bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyaline globules in ectopic decidua in a pregnant woman with cervical squamous cell carcinoma
Authors: Dharan Muralee 
Published: June 2009

AbstractDecidual reaction in pelvic lymph nodes has been increasingly documented during pregnancy. This may pose diagnostic difficulty during intraoperative frozen section (FS) and cytological consultation in women undergoing surgical procedures for cervical Squamous cell carcinoma (SCC). A 34‐year‐woman diagnosed to have invasive SCC (stage IB1) of the cervix at 14th week of her first pregnancy underwent abdominal radical trachelectomy and pelvic lymphadenectomy at 22 weeks of gestation. Cytological smears of two of the lymph nodes from intraoperative FS revealed isolated eosinophilic hyaline globules (HG) measuring 45–50 microns, in addition to large polygonal cells with amphophilic cytoplasm and hypochromatic nuclei and occasional squamous‐looking cells with atypical hyperchomatic nuclei. These findings posed a diagnostic dilemma at intraoperative consultation and no definitive diagnosis was rendered. The formlin‐fixed, paraffin‐embedded histological sections of the same lymph nodes showed ectopic decidua with no evidence of metastatic SCC. Decidual cells are a cause of concern for both cytologists and histopathologists. In pregnant women complicated by cervical cancer intraoperative evaluation of pelvic lymph nodes is of utmost importance in order to adopt the optimal conservative treatment modality. In the absence of clear cut evidence of malignancy, a diagnosis of metastatic SCC should not be rendered. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Thyroid metastasis of clear cell renal carcinoma: Report of a case
Authors: Rizzo Massimo , Rossi Raffaele Talamo , Bonaffini Orsola , Scisca Claudio , Sindoni Alessandro , Altavilla Giuseppe , Benvenga Salvatore 
Published: June 2009

AbstractRenal cell carcinoma can recur many years after diagnosis and nephrectomy metastasizing even in uncommon sites, including thyroid gland. Thyroid metastases are extremely rare, the most frequent site of origin are renal tumors. Metastases in thyroid gland appear as painless nodules or masses, “cold” at scintiscan. We report the case of a 67‐year‐old male patient affected by clear cell renal carcinoma, diagnosed by fine‐needle aspiration cytology procedures, and treated with anticancer medical therapy, who noticed after some months a mass in the neck‐thyroid region requiring deeper medical investigations. By this way, thyroid fine‐needle aspiration cytology reported a lesion made of malignant epithelial cells compatible with metastases of renal carcinoma (clear cell). Clinical and pathological data, together with immunostaining, supported the diagnosis of metastatic clear cell renal carcinoma. The diagnosis of metastatic disease, although difficult clinically and pathologically, should be suspected in patients with a clinical history of cancer, particularly in case of renal cell carcinoma, but fine‐needle aspiration cytology can provide the clue for diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Role of fine‐needle aspiration cytology in evaluation of cutaneous metastases
Authors: Sharma Sonal , Kotru Mrinalini , Yadav Amit , Chugh Manish , Chawla Anu , Makhija Mani 
Published: June 2009

AbstractSkin is an uncommon site for metastasis. This study was done to evaluate the role of FNAC as an important tool for investigating cutaneous and subcutaneous nodules in patients with known malignancy or as a primary manifestation of an unknown malignancy.All the FNAC done from January 2003 to August 2008 were reviewed (n = 55,556). Ninty‐five patients (49 males and 46 females with age range of 4–96 years) with cutaneous/subcutaneous nodules which were diagnosed as metastasis were analyzed. Primary tumors of skin/subcutis were excluded from the study.In our study, 63 out of 95 cases had a known primary malignancy. Of these, five had underlying hematological malignancy and 58 patients had solid organ tumors. Lung carcinoma was seen to metastasize most commonly to skin in males and breast carcinoma in females. The most common site for a cutaneous/subcutaneous metastasis was chest wall [40 followed by abdominal wall (14) and scalp (9)]. Multiple site involvement was also observed (8). In 32 cases primary site was not known. They were most commonly diagnosed as poorly differentiated carcinoma followed by adenocarcinoma.FNAC can diagnose a variety of tumors in the skin and support the diagnosis of a metastasis in case of a known primary and offer a clue to underlying malignancy in case of an occult primary. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Does the new automated “HALO” nipple aspiration fluid system really deliver as promised? The answer is “No, but…”: A literature review of the role of breast fluid cytology in cancer risk assessment
Authors: Elsheikh Tarik M. 
Published: June 2009

AbstractThe HALO breast Pap test is a new automated nipple aspiration fluid (NAF) system that was recently introduced into the market. In an extensive marketing campaign directed principally toward OB/GYN practices, including endorsements from few local news media, HALO has been promoted as the “new Pap screening test for breast.” Physicians are encouraged to perform this test on all women, as part of their annual examination, with claims that HALO will detect breast cancers as early as 10 years before mammography. These arguments are made more appealing to physician's offices by highlighting the potential positive financial impact on their practices, without consuming physician time, as medical assistants or technicians can perform this test. As a result of this directed campaign, cytology laboratories are increasingly confronted with implementing the HALO system and clinicians are increasingly soliciting pathologist's input regarding its validity. Yet, there is no data available regarding this new system, outside rare reports sponsored by the manufacturer. In this discussion, I examine the pros and cons of this new NAF system, including literature review of breast fluid cytology, and how it relates to breast cancer risk assessment. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Pemphigus vulgaris of the vagina—Its cytomorphologic features on liquid‐based cytology and pitfalls: Case report and cytological differential diagnosis
Authors: Onuma Kazuya , Kanbour‐Shakir Amal , Modery Judith , Kanbour Anisa 
Published: June 2009

AbstractPemphigus vulgaris is an autoimmune bullous disease that involves skin and mucous membrane. Although the female genital tract is rarely affected, its cytomorphologic features on a conventional cervicovaginal smear have been notoriously described with a possibility of being misdiagnosed as neoplastic lesions. Its cytological mimicry for squamous cell carcinoma has been described as having serious misdiagnostic potential, particularly if appropriate clinical information is not provided. We report a case of pemphigus vulgaris involving the vagina diagnosed on a liquid‐based cervicovaginal smear Thin PrepR (TP). The smear was initially reported as squamous cell carcinoma. However, re‐evaluation of the TP smear raised the suspicion of pemphigus, which was supported subsequently by clinical information and tissue biopsy confirmation. We described the cytologic features of pemphigus vulgaris on a TP smear and compared them with those of neoplastic conditions. Pemphigus cells on a TP smear exhibit similar cytomorphologic features to those on a conventional smear. Recognizing euchromatin pattern and smooth nuclear contours which may be better appreciated on a TP can prevent overdiagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Maximizing the use of Project Bioshield contracting opportunities
Authors: Pashkoff Dana B. , Clerici John M. 
Published: June 2009

AbstractThis article explores the often complicated relationship between agency policymakers and the contracting officers that are charged with executing agency procurements. In particular, the article explores the role of the contracting officer in maximizing the use of streamlined contracting practices under the Project BioShield Act of 2004 (Public Law 108–276). Project BioShield, which is implemented through the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services (DHHS), is designed to encourage procurement activity that protects Americans against a chemical, biological, radiological or nuclear attack. To do so, the Act permits the use of special streamlined contracting authorities, many of which are often unused or ignored by the contracting officers engaged in executing and administering Project BioShield procurements. This article argues that these contracting officers are bound to conduct their duties within the confines of overall agency policy, and they cannot use their contracting discretion to circumvent that policy. As a result, DHHS contracting officers are required to use the Project BioShield streamlined contracting methods. In order to assist the agency in encouraging the use of these procedures, this article also recommends techniques that BARDA can apply in order to encourage contracting officers to take advantage of these contracting opportunities and advance agency's policy with respect to Project BioShield. Drug Dev Res 70:234–238, 2009. © 2009 Wiley‐Liss, Inc.
Conducting biodefense‐related research in a highly regulated academic environment
Authors: Chopra Ashok K. , Peterson Johnny W. 
Published: June 2009

AbstractIn this article, we discuss the impact of regulations pertaining to national security and quality control on scientific inquiry, especially as it relates to performing research in an academic setting. Specifically, the increasing burden of regulatory requirements on programs investigating select agents has negatively impacted the extent and quality of the research on these microbes, despite the fact that funds for these programs have become more readily available. Most of these regulations were created and are enforced to control access to a limited number of microbial agents considered to be the greatest threat to civilians and military personnel. While most scientists understand the need for some control, the extent of recent restrictions is seen by some as an almost insurmountable barrier to effective research, and perhaps as tantamount to a breach of academic freedom. Drug Dev Res 70:239–245, 2009. © 2009 Wiley‐Liss, Inc.
Toward RNA interference‐based therapy for filovirus infections
Authors: Spurgers Kevin B. , Silvestri Lynn S. , Warfield Kelly L. , Bavari Sina 
Published: June 2009

AbstractEbola (EBOV) and Marburg (MARV) viruses, of the family filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with mortality rates of up to 90%. Infection is thought to occur through mucous membranes or breaks in the skin after contact with infected animal tissue or body fluids of infected individuals. Beyond naturally occurring outbreaks, the potential use of these viruses in acts of bioterrorism remains a public health and national security concern. EBOV and MARV are classified as category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). To date, there are no licensed vaccines or therapeutics for filovirus infections. Major efforts are now under way to develop anti‐viral therapeutics that use the cellular RNA interference (RNAi) pathway. Small synthetic double‐stranded RNA oligonucleotides (siRNAs), or small hairpin RNAs (shRNAs) enter the RNAi pathway and guide the degradation of target mRNA transcripts with homologous sequence, for experimental or therapeutic benefit. Chemical modifications improve the in vivo stability of siRNAs and various strategies are being investigated to improve delivery. Importantly, siRNAs and shRNAs have been successfully used to inhibit virus replication in vitro, and in animal models. siRNAs as therapy for a variety of ailments have now moved into clinical trials. This review provides an overview of therapeutic siRNAs and details preclinical efforts to use these molecules as therapy for filovirus infections. Drug Dev Res 70:246–254, 2009. Published 2009 Wiley‐Liss, Inc.
Identification of novel cellular targets for therapeutic intervention against Ebola virus infection by siRNA screening
Authors: Kolokoltsov Andrey A. , Saeed Mohammad F. , Freiberg Alexander N. , Holbrook Michael R. , Davey Robert A. 
Published: June 2009

AbstractWhile much progress has been made in developing drugs against a few prominent viruses such as HIV, few examples exist for emerging infectious agents. In some cases, broad spectrum anti‐viral drugs, such as ribavirin, are effective, but for some groups of viruses, these show little efficacy in animal models. Traditional methods focus on screening small molecule libraries to identify drugs that target virus factors, with the intention that side‐effects to the host can be minimized. However, this greatly limits potential drug targets and virus genes can rapidly mutate to avoid drug action. Recent advances in siRNA gene‐targeting technologies have provided a powerful tool to specifically target and suppress the expression of cell genes. Since viruses are completely dependent upon host cell proteins for propagation, siRNA screening promises to reveal novel cell proteins and signaling pathways that may be viable targets for drug therapy regimens. Here we used an siRNA screening approach to identify gene products that play critical roles in Ebola virus infection. By gene cluster analysis, proteins in phosphatidylinositol‐3‐kinase and calcium/calmodulin kinase related networks were identified as important for Zaire Ebola virus infection and prioritized for further evaluation. The key roles of each were confirmed by testing available drugs specific for members of each pathway. Interestingly, both sets of proteins are also important in cancer and subject to intense investigation. Thus, development of new drugs against these cancer targets may also prove useful in combating Ebola virus. Drug Dev Res 70:255–265, 2009. © 2009 Wiley‐Liss, Inc.
U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directions
Authors: Larsen Joseph C. 
Published: June 2009

AbstractThe United States Army (USA) under the auspices of the Medical Research and Material Command (USAMRMC) and the Defense Threat Reduction Agency (DTRA) sponsored several major efforts to develop an effective medical countermeasure against botulinum neurotoxin (BoNT). This review focuses on the U.S. Army's research and development efforts for a BoNT therapeutic over the period from 1975–2007. Two antitoxin preparations: Human botulism immunoglobulin (BIG) and Botulism Immune Globulin F(ab')2 Heptavalent Equine (BIGHE) were administered to humans and shown to possess acceptable efficacy and safety levels. BIGHE was deployed in Operation Desert Storm/Desert Shield. BoNT/A monoclonal antibodies were developed and are currently undergoing clinical evaluation with funding from the National Institute of Allergy and Infectious Disease (NIAID). The development of small molecules for the treatment of BoNT has also been supported. Efforts have focused on molecules to inhibit nearly every aspect of BoNT pathogenesis. This would include toxin binding, translocation, catalytic activity, and recovery following intoxication. Several compounds capable of inhibiting toxin activity or mitigating the severity of paralysis have been identified. To date, none of the compounds possess the appropriate properties (safety, efficacy, solubility) to be considered for clinical studies. Drug Dev Res 70:266–278, 2009. Published 2009 Wiley‐Liss, Inc.
Manufacturing a rapid biologic response
Authors: Latham Peter W. 
Published: June 2009

AbstractThere are two major components in making new biologic medical countermeasures available for bio‐defense and pandemic response: (1) the detection/discovery of effective countermeasures, and (2) their subsequent Process Development (PD) and manufacture. PD and manufacturing, however, are often the most costly and time‐consuming parts of the process, potentially taking years and costing hundreds of millions to billions of dollars. To address these long timelines, governments have historically stockpiled countermeasures for known biothreats. Unfortunately, this kind of stockpiling is very expensive, and does not provide protection against novel threats. Fortunately, there currently exist many new technologies that, when combined strategically, have the potential to significantly reduce the time and cost associated with the PD and manufacturing of biologic countermeasures. Drug Dev Res 70:288–295, 2009. © 2009 Wiley‐Liss, Inc.
Using a systems biology approach to dissect parasite–host interactions
Authors: Vaidyanathan Rajeev , Kodukula Krishna 
Published: June 2009

AbstractThe reductionist approach to biology has allowed us to understand the cell at a component level. But in recent years, with the deluge of genome‐derived and empirically obtained data, we must interpret biological complexity holistically. Thus, systems biology research allows us to connect the seemingly independent elements in biological networks. Protozoan parasites in the genus Leishmania cause clinically distinct diseases in humans with visceral, cutaneous, and mucocutaneous pathologies. In this article, we take the example of Leishmania parasites and their interactions with the vertebrate host as a model to generate a global view of molecular and biochemical processes in both spatial and temporal compartments, based on genomic, transcriptomic, proteomic, and metabolomic data. Furthermore, we propose extending this approach to other pathogen‐host relationships, thus enabling us to identify novel therapeutic targets, vaccine candidates, and to develop immune monitoring and diagnosis. Drug Dev Res 70:296–302, 2009 © 2009 Wiley‐Liss, Inc.
Accelerating botulism therapeutic product development in the Department of Defense
Authors: Stahl Andrea M. , Adler Michael , Millard Charles B. , Gilfillan Lynne 
Published: June 2009

AbstractCoordinated small‐molecule drug discovery research efforts for the treatment of botulism by the public sector, especially the U.S. Department of Defense (DoD) and Department of Health and Human Services (DHHS), began in the 1990s and represent a significant resource investment. Organization of an effective botulism therapeutic drug program, however, presents formidable technical and logistical challenges. Seven distinct BoNT serotypes are known, each representing a different target. Moreover, BoNT exerts its action inside peripheral cholinergic neurons, and some serotypes may persist functionally within nerve cells for weeks or months. Clinical botulism occurs infrequently, and the effectiveness of prolonged mechanical ventilation to treat poisoning further limits experimental drug testing. The efficacy of experimental compounds must be extrapolated from disparate cell‐ or tissue‐based or rodent models. Numerous compounds with moderate efficacy in experimental laboratory assays have been reported, but may not possess the necessary safety, efficacy, and pharmacokinetic profile to support therapeutic development. To mitigate these challenges, we propose product development tools to assist in management of the BoNT portfolio and to clearly define the desired therapeutic product. Establishing a target product profile (TPP) is proposed to guide public sector managers toward critical aspects of the desired therapeutic product. Additional product development tools to assist in shaping research portfolios and to inform decisions regarding lead candidates to pursue are also discussed. Product development tools that facilitate the characterization of the ideal therapeutic product, and assist in the maintenance of a robust portfolio, will ameliorate the inherent financial risk in drug development for treating BoNT intoxication. Drug Dev Res 70:303–326, 2009. Published 2009 Wiley‐Liss, Inc.
Tools for planning and coordinating development of medical countermeasures in the public sector
Authors: Manger Ian , Pearson Jay , Winegar Richard , Gilfillan Lynne 
Published: June 2009

AbstractIn spite of significant increases in biodefense spending in the 7 years since the 2001 anthrax attacks, the United States may not yet be fully prepared to respond effectively to many potential biothreats. The principal reasons appear to be that: (1) the problem is extremely complex, and the metrics for success are often unclear; (2) although the US Congress has allocated substantial resources for this effort, these funds are insufficient for the task as initially conceived, i.e., “one drug for each bug;” and (3) there is insufficient coordination among the many agencies working to achieve the goal of protecting the nation from biothreats. In the last few years, much of the biodefense community has come to recognize that an approach that focuses on developing and stockpiling a medical countermeasure (MCM) for each possible biothreat agent is unachievable for reasons of cost, time, and the sheer diversity of emerging threats. Promising alternative models are emerging, including broad spectrum and technology platform approaches, but the requisite cross‐agency planning and coordination, although improving, is still problematic. We have developed a set of software tools and methods for using them that could support the desired coordination and that could also provide for more rapid, comprehensive, and shared identification of key enabling technologies for accomplishing the development of effective medical countermeasures in time to counter or prevent a biothreat. The tools and methods could also make possible a collaborative public‐private partnership for the development of MCM, which many believe is critical to success. Drug Dev Res 70:327–334, 2009 © 2009 Wiley‐Liss, Inc.
Temperament does not affect the overall establishment of mutual preference between the mother and her young in sheep measured in a choice test
Authors: Bickell S.L. , Nowak R. , Poindron P. , Sèbe F. , Chadwick A. , Ferguson D. , Blache D. 
Published: June 2009

AbstractTemperament influences maternal behavior and lamb survival in Merino sheep selected for calm or nervous temperament. The impact of this selection on mother‐young recognition and early expression of temperament in lambs is unknown. We tested the ability of multiparous ewes selected for calm (n = 16) or nervous (n = 18) temperament to recognize their own lambs 6 hr after parturition, the ability of the lambs to display a preference for their own mother at 18 hr, and the temperament of the lambs at 1 and 16 weeks of age. Ewes and lambs from both genotypes showed a similar preference for their familiar kin. In contrast, differences in temperament were detectable at 1 and 16 weeks of age. Nervous lambs showed higher vocal and locomotor activity than calm lambs. Thus, temperament did not affect the early process of ewe‐lamb bonding but might affect the quality of the mother‐young relationship under more challenging situations. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 429–438, 2009.