bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoleamine 2,3‐dioxygenase expression in patients with allergic rhinitis: a case‐control study
Authors: Luukkainen Annika , Karjalainen Jussi , Honkanen Teemu , Lehtonen Mikko , Paavonen Timo , Toppila‐Salmi Sanna 
Published: December 2011

AbstractBackgroundIndoleamine 2,3‐dioxygenase (IDO) is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated.ObjectiveOur aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non‐atopic patients.MethodsIDO expression was immunohistochemically evaluated from nasal specimens obtained in‐ and off‐season from otherwise healthy non‐smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis) and non‐allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in‐ and off‐season in either healthy or allergic subjects.ConclusionsThere is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.
The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study
Authors: Zhang Jie , Delzell Elizabeth , Xie Fenglong , Baddley John W , Spettell Claire , Mcmahan Raechele M , Fernandes Joaquim , Chen Lang , Winthrop Kevin , Curtis Jeffrey R 
Published: December 2011

Abstract
Introduction
Zostavax, a live attenuated vaccine, has been approved in the United States for use in older individuals to reduce the risk and severity of herpes zoster (HZ), also known as shingles. The vaccine is contraindicated in individuals taking anti-tumor necrosis factor alpha (anti-TNF) therapies or other biologics commonly used to treat autoimmune diseases because of the safety concern that zoster vaccine may be associated with a short-term HZ risk. The objective of the study was to examine the use, safety (short-term HZ risk after vaccination), and effectiveness of zoster vaccine in individuals with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases.

Methods
We conducted a cohort study of patients aged 50 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases by using administrative claims data from a nationwide health plan from January 1, 2005, to August 31, 2009. We examined the extent to which zoster vaccine was used; assessed factors associated with vaccine use (Cox proportional hazards regression); and compared the incidence rates of herpes zoster (HZ) between vaccinated and unvaccinated patients.

Results
Among 44,115 patients with the autoimmune diseases, 551 (1.2%) received zoster vaccine, and 761 developed HZ. Zoster vaccine use increased continuously after approval in 2006. Younger and healthier patients, those who had an HZ infection within the past 6 months, and those who were not using anti-TNF therapies were more likely to receive the vaccine. Approximately 6% of vaccinated patients were using anti-TNF therapies at the time of vaccination. The incidence rates of HZ were similar in vaccinated and unvaccinated patients (standardized incidence ratio, 0.99; 95% confidence interval, 0.29 to 3.43).

Conclusions
Use of the zoster vaccine was uncommon among older patients with autoimmune diseases, including those not exposed to immunosuppressive medications. The short-term risk of HZ did not appear to be increased in vaccinated patients, even among those using immunosuppressive therapies (for example, biologics) at the time of vaccination. However, our study was limited by the small number of vaccinated patients, and further evidence is needed to confirm the vaccine's safety and efficacy in this population.
Primary care physicians' perspectives towards managing rheumatoid arthritis: room for improvement
Authors: Garneau Katie L , Iversen Maura D , Tsao Hsun , Solomon Daniel H 
Published: December 2011

Abstract
Introduction
Many people with rheumatoid arthritis (RA) do not receive care from a rheumatologist. We surveyed primary care physicians (PCPs) to better understand their attitudes, knowledge, and practices regarding the optimal treatment of RA.

Methods
Randomly selected PCPs practicing in the US were surveyed. The survey encompassed their experience with RA, use of disease modifying anti-rheumatic drugs (DMARDs), and experience with rheumatology referrals. Logistic regression analyses described the responses and examined the correlation between physician variables and use of DMARDs.

Results
E-mail invitations were opened by 1, 103 PCPs and completed by 267 (25%). Most respondents were men (68%) in practice for over 10 years (64%) who reported 6 or more RA patients under their care in the last year (71%). The majority reported some RA training after medical school (59%), but only one-third felt very confident managing this condition. Most (81%) reported prescribing DMARDs, but 37% do not initiate them, with only 9% reporting being very confident starting a DMARD. In unadjusted analyses, several respondent characteristics were strongly associated with not prescribing DMARDs, but none was significant after adjustment. Almost half (44%) of PCPs noted that patients report difficulty getting appointments with rheumatologists.

Conclusions
We found many PCPs are uncomfortable managing RA with DMARDs, despite common beliefs that their patients lack access to a rheumatologist. Lack of accessibility to rheumatologists and discomfort in prescribing DMARDs for patients with RA are potential barriers to optimal treatment.
Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells
Authors: Oh Keunhee , Ko Eunyoung , Kim Hee Sung , Park Ae Kyung , Moon Hyeong-Gon , Noh Dong-Young , Lee Dong-Sup 
Published: December 2011

Abstract
Introduction
Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis.

Methods
To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study.

Results
IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival (P = 0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only (P = 0.013).

Conclusions
We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer.
Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion
Authors: Victor Bernadette C , Anbalagan Arulselvi , Mohamed Mona M , Sloane Bonnie F , Cavallo-Medved Dora 
Published: December 2011

Abstract
Introduction
Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods
We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real time the degradation of type IV collagen by IBC cells. IBC patient biopsies were examined for expression of cathepsin B and caveolin-1.

Results
Both cell lines expressed comparable levels of cathepsin B and uPA. In contrast, levels of caveolin-1 and uPAR were greater in SUM149 cells. We observed that uPA, uPAR and enzymatically active cathepsin B were colocalized in caveolae fractions isolated from SUM149 cells. Using a live-cell proteolysis assay, we demonstrated that both IBC cell lines degrade type IV collagen. The SUM149 cells exhibit predominantly pericellular proteolysis, consistent with localization of proteolytic pathway constitutents to caveolar membrane microdomains. A functional role for cathepsin B was confirmed by the ability of CA074, a cell impermeable and highly selective cathepsin B inhibitor, to significantly reduce pericellular proteolysis and invasion by SUM149 cells. A statistically significant co-expression of cathepsin B and caveolin-1 was found in IBC patient biopsies, thus validating our in vitro data.

Conclusion
Our study is the first to show that the proteolytic activity of cathepsin B and its co-expression with caveolin-1 contributes to the aggressiveness of IBC.
Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: Support for the 2009 IDSA treatment guidelines for candidiasis
Authors: Kett Daniel H , Shorr Andrew F , Reboli Annette C , Reisman Arlene L , Biswas Pinaki , Schlamm Haran T 
Published: December 2011

Abstract
Introduction
During the past decade, the incidence of Candida infections in hospitalized patients has increased, with fluconazole being the most commonly prescribed systemic antifungal agent for these infections. However, the 2009 Infectious Diseases Society of America (IDSA) candidiasis guidelines recommend an echinocandin for the treatment of candidemia/invasive candidiasis in patients who are considered to be "moderately severe or severely" ill. To validate these guidelines, clinical trial data were reviewed.

Methods
A secondary analysis of data from a previously published prospective, randomized, double-blind clinical trial was performed; it compared anidulafungin with fluconazole for the treatment of invasive candidiasis and candidemia. Patients with critical illness were identified at study entry by using the following criteria: Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥ 15, evidence of severe sepsis (sepsis and one or more end-organ dysfunctions) present, and/or patient was in intensive care. Global response rates were compared at the end of intravenous study treatment (the primary end point of the original study) and all-cause mortality at 14 and 28 days from study entry in this group.

Results
The patients (163 (66.5%) of 245) fulfilled at least one criterion for critical illness (anidulafungin, n = 89; fluconazole, n = 74). No significant differences were found in baseline characteristics between the two treatment groups. The global response rate was 70.8% for anidulafungin and 54.1% for fluconazole (P = 0.03; 95% confidence interval (CI): 2.0 to 31.5); all-cause mortality was 10.1% versus 20.3% at 14 days (P = 0.08; 95% CI, -0.9 to 21.3) and was 20.2% versus 24.3% at 28 days (P = 0.57; 95% CI, -8.8 to 17.0) for anidulafungin and fluconazole, respectively.

Conclusions
In this post hoc analysis, anidulafungin was more effective than fluconazole for treatment of severely ill patients with candidemia, thus supporting the 2009 IDSA guidelines.

Trial registration
Clinicaltrials.gov NCT00058682.
Acute phase proteins and white blood cell levels for prediction of infectious complications in status epilepticus
Authors: Sutter Raoul , Tschudin-Sutter Sarah , Grize Leticia , Widmer Andreas F , Marsch Stephan , Rüegg Stephan 
Published: December 2011

Abstract
Introduction
Infections in status epilepticus (SE) patients result in severe morbidity making early diagnosis crucial. As SE may lead to inflammatory reaction, the value of acute phase proteins and white blood cells (WBC) for diagnosis of infections during SE may be important. We examined the reliability of C-reactive protein (CRP), procalcitonin (PCT), and WBC for diagnosis of infections during SE.

Methods
All consecutive SE patients treated in the ICU from 2005 to 2009 were included. Clinical and microbiological records, and measurements of CRP and WBC during SE were analyzed. Subgroup analysis was performed for additional PCT measurements in the first 48 hours of SE.

Results
A total of 22.5% of 160 consecutive SE patients had infections during SE. Single levels of CRP and WBC had no association with the presence of infections. Their linear changes over the first three days after SE onset were significantly associated with the presence of infections (P = 0.0012 for CRP, P = 0.0137 for WBC). Levels of PCT were available for 31 patients and did not differ significantly in patients with and without infections. Sensitivity of PCT and CRP was high (94% and 83%) and the negative predictive value of CRP increased over the first three days to 97%. Specificity was low, without improvement for different cut-offs.

Conclusions
Single levels of CRP and WBC are not reliable for diagnosis of infections during SE, while their linear changes over time significantly correlate with the presence of infections. In addition, low levels of CRP and PCT rule out hospital-acquired infections in SE patients.
SpeCond: a method to detect condition-specific gene expression
Authors: Cavalli Florence MG , Bourgon Richard , Huber Wolfgang , Vaquerizas Juan M , Luscombe Nicholas M 
Published: December 2011

AbstractTranscriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html.
Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: Signorello Lisa B. , Mulvihill John J. , Green Daniel M. , Munro Heather M. , Stovall Marilyn , Weathers Rita E. , Mertens Ann C. , Whitton John A. , Robison Leslie L. , Boice John D. 
Published: December 2011

Purpose Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses. Methods Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression. Results One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors. Conclusion Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.
Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14
Authors: de Veer Simon J. , Swedberg Joakim E. , Parker Edward A. , Harris Jonathan M. 
Published: December 2011

Abstract
An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme’s active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (kcat/Km=3.81±0.4×106 m-1 s-1) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.
Regulation of protein function by interfering protein species
Authors: Graeff Moritz , Wenkel Stephan 
Published: December 2011

AbstractMost proteins do not function alone but act in protein complexes. For several transcriptional regulators, it is known that they have to homo- or heterodimerize prior to DNA binding. These protein interactions occur through defined protein-protein-interaction (PPI) domains. More than two decades ago, inhibitor of DNA binding (ID), a small protein containing a single helix-loop-helix (HLH) motif was identified. ID is able to interact with the larger DNA-binding basic helix-loop-helix (bHLH) transcription factors, but due to the lack of the basic domain required for DNA binding, ID traps bHLH proteins in non-functional complexes. Work in plants has, in the recent years, identified more small proteins acting in analogy to ID. A hallmark of these small negative acting proteins is the presence of a protein-interaction domain and the absence of other functional domains required for transcriptional activation or DNA binding. Because these proteins are often very small and function in analogy to microRNAs (meaning in a dominant-negative manner), we propose to refer to these protein species as ‘microProteins’ (miPs). miPs can be encoded in the genome as individual transcription units but can also be produced by alternative splicing. Other negatively acting proteins, consisting of more than one domain, have also been identified, and we propose to call these proteins ‘interfering proteins’ (iPs). The aim of this review is to state more precisely how to discriminate miPs from iPs. Therefore, we will highlight recent findings on both protein species and describe their mode of action. Furthermore, miPs have the ability to regulate proteins of diverse functions, emphasizing their value as biotechnological tools.
On the distribution of cubic exponential sums
Authors: Louvel Benoît 
Published: December 2011

Abstract.
Using the theory of metaplectic forms, we study the asymptotic behavior of cubic exponential sums over the ring of Eisenstein integers. In the first part of the paper, some non-trivial estimates on average over arithmetic progressions are obtained. In the second part of the paper, we prove that the sign of cubic exponential sums changes infinitely often, as the modulus runs over almost prime integers.
On some multiplicity and mixed multiplicity formulas
Authors: Viet Duong Quoc , Thanh Truong Thi Hong 
Published: December 2011

Abstract
This paper gives the additivity and reduction formulas for mixed multiplicities of multi-graded modules M and mixed multiplicities of arbitrary ideals, and establishes the recursion formulas for the sum of all the mixed multiplicities of M. As an application of these formulas we get the recursion formulas for the multiplicity of multi-graded Rees modules.
A comparison of green chemistry metrics for two methods of bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines
Authors: Marcinkowska Magdalena , Rasała Danuta , Puchała Agnieszka , Gałuszka Agnieszka 
Published: December 2011

Abstract
Green chemistry metrics (E-factor, atom economy, reaction mass efficiency) and the EcoScale have been compared for conventional heating and microwave assisted bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines. The major advantages in microwave-assisted reactions in relation to traditional evaluation of the process have encompassed higher yields, shorter reaction time and higher selectivity. The microwave-assisted reactions have shown better green chemistry parameters and EcoScale ranks than those in conventionally heated reactions. Mass reaction efficiency values have been critical for considering ‘green’ the reactions conducted under traditional conditions. Additional advantages of using microwaves, not considered in calculated parameters, include easier purification of the reaction mixture and isolation of the product.
Sulfamic acid as an efficient and cost-effective catalyst for the synthesis of 2,4,5-triarylimidazoles and 2-arylphenanthrimidazoles
Authors: Peng Hua-Nan , Peng Xiao-Ming , Zheng Da-Gui , Yu Fei , Rao Min 
Published: December 2011

Abstract
A simple and efficient synthesis of 2,4,5-triarylimidazoles and 2-arylphenanthrimidazoles was developed using the one-pot, three-component condensation reaction of an aromatic aldehyde, benzil or 9,10-phenanthroquinone and ammonium acetate in refluxing ethanol in the presence of the catalyst sulfamic acid.
Synthesis of novel thiazolo[2,3-b]quinazolines by cyclization reaction of octahydroquinazoline-2-thiones with α-bromoketones
Authors: Quan Zheng-Jun , Wei Ying , Wang Xi-Cun 
Published: December 2011

Abstract
Novel thiazolo[2,3-b]quinazolines were prepared by the cyclization reaction between octahydroquinazoline-2-thiones with α-bromoketones, which provides a readily accessible multifunctionalized quinazoline template for diversity-oriented synthesis.