bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dressed to impress: impact of environmental adaptation on the Candida albicans cell wall
Authors: Hall Rebecca A. 
Published: April 2015

SummaryCandida albicans is an opportunistic fungal pathogen of humans causing superficial mucosal infections and life‐threatening systemic disease. The fungal cell wall is the first point of contact between the invading pathogen and the host innate immune system. As a result, the polysaccharides that comprise the cell wall act as pathogen associated molecular patterns, which govern the host–pathogen interaction. The cell wall is dynamic and responsive to changes in the external environment. Therefore, the host environment plays a critical role in regulating the host–pathogen interaction through modulation of the fungal cell wall. This review focuses on how environmental adaptation modulates the cell wall structure and composition, and the subsequent impact this has on the innate immune recognition of C. albicans.
Rice cyclophilin OsCYP18‐2 is translocated to the nucleus by an interaction with SKIP and enhances drought tolerance in rice andArabidopsis
Authors: Lee Sang Sook , Park Hyun Ji , Yoon Dae Hwa , Kim Beom‐Gi , Ahn Jun Cheul , Luan Sheng , Cho Hye Sun 
Published: April 2015

AbstractCyclophilin 18‐2(CYP18‐2) genes, homologues of humanpeptidyl‐prolyl isomerase‐like 1(PPiL1), are conserved across multicellular organisms andSchizosaccharomyces pombe. AlthoughPPiL1is known to interact with ski‐interacting protein (SKIP), a transcriptional co‐regulator and spliceosomal component, there have been no functional analyses ofPPiL1homologues in plants. Rice cyclophilin 18‐2 (OsCYP18‐2) bound directly to amino acids 56–95 ofOsSKIPand its binding was independent of cyclosporinA, a cyclophilin‐binding drug. Moreover,OsCYP18‐2 exhibitedPPIaseactivity regardless of its interaction withOsSKIP. Therefore, the binding site forOsCYP18‐2's interaction withSKIPwas distinct from thePPIaseactive site.OsCYP18‐2's interaction withSKIPfull‐length protein enabledOsCYP18‐2's translocation from the cytoplasm into the nucleus andAtSKIPinteractedin plantawith bothAtCYP18‐2 andOsCYP18‐2. Drought and salt stress induced similar expression ofOsCYP18‐2andOsSKIP. Overexpression ofOsCYP18‐2in transgenic rice andArabidopsis thalianaplants enhanced drought tolerance and altered expression and pre‐mRNAsplicing patterns of stress‐related genes inArabidopsisunder drought conditions. Furthermore,OsCYP18‐2 caused transcriptional activation with/withoutOsSKIPin theGAL4 system of yeast; thus theOsSKIP‐OsCYP18‐2 interaction has an important role in the transcriptional and post‐transcriptional regulation of stress‐related genes and increases tolerance to drought stress.
Two cases of transplant renal artery thrombosis and spontaneous rupture caused by mucormycosis
Authors: Zhu X. , Liu H. , Wang W. , Song S. , Jin M. , Hu X. , Zhang X. 
Published: April 2015

AbstractMucormycosis is an uncommon infectious complication after renal transplantation and is associated with fatal outcomes. We report 2 cases of transplant renal artery thrombosis and spontaneous rupture caused by mucormycosis. As stenosis, thrombosis, and spontaneous rupture of the transplant renal artery began to occur in both cases after renal transplantation, nephrectomy of the transplanted kidney was performed. Postoperative pathological findings in the transplanted kidney revealed an invasive mucormycosis infection in the renal artery. One patient survived, but the other patient died. This report also presents the diagnosis and treatment processes used for this transplant complication.
Pre‐transplant antibody screening and anti‐CD154 costimulation blockade promote long‐term xenograft survival in a pig‐to‐primate kidney transplant model
Authors: Higginbotham Laura , Mathews Dave , Breeden Cynthia A. , Song Mingqing , Farris Alton Brad , Larsen Christian P. , Ford Mandy L. , Lutz Andrew J. , Tector Matthew , Newell Kenneth A. , Tector A. Joseph , Adams Andrew B. 
Published: April 2015

AbstractXenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end‐stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig‐to‐primate kidney xenotransplantation has met limited success. Preformed anti‐pig antibodies are an important component of the xenogeneic immune response. To address this, we screened a cohort of 34 rhesus macaques for anti‐pig antibody levels. We then selected animals with both low and high titers of anti‐pig antibodies to proceed with kidney transplant from galactose‐α1,3‐galactose knockout/CD55 transgenic pig donors. All animals received T‐cell depletion followed by maintenance therapy with costimulation blockade (either anti‐CD154 mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high titer of anti‐pig antibody rejected the kidney xenograft within the first week. Low‐titer animals treated with anti‐CD154 antibody, but not belatacept exhibited prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days, respectively). Long‐term surviving animals treated with the anti‐CD154‐based regimen continue to have normal kidney function and preserved renal architecture without evidence of rejection on biopsies sampled at day 100. This description of the longest reported survival of pig‐to‐non‐human primate kidney xenotransplantation, now >125 days, provides promise for further study and potential clinical translation.
Pig‐to‐baboon heterotopic heart transplantation – exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade‐based regimens
Authors: Iwase Hayato , Ekser Burcin , Satyananda Vikas , Bhama Jay , Hara Hidetaka , Ezzelarab Mohamed , Klein Edwin , Wagner Robert , Long Cassandra , Thacker Jnanesh , Li Jiang , Zhou Hao , Jiang Maolin , Nagaraju Santosh , Zhou Huidong , Veroux Massimiliano , Bajona Pietro , Wijkstrom Martin , Wang Yi , Phelps Carol , Klymiuk Nikolai , Wolf Eckhard , Ayares David , Cooper David K. C. 
Published: April 2015

AbstractBackgroundThree costimulation blockade‐based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4‐Ig (abatacept) or anti‐CD40mAb+CTLA4‐Ig (belatacept) can successfully replace anti‐CD154mAb.MethodsAll pigs were on an α1,3‐galactosyltransferase gene‐knockout/CD46 transgenic (GTKO.CD46) background. Hearts transplanted into Group A baboons (n = 4) expressed additional CD55, and those into Group B (n = 3) expressed human thrombomodulin (TBM). Immunosuppression included anti‐thymocyte globulin with anti‐CD154mAb (Regimen 1: n = 2) or abatacept (Regimen 2: n = 2) or anti‐CD40mAb+belatacept (Regimen 3: n = 2). Regimens 1 and 2 included induction anti‐CD20mAb and continuous heparin. One further baboon in Group B (B16311) received a modified Regimen 1. Baboons were followed by clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft failure, or euthanasia, the graft was examined by microscopy.ResultsGroup A baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days, respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21 days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by histopathology. In Group B, with follow‐up for >4 m, areas of myofiber degeneration and scarring were seen in two hearts at necropsy. A T‐cell response was documented only in baboons receiving Regimen 2.ConclusionsThe combination of anti‐CD40mAb+belatacept proved effective in preventing a T‐cell response. The expression of TBM prevented thrombocytopenia and may possibly delay the development of TM and/or consumptive coagulopathy.
Psychotropic drug use in adolescents born with an orofacial cleft: a population-based study
Authors: Nilsson Sofia , Merlo Juan , Lyberg-Åhlander Viveka , Psouni Elia 
Published: April 2015

ObjectivesBeing born with an orofacial cleft (OFC) can, due to an incomplete closure of the lip and/or palate, convey a deviant speech and/or deviant facial aesthetics, which may in turn increase the risk for poor psychological health later in life. Previous investigations have been based on small samples and self-reports, not distinguishing between the three different types of OFC: cleft lip (CL), CL and palate (CLP) and cleft palate only (CPO). We present a large population-based study, considering psychotropic drug use as a proxy for poor psychological health and distinguishing between three different types of OFC.Design and methodsUsing theSwedish Medical Birth Register, and linking to it theSwedish Prescribed Drug Register, theNational Mortality Register, theEmigration Registerand theNational Inpatient Register, we identified all singletons born to native mothers in Sweden between 1987 and 1993, alive and residing in Sweden at the end of an 18-year follow-up period (N=626 109). We compared psychotropic drug use among individuals with and without OFC during the individuals’ adolescence (2005–2008) by multiple logistic regressions, using ORs with 95% CIs.ResultsWhen adjusted for potential confounders, having a CL (OR=1.63, 95% CI 1.08 to 2.46) or a CPO (OR=1.54, 95% CI 1.18 to 2.01) increased the risk of psychotropic drug use. Results were not significant regarding adolescents who had a CLP (OR=1.21, 95% CI 0.81 to 1.80).ConclusionsBeing born with a CL or a CPO increases the risk for psychotropic drug use in adolescence, but not for adolescents born with a CLP. Our findings suggest that, since the three OFC types are associated with different long-term risks of poor psychological health, the three groups should be studied separately concerning long-term psychosocial consequences.
Risk factors for emergency presentation with lung and colorectal cancers: a systematic review
Authors: Mitchell Elizabeth D , Pickwell-Smith Benjamin , Macleod Una 
Published: April 2015

ObjectiveTo identify patient and practitioner factors that influence cancer diagnosis via emergency presentation (EP).DesignSystematic review.Data sourcesMEDLINE, EMBASE, CINAHL, EBM Reviews, Science and Social Sciences Citation Indexes, Conference Proceedings Citation Index-Science and Conference Proceedings Citation Index-Social Science and Humanities. Searches were undertaken from 1996 to 2014. No language restrictions were applied.Study selectionStudies of any design assessing factors associated with diagnosis of colorectal or lung cancer via EP, or describing an intervention to impact on EP, were included. Studies involving previously diagnosed cancer patients, assessing only referral pathway effectiveness, outcomes related to diagnosis or post-EP management were excluded. The population was individual or groups of adult patients or primary care practitioners. Two authors independently screened studies for inclusion.Results22 studies with over 200 000 EPs were included, most providing strong evidence. Five were graded ‘insufficient’, primarily due to missing information rather than methodological weakness. Older patient age was associated with EP for lung and colorectal cancers (OR 1.11–11.03 and 1.19–5.85, respectively). Women were more at risk of EP for lung but not colorectal cancer. Higher deprivation increased the likelihood of lung cancer EP, but evidence for colorectal was less conclusive. Being unmarried (or divorced/widowed) increased the likelihood of EP for colorectal cancer, which was also associated with pain, obstruction and weight loss. Lack of a regular source of primary care, and lower primary care use were positively associated with EP. Only three studies considered practitioner factors, two involving diagnostic tests. No conclusive evidence was found.ConclusionsPatient-related factors, such as age, gender and deprivation, increase the likelihood of cancer being diagnosed as the result of an EP, while cancer symptoms and patterns of healthcare utilisation are also relevant. Further work is needed to understand the context in which risk factors for EP exist and influence help-seeking.
Industrial hygiene, occupational safety and respiratory symptoms in the Pakistani cotton industry
Authors: Khan Abdul Wali , Moshammer Hanns Michael , Kundi Michael 
Published: April 2015

ObjectivesIn the cotton industry of Pakistan, 15 million people are employed and exposed to cotton dust, toxic chemicals, noise and physical hazards. The aim of this study was to determine the prevalence of health symptoms, particularly respiratory symptoms, and to measure cotton dust and endotoxin levels in different textile factories of Faisalabad, Pakistan.MethodsA cross-sectional investigation was performed in a representative sample of 47 cotton factories in the Faisalabad region in Punjab, Pakistan. Respiratory symptoms of 800 workers were documented by questionnaire. Occupational safety in the factories was assessed by a trained expert following a checklist, and dust and endotoxin levels in different work areas were measured.ResultsPrevalence of respiratory disease symptoms (fever, shortness of breath, chest tightness and cough) was generally high and highest in the weaving section of the cotton industry (20–40% depending on symptoms). This section also displayed the poorest occupational safety ratings and the highest levels of inhalable cotton dust (mean±SD 4.6±2.5 vs 0.95±0.65 mg/m3in compact units). In contrast, endotoxin levels were highest in the spinning section (median 1521 EU/m3), where high humidity is maintained.ConclusionsThere are still poor working conditions in the cotton industry in Pakistan where workers are exposed to different occupational hazards. More health symptoms were reported from small weaving factories (power looms). There is a dire need for improvements in occupational health and safety in this industrial sector with particular focus on power looms.
Experience with vertebral artery origin stenting and ostium dilatation: results of treatment and clinical outcomes
Authors: Rangel-Castilla Leonardo , Gandhi Sirin , Munich Stephan A , Cress Marshall C , Sonig Ashish , Krishna Chandan , Hopkins L Nelson , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H 
Published: April 2015

BackgroundThe vertebral artery (VA) ostium (VAO) is a common stenosis site. Most patients with VAO stenosis refractory to medical treatment are treated endovascularly using stenting. To optimally cover the ostial plaque, which frequently extends into the adjacent subclavian artery, part of the stent must overhang in the subclavian artery. This configuration makes subsequent VA access very challenging in cases of in-stent or distal vertebrobasilar pathology; it also obstructs the distal subclavian artery.ObjectiveTo determine whether angioplasty at the ostium with a dual balloon (Flash Ostial) specially designed to allow the subclavian end of the stent to flare might circumvent these problems and, most importantly, provide optimal plaque coverage around the vertebral ostium.MethodsBetween June 2012 and July 2014, 11 patients with symptomatic VAO stenosis refractory to best medical therapy were treated with stenting and dual balloon Flash angioplasty. Demographics, results, and outcomes were reviewed.ResultsA total of 12 VAO stenting–dual balloon angioplasty procedures were performed (mean stenosis, 83.6%; range, 78–90%). Nine patients had mild-to-moderate (40–60%) contralateral VAO stenosis. The initial average modified Rankin Scale (mRS) score was 1.25. In all cases, immediate postangioplasty angiography showed excellent stent apposition against the VA and around the ostium in the subclavian artery. No permanent perioperative complications or deaths occurred. At a mean follow-up of 10.8 months (range 2–24), all patients had symptom resolution and no evidence of symptomatic restenosis on neuroimaging/Doppler studies; the average mRS score was 0.66. Three patients continued to have previously diagnosed mid-cervical VA stenosis; one of them had postprocedure dissection and an asymptomatic in-stent stenosis at 8 months.ConclusionsSafety and feasibility were demonstrated using the Ostial Flash system for VAO stenting and angioplasty. No permanent perioperative complications were seen.
Data Mining of Online Genealogy Datasets for Revealing Lifespan Patterns in Human Population
Authors: Fire Michael , Elovici Yuval 
Published: April 2015

Online genealogy datasets contain extensive information about millions of people and their past and present family connections. This vast amount of data can help identify various patterns in the human population. In this study, we present methods and algorithms that can assist in identifying variations in lifespan distributions of the human population in the past centuries, in detecting social and genetic features that correlate with the human lifespan, and in constructing predictive models of human lifespan based on various features that can easily be extracted from genealogy datasets.
We have evaluated the presented methods and algorithms on a large online genealogy dataset with over a million profiles and over 9 million connections, all of which were collected from the WikiTree website. Our findings indicate that significant but small positive correlations exist between the parents’ lifespan and their children’s lifespan. Additionally, we found slightly higher and significant correlations between the lifespans of spouses. We also discovered a very small positive and significant correlation between longevity and reproductive success in males, and a small and significant negative correlation between longevity and reproductive success in females. Moreover, our predictive models presented results with a Mean Absolute Error as low as 13.18 in predicting the lifespans of individuals who outlived the age of 10, and our classification models presented better than random classification results in predicting which people who outlive the age of 50 will also outlive the age of 80.
We believe that this study will be the first of many studies to utilize the wealth of data on human populations, existing in online genealogy datasets, to better understand factors that influence the human lifespan. Understanding these factors can assist scientists in providing solutions for successful aging.
CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells
Authors: Wang Xiuli , Wong ChingLam W. , Urak Ryan , Mardiros Armen , Budde Lihua E. , Chang Wen-Chung , Thomas Sandra H. , Brown Christine E. , La Rosa Corinna , Diamond Don J. , Jensen Michael C. , Nakamura Ryotaro , Zaia John A. , Forman Stephen J. 
Published: April 2015

Abstract
Purpose: T cells engineered with chimeric antigen receptors (CAR) recognizing CD19 can induce complete remission of B-cell malignancies in clinical trials; however, in some disease settings, CAR therapy confers only modest clinical benefit due to attenuated persistence of CAR T cells. The purpose of this study was to enhance persistence and augment the antitumor activity of adoptively transferred CD19CAR T cells by restimulating CAR+ T cells through an endogenous cytomegalovirus (CMV)-specific T-cell receptor.
Experimental Design: CMV-specific T cells from CMV seropositive healthy donors were selected after stimulation with pp65 protein and transduced with clinical-grade lentivirus expressing the CD19R:CD28:ζ/EGFRt CAR. The resultant bispecific T cells, targeting CMV and CD19, were expanded via CD19 CAR-mediated signals using CD19-expressing cells.
Results: The bispecific T cells proliferated vigorously after engagement with either endogenous CMVpp65 T-cell receptors or engineered CD19 CARs, exhibiting specific cytolytic activity and IFNγ secretion. Upon adoptive transfer into immunodeficient mice bearing human lymphomas, the bispecific T cells exhibited proliferative response and enhanced antitumor activity following CMVpp65 peptide vaccine administration.
Conclusions: We have redirected CMV-specific T cells to recognize and lyse tumor cells via CD19CARs, while maintaining their ability to proliferate in response to CMV antigen stimulation. These results illustrate the clinical applications of CMV vaccine to augment the antitumor activity of adoptively transferred CD19CAR T cells in patients with B-cell malignancies. Clin Cancer Res; 21(13); 2993–3002. ©2015 AACR.
Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab
Authors: Napolitano Stefania , Martini Giulia , Rinaldi Barbara , Martinelli Erika , Donniacuo Maria , Berrino Liberato , Vitagliano Donata , Morgillo Floriana , Barra Giusy , De Palma Raffaele , Merolla Francesco , Ciardiello Fortunato , Troiani Teresa 
Published: April 2015

Abstract
Purpose: In colorectal cancer, the activation of the intracellular RAS–RAF and PIK3CA–AKT pathways has been implicated in the resistance to anti-EGFR mAbs. We have investigated the role of regorafenib, an oral multikinase inhibitor, in combination with cetuximab, an anti-EGFR mAb, to overcome anti-EGFR resistance.
Experimental Design: We have tested, in vitro and in vivo, the effects of regorafenib in a panel of human colorectal cancer cell lines with a KRAS mutation (SW480, SW620, HCT116, LOVO, and HCT15) or with a BRAF mutation (HT29), as models of intrinsic resistance to cetuximab treatment, and in two human colorectal cancer cell lines (GEO and SW48) that are cetuximab-sensitive, as well as in their derived cells with acquired resistance to cetuximab (GEO-CR and SW48-CR).
Results: Treatment with regorafenib determined a dose-dependent growth inhibition in all colorectal cancer cell lines. The combined treatment with cetuximab and regorafenib induced synergistic antiproliferative and apoptotic effects in cetuximab-resistant cell lines by blocking MAPK and AKT pathways. Nude mice were injected s.c. with HCT116, HCT15, GEO-CR, and SW48-CR cells. The combined treatment caused significant tumor growth inhibition. Synergistic antitumor activity of regorafenib plus cetuximab was also observed in an orthotopic colorectal cancer model of HCT116 cells. In particular, the combined treatment induced a significant tumor growth inhibition in the primary tumor site (cecum) and completely prevented metastasis formation.
Conclusions: The combined treatment with cetuximab and regorafenib could be a strategy to overcome resistance to anti-EGFR therapies in metastatic colorectal cancer patients. Clin Cancer Res; 21(13); 2975–83. ©2015 AACR.