bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Algorithm to Detect Adverse Drug Reactions in the Neonatal Intensive Care Unit
Authors: Du Wei , Lehr Victoria Tutag , Lieh‐Lai Mary , Koo Winston , Ward Robert M. , Rieder Michael J. , Van Den Anker John N. , Reeves Jaxk H. , Mathew Merene , Lulic‐Botica Mirjana , Aranda Jacob V. 
Published: January 2012

AbstractCritically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24‐item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus “gold standard” was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.
Differential Diagnosis of Primary Nasopharyngeal Lymphoma and Nasopharyngeal Carcinoma Focusing on CT, MRI, and PET/CT
Authors: Cho Kyu‐Sup , Kang Dae‐Woon , Kim Hak‐Jin , Lee Jong‐Kil , Roh Hwan‐Jung 
Published: January 2012

ObjectiveNo study has done a comparative analysis of radiologic imaging findings between primary nasopharyngeal lymphoma (PNL) and nasopharyngeal carcinoma (NPC). The purpose of this study was to analyze computed tomography (CT) and magnetic resonance (MR) images and to evaluate the maximum standardized uptake value (SUV max) of positron emission tomography (PET)/CT between PNL and NPC, knowing the imaging features that distinguish PNL from NPC.Study DesignCross‐sectional study.SettingUniversity tertiary care facility.Subjects and MethodsThe authors analyzed the features on CT, MR imaging, and PET/CT of 16 patients diagnosed with PNL and 32 patients diagnosed with NPC histopathologically.ResultsPatients with PNL had a larger tumor volume and showed symmetry of tumor shape than did patients with NPC. Patients with PNL also had higher tumor homogeneity than NPC patients on CT, T2‐weighted, and postcontrast MR images. All PNL patients showed a high degree of enhancement without invasion to the adjacent deep structure. The involvement of the Waldeyer ring was significantly higher in PNL patients. Cervical and retropharyngeal lymphadenopathy and PET/CT SUV max showed no significant difference between PNL and NPC.ConclusionsIf the images present a bulky, symmetric nasopharyngeal mass with marked homogeneity, a high degree of enhancement, and a higher Waldeyer ring involvement combined with no invasion into the deep structure, PNL should be considered over NPC.
Office‐Based Laser Surgery of the Larynx
Authors: Kuo Connie Y. , Halum Stacey L. 
Published: January 2012

ObjectiveWhile office‐based laser surgery (OBLS) for benign laryngeal disease is cost‐effective for the patient, the financial impact on the office offering the service has not been characterized. We hypothesize that OBLS offers savings to the patient that are not widely realized because of the financial liability the technology poses.Study DesignA 2‐part financial analysis.Setting(1) Hospital operating room and (2) non–facility‐based office.Subjects and MethodsFirst, the average cost and reimbursements for 50 patients undergoing OBLS were compared with those of 50 patients undergoing operative direct laryngoscopy with laser (DLL). Second, a detailed financial comparison was performed on a self‐paired series of patients who had each undergone both OBLS and DLL for benign laryngeal disease.ResultsWhen compared with DLL, OBLS provides more than a $5000 per‐case cost savings for the third‐party payer. Average DLL reimbursement was $6453.44 per case, including hospital, anesthesiologist, and surgeon reimbursements of $5150, $745.66, and $357.78, respectively. Based on the calculated hospital cost of $2069.15 per case, the hospital profited more than $3000 per DLL. For OBLS in a non–facility office setting, the average reimbursement was $643.08 per case, with procedure and laser fiber reimbursements of $596.52 and $46.56, respectively. Based on office expenditures of $1388.06 per case, the office lost more than $500 per OBLS case.ConclusionOBLS in a non–facility‐based office setting leads to a net financial loss for the office, making OBLS‐associated health care cost savings unlikely to be widely realized unless reimbursement patterns are changed.
A Prostate Fibromyxoid Sarcoma With Smooth Muscle Differentiation in a F344xBNF1 Rat
Authors: Berman-Booty L. D. , Garzel L. M. , Bergdall V. , Perle K. M. D. La 
Published: January 2012

This report describes a spontaneous prostate fibromyxoid sarcoma with smooth muscle differentiation in an approximately 136-week-old intact male F344xBNF1 rat on a diet study for 2 weeks. At necropsy, the prostate was markedly distorted and enlarged by a firm white multinodular mass (6.0 × 4.5 × 3.5 cm). Histopathologically, the mass consisted of solid sheets of interlacing mesenchymal spindle cells with indistinct cell borders. Nuclei were separated by variable amounts of hyaline to fibrillar eosinophilic and/or myxomatous material. The extracellular myxomatous material tended to form whorls and stained positively with alcian blue. The mass stained strongly with Masson trichrome and vimentin throughout. Approximately 5% of the neoplastic cells were positive for smooth muscle actin, and none stained for desmin and pancytokeratin. To the authors’ knowledge, this fibromyxoid sarcoma with smooth muscle differentiation is the first such described prostatic sarcoma in a rat.
PDMS embedded microneedles as a controlled release system for the eye
Authors: Mahadevan Geetha , Sheardown Heather , Selvaganapathy Ponnambalam 
Published: January 2012

Purpose: To demonstrate intraocular drug delivery using a novel device fabricated by embedding hollow glass microneedles within a soft and flexible poly (dimethylsiloxane) (PDMS) substrate for ease of device insertion into the eye. Methods: Hollow glass microneedles (5 µm ID tips), fabricated using standard glass drawing techniques, were assembled into a photolithographically micropatterned PDMS substrate. The microneedles were fluidically coupled to a drug reservoir through a 300 µm microchannel to test for in vitro release of 6-aminoquinolone (144 Da) and Rose Bengal (1044 Da). Intravitreal delivery in ex vivo bovine eyes was also studied. Results: The microneedles penetrated UV-crosslinked collagen and excised bovine sclera without breaking or delaminating from the PDMS matrix. A total of 45 ng of 6-aminoquinolone and 16 µg of Rose Bengal was released into buffered saline over a 20-min infusion at a delivery rate of 50 µL/min. Microinjection of Rose Bengal for 8 h into ex vivo bovine vitreous resulted in a total mass accumulation of 0.0202 mg into both phases of the vitreous humor and to the uveal face of the sclera without clogging of the internal needle microchannel. Conclusions: PDMS-embedded microneedles offer an integrated method of drug targeting to the intraocular tissues using a less invasive and less painful approach when compared with macroscale hypodermic needles. The release rates from the microneedles were controllable on demand using a syringe pump and were independent of the properties of the drugs tested. The device demonstrated a new hybrid approach of coupling rigid microneedles strong enough to penetrate the tough, fibrous sclera with a soft and pliable PDMS substrate that could conform to the contours of the eye.
Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats
Authors: Khurana S , Jain S , Mediratta PK , Banerjee BD , Sharma KK 
Published: January 2012

Dementia is a syndrome of progressive nature, affects wide range of cognitive abilities like memory, language, calculation and so on, neuropsychiatric and social deficits to impair the routine social functions. The present study was designed to assess the effect of curcumin against colchicine-induced cognitive dysfunction and oxidative stress in rats and compare it with rivastigmine. Colchicine (15 µg/5µl) was administered to male Wistar rats intracerebroventricularly (i.c.v.) by stereotaxic apparatus to induce cognitive dysfunction. Administration of colchicine caused poor retention of memory in elevated plus maze, passive avoidance apparatus and Morris water maze paradigms. Chronic treatment with curcumin (100, 200 and 400 mg/kg, p.o.) twice daily and rivastigmine (2.5 mg/kg, p.o.) daily for a period of 28 days beginning 7 days prior to colchicine injection significantly improved colchicine-induced cognitive impairment. Biochemical assessment revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, depleted reduced glutathione levels and decreased acetyl cholinesterase (AChE) activity in rat brains. Chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the reduced glutathione levels and AChE activity; however, rivastigmine failed to prevent oxidative stress. The results of the current study indicate that curcumin (100, 200 and 400 mg/kg, p.o.) twice daily has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.
t-PA–specific modulation of a human blood-brain barrier model involves plasmin-mediated activation of the Rho kinase pathway in astrocytes
Authors: Niego Be'eri , Freeman Roxann , Puschmann Till B. , Turnley Ann M. , Medcalf Robert L. 
Published: January 2012

AbstractTissue-type plasminogen activator (t-PA) can modulate permeability of the neurovascular unit and exacerbate injury in ischemic stroke. We examined the effects of t-PA using in vitro models of the blood-brain barrier. t-PA caused a concentration-dependent increase in permeability. This effect was dependent on plasmin formation and potentiated in the presence of plasminogen. An inactive t-PA variant inhibited the t-PA–mediated increase in permeability, whereas blockade of low-density lipoprotein receptors or exposed lysine residues resulted in similar inhibition, implying a role for both a t-PA receptor, most likely a low-density lipoprotein receptor, and a plasminogen receptor. This effect was selective to t-PA and its close derivative tenecteplase. The truncated t-PA variant reteplase had a minor effect on permeability, whereas urokinase and desmoteplase were ineffective. t-PA also induced marked shape changes in both brain endothelial cells and astrocytes. Changes in astrocyte morphology coincided with increased F-actin staining intensity, larger focal adhesion size, and elevated levels of phosphorylated myosin. Inhibition of Rho kinase blocked these changes and reduced t-PA/plasminogen–mediated increase in permeability. Hence plasmin, generated on the cell surface selectively by t-PA, modulates the astrocytic cytoskeleton, leading to an increase in blood-brain barrier permeability. Blockade of the Rho/Rho kinase pathway may have beneficial consequences during thrombolytic therapy.
Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production
Authors: Fortes Guilherme B. , Alves Leticia S. , de Oliveira Rosane , Dutra Fabianno F. , Rodrigues Danielle , Fernandez Patricia L. , Souto-Padron Thais , De Rosa María José , Kelliher Michelle , Golenbock Douglas , Chan Francis K. M. , Bozza Marcelo T. 
Published: January 2012

AbstractDiseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.
R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes
Authors: Nian Hua , Geng Wen-Qing , Cui Hua-Lu , Bao Ming-jia , Zhang Zi-ning , Zhang Min , Pan Ying , Hu Qing-Hai , Shang Hong 
Published: January 2012

Abstract

Background
Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.

Methods
Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.

Results
We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.

Conclusions
Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.
Psychological characteristics in high-risk MSM in China
Authors: Chen Guanzhi , Li Yang , Zhang Beichuan , Yu Zengzhao , Li Xiufang , Wang Lixin , Yu Ziming 
Published: January 2012

Abstract

Background
Men who have sex with men (MSM) have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult.

Methods
A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed.

Results
Of the 714 MSM analyzed, 59 (8.26%) had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P < 0.05). In contrast, the two groups did not differ significantly the sexual orientation, level of education, types of profession, drug use, condom use and experience of social stigma and discrimination (P > 0.05). A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms.

Conclusions
MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to the general population in China.
VPA: an R tool for analyzing sequencing variants with user-specified frequency pattern
Authors: Hu Qiang , Wang Dan , Yan Li , Zhao Hua , Liu Song 
Published: January 2012

Abstract

Background
The massive amounts of genetic variant generated by the next generation sequencing systems demand the development of effective computational tools for variant prioritization.

Findings
VPA (Variant Pattern Analyzer) is an R tool for prioritizing variants with specified frequency pattern from multiple study subjects in next-generation sequencing study. The tool starts from individual files of variant and sequence calls and extract variants with user-specified frequency pattern across the study subjects of interest. Several position level quality criteria can be incorporated into the variant extraction. It can be used in studies with matched pair design as well as studies with multiple groups of subjects.

Conclusions
VPA can be used as an automatic pipeline to prioritize variants for further functional exploration and hypothesis generation. The package is implemented in the R language and is freely available from http://vpa.r-forge.r-project.org.
STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas
Authors: Chan Szeman Ruby , Vermi William , Luo Jingqin , Lucini Laura , Rickert Charles , Fowler Amy M , Lonardi Silvia , Arthur Cora , Young Larry JT , Levy David E , Welch Michael J , Cardiff Robert D , Schreiber Robert D 
Published: January 2012

Abstract
Introduction
Although breast cancers expressing estrogen receptor-α (ERα) and progesterone receptors (PR) are the most common form of mammary malignancy in humans, it has been difficult to develop a suitable mouse model showing similar steroid hormone responsiveness. STAT transcription factors play critical roles in mammary gland tumorigenesis, but the precise role of STAT1 remains unclear. Herein, we show that a subset of human breast cancers display reduced STAT1 expression and that mice lacking STAT1 surprisingly develop ERα+/PR+ mammary tumors.

Methods
We used a combination of approaches, including histological examination, gene targeted mice, gene expression analysis, tumor transplantaion, and immunophenotyping, to pursue this study.

Results
Forty-five percent (37/83) of human ERα+ and 22% (17/78) of ERα- breast cancers display undetectable or low levels of STAT1 expression in neoplastic cells. In contrast, STAT1 expression is elevated in epithelial cells of normal breast tissues adjacent to the malignant lesions, suggesting that STAT1 is selectively downregulated in the tumor cells during tumor progression. Interestingly, the expression levels of STAT1 in the tumor-infiltrating stromal cells remain elevated, indicating that single-cell resolution analysis of STAT1 level in primary breast cancer biopsies is necessary for accurate assessment. Female mice lacking functional STAT1 spontaneously develop mammary adenocarcinomas that comprise > 90% ERα+/PR+ tumor cells, and depend on estrogen for tumor engraftment and progression. Phenotypic marker analyses demonstrate that STAT1-/- mammary tumors arise from luminal epithelial cells, but not myoepithelial cells. In addition, the molecular signature of the STAT1-/- mammary tumors overlaps closely to that of human luminal breast cancers. Finally, introduction of wildtype STAT1, but not a STAT1 mutant lacking the critical Tyr701 residue, into STAT1-/- mammary tumor cells results in apoptosis, demonstrating that the tumor suppressor function of STAT1 is cell-autonomous and requires its transcriptional activity.

Conclusions
Our findings demonstrate that STAT1 suppresses mammary tumor formation and its expression is frequently lost during breast cancer progression. Spontaneous mammary tumors that develop in STAT1-/- mice closely recapitulate the progression, ovarian hormone responsiveness, and molecular characteristics of human luminal breast cancer, the most common subtype of human breast neoplasms, and thus represent a valuable platform for testing novel treatments and detection modalities.
Genetic adaptation to high altitude in the Ethiopian highlands
Authors: Scheinfeldt Laura B , Soi Sameer , Thompson Simon , Ranciaro Alessia , Woldemeskel Dawit , Beggs William , Lambert Charla , Jarvis Joseph P , Abate Dawit , Belay Gurja , Tishkoff Sarah A 
Published: January 2012

Abstract
Background
Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.

Results
We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.

Conclusions
We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.