia, and deformity of the thumbs. The brother with hypoplastic anemia also had aortic hypoplasia and his left kidney was absent.
No previous report has been discovered of the association of Fanconi’s syndrome (of bone marrow hypoplasia with congenital defects) and leukemia with similar congenital defects in brothers. In two reports of leukemia affecting cousins of patients with Fanconi's syndrome, the leukemic cousins were without congenital defects.
An Evaluation of Paraffin Sections of Aspirated Bone Marrow in Malignant Lymphomas
Authors: PETTET JACQUELINE D. , PEASE GERTRUDE L. , COOPER TALBERT 
Published: October 2019

Abstract
Examination of serial paraffin sections of bone-marrow aspirations has increased the known incidence of marrow involvement in malignant lymphomas. The results of this study can be seen in the table. In the 72 cases reviewed here, lesions compatible with malignant lymphoma were seen in paraffin sections in 22 cases. In 12 cases this was the only material available for diagnosis at the time. In an additional seven cases paraffin sections were considered suggestive of malignant lymphoma and in five of these a diagnosis could be made on the basis of examination of both smear and paraffin section. This procedure is particularly helpful in Hodgkin’s disease and reticulum cell sarcoma, where marrow smears are only rarely diagnostic.
In general, the patients in whom lesions were found in the bone marrow tended to have more advanced disease than those in whom lesions were not found, and abnormalities in the peripheral blood were more common. This was especially true of patients with Hodgkin’s disease, less so in those with reticulum cell sarcoma. Patients with lymphosarcoma, lymphocytic type, did not show this difference, either in the extent of the disease or in findings on examination of peripheral blood.
Diagnosis was most difficult in patients who had lymphocytic lymphosarcoma, since it was occasionally difficult to distinguish between the benign aggregations of lymphocytes which are not infrequently found in a large number of unrelated conditions and those aggregations which represented malignancy. Differentiation was made on the basis of number of aggregations, degree of circumscription, presence or absence of reaction centers and the cytologic appearance of the cells. Examination of the smears of the marrow is most helpful in these cases.
Seven patients in this series (9.7 per cent) had granulomatous lesions in the marrow. In five of these the final diagnosis was Hodgkin’s disease, in one reticulum cell sarcoma and in one follicular lymphoma. Although these lesions were not specific, the incidence is high enough to make the finding of a granuloma of some significance in any patient suspected of having malignant lymphoma.
The importance of thorough examination of any material obtained in an apparent dry tap and the value of repeated marrow-examinations is emphasized by three cases in this series.
Since in many cases diagnostic lesions are found in only one portion of the material, examination of only one section of the paraffin sections of aspirated bone marrow is not sufficient for proper evaluation. This fact is emphasized by the greater incidence of positive findings in this report than in that of Cooper and Watkins.
Studies of bone marrow should be particularly helpful in instances in which the diagnosis of malignant lymphoma is suggested by clinical features but cannot be proved by biopsy of peripheral nodes or other readily accessible tissue.