bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lead level in seminal plasma may affect semen quality for men without occupational exposure to lead
Authors: Wu Hsien-Ming , Lin-Tan Dan-Tzu , Wang Mei-Li , Huang Hong-Yuan , Lee Chyi-Long , Wang Hsin-Shih , Soong Yung-Kuei , Lin Ja-Liang 
Published: November 2012

Abstract

Background
Infertility affects approximately 10–15% of reproductive-age couples. Poor semen quality contributes to about 25% of infertile cases. Resulting from the direct effect on testicular function or hormonal alterations, heavy metals exposure has been related to impaired semen quality. The objective of this study was to assess the level of lead in the seminal plasma in men without occupational exposure to lead, and to determine the relationship between semen quality and lead concentration in the semen.

Methods
This is a prospective and nonrandomized clinical study conducted in University infertility clinic and academic research laboratory. Three hundred and forty-one male partners of infertile couples undergoing infertility evaluation and management were recruited to the study. Semen samples collected for the analyses of semen quality were also used for the measurement of lead concentrations. Semen samples were evaluated according to the WHO standards.

Results
All subjects were married and from infertile couples without occupational exposure to lead. There is a significant inverse correlation between the lead concentration in seminal plasma and sperm count. A higher semen lead concentration was correlated with lower sperm count, but not with semen volume, sperm motility or sperm morphology as assessed by simple linear regression.

Conclusions
We found that semen lead concentration was significantly higher among the patients with lower sperm count. To our knowledge, this is the first study to demonstrate that a high level of lead accumulation in semen may reduce the sperm count contributing to infertility of men without occupational exposure to lead.
Prognostic value of KRAS genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease
Authors: Bruera Gemma , Cannita Katia , Di Giacomo Daniela , Lamy Aude , Troncone Giancarlo , Dal Mas Antonella , Coletti Gino , Frébourg Thierry , Sabourin Jean Christophe , Tosi Mario , Ficorella Corrado , Ricevuto Enrico 
Published: November 2012

Abstract

Background
Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic value of the KRAS genotype in L-L and other or multiple metastatic (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively evaluated.

Methods
Tumoral and metastatic samples were screened for KRAS codon 12 and 13 and BRAF mutations by SNaPshot and/or direct sequencing. Fit MCRC patients <75 years were consecutively treated with FIr-B/FOx regimen: weekly 12-h timed flat-infusion/5-fluorouracil (TFI 5-FU) 900 mg/m2, days 1, 2, 8, 9, 15, 16, 22 and 23; irinotecan (CPT-11) 160 mg/m2 plus BEV 5 mg/kg, days 1, 15; oxaliplatin (OXP) 80 mg/m2, days 8, 22; every 4 weeks. MCRC patients were classified as L-L and O/MM. Activity and efficacy were evaluated and compared using log-rank test.

Results
In all, 59 patients were evaluated: 31 KRAS wild-type (53%), 28 KRAS mutant (47%). At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11 months, 20 months. PFS and OS were not significantly different. PFS and OS were significantly different in L-L compared to O/MM evaluable patients. In KRAS wild-type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In KRAS mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not significantly different: PFS 11 months equivalently and OS 39 versus 19 months, respectively.

Conclusions
The KRAS genotype wild-type and mutant does not significantly affect different clinical outcomes for MCRC patients treated with the first-line FIr-B/FOx intensive regimen. KRAS wild-type patients with L-L disease may achieve a significantly prolonged clinical outcome due to integration with secondary liver surgery, with respect to KRAS mutant patients.
Polymers containing phosphorus groups and polyethers: from synthesis to application
Authors: Iliescu Smaranda , Zubizarreta Leire , Plesu Nicoleta , Macarie Lavinia , Popa Adriana , Ilia Gheorghe 
Published: November 2012

Abstract

Background
Phosphorus-containing high performance polymers have aroused wide interest, mainly due to good mechanical properties and their excellent fire resistance. The flexibility of synthetic polyphosphoesters allows the development of polymers in order to obtain solid polymer electrolytes for rechargeable lithium batteries based on solid films with superior fire resistance.

Results
Novel linear Phosphonate-PEG polymers were synthesized by solution polycondensation of 4-chlorophenyldichlorophosphonate as a linking agent and poly(ethylene glycol)s with different molecular weights in the presence of triethylamine or 1-methylimidazole as acid scavenger. The yields were between 54% and 88% and inherent viscosity between 0.18-0.48 dl/g. Molar masses, Mn were about 26300 g/mol for polyphosphonates with PEG 2000 and 4600 g/mol for polyphosphonates with PEG 200. The LOI values for these polymers and membranes are in the range of 26–29. The membranes based on polyphosphonate with PEG 200 and 2000 showed conductivity between 6 × 10-8 S.cm-1 and 6 × 10-7 S.cm-1 at room temperature and total ionic transference number between 0.87- 0.96. The evolution of conductivity vs. temperature is linear.

Conclusions
1-methylimidazole was found to be better HCl scavenger than triethylamine, and allowed higher yields and more eco-friendly synthesis of the Phosphonate-PEG polymers for SPE. These polymers and membranes based on these polymers showed good LOI values and indicate an improvement of the safety of lithium batteries. The membranes present conductivities around 6 × 10-7 S.cm-1at room temperature and total ionic transference number is higher for membranes based on polymers with high EG unit content. Best results yield 88%, inherent viscosities 0.48 dl/g and Mn 26000 were obtained with 1-methylimidazole and PEG 2000. These membranes based on these polymers showed good LOI values (in the range 26-29%) and indicate an improvement of the safety of lithium batteries.
Crystal structures of wild-type and mutated cyclophilin B that causes hyperelastosis cutis in the American quarter horse
Authors: Boudko Sergei P , Ishikawa Yoshihiro , Lerch Thomas F , Nix Jay , Chapman Michael S , Bächinger Hans Peter 
Published: November 2012

Abstract

Background
Hyperelastosis cutis is an inherited autosomal recessive connective tissue disorder. Affected horses are characterized by hyperextensible skin, scarring, and severe lesions along the back. The disorder is caused by a mutation in cyclophilin B.

Results
The crystal structures of both wild-type and mutated (Gly6->Arg) horse cyclophilin B are presented. The mutation neither affects the overall fold of the enzyme nor impairs the catalytic site structure. Instead, it locally rearranges the flexible N-terminal end of the polypeptide chain and also makes it more rigid.

Conclusions
Interactions of the mutated cyclophilin B with a set of endoplasmic reticulum-resident proteins must be affected.
Immunoregulatory properties of rapamycin-conditioned monocyte-derived dendritic cells and their role in transplantation
Authors: Macedo Camila , Turquist Hēth , Metes Diana , Thomson Angus W 
Published: November 2012

Abstract
In efforts to minimize the chronic administration of immunosuppression (IS) drugs in transplantation and autoimmune disease, various cell-based tolerogenic therapies, including the use of regulatory or tolerogenic dendritic cells (tolDC) have been developed. These DC-based therapies aim to harness the inherent immunoregulatory potential of these professional antigen-presenting cells. In this short review, we describe both the demonstrated tolerogenic properties, and current limitations of rapamycin-conditioned DC (RAPA-DC). RAPA-DC are generated through inhibition of the integrative kinase mammalian target of rapamycin (mTOR) by the immunosuppressive macrolide rapamycin during propagation of monocyte-derived DC. Consistent with the characteristics of tolDC, murine RAPA-DC display resistance to phenotypic maturation induced by pro-inflammatory stimuli; exhibit the ability to migrate to secondary lymphoid tissue (important for ‘cross-presentation’ of antigen to T cells), and enrich for naturally-occurring CD4+ regulatory T cells. In rodent models, delivery of recipient-derived RAPA-DC pulsed with donor antigen prior to organ transplantation can prolong allogeneic heart-graft survival indefinitely, especially when combined with a short course of IS. These encouraging data support ongoing efforts to develop RAPA-DC for clinical testing. When compared to murine RAPA-DC however, human RAPA-DC have proven only partially resistant to maturation triggered by pro-inflammatory cytokines, and display heterogeneity in their impact on effector T-cell expansion and function. In total, the evidence suggests the need for more in-depth studies to better understand the mechanisms by which mTOR controls human DC function. These studies may facilitate the development of RAPA-DC therapy alone or together with agents that preserve/enhance their tolerogenic properties as clinical immunoregulatory vectors.
Organic amendment of an ultisol: effects on soil properties, growth, and yield of maize in Southern Guinea savanna zone of Nigeria
Authors: Ogundare Kayode , Agele Samuel , Aiyelari Peter 
Published: November 2012

Abstract

Background
The Southern Guinea savanna zone of Nigeria is characterized by inherently low soil fertility status and rapid nutrient depletion especially soil organic matter. However, this zone is characterized by abundant agricultural land and is a potential for crop production. Field experiments were conducted in order to evaluate the effects of integrated use of agricultural waste materials and compound mineral fertilizer on soil and plant nutrient status, growth, and yield of maize in ultisol in the Southern Guinea savanna zone of Nigeria.

Results
Application of organic waste alone and in combination with mineral fertilizer enhanced root and shoot biomass, leaf area development, and yield and components of maize. Treatment effects were significant on growth characteristics of maize (stem girth, leaf area, plant height and days to 50% tasselling, root and shoot biomass). Sole application of NPK fertilizer (400 kg/ha) was not significant over the combined use of poultry manure and NPK on girth, leaf area, and plant height. Mean values of stem girth, leaf area, and plant height ranged between 2.05 and 3.8 cm, 0.26 and 0.54 m2, and 84.7 and 209.4 cm, respectively. Root and shoot dry weights were highest under sole NPK application compared with plots where either sole wastes or wastes in combination with reduced NPK were application of NPK fertilizer (400 kg/ha) was not significant over combined use of poultry manure and NPK on stem applied. Integrated use of agricultural wastes and NPK also enhanced root and shoot dry weights compared with sole application of wastes as well as seed weight per plant, 100-seed weight, and number of seeds per cob and grain yield. Among the agricultural wastes applied, poultry manure enhanced the growth and seed yield characteristics of maize. This treatment increased the seed weight per plant, number of seeds per cob, 100-seed weight and seed yield by 55.6%, 66.5%, and 55.4%, respectively over Chromolaena and neem seed cake. Chromolaena and neem seed cake produced similar grain weight per plant, 100-seed weight, number of seed per cob, and seed yield. Poultry manure significantly enhanced the growth and seed yield characteristics of maize over Chromolaena and neem seed cake.

Conclusions
Integrated use of organic wastes and mineral NPK fertilizer showed promising potential for improving soil fertility, growth, and yield of maize in the Southern Guinea savanna agroecological zone of Nigeria. It is recommended that poultry manure at 7 t/ha plus NPK fertilizer at 200 kg/ha be adopted for maize cultivation in the study area.
Aggressive disease defined by cytogenetics is associated with cytokine dysregulation in CLL/SLL patients
Authors: Karmali Reem , Paganessi Laura A , Frank Robin R , Jagan Sucheta , Larson Melissa L , Venugopal Parameswaran , Gregory Stephanie A , Christopherson Kent W 
Published: November 2012

Abstract
Specific cytokine signatures correlate with genetic aberrations in CLL/SLL, reflecting a pattern of Th1/Th2/Treg dysregulation that may predict aggressive disease, and a need for therapy.
Early treatment of CLL/SLL does not impact survival-reflecting limitations in detecting progression early and identifying asymptomatic patients likely to benefit from early treatment. Improved understanding of CLL/SLL biology would identify better prognostic/predictive markers. This study attempts to address these issues by determining the relationship between cytokine aberrations and poor clinical outcomes in CLL/SLL in the context of a genetic–based prognostic model. Fifty-nine serum cytokines/chemokines were measured in 28 untreated CLL/SLL patients. Patients were stratified as GR or int/PR using cytogenetics. Comparison of CLL/SLL with 28 HCs revealed increased expression of Th2 cytokines (IL-10, IL-5, sIL-2Rα; P≤0.01) and decreased levels of Th1 cytokines (IL-17, IL-23, IFN-γ; P≤0.003). In a multivariate analysis of GR versus int/PR groups, differential expression of sIL-2Rα maintained significance with increased expression in int/PR CLL/SLL. With median follow-up of 54.3 months after diagnosis, four patients incurred disease progression, with an IL-17/sIL-2Rα model predicting need for treatment in all cases. In summary, specific cytokine signatures are associated with genetically defined aggressive disease and predict need for therapy. This suggests utility in detecting disease progression early, identifying those likely to incur a survival advantage with early treatment, and directing future therapy.
Current trends in inflammatory and immunomodulatory mediators in sepsis
Authors: Aziz Monowar , Jacob Asha , Yang Weng-Lang , Matsuda Akihisa , Wang Ping 
Published: November 2012

Abstract
Review on sepsis mediators, and roles in innate and adaptive immune systems, as well as implications for therapeutics.
Sepsis refers to severe systemic inflammation in response to invading pathogens. An overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Cytokines, proteases, lipid mediators, gaseous substances, vasoactive peptides, and cell stress markers play key roles in sepsis pathophysiology. Various adhesion molecules and chemokines sequester and activate neutrophils into the target organs, further augmenting inflammation and tissue damage. Although the anti-inflammatory substances counterbalance proinflammatory mediators, prolonged immune modulation may cause host susceptibility to concurrent infections, thus reflecting enormous challenge toward developing effective clinical therapy against sepsis. To understand the complex interplay between pro- and anti-inflammatory phenomenon in sepsis, there is still an unmet need to study newly characterized mediators. In addition, revealing the current trends of novel mediators will upgrade our understanding on their signal transduction, cross-talk, and synergistic and immunomodulating roles during sepsis. This review highlights the latest discoveries of the mediators in sepsis linking to innate and adaptive immune systems, which may lead to resolution of many unexplored queries.
The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with retinoic acid receptors (RARs) in the regulation of myeloid differentiation
Authors: Chee Lynette C Y , Hendy Jean , Purton Louise E , McArthur Grant A 
Published: November 2012

Abstract
Residual granulopoiesis persists in mice lacking both G-CSFR and RARα, or RARγ; G-CSFR is required for granulopoietic expansion seen with loss of RARγ.
The key roles of RARs and G-CSFR in the regulation of granulopoiesis have been well-documented. In this study, we sought to investigate the interaction between G-CSFR and RARs in myeloid differentiation of adult mice through conditional deletion of RARα or RARγ on a G-CSFR−/− background and by pharmacological intervention of WT and G-CSFR−/− mice with a pan-RAR inverse agonist, NRX194310. Our findings show that residual granulopoiesis still persists in mice doubly null for G-CSFR and RARα or RARγ, confirming that RARs and G-CSFR are dispensable in maintaining residual granulopoiesis. Moreover, an increase in mature myeloid cells was seen in the conditional RARγΔ/Δ mice and WT mice treated with NRX194310, likely mediated through increased G-CSF production. However, with the loss of G-CSFR, this expansion in granulopoiesis was attenuated, supporting the hypothesis that G-CSFR signaling interacts with RARs in the regulation of myeloid differentiation.
Reduction of pro-tumorigenic activity of human prostate cancer-associated fibroblasts using Dlk1 or SCUBE1
Authors: Orr Brigid , Grace O. Cathal , Brown Pam , Riddick Antony C. P. , Stewart Grant D. , Franco Omar E. , Hayward Simon W. , Thomson Axel A. 
Published: November 2012

Summary
Human prostatic cancer-associated fibroblasts (CAFs) can elicit malignant changes in initiated but non-tumorigenic human prostate epithelium, demonstrating that they possess pro-tumorigenic properties. We set out to reduce the pro-tumorigenic activity of patient CAFs using the Dlk1 and SCUBE1 molecules that we had previously identified in prostate development. Our hypothesis was that mesenchymally expressed molecules might reduce CAF pro-tumorigenic activity, either directly or indirectly. We isolated primary prostatic CAFs and characterised their expression of CAF markers, expression of Notch2, Dlk1 and SCUBE1 transcripts, and confirmed their ability to stimulate BPH1 epithelial cell proliferation. Next, we expressed Dlk1 or SCUBE1 in CAFs and determined their effects upon tumorigenesis in vivo following recombination with BPH1 epithelia and xenografting in SCID mice. Tumour size was reduced by about 75% and BPH1 proliferation was reduced by about 50% after expression of Dlk1 or SCUBE1 in CAFs, and there was also a reduction in invasion of BPH1 epithelia into the host kidney. Inhibition of Notch signalling, using inhibitor XIX, led to a reduction in BPH1 cell proliferation in CAF-BPH1 co-cultures, whereas inhibition of Dlk1 in NIH3T3-conditioned media led to an increase in BPH1 growth. Our results suggest that pro-tumorigenic CAF activity can be reduced by the expression of developmental pathways.
An Overloaded Multiclass FIFO Queue with Abandonments
Authors: Jennings Otis B. , Reed Josh E. 
Published: November 2012

In this paper we consider a single-server queue fed by K independent renewal arrival streams, each representing a different job class. Jobs are processed in a FIFO fashion, regardless of class. The total amount of work arriving to the system exceeds the server's capacity. That is, the nominal traffic intensity of the system is assumed to be greater than one. Jobs arriving to the system grow impatient and abandon the queue after a random amount of time if service has not yet begun. Interarrival, service, and abandonment times are assumed to be generally distributed and class specific. We approximate this system using both fluid and diffusion limits. To this end, we consider a sequence of systems indexed by n in which the arrival and service rates are proportional to n; the abandonment distribution remains fixed across the sequence. In our first main result, we show that in the limit as n tends to infinity, the virtual waiting time process converges to a limiting deterministic process. This limit may be characterized as the solution to a first-order ordinary differential equation (ODE). Specific examples are then presented for which the ODE may be explicitly solved. In our second main result, we refine the deterministic fluid approximation by showing that the fluid-centered and diffusion-scaled virtual waiting time process weakly converges to an Ornstein-Uhlenbeck process whose drift and infinitesimal variance both vary over time. This process may also be solved for explicitly, thus yielding approximations to the transient as well as steady-state behavior of the virtual waiting time process.
Pancreatitis: A Potential Complication of Liraglutide?
Authors: Franks Andrea S , Lee Phillip H , George Christa M 
Published: November 2012

OBJECTIVE: To review the evidence surrounding a potential association between liraglutide and pancreatitis. DATA SOURCES: A literature search was conducted in MEDLINE (1948-July 12, 2012) and EMBASE (1974-week 27, 2012) using the search terms pancreatitis, liraglutide, and glucagon-like peptide 1/adverse effects. Reference citations from identified publications were reviewed. The manufacturer was contacted and regulatory documents from the Food and Drug Administration website were reviewed for unpublished data related to cases of pancreatitis associated with liraglutide use. STUDY SELECTION AND DATA EXTRACTION: All identified sources that were published in English were considered for inclusion. DATA SYNTHESIS: Eleven cases of pancreatitis have been reported in patients taking liraglutide. Seven were from the LEAD (Liraglutide Effect and Action in Diabetes) studies, 1 was reported in the extension of a clinical trial, and 1 was in an unpublished obesity trial. Two were published postmarketing case reports. Nine of the cases reported were diagnosed as acute pancreatitis, while 2 were classified as chronic pancreatitis. The mean age of the patients was 57.5 years and mean body mass index was 33.92 kg/m2. Six of the 11 cases occurred in male patients. Nine of the patients were white and 1 was African American. In 7 of the cases, onset occurred at liraglutide doses at or above 1.8 mg daily. Common comorbidities included history of pancreatitis, cholelithiasis, and diabetes. One case was fatal. CONCLUSIONS: Pancreatitis is a potential complication with liraglutide therapy. Liraglutide should be used cautiously in patients at risk of pancreatitis (eg, alcohol abuse, history of pancreatitis, cholelithiasis).