bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flucytosine
Authors: Larsen Robert A 
Published: October 2023

Abstract
Flucytosine (5-fluorocytosine; 5-flucytosine; 5-FC) is one of the oldest antifungal agents in use (Utz, 1972). It was initially synthesized in 1957, but was not discovered to possess significant antifungal properties until 1964, when activity against Cryptococcus neoformans and Candida species was shown (Grunmberg et al, 1964). Human clinical trials were initiated in the late 1960s for both cryptococcal meningitis and disseminated candidiasis (Tassel and Madoff, 1968; Utz et al, 1968). The rapid emergence of flucytosine resistance was observed, particularly among C. neoformans isolates, limiting its utility as single agent therapy (Normark and Schönebeck, 1972; Block et al, 1973; Hospenthal and Bennett, 1998). Presently, flucytosine is utilized as single agent therapy in only a limited number of settings including urinary candidiasis and chromo-blastomycosis (Graybill and Craven, 1983). The seminal studies of combination therapy of flucytosine with amphotericin B for patients with cryptococcal meningitis were the first to firmly establish a role for combination antifungal therapy in a well defined invasive fungal infection (Bennett et al, 1979; Dismukes et al, 1987). Flucytosine is taken up by fungal cells by a unique fungal-specific cytosine permease. Two important and independent pathways for fungal cell injury occur: one leading to protein synthesis inhibition, and the other resulting in DNA synthesis inhibition. Flucytosine is converted by intracellular deamination to 5-fluorouracil and ultimately processed into 5-fluorourindine triphosphate, which is incorporated into fungal RNA. This results in miscoding during translation from RNA into amino acid sequencing, causing structural abnormalities during protein synthesis (Bennett, 1977; Diasio et al, 1978). The second mechanism of action is characterized by the conversion of 5-fluorouracil to 5-fluorodeoxyuridine monophosphate, which inhibits thymidylate synthetase and subsequently DNA biosynthesis (Polak and Scholer, 1980; Waldorf and Polak, 1983). Resistance to flucytosine may arise from mutations that affect the production of three key enzymes, uridine monophosphate pyrophosphorylase, cytosine permease, and cytosine deaminase, or through increased production of pyrimidines (Francis and Walsh, 1992).
Resistance to Antifungal Drugs
Authors: Sanglard Dominique 
Published: October 2023

Abstract
Fungal infections caused by fungal pathogens remain quite common in immunocompromised hosts, especially in HIV-infected individuals, and in patients given immunosuppressive drugs or broad-spectrum antibiotics. Candida spp. represent the major group of yeast species recovered from these infected individuals; however, other yeasts such as Cryptococcus neoformans are also pathogens (Fridkin and Jarvis, 1996). Among filamentous fungi causing infections in humans, Aspergillus fumigatus is a common pathogen and is associated with a high mortality (Latge, 1999). Not only are a restricted number of antifungal agents available to treat these infections, but also resistance to antifungal drugs can occur. Table 9–1 summarizes the activity of known antifungal agents against Candida spp., C. neoformans; and A. fumigatus and also includes drugs in the late stages of development. The data given in Table 9–1 indicate that most of the agents show some activity against these pathogens. However, weak anti-fungal activity can be seen for the pyrimidine analogue, flucytosine, and azole agent, fluconazole, against A. fumigatus, for fluconazole against C. glabrata and C. kruseiand for the echinocandins againstC. neoformans. Resistance to antifungal treatment can develop on the basis of clinical and microbiological factors. A persistent infection despite treatment with an antifungal drug at maximal dosage may be described as clinically resistant to the therapeutic agent. However, the infecting organism may show normal susceptibility to the agent in vitro (Rex et al, 1997). Clinical resistance to treatment may result from microbial resistance to an agent, but may also be the result of complex interactions between an antimicrobial agent and the infecting microbe in a human host. Microbiological resistance can be defined as a shift (i.e., a decrease) in antifungal drug susceptibility that can be measured in vitro by appropriate laboratory methods. Resistance to specific antifungal drugs can be intrinsic (primary resistance) in some fungal pathogens as indicated above, and resistance can be also acquired (secondary resistance) either in a transient or permanent manner.
Coccidioidomycosis
Authors: Ampel Neil M 
Published: October 2023

Abstract
Coccidioidomycosis is a disease of the Western hemisphere caused by the dimorphic soil-dwelling fungus that until recently was recognized as the single species Coccidioides immitis (see Taxonomy). First recognized as a clinical entity in Argentina in 1882, the first case associated with the San Joaquin Valley in California was reported soon after (Rixford and Gilchrist, 1896). Early cases presented with inflammatory lesions of the skin, bones, and joints that progressed to death despite attempts at treatment. By the turn of the century, the causative organism was identified as a mould despite its resemblance in tissue to a protozoan (Ophüls, 1905). For the first 40 years, coccidioidomycosis was thought to be a relatively rare but disfiguring and usually fatal disease. However, benign cases of pulmonary disease associated with erythema nodosum or erythema multiforme were increasingly observed (Dickson and Gifford, 1938). This form of illness, called Valley Fever, led to speculation that not all cases of coccidioidomycosis were fatal and that there was a wide spectrum of clinical manifestations of infection (Smith, 1940). These observations ushered in a watershed period in the understanding of coccidioidomycosis led by Charles E. Smith and his colleagues. Smith developed the coccidioidin skin test, defined the incidence and prevalence of infection within the San Joaquin Valley, and described the relationship of skin-test reactivity to clinical disease (Smith et al, 1948). He also developed the coccidioidal serum antibody tests (Smith et al, 1950), variations of which are still in use today. However, there was no treatment for coccidioidomycosis until 1957, when Fiese reported the first use of amphotericin B to manage a case of disseminated disease (Fiese, 1957). Further strides in the therapy of coccidioidomycosis using amphotericin B were pioneered and described by Winn (Winn, 1959).
Penicilliosis
Authors: Nelson Kenrad E , Sirisanthana Thira 
Published: October 2023

Abstract
More than 200 species of the Penicillium genus have been described. Penicillium organisms are abundant in nature and are common laboratory contaminants. However, Penicillium marneffei is the only dimorphic species. The organism is commonly responsible for disseminated invasive infections in humans with HIV infection or AIDS in the endemic areas of Southeast Asia and southern China. Penicillium marneffei has also been found to cause natural infections in several species of rodents in the endemic areas and rodents can be infected experimentally. Penicillium marneffei was originally isolated from the liver of a bamboo rat (Rhizomys sinensis) at the Pasteur Institute in Dalat, Viet Nam in 1956. Capponi and colleagues observed the death of bamboo rats due to disseminated infections with P. marneffei involving their reticuloendothelial system (Capponi et al, 1956). These investigators passed the newly discovered organism experimentally in mice, and it was sent to the Pasteur Institute in Paris for further study. At the Pasteur Institute, the fungus was characterized by Segretain and named Penicillium marneffei in honor of Dr. Hubert Marneffe, the Director of the Pasteur Institute of Indochina (Segretain, 1959a). Subsequently, Segretain became the first known human to be infected with the organism in 1959 when he accidentally stuck his finger with a needle he was using to inoculate a hamster. The clinical manifestations of his infection were a subcutaneous nodule at the site of the inoculation and lymphadenitis involving the draining auxiliary lymph nodes. The infection responded to treatment with high doses of oral nystatin. The first natural human infection with P. marneffei was reported in 1973 in a 61-year-old U.S. missionary who was suffering from Hodgkin’s disease. His infection was discovered when he underwent a staging splenectomy for Hodgkin’s disease (Di Salvo et al, 1973). The missionary had visited Southeast Asia after Hodgkin’s disease had been diagnosed 1 year prior to the splenectomy. At surgery the excised spleen contained a tan nodular mass, 9 cm in diameter with a necrotic center, which grew P. marneffei when cultured on Sabouraud dextrose agar at 25°C. The patient survived after being treated with amphotericin B. The second case of penicilliosis was reported in 1984 in a 59-year-old man who had traveled in Southeast Asia (Pautler et al, 1984). He had recurrent episodes of hemoptysis and P. marneffei organisms were isolated from his sputum. Also in 1984, five additional cases who had been seen at Ramathibodi Hospital in Bangkok, Thailand between 1974 and 1982 were reported (Jayanetra et al, 1984). Eight cases of P. marneffei infection were reported from Guangxi province in southern China that had occurred between 1964 and 1983 (Deng et al, 1985). Additional cases were recognized from 1985 to 1991 in southern China (Li et al, 1985; Wang et al, 1989; Li et al, 1991). These patients were not immunocompromised. All cases had occurred prior to the AIDS epidemic in Southeast Asia.
Superficial Cutaneous Fungal Infections
Authors: weeks Jeff , Moser stephen A , Elewski boni E 
Published: October 2023

Abstract
In this chapter, we review cutaneous diseases caused by a variety of fungal pathogens infecting the skin, hair, and nails. These diseases are divided into the following classification based on level of invasion, host inflammatory response, and pathogen: (1) superficial mycoses, (2) dermatophytoses, (3) cutaneous disease caused by nondermatophyte moulds, and (4) cutaneous candidiasis. Superficial mycoses are characterized by fungal invasion into the superficial stratum corneum with little to no inflammatory response. Dermatophytoses are caused by dermatophytes, which are a closely related group of fungi that invade the full thickness of the stratum corneum and result in a host-mediated immune response. Several nondermatophyte moulds produce infections that mimic dermatophytoses. Cutaneous candidiasis results from invasion of deep layers of the skin by members of the Candida genus. Superficial mycoses are fungal infections of the skin and hair that invade only the most superficial layers and cause little or no inflammatory response. These mycoses include the malassezioses, tinea nigra, blacpiedra, and white piedra. Superficial invasion of the nail plate, so-called white superficial onychomycosis, is discussed in the Dermatophytoses section.
Pneumocystosis
Authors: Decker Catherine F , Masur Henry 
Published: October 2023

Abstract
Although considered an organism of low virulence, Pneumocystis carinii is an important cause of pneumonia in immunocompromised hosts, especially those with hematologic malignancies, organ transplants, HIV, certain congenital immunodeficiencies, and those receiving high-dose corticosteroids. Unfortunately, this pneumonia has continued to occur despite the recognition in the 1970s that chemoprophylaxis could greatly reduce the incidence of this disease in the immunocompromised host. A dramatic increase in incidence of P. carinii pneumonia occurred as the AIDS epidemic grew as did our knowledge of the initial manifestations, diagnosis, treatment and prevention of P. carinii pneumonia. Soon, thereafter, with the implementation of chemoprophylaxis in the late 1980s for the HIV-infected population, and with the widespread use of highly active antiretroviral therapy (HAART) in 1995, there has been a steady decline in cases (Kaplan, et al, 2000). However, P. carinii pneumonia will continue to occur in those who do not have access to medical care, those who are unaware they are infected, those who elect not to treat their HIV infection aggressively, or those who fail to respond to therapy. Pneumocystis was traditionally considered a protozoan since it was originally identified by Chagas in 1906. However, recent applications of molecular techniques demonstrated that the organism shares many characteristics with fungi, especially Saccharomyces (Edman et al, 1988; Stringer et al, 1989; Cailliez et al, 1996). However, P. carinii is unusual among fungi in that the organism lacks ergosterol in its plasma membranes and is insensitive to antifungal drugs that target ergosterol biosynthesis. Based on its morphology, which is similar to that of protozoa, the life cycle of P. carinii has been divided into three stages: the trophozoite, found outside the cyst and believed to be intermediate between the sporozoite and the cyst; the cyst, a spherical or crescent-shaped form; and the sporozoite or intracystic bodies, found within the cysts (Barton et al, 1969). Since human P. carinii is not cultivatable in vitro, the life-cycle has not been fully elucidated. It has been suggested that the mode of replication occurs through binary fission and excystment (Hughes et al, 1977).
Memory and Cognitive Functioning After Electroconvulsive Therapy
Authors: Abrams Richard 
Published: October 2023

Abstract
Several aspects of cerebral functioning can be affected for varying intervals by ECT, depending on the number, frequency, and duration of the induced seizures, the anatomical placement of the stimulating electrodes, and the stimulus wave-form, parameters, and charge. Depending on which particular combination of these variables they receive, patients during the immediate postictal period may experience confusion and neurological dysfunction that occasionally progresses to delirium. After the postictal confusion has cleared, two specific types of memory impairment can be demonstrated: retrograde amnesia for events preceding the seizure and anterograde amnesia (rapid forgetting) for events following it. Non-memory cognitive impairments may also be detectable in the interictal period using various modem neuropsychological procedures. Finally, patients may experience subjective memory dysfunction that may or may not be objectively confirmed. Studies of the various aspects of ECT-induced disruption of functioning naturally divide themselves into those conducted during the immediate postictal period before reorientation has occurred, those conducted after full alertness and orientation have been reestablished, and those conducted days, weeks, or months later.
Neurobiological Correlates and Mechanisms
Authors: Abrams Richard 
Published: October 2023

Abstract
In this chapter, the word “neurobiological” subsumes all of the following terms unless more particularly specified: neurochemical, neurohumoral, neurotransmitter, neuroendocrine, neurohormonal, neuropeptide, neurogenetic, neurophysiological, and neurometabolic.
The literature on neurobiological consequences of induced seizures contains a dearth of human ECT studies compared with electroconvulsive shock (ECS) trials in animals, yet normal animal data have not helped to explain how ECT works in mentally ill patients.
How to Help Yourself without Taking Medicine
Authors: Wallace Daniel J , Wallace Janice Brock 
Published: October 2023

Abstract
Although there is no cure for fibromyalgia, patients can initiate numerous changes and make adjustments that improve their sense of wellbeing. Simply stated, there are things patients can do without spending money or seeing a healthcare provider. Demonstrating a certain amount of control over the syndrome also improves self-esteem and instills a sense of self-worth.
Even though certain general dietary principles allow fibromyalgia patients to feel better, there is no “fibromyalgia diet.” No specific food regimens or supplements have ever been shown in any published, controlled study to be helpful for fibromyalgia despite the observation that “arthritis diet” books are a multimillion-dollar-a-year industry.
How can we explain this discrepancy? First, people feel better when they eat healthy foods. Most arthritis diet books urge patients to eat three well-balanced meals a day and caution against overeating. Many recommend having the main meal at midday; heavy, late-evening dinners don’t give the body enough time to burn off calories and are associated with bedtime esophageal spasm or heartburn. Similarly, consuming alcohol, nicotine, or caffeine (in the form of coffee, tea, or even chocolate) at a late dinner can make it harder to get a good night’s sleep. Alcohol, in particular, should not be used as a painkiller. In turn, poor sleep can increase musculoskeletal pain. An acceptable healthy balance of proteins, carbohydrates, and fats can also increase energy and fight fatigue.
Anti-Imperialist Wit in Horace Walpole’s Letters
Authors: Sabin Margery 
Published: October 2023

Abstract
A by-stander often sees more of the game than those that play. -Horace Walpole, The Castle of Otranto Horace Walpole’s letters to his friend Horace Mann from the late 1760s to the 178os follow the scandals of the British rise to power in India from the perspective of a bystander rather than a player.1 As the son of Robert Walpole, the most powerful political figure in parliamentary politics for a generation in the middle of the eighteenth century, Horace Walpole had an insider’s grasp of political machination, but without his father’s relish or skill for it.
Burke’s India Campaign: Goliath, Scourge, Redeemer
Authors: Sabin Margery 
Published: October 2023

Abstract
Although Walpole and Burke both represent the critical side of eighteenthcentury British debate about India, in other ways they stand at opposite ends of the spectrum of writing on the subject. Instead of Walpole’s cynical wit mixed with observations on other items of the daily news, Burke offers impassioned exhortations in speeches and writings through a parliamentary campaign of fifteen years, from 1781 to 1795; instead of the bits and pieces gleaned by Walpole from rumor and newspapers, Burke’s research and analytic mastery of what was already the massive British Indian archive constitute a feat of herculean energy and sustained concentration.
The Beast in Nirad Chaudhuri’s Garden
Authors: Sabin Margery 
Published: October 2023

Abstract
If your first order of business is to “decolonize “ the mind, there seems little to be said on behalf of Nirad C. Chaudhuri’s Autobiography of an Unknown Indian,1 with its fond childhood memories of Palgrave’s Golden Treasury and the Encyclopedia Britannica in turn-of-the-century Bengal. Many anticolonial critics simply fix Chaudhuri as one of Macaulay’s freakish progeny: the Anglicized mind in brown skin created to serve imperial power in British India.
The Politics of Cultural Freedom: India in the I950s
Authors: Sabin Margery 
Published: October 2023

Abstract
Dissent in British writing about India during the colonial period is comparatively easy to recognize and define, even while it changes tone and shape in response to shifting historical contingencies over the long period of British rule. In India, after independence and the trauma of Partition, the nationalist consensus against imperial domination that had held the freedom movement together broke apart into complex and aggressive internal conflicts: regional, political, religious, and social.
Gene Insurance
Authors: Tabarrok Alexander 
Published: October 2023

Abstract
Not so long ago, the only way to get a glimpse of your future health was to take a trip to the local psychic for a tarot card reading. Now, thanks to advances in genetic research, medical practitioners are increasingly able to read your health future from a much more reliable source-your individual genetic code. The correlation between specific genes and some diseases is now well established, and further discoveries are announced almost weekly.
Time-Consistent Health Insurance
Authors: Cochrane John H 
Published: October 2023

Abstract
Currently available health insurance contracts do not fully insure many long-term illnesses, such as AIDS, cancer, senile dementia, heart disease, or organ failure. Many people who get such diseases face ruinous increases in premiums. Others lose their health insurance by losing their job or their spouse or by exceeding a lifetime cap on benefits. Some are bankrupted by health expenses; some are unable to get further medical care. Many other kinds of insurance do not cover long-term risks in the same way, for example, medical malpractice and product liability insurance.
Patent Buyouts: A Mechanism for Encouraging Innovation
Authors: Kremer Michael 
Published: October 2023

Abstract
Economic growth ultimately depends on the production of new ideas, but competitive markets do not provide appropriate incentives for the production of ideas. If consumers pay only the marginal cost of transmitting ideas, revenues will be insufficient to cover the cost of producing ideas. Historically, societies have used a wide variety of mechanisms to encourage production of ideas. Some, such as patents and copyrights, provide inventors with monopolies over goods produced using their ideas. Others, such as the National Science Foundation (NSF) and the synthetic fuels program, directly subsidize research. The United States uses both types of mechanisms; for example, government and industry each spent about $13 billion on health research in 1992 (National Science Board 1993).
Curb Rights: Eliciting Competition and Entrepreneurship in Urban Transit
Authors: Klein Daniel B , Moore Adrian T , Reja Binyam 
Published: October 2023

Abstract
Urban transit in the United States has long been dominated by government ownership and regulation, and it has been declining steadily in ridership and productivity (APTA 1995). An economist-cum-policymaker would seek to inject competition and entrepreneurship into the sector by privatizing it. The two types of privatization often advocated are contracting out and “free competition” (Department of Transportation 1984; Lave 1985; Gomez-Ibanez and Meyer 1993). Experience has shown, however, that each approach has serious shortcomings.