bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo and Functional Imaging in Developmental Physiology
Authors: Brainerd Elizabeth L , Hale Melina E 
Published: November 2023

Abstract
Recent advances in functional and in vivo imaging provide powerful tools for the study of developmental physiology. Techniques such as confocal microscopy, magnetic resonance microscopy (MRM), microtomography (microCT), and ultrasound microscopy allow developmental physiologists to collect high-resolution images of living embryos and larvae. In vivo imaging techniques can be applied repeatedly over time, allowing longitudinal studies of development in the same individual (Fenster 2002).
Introduction
Authors: Emanuel Ezekiel J , Grady Christine , Crouch Robert A , Lie Reidar K , Miller Franklin G , Wendler David 
Published: November 2023

Abstract
The last decade has witnessed tremendous controversy surrounding the ethics of clinical research. There have been disagreements over the use of placebos in developing countries when there are effective but costly therapies available in more developed countries; there has been uncertainty over researchers’ obligations to participants once trials are complete; there have been disagreements over research with children and mentally incapacitated patients; and there is widespread condemnation of academic researchers’ financial conflicts of interest. The deaths of Jesse Gelsinger and Ellen Roche while both were enrolled in clinical research, and the suspension of clinical research at Duke, Johns Hopkins, and other major research institutions has created concern over the safety of clinical research. Suppression of data on adverse drug events by pharmaceutical corporations has created concern over the integrity of both researchers and the research enterprise. Probably nothing signifies this controversy and its public nature better than the April 22, 2002, issue of Time magazine, whose cover depicted a human being in a hospital gown inside a cage, under a caption that read, “How Medical Testing Has Turned Millions of Us into . . . Human Guinea Pigs”
The Imperial Japanese Experiments in China
Authors: Tsuchiya Takashi 
Published: November 2023

Abstract
Between 1933 and the end of World War II, Japanese researchers—mostly under the aegis of the Japanese Imperial Army—killed thousands of humans in medical experiments. The experiments, which included vivisection, fell broadly into three categories: explanation of diseases, development of therapies, and research into and development of biological and chemical warfare. Most of the human experimentation took place in Japaneseoccupied Manchuria and China, although the Japanese army also operated experimental centers in Southeast Asia and on the main Japanese islands. Most of the victims were Manchurian or Chinese criminals, political prisoners, or prisoners of war, although some Allied prisoners of war—such as Americans, Australians, and New Zealanders—were also used and killed in these experiments.
The Salk Polio Vaccine Field Trial of 1954
Authors: Meldrum Marcia L 
Published: November 2023

Abstract
In the first half of the 20th century, poliomyelitis meant long summers of fear and suffering for families living in the United States. The disease, hardly recognized before the 20th century, had become a significant danger to children and to general quality of life, especially in the post–World War II era. The epidemiological work of John Paul, Thomas Francis, Dorothy Horstmann, and others had only recently shown that the apparent increased danger of the infection was directly related to modern American affluence. In less prosperous, less sanitized times and places, babies usually contracted the polio, or infantile paralysis, virus early in life, while still protected by their mother’s immune system. In the postwar United States, a whole generation was growing up healthy, well nourished and often bottle-fed, protected from infection until they began nursery school. But these practices left them defenseless against polio virus. Although the incidence of the paralytic form of the disease was quite low, it was disproportionately high among young, middle-class children. As prosperity increased, so did crippling and death; for Americans, polio took on the face of a fearful plague. In 1948, polio incidence had risen to 19 per 100,000 people in the population, the highest since the horrible epidemic of 1916. In 1949, it rose again to 28.3 per 100,000.
The Nature, Scope, and Justification of Clinical Research What Is Research? Who Is a Subject?
Authors: Levine Robert J 
Published: November 2023

Abstract
This chapter begins with an examination of the nature and scope of medical practice. As we shall see, there are several alternative visions of the nature and scope of medical practice. Clinical research is a subset of a larger category called biomedical research, which has as its purpose the enhancement or improvement of medical practice. We cannot begin to consider the nature, scope, and justification of clinical research until we have a clear understanding of the enterprise it is intended to serve. This chapter also includes a review of the definitions of research and human subject that have been developed in the context of developing policy to safeguard the rights and welfare of human research subjects.
The Ethics of Placebo-Controlled Trials
Authors: Miller Franklin G 
Published: November 2023

Abstract
Randomized clinical trials test the efficacy of experimental or existing treatments by comparing them with a control intervention. The control group may receive a placebo disguised to appear indistinguishable from the treatment under investigation or standard treatment. Placebo-controlled trials have generated considerable ethical controversy and debate when they are used to evaluate treatments for patients with particular disorders despite the availability of proven effective treatment. Critics of placebocontrolled trials in these circumstances have argued that the use of placebos in the control group rather than proven effective treatment is unethical. It is alleged to violate the therapeutic obligation of physicians, by randomizing patients to an intervention known to be inferior to standard treatment. These placebocontrolled trials contravene the principle of “clinical equipoise,” which is widely held to be an ethical foundation for the design and conduct of randomized clinical trials. Defenders of such placebo-controlled trials have contended that placebo controls are ethically justifiable in these circumstances provided that sound methodological reasons support their use and that they do not expose research participants to excessive risks of harm. At the heart of the debate are fundamental issues concerning the nature and ethical justification of clinical research.
Challenge Experiments
Authors: Miller Franklin G , Rosenstein Donald L 
Published: November 2023

Abstract
Challenge experiments are among the most controversial forms of clinical research. They involve experimental interventions aimed at perturbing the biological or psychological functioning of human beings for the purpose of developing scientific knowledge about diseases and their treatment. Challenge agents include drugs, inhaled or ingested substances, physical or psychological stimuli, and pathogens. No precise definition of challenge experiments has been developed, such that it is not always clear whether a particular investigation falls into this category. These studies characteristically offer no prospect of medical benefit for the enrolled participants. In this chapter we concentrate on two types of challenge studies: symptom-provoking experiments with psychiatric patients and infection-inducing experiments with healthy volunteers. Psychiatric symptom-provoking studies include administering challenge procedures known to evoke panic attacks, depressive symptoms, obsessions, and psychotic experiences. Infection challenge experiments have induced diseases such as cholera, malaria, influenza, shigella, and E. coli.
Phase I Oncology Research
Authors: Agrawal Manish , Emanuel Ezekiel J 
Published: November 2023

Abstract
Despite substantial improvements in treatments for individual cancers, 50% of people diagnosed with cancer—more than 550,000 per year in the United States—still die from it. As the average age of developed country populations rises, both the absolute number and proportion of deaths from cancer will also rise in those countries. Therefore, research into finding novel therapies for most cancers remains an important priority. The process of translating basic research into clinical applications that could potentially lead to larger clinical trials and eventually to effective cancer therapies begins with Phase I oncology studies (see Table 33.1). Classic Phase I oncology studies are cohort studies in which patients are treated with increasing doses of investigational agents to learn about toxicities, maximum tolerated dose, and the pharmacokinetics of the agents, thereby permitting planning for Phase II studies of efficacy.
Research Involving Women
Authors: Denny Colleen , Grady Christine 
Published: November 2023

Abstract
As of July 2005, the U.S. Census Bureau estimated that there were approximately 150,410,658 women living in the United States, a little less than 51% of the total population. This percentage is not a new phenomenon; due to a greater death rate in men of a number of age groups, women have long been the majority sex in the United States. Yet despite this majority, women have long found themselves excluded or at least underrepresented in many areas of society, including academia, the business sector, and the political arena. What has recently come to be recognized, however, is that women have long been underserved in the context of modern medicine as well. Since the United States began seriously engaging in clinical research in the mid-20th century, views on women as participants and as a source of valuable research questions have changed enormously, fluctuating from a sort of indifference, to active exclusion, to today’s state of deliberate inclusion. This oscillation is in large part attributable to the unique ethical dilemmas that surround the participation of female subjects in clinical research: Not only might women in general be subject to particular pressures and risks due to their status as a historically oppressed population, but their biological capacity to become pregnant and gestate may also put both them and future human beings at risk of dignitary and=or physical harm. Balancing these unspecified risks with the desire to enable research participation in hopes of more fairly distributing research’s benefits has been a difficult and ongoing struggle.
Research With Identifiable and Targeted Communities
Authors: Foster Morris W , Sharp Richard R 
Published: November 2023

Abstract
Most research studies that involve human participants target specific categories of people through inclusion=exclusion criteria. Some of those targeted categories are defined by scientific criteria, such as people with a diagnosis of a particular disease or people without the disease who can serve as “healthy” controls. Other targeted categories are defined by demographic criteria, used either as proxies for specific life experiences, exposures, or incidence rates or as measures of inclusiveness. As an example of the latter, even studies that recruit members of the “general public” often use social identities such as gender, race, or ethnicity to ensure that a sample resembles the makeup of that larger general population.
A History of Informed Consent in Clinical Research
Authors: Moreno Erika Blacksher Jonathan D 
Published: November 2023

Abstract
This chapter traces the evolution of informed consent as a concept and practice in biomedical research, attending to the evolving content and justification of consent, and when possible, the actual consent practices of researchers. We include the predecessors of informed consent, some of which bear only a faint resemblance to the concept and practice as we understand them today. These precursors lack what are now considered essential features of informed consent, having evolved from mere acquiescence to become informed, comprehending, and voluntary. As there was no clear policy delineation between medical research and clinical care until perhaps the 1960s, we find that the evolution of informed consent doctrine occurred in both contexts and actually helped to distinguish these medical encounters.
Philosophical Justifications of Informed Consent in Research
Authors: Brock Dan W 
Published: November 2023

Abstract
The rule that, with a few exceptions, research with humans should not take place without participants’ informed consent is a settled ethical and legal principle. This chapter explores the philosophical foundations of this principle. Exploring these foundations helps to clarify how the requirement of informed consent should be understood as well as what limits, if any, should be placed on its implementation. No such requirement exists for the use of things or nonhuman animals, such as microorganisms or mice. The simple explanation of the difference, of course, is that things and animals are not capable of giving informed consent, so it would not be possible to require it of them, whereas human beings or persons are so capable. But that tells us only why it is possible to require informed consent of human research participants, not why we should do so. Why can’t people be used in research in the way that we use things? We have reason not to be wasteful of things and animals because they have instrumental and economic value to others, but that is a limitation on their use for the sake of other persons, not for the sake of the things or animals themselves.
Empirical Data on Conflicts of Interest
Authors: et.al. Lindsay A Hampson 
Published: November 2023

Abstract
The clinical research landscape changed dramatically during the final two decades of the twentieth century. Unprecedented investment in both basic and clinical research led to a six-fold increase in biomedical research expenditures. In 2001, industry funded 60% of biomedical research expenditures, compared to 32% in 1980, with industry providing a majority of funding by the mid-1990s (see Figure 70.1). This shift in funding sources was fueled in large part by the passage of the Bayh-Dole Act in 1980. The act encouraged universities and medical schools to commercialize research conducted with government funds by providing them the exclusive patent rights. The potential revenues from these arrangements, combined with decreasing clinical revenues, resulted in a substantive growth partnership between academic medical centers and industry.
Industrialization of Academic Science and Threats to Scientific Integrity
Authors: Campbell Eric G , Blumenthal David 
Published: November 2023

Abstract
Relationships between academia and industry have existed since the early 1900s, when more than half of all trustees of U.S. universities were from the industrial sector.1 However, academicindustry relationships (AIRs) and commercialization began in earnest when chemical and pharmaceutical companies began to undertake research and sought university help in solving scientific problems. Commercialization of research got another boost as universities established independent organizations to commercialize the results of faculty research. The earliest of these was the Research Corporation, which was formed in 1912 to manage pollution technology developed at the University of California. A similar technology transfer organization was created in 1925 when the University of Wisconsin formed the Wisconsin Alumni Research Foundation (WARF ) to commercialize a patent on the technology for irradiating dairy products to instill vitamin D in them— a process that virtually eliminated rickets as a childhood disease. The purpose of organizations like WARF and the Research Corporation was to keep commercial activities “at arm’s length” out of fear that they would compromise the integrity of the academic research enterprise. Despite the fact that these firms conferred great benefit on the public, their creation met with considerable angst within the halls of the academy.
Fraud, Fabrication, and Falsification
Authors: Resnik David B 
Published: November 2023

Abstract
Honesty is one of the core values of science, but for many years there have been concerns about dishonesty and deception in research. In 1830, the mathematician and inventor Charles Babbage (1791–1871) wrote about unethical practices that he had observed in British science. He discussed examples of hoaxing, forging, trimming, and cooking data. Hoaxing and forging occur when one makes up data; trimming occurs when one clips off pieces of data that do not agree with one’s hypothesis; and cooking occurs when one manipulates data in order to make them appear to be more accurate than they really are. In 1847, the American Medical Association (AMA) was formed to promote professionalism in medical practice and research. In 1849, the AMA formed a board to analyze quack remedies and debunk fraudulent claims made by snake oil salesmen.
The Scleroderma Book
Authors: Mayes Maureen D 
Published: November 2023

Abstract
Scleroderma means hardening of the skin, due to a malfunction of the vascular and immune system resulting in the overproduction of collagen (a protein substance found in the body’s connective tissue). In this second edition of The Scleroderma Book, Dr Maureen Mayes—the leading authority in the field—draws on her extensive experience treating scleroderma to provide up-to-date, practical information that will help patients manage their symptoms and improve their quality of life. Scleroderma can be localized (small patches of hardened skin, which tend to clear up over time), but may become systemic with excess collagen building up in various organs such as the oesophagus, kidneys, lungs, gastrointestinal tract, heart skin, and peripheral nervous system. The disorder most commonly occurs in women between the ages of 20 and 40. However, men and children can be affected as well. The disease is not contagious and is not thought to be inherited and currently, there is no known cure. Writing specifically for patients and their families, Dr. Mayes offers sympathetic and reassuring advice on matters that often concern those living with scleroderma, such as the best course of action for those who want children, what to do if the disease affects your sex life, and what you can do to help your doctor treat your illness more effectively. The book concludes with a good humoured, frank discussion about how to cope, day in and day out, with an uncertain future—how to be a “person living with” scleroderma, not a “victim suffering from” it. Touching on virtually every aspect of this disorder, The Scleroderma Book provides a reliable source of information and reassurance for patients of any age, no matter how severe their form of the disease.
Scleroderma And The Heart
Authors: Mayes Maureen D 
Published: November 2023

Abstract
Scleroderma can affect the heart in several ways. In some cases, heart rhythm can be affected. This is demonstrated. by a slow or irregular heartbeat or by an abnormality that is seen only on an electrocardiogram (EKG or ECG). In these cases, the approach to treatment involves either medication to help keep the heartbeat regular or a pacemaker to override the natural electrical system that controls the heartbeat. Heart rhythm is controlled by an electrical conduction system comprised of specialized cells that generate an electrical current to stimulate the heart muscle to contract in a smooth and regular way. There is a complex system of reflexes that tells the heart to speed up (as with exercise) or to slow down (as with rest), but there is only one electrical system that sends signals to both sides of the heart so that all four chambers contract or pump in a synchronized fashion. The problem that occurs in some cases of scleroderma is that scar tissue (the same culprit we have discussed in the previous chapters) is deposited in the path of the electrical current, so the current is interrupted or blocked. This can be partial or a complete block depending on exactly where it is and how much scar tissue is present. Sometimes the irregular\heartbeat is noticed by the patient and sometimes not. It is important to get an EKG to determine exactly what type of problem exists. If no irregularity is picked up on the EKG, then a portable Holter monitor can be given to the patient, which records the EKG for an entire day. This test can pick up heart irregularities that occur only occasionally and are not captured during the short period of time that the EKG is recorded in the doctor’s office.
Scleroderma And Joints, Tendons, Muscles, And Nerves
Authors: Mayes Maureen D 
Published: November 2023

Abstract
Stiffness and achiness are common problems in scleroderma. Sometimes patients can’t tell whether the aching is coming from the joints, the muscles, both, or neither. The thickness and tightness of the overlying skin can make it hard even for the doctor to determine if joint swelling is present. This can be an important distinction to make, since joint pain and swelling (arthritis) may require different treatment than muscle aches or tendon inflammation. A small percentage of patients will have a true overlap between rheumatoid arthritis and scleroderma and may need to be treated with medications that are usually considered to be specific for rheumatoid arthritis. Most, however, will not have this overlap.
Systemic Scleroderma And Pregnancy
Authors: Mayes Maureen D 
Published: November 2023

Abstract
Young women with systemic scleroderma often ask me if it is okay to get pregnant. The answer is that it depends on several factors: the stage of the disease, the medications that are required to control the disease, and the risks that people are willing to take in order to have a child. (Note that this does not apply to people with localized scleroderma, a condition that does not present a higher-than-usual risk during pregnancy. However, the use of any medication needs to be reviewed by the patient and her doctor before pregnancy occurs.)
The Courtesan’s Voice: Petrarchan Lovers, Pop Philosophy, and Oral Traditions
Authors: Feldman Martha 
Published: November 2023

Abstract
Like the donna angelicata (the revered woman) of Petrarch’s lyric canon, so immensely popular in the sixteenth century, courtesans were often reproached by abject lovers but also venerated by them. A painting by Parrasio Michel of ca. 1560 (fig. 4.1) condenses this double status of the courtesan by presenting her in a performative guise. She gazes heavenward as she sings to the lute but with breasts exposed and is attended by a secularized Cupid who stands in as both son of Venus (herself a standin for the courtesan) and the Roman God of Love deployed so prolifically in sacred and secular images.
The City Geisha and Their Role in Modern Japan: Anomaly or Artistes?
Authors: Downer Lesley 
Published: November 2023

Abstract
From the very beginning of their history, geisha were always a profession entirely separate from courtesans as they were conceived of in Japan. They originated in eighteenth-century Japan, both inside and outside the pleasure quarters, and were defined as “entertainers” or “artistes”: the word gei-sha literally means “arts person.” The courtesans of the pleasure quarters (known as tayu in seventeenthand eighteenth-century Kyoto and oiran in eighteenthand nineteenth-century Edo [Tokyo]) offered their bodies as currency—though very often at a price too high for all but the wealthiest and most powerful men to afford. The geisha conversely were defined as selling music, singing, and dancing.