bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of multiple sclerosis in south-western Sardinia
Authors: Cocco Eleonora , Sardu Claudia , Massa Rita , Mamusa Elena , Musu Luigina , Ferrigno Paola , Melis Maurizio , Montomoli Cristina , Ferretti Virginia , Coghe Giancarlo , Fenu Giuseppe , Frau Jessica , Lorefice Lorena , Carboni Nicola , Contu Paolo , Marrosu Maria G 
Published: June 2011

Background: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south-western Sardinia (SWS) are available. SWS has a genetically homogeneous population, apart from St Peter Island, and represents a peculiar environment related to the industrial, mineralogical and military economy. Objective: To estimate prevalence and incidence and to evaluate temporal trends and geographical distribution of MS in SWS. Methods: MS prevalence was evaluated on 31 December 2007 and crude mean annual incidence rate was defined between 2003 and 2007. Temporal trend in MS incidence was assessed using the Armitage test. To identify MS clusters, Standard Morbidity Ratio (SMR) was calculated for each village and geographical distribution prevalence by means of a Bayesian hierarchical model. Results: Total crude prevalence rate was 210.4 (95% CI 186.3–234.5): 280.3 (95% CI 241.4–319.3) for females, 138 (95% CI 110.1–165.8) for males. The crude mean annual incidence rate was 9.7/100,000 (95% CI 3.4–13.2): 4.7/100,000 (95% CI 2.4–17.0) and 14.6/100,000 (95% CI 11.8–34.8) for males and females respectively. MS incidence has increased over the last 50 years. Cluster analysis showed an SMR of 0.2 (95% CI 0.05–0.68, p = 0.002) on the island of San Pietro, and 2.0 (95% CI 1.35–2.95, p = 0.001) in Domusnovas. Spatial distribution of MS was confirmed by Bayesian geographical analysis. Conclusions: Our data confirm Sardinia as a high-risk area for MS and support the relevance of genetic factors in MS, as evidenced in St Peter Island. However, we found an unexpectedly high MS prevalence in one village, in particular in males, suggesting an environmental influence on MS occurrence.
The association between angiotensin-converting enzyme insertion/deletion gene variant and risk of focal segmental glomerulosclerosis: a systematic review and meta-analysis
Authors: Zhou Tian-Biao , Qin Yuan-Han , Su Li-Na , Lei Feng-Ying , Huang Wei-Fang , Zhao Yan-Jun , Pang Yu-Sheng , Yang Kun-Peng 
Published: June 2011

Background and objective: The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with the risk of focal segmental glomerulosclerosis (FSGS) is still controversial. A meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and FSGS susceptibility. Method: We performed a predefined literature search and selection of eligible relevant studies to collect data from electronic databases. Results: In total, 12 articles were identified for the analysis of the association between ACE I/D gene polymorphism and FSGS risk. One report included an investigation in Arab and Jewish populations separately. Thus, there were seven reports in Asians, two in Caucasians, one in Africans, two in Arabs and one in Jews. In Asians, there was a markedly positive association between the D allele or DD genotype and FSGS susceptibility ( p = 0.008; p = 0.002), and the II genotype may play a protective role against FSGS onset ( p = 0.002). However, a link between ACE I/D gene polymorphism and FSGS risk was not found in Caucasians, Africans, Arabs or Jews (Caucasians: D: p = 0.11, DD: p = 0.19, II: p = 0.70; Africans: D: p = 0.40, DD: p = 0.49, II: p = 0.61; Arabs: D: p = 0.34, DD: p = 0.10, II: p = 0.42; Jews: D: p = 0.90, DD: p = 0.97, II: p = 0.83). Conclusion: The D allele or DD homozygosity may become a significant genetic molecular marker for the onset of FSGS in Asians, but not for Caucasians, Africans, Arabs or Jews.
Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells
Authors: Schaniel Christoph , Sirabella Dario , Qiu Jiajing , Niu Xiaohong , Lemischka Ihor R. , Moore Kateri A. 
Published: June 2011

AbstractThe role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow and spleen, manifesting an impaired ability to maintain a self-renewing stem cell pool. Exhaustion of the stem cell pool was apparent only in the context of systemic stress by chemotherapy or transplantation of wild-type stem cells into irradiated Wif1 hosts. Paradoxically this is mediated, at least in part, by an autocrine induction of canonical Wnt signaling in stem cells on sequestration of Wnts in the environment. Additional signaling pathways are dysregulated in this model, primarily activated Sonic Hedgehog signaling in stem cells as a result of Wif1-induced osteoblastic expression of Sonic Hedgehog. We find that dysregulation of the stem cell niche by overexpression of an individual component impacts other unanticipated regulatory pathways in a combinatorial manner, ultimately disrupting niche mediated stem cell fate decisions.
Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia
Authors: Slupianek Artur , Dasgupta Yashodhara , Ren Shu-yue , Gurdek Ewa , Donlin Milene , Nieborowska-Skorska Margaret , Fleury Fabrice , Skorski Tomasz 
Published: June 2011

Abstract
Chronic myeloid leukemia chronic phase (CML-CP) CD34+ cells contain numerous DNA double-strand breaks whose unfaithful repair may contribute to chromosomal instability and disease progression to blast phase (CML-BP). These phenomena are often associated with the appearance of imatinib-resistant BCR-ABL1 kinase mutants (eg, T315I) and overexpression of BCR-ABL1. Here we show that BCR-ABL1 (nonmutated and T315I mutant) promoted RAD51 recombinase-mediated unfaithful homeologous recombination repair (HomeoRR) in a dosage-dependent manner. BCR-ABL1 SH3 domain interacts with RAD51 proline-rich regions, resulting in direct phosphorylation of RAD51 on Y315 (pY315). RAD51(pY315) facilitates dissociation from the complex with BCR-ABL1 kinase, migrates to the nucleus, and enhances formation of the nuclear foci indicative of recombination sites. HomeoRR and RAD51 nuclear foci were strongly reduced by RAD51(Y315F) phosphorylation-less mutant. In addition, peptide aptamer mimicking RAD51(pY315) fragment, but not that with Y315F phosphorylation-less substitution, diminished RAD51 foci formation and inhibited HomeoRR in leukemia cells. In conclusion, we postulate that BCR-ABL1 kinase-mediated RAD51(pY315) promotes unfaithful HomeoRR in leukemia cells, which may contribute to accumulation of secondary chromosomal aberrations responsible for CML relapse and progression.
Responsiveness of HIV-specific CD4 T cells to PD-1 blockade
Authors: Porichis Filippos , Kwon Douglas S. , Zupkosky Jennifer , Tighe Daniel P. , McMullen Ashley , Brockman Mark A. , Pavlik David F. , Rodriguez-Garcia Marta , Pereyra Florencia , Freeman Gordon J. , Kavanagh Daniel G. , Kaufmann Daniel E. 
Published: June 2011

AbstractDefining the T helper functions impaired by programmed death–1 (PD-1) is crucial for understanding its role in defective HIV control and determining the therapeutic potential of targeting this inhibitory pathway. We describe here the relationships among disease stage, levels of PD-1 expression, and reversibility of CD4 T-cell impairment. PD-L1 blockade in vitro enhanced HIV-specific production of Th0 (IL-2), Th1 (IFN-γ), Th2 (IL-13), and TFH (IL-21) cytokines by CD4 T cells. PD-L1 blockade caused an early increase in cytokine transcription and translation that preceded cell proliferation. Although the impact of PD-L1 blockade on cytokine expression and, to a lesser extent, cell proliferation was associated with markers of disease progression, restoration of cytokine secretion was also observed in most subjects with undetectable viremia. PD-L1 blockade restored cytokine secretion in both PD-1intermediate and PD-1high sorted CD4 T-cell subsets. Compared with PD-1high HIV-specific CD8 T cells, PD-1high HIV-specific CD4 T cells showed lower expression of the inhibitory molecules CD160 and 2B4, demonstrating marked differences in expression of inhibitory receptors between T-cell subsets. These data show that PD-1 impairs HIV-specific T helper responses both by limiting expansion of these cells and by inhibiting effector functions of multiple differentiated CD4 T-cell subsets.
Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models
Authors: Bertilaccio Maria Teresa Sabrina , Simonetti Giorgia , Dagklis Antonis , Rocchi Martina , Rodriguez Tania Veliz , Apollonio Benedetta , Mantovani Alberto , Ponzoni Maurilio , Ghia Paolo , Garlanda Cecilia , Caligaris-Cappio Federico , Muzio Marta 
Published: June 2011

AbstractInflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R–like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.
Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation
Authors: Morgan Gareth J. , Davies Faith E. , Gregory Walter M. , Russell Nigel H. , Bell Sue E. , Szubert Alexander J. , Coy Nuria Navarro , Cook Gordon , Feyler Sylvia , Byrne Jenny L. , Roddie Huw , Rudin Claudius , Drayson Mark T. , Owen Roger G. , Ross Fiona M. , Jackson Graham H. , Child J. Anthony ,   for the NCRI Haematological Oncology Study Group
Published: June 2011

Abstract
As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.
Decay-accelerating factor regulates T-cell immunity in the context of inflammation by influencing costimulatory molecule expression on antigen-presenting cells
Authors: Fang Chongyun , Miwa Takashi , Song Wen-Chao 
Published: June 2011

AbstractRecent studies have indicated a role of complement in regulating T-cell immunity but the mechanism of action of complement in this process remains to be clarified. Here we studied mice deficient in decay-accelerating factor (DAF), a key membrane complement regulator whose deficiency led to increased complement-dependent T-cell immune responses in vivo. By crossing OT-II and OT-I T-cell receptor transgenic mice with DAF-knockout mice, we found that lack of DAF on T cells did not affect their responses to antigen stimulation. Similarly, lack of DAF on antigen-presenting cells (APCs) of naive mice did not alter their T-cell stimulating activity. In contrast, APCs from DAF-knockout mice treated with inflammatory stimuli were found to be more potent T-cell stimulators than cells from similarly treated wild-type mice. Acquisition of higher T-cell stimulating activity by APCs in challenged DAF-knockout mice required C3 and C5aR and was correlated with decreased surface PD-L1 and/or increased CD40 expression. These findings implied that DAF suppressed T-cell immunity as a complement regulator in the context of inflammation but did not play an intrinsic role on T cells or APCs. Collectively, our data suggest a systemic and indirect role of complement in T-cell immunity.
Ear diseases among secondary school students in Xi'an, China: The role of portable audio device use, insomnia and academic stress
Authors: Chen Yang , Li Xu , Xu Zhan , Li Zonghua , Zhang Pengzhi , He Ya , Wang Fangyuan , Qiu Jianhua 
Published: June 2011

AbstractBackgroundHearing impairment negatively impacts students' development of academic, language and social skills. Even minimal unilateral hearing loss can hinder educational performance. We investigated the prevalence of ear diseases among secondary school students in the city of Xi'an, China in order to provide a foundation for evidence-based hearing healthcare.MethodsA stratified random sampling survey was conducted in 29 secondary schools. Demographics and medical histories were collected, and otologic examinations were performed. Questionnaires were administered to assess insomnia, academic stress and use of portable audio devices. Logistic regression analysis was used to identify factors associated with hearing impairment, and the association of sensorineural hearing loss with insomnia, academic stress and the use of portable audio devices was analyzed with the chi-square test.ResultsThe percentage of students with some form of ear disease was 3.32%. External ear disease, middle ear disease and sensorineural hearing loss occurred in 1.21%, 0.64% and 1.47% of the students, respectively. Boys had a relatively higher prevalence of ear disease than girls. According to our survey, the prevalence of sensorineural hearing loss increased significantly among the students with insomnia and extended use of portable audio devices, but not among those with elevated levels of academic stress. Hearing aids and surgical treatment were needed in 1.47% and 0.89% of the students, respectively.ConclusionsThere is a high prevalence of ear disease among secondary school students, and this should be given more attention. Insomnia and the excessive use of portable audio devices may be related to adolescent sensorineural hearing loss. It is important to establish and comply with an evidence-based preventive strategy.
Fatty acids intake in the Mexican population. Results of the National Nutrition Survey 2006
Authors: Ramírez-Silva Ivonne , Villalpando Salvador , Moreno-Saracho Jessica E , Bernal-Medina Daniel 
Published: June 2011

Abstract

Background
There is growing evidence that quality, rather that quantity of fat is the determinant of cardiovascular risk. The objective of the study is to describe quantitatively the intake and adequacy of fatty acid classes among the Mexican population aged 5-90 years from a probabilistic survey.

Methods
Dietary intake of individual and classes of fatty acids was computed from the dataset of the 2006 Mexican National Health and Nutrition Survey (ENSANUT2006), collected by a food frequency questionnaire. Adequacy was calculated in reference to authoritative recommendations.

Results
The mean intake of total fatty acids (TFA ≈ 25%E) fell within WHO recommendations; the intakes of saturated fatty acids (SFA) among all age-groups (45-60%) and of trans fatty acids (TrFA) in 30% of school-age children and adolescents and 20% of adults exceeded international recommendations. The mean intake of polyunsaturated fatty acids (PUFA) and particularly of n6 and n3 PUFAS, was inadequately insufficient in 50% of the sample.

Conclusions
The main public health concerns are the high intake of SFA and the suboptimal intake of PUFA in Mexican population. The TrFA intake represents a low public health risk.
Molecular interplay between leptin, insulin-like growth factor-1, and β-amyloid in organotypic slices from rabbit hippocampus
Authors: Marwarha Gurdeep , Prasanthi Jaya RP , Schommer Jared , Dasari Bhanu , Ghribi Othman 
Published: June 2011

AbstractBackgroundEvidence shows that the insulin-like growth factor-1 (IGF-1) and leptin reduce β-amyloid (Aβ) production and tau phosphorylation, two major hallmarks of Alzheimer's disease (AD). IGF-1 expression involves the JAK/STAT pathway and the expression of leptin is regulated by the mammalian target of rapamycin complex 1 (mTORC1). We have previously shown that Aβ reduces leptin by inhibiting the mTORC1 pathway and Aβ was also suggested to inhibit the JAK/STAT pathway, potentially attenuating IGF-1 expression. As IGF-1 can activate mTORC1 and leptin can modulate JAK/STAT pathway, we determined the extent to which IGF-1 and leptin can upregulate the expression of one another and protect against Aβ-induced downregulation.ResultsWe demonstrate that incubation of organotypic slices from adult rabbit hippocampus with Aβ42 downregulates IGF-1 expression by inhibiting JAK2/STAT5 pathway. Leptin treatment reverses these Aβ42 effects on IGF-1 and treatment with the STAT5 inhibitor completely abrogated the leptin-induced increase in IGF-1. Furthermore, EMSA and ChIP analyses revealed that leptin increases the STAT5 binding to the IGF-1 promoter. We also show that IGF-1 increases the expression of leptin and reverses the Aβ42-induced attenuation in leptin expression via the activation of mTORC1 signaling as the mTORC1 inhibitor rapamycin completely precluded the IGF-1-induced increase in leptin expression.ConclusionOur results demonstrate for the first time that Aβ42 downregulates IGF-1 expression and that leptin and IGF-1 rescue one another from downregulation by Aβ42. Our study provides a valuable insight into the leptin/IGF-1/Aβ interplay that may be relevant to the pathophysiology of AD.
17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and liveE. coli
Authors: Palmer Christine D , Mancuso Christy J , Weiss Jerrold P , Serhan Charles N , Guinan Eva C , Levy Ofer 
Published: June 2011

ABSTRACTDetection and clearance of bacterial infection require balanced effector and resolution signals to avoid chronic inflammation. Detection of GNB LPS by TLR4 on mϕ induces inflammatory responses, contributing to chronic inflammation and tissue injury. LXs and Rvs are endogenous lipid mediators that enhance resolution of inflammation, and their actions on primary human mϕ responses toward GNB are largely uncharacterized. Here, we report that LXA4, LXB4, and RvD1, tested at 0.1–1 μM, inhibited LPS-induced TNF production from primary human mϕ, with ATL and 17(R)-RvD1, demonstrating potent inhibition at 0.1 μM. In addition, 17(R)-RvD1 inhibited LPS-induced primary human mϕ production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1α without reducing that of IL-6 or IL-10. Remarkably, when stimulated with live Escherichia coli, mϕ treated with 17(R)-RvD1 demonstrated increased TNF production and enhanced internalization and killing of the bacteria. 17(R)-RvD1-enhanced TNF, internalization, and killing were not evident for an lpxM mutant of E. coli expressing hypoacylated LPS with reduced inflammatory activity. Furthermore, 17(R)-RvD1-enhanced, E. coli-induced TNF production was evident in WT but not TLR4-deficient murine mϕ. Thus, Rvs differentially modulate primary human mϕ responses to E. coli in an LPS- and TLR4-dependent manner, such that this Rv could promote resolution of GNB/LPS-driven inflammation by reducing mϕ proinflammatory responses to isolated LPS and increasing mϕ responses important for clearance of infection.
Protein kinase Cδ is a critical component of Dectin-1 signaling in primary human monocytes
Authors: Elsori Deena H , Yakubenko Valentin P , Roome Talat , Thiagarajan Praveena S , Bhattacharjee Ashish , Yadav Satya P , Cathcart Martha K 
Published: June 2011

ABSTRACTZymosan, a mimic of fungal pathogens, and its opsonized form (ZOP) are potent stimulators of monocyte NADPH oxidase, resulting in the production of O2.–, which is critical for host defense against fungal and bacterial pathogens and efficient immune responses; however, uncontrolled O2.– production may contribute to chronic inflammation and tissue injury. Our laboratory has focused on characterizing the signal transduction pathways that regulate NADPH oxidase activity in primary human monocytes. In this study, we examined the involvement of various pattern recognition receptors and found that Dectin-1 is the primary receptor for zymosan stimulation of O2.– via NADPH oxidase in human monocytes, whereas Dectin-1 and CR3 mediate the activation by ZOP. Further studies identified Syk and Src as important signaling components downstream of Dectin-1 and additionally identified PKCδ as a novel downstream signaling component for zymosan-induced O2.– as well as phagocytosis. Our results show that Syk and Src association with Dectin-1 is dependent on PKCδ activity and expression and demonstrate direct binding between Dectin-1 and PKCδ. Finally, our data show that PKCδ and Syk but not Src are required for Dectin-1-mediated phagocytosis. Taken together, our data identify Dectin-1 as the major PRR for zymosan in primary human monocytes and identify PKCδ as a novel downstream signaling kinase for Dectin-1-mediated regulation of monocyte NADPH oxidase and zymosan phagocytosis.