bluuebunny/crossref_metadata_2025_split huggingface dataset:
PucC and LhaA direct efficient assembly of the light‐harvesting complexes in Rhodobacter sphaeroides
Authors: Mothersole David J. , Jackson Philip J. , Vasilev Cvetelin , Tucker Jaimey D. , Brindley Amanda A. , Dickman Mark J. , Hunter C. Neil 
Published: September 2015

SummaryThe mature architecture of the photosynthetic membrane of the purple phototroph Rhodobacter sphaeroides has been characterised to a level where an atomic‐level membrane model is available, but the roles of the putative assembly proteins LhaA and PucC in establishing this architecture are unknown. Here we investigate the assembly of light‐harvesting LH2 and reaction centre‐light‐harvesting1‐PufX (RC‐LH1‐PufX) photosystem complexes using spectroscopy, pull‐downs, native gel electrophoresis, quantitative mass spectrometry and fluorescence lifetime microscopy to characterise a series of lhaA and pucC mutants. LhaA and PucC are important for specific assembly of LH1 or LH2 complexes, respectively, but they are not essential; the few LH1 subunits found in ΔlhaA mutants assemble to form normal RC‐LH1‐PufX core complexes showing that, once initiated, LH1 assembly round the RC is cooperative and proceeds to completion. LhaA and PucC form oligomers at sites of initiation of membrane invagination; LhaA associates with RCs, bacteriochlorophyll synthase (BchG), the protein translocase subunit YajC and the YidC membrane protein insertase. These associations within membrane nanodomains likely maximise interactions between pigments newly arriving from BchG and nascent proteins within the SecYEG‐SecDF‐YajC‐YidC assembly machinery, thereby co‐ordinating pigment delivery, the co‐translational insertion of LH polypeptides and their folding and assembly to form photosynthetic complexes.
Animal toxins and renal ion transport: Another dimension in tropical nephrology
Authors: Sitprija Visith , Sitprija Siravit 
Published: September 2015

AbstractRenal vascular and tubular ion channels and transporters involved in toxin injury are reviewed. Vascular ion channels modulated by animal toxins, which result in haemodynamic alterations and changes in blood pressure, include ENaC/Degenerin/ASIC, ATP sensitive K channels (KATP), Ca activated K channels (Kca) and voltage gated Ca channels, mostly L‐type. Renal tubular Na channels and K channels are also targeted by animal toxins. NHE3 and ENaC are two important targets. NCC and NKCC may be involved indirectly by vasoactive mediators induced by inflammation. Most renal tubular K channels including voltage gated K channels (Kv1), KATP, ROMK1, BK and SK are blocked by scorpion toxins. Few are inhibited by bee, wasp and spider venoms. Due to small envenoming, incomplete block and several compensatory mechanisms in renal tubules, serum electrolyte charges are not apparent. Changes in serum electrolytes are observed in injury by large amount of venom when several channels or transporters are targeted. Envenomings by scorpions and bees are examples of toxins targeting multiple ion channels and transporters.
Dipstick albuminuria and acute kidney injury recovery in critically ill septic patients
Authors: Neyra Javier A , Li Xilong , Yessayan Lenar , Adams‐Huet Beverley , Yee Jerry , Toto Robert D ,   for the Acute Kidney Injury in Critical Illness Study Group
Published: September 2015

AbstractAimAcute kidney injury (AKI) is a frequent complication of sepsis, a pro‐inflammatory state that alters tubular handling of filtered albumin. We hypothesized that dipstick albuminuria (DA) is associated with a lower rate of AKI recovery in septic patients.MethodsThis was a single‐centre, retrospective cohort study of adults with sepsis‐associated AKI in an urban academic intensive care unit (ICU). Patients with unknown baseline serum creatinine (SCr), absent urinalysis, and those with estimated glomerular filtration rate (eGFR) <15 mL/min per 1.73m2 or receiving chronic renal replacement therapy (RRT) were excluded. The independent variable was DA (negative or trace, 30 mg/dL, and ≥100 mg/dL) within the first 72 h of ICU stay. The outcome variable was AKI recovery at 30 days following hospital discharge, defined as the last SCr returning to a level less than 1.5 times the baseline SCr level and independence of RRT.ResultsA total of 988 patients were included in the study. The median length of hospitalization was 11 days. The patients with higher degree of DA had worse critical illness scores. After adjustment for several confounders, DA ≥30 mg/dL was independently associated with “no AKI recovery” at 30 days post‐discharge (adjusted OR 1.40, 95% CI, 1.01–1.95 for DA =30 mg/dL and 1.67, 1.15–2.42 for DA ≥100 mg/dL, P = 0.02). Other independent predictors of “no AKI recovery” were cumulative fluid balance, Sequential Organ Failure Assessment (SOFA) score, exposure to diuretics, and the need for mechanical ventilation.ConclusionDipstick albuminuria ≥30 mg/dL is independently associated with lower rate of AKI recovery at 30 days post‐discharge. Our findings emphasize the potential utility of a simple routine test of DA in the risk‐stratification of AKI recovery in ICU septic patients.
A longitudinal twin study on Tojikomori and depressive symptoms in Japanese elderly
Authors: Inui Fujio , Honda Chika , Kato Kenji , Tomizawa Rie , Nishihara Reiko , Hayakawa Kazuo 
Published: September 2015

AbstractBackgroundGenetic factors associated with Tojikomori (being housebound without any limitations in physical functioning or mental problems) are unclear. We performed a twin study to help clarify the causes of Tojikomori and investigate the association between Tojikomori and depressive symptoms.MethodsParticipants were members of the Osaka University Aged Twin Registry. A total of 157 twin pairs (314 individuals) who provided data in 2008 and 2012 were included. Depressive symptoms were measured by the Geriatric Depression Scale short version (GDS). Social Activities Scores (SAS) were measured with questions assessing the frequency of going out and contact with others. Activities of daily living were assessed with the Barthel index. Structural equation modelling analysis was used to evaluate the relative importance of genes and environments for the phenotypes measured.ResultsIn the first analysis, for SAS (2012), 25% of the variance was explained by additive genetic effects, and 75% was explained by unique environmental (including error) effects. For the GDS (2012), 28% of the variance was explained by additive genetic effects, and 72% was explained by unique environmental (including error) effects. In the second analysis, 25% of the total variance in SAS (2012) was explained by additive genetic factors, which influenced GDS scores (2008 and 2012). However, only 10% of the total variance in GDS scores (2012) was explained by additive genetic factors that influenced SAS (2008 and 2012).ConclusionsTojikomori was influenced by genetic factors in the elderly Japanese subjects. The association between Tojikomori and depressive symptoms was explained by genetic and environmental factors that are common to both phenotypes. Depressive symptoms were a cause of future Tojikomori and were affected by additive genetic factors. Genetic factors of Tojikomori were not a major cause of future depressive symptoms.
Five‐day stability of thawed plasma: solvent/detergent‐treated plasma comparable with fresh‐frozen plasma and plasma frozen within 24 hours
Authors: Neisser‐Svae Andrea , Trawnicek Laurenz , Heger Andrea , Mehta Trupti , Triulzi Darrell 
Published: September 2015

BACKGROUNDPlasma stored refrigerated for up to 5 days after thawing is common practice in many US hospitals. Therefore, clotting factor activities in fresh‐frozen plasma (FFP), plasma frozen within 24 hours (PF24), and solvent/detergent‐treated plasma (SDP), thawed and stored at 1 to 6°C for up to 5 days, were investigated.STUDY DESIGN AND METHODSFive A, B, O, and AB units of FFP, PF24, and SDP were thawed and maintained for 5 days at 1 to 6°C. The activity of factor (F)V, FVII, FVIII, protein S (PS), and ADAMTS13 was determined in each unit at baseline and every 24 hours thereafter for 5 days.RESULTSAfter thaw, mean values of the variables tested were within the normal range in all three plasma products although, in SDP, FVIII activity was significantly lower (p = 0.0039). After 5 days of storage all factors significantly declined except for ADAMTS13 activity, which was stable. Mean FVIII and ADAMTS13 activity was comparable in all three plasma products and within the normal range, mean FV activity was significantly lower in FFP and PF24 (p<0.0001) compared to SDP, and mean FVII activity was significantly lower in PF24 (p<0.03) than in FFP or SDP. Mean PS activity was below the normal range in all three plasma products with the lowest values in SDP (p = 0.0001).CONCLUSIONOver 5 days of refrigerated storage the changes in the measured coagulation factors in FFP, PF24, and SDP are comparable. Clinical follow‐up is needed to assess whether slightly lower PS levels in SDP are clinically important.
Using the Program Logic Model to Evaluate ¡Cuídate!: A Sexual Health Program for Latino Adolescents in a School‐Based Health Center
Authors: Serowoky Mary L. , George Nancy , Yarandi Hossein 
Published: September 2015

ABSTRACTBackgroundAddressing the disparities in pregnancy and sexually transmitted infection (STI) rates for Latino youth in the United States requires an evidence‐based approach. Although randomized controlled trials for sexual risk reduction interventions have shown promise in improving short‐term outcomes, program sustainability has not been extensively examined in school settings where teens spend time. Latina teen pregnancy rates are nearly twice the national average. Adolescents comprise only 17% of the U.S. population, yet they account for 50% of STIs. ¡Cuídate! is a high‐impact sexual health group program endorsed by the Centers for Disease Control and Prevention that has not been replicated in a real‐world setting.AimsThe program logic model (PLM) was used as the systematic approach to plan, implement, and evaluate a sustainable model of sexual health group programing (¡Cuídate!) in a U.S. high school with a large Latino student population.MethodsThe PLM provided the framework for the evaluation of outputs, outcome, and impact. A multivariate repeated measures analysis of variance was used as the means to evaluate the participant outcomes immediately postprogram and at 8–12 weeks.Results¡Cuídate! was executed within an existing school structure and time constraints, below cost projections, and with high participant retention (95.8%). Three cohorts (N = 24) of female teens demonstrated significant increases in STI or HIV knowledge, self‐efficacy, and intention to use condoms (p < .01). Condom use increased postprogram. No participants initiated sexual behavior, nor were there any reported pregnancies or STIs.ConclusionsAn evidence‐based intervention previously tested in randomized controlled trials can be sustained in a school‐based health center with similar results of efficacy.Linking Evidence to ActionOur success served as a platform for a sustainable program. We continue to extend the impact of the program by delivering ¡Cuídate! in the school setting using a community health worker.
Lymphangiogenic factors are associated with the severity of hypersensitivity pneumonitis
Authors: Yamashita Masahiro , Mouri Takashi , Niisato Miyuki , Nitanai Hiroo , Kobayashi Hitoshi , Ogasawara Masahito , Endo Ryujin , Konishi Kazuki , Sugai Tamotsu , Sawai Takashi , Yamauchi Kohei 
Published: September 2015

BackgroundAntigen presenting cells play a pivotal role in the adaptive immune response in hypersensitivity pneumonitis (HP). It was hypothesised that lymphangiogenesis is involved in the pathophysiology of HP via cell transport.ObjectiveTo determine the clinical significance of lymphangiogenic factors in HP.MethodsLevels of vascular endothelial growth factors (VEGF)-A, VEGF-C, VEGF-D and CCL21 in the serum and bronchoalveolar lavage fluid (BALF) were measured in 29 healthy volunteers, 14 patients with idiopathic pulmonary fibrosis (IPF) and 26 patients with HP by ELISA. Additionally, immunohistochemical analyses were performed using lung specimens of patients with HP (n=8) and IPF (n=10).ResultsBALF VEGF-D levels were significantly elevated in patients with HP compared to the other groups. BALF VEGF–D levels in patients with HP correlated significantly with the BALF total cell and lymphocyte counts (r=0.485, p=0.014 and r=0.717, p<0.0001, respectively). BALF VEGF-C and CCL21 levels were increased in patients with HP compared to healthy volunteers, but not patients with IPF. BALF CCL21 levels were negatively correlated with the forced expiratory volume in 1 s percentage and diffuse capacity of the lung for carbon monoxide (r=−0.662, p=0.007 and r=−0.671, p=0.024, respectively). According to the immunohistochemical analyses, CCL21 was expressed in the lymphatic endothelium in both conditions and CCR7+cells were aggregated around lymphatics in patients with HP, but not in patients with IPF.ConclusionsLymphangiogenic factors might be associated with the inflammatory and functional severity of HP. The increased BALF VEGF-D levels were associated with lymphatic alveolitis intensity, and CCL21 with lung function impairment.
Key to enhance thermoelectric performance by controlling crystal size of strontium titanate
Authors: Wang Jun , Ye Xinxin , Yaer Xinba , Wu Yin , Zhang Boyu , Miao Lei 
Published: September 2015

One-step molten salt synthesis process was introduced to fabricate nano to micrometer sized [Formula: see text] powders in which effects of synthesis temperature, oxide-to-flux ratios and raw materials on the generation of [Formula: see text] powders were examined. 100 nm or above sized pure [Formula: see text] particles were obtained at relatively lower temperature of 900[Formula: see text]C. Micro-sized rhombohedral crystals with a maximum size of approximately 12 [Formula: see text]m were obtained from [Formula: see text] or [Formula: see text] strontium source with 1:1 O/S ratio. Controlled crystal size and morphology of Nb-doped [Formula: see text] particles are prepared by using this method to confirm the performance of thermoelectric properties. The Seebeck coefficient obtained is significantly high when compared with the reported data, and the high ratio of nano particles in the sample has a positive effect on the increase of Seebeck coefficient too, which is likely due to the energy filtering effect at large numbers of grain boundaries resulting from largely distributed structure.
Impact of the AYA HOPE Comorbidity Index on Assessing Health Care Service Needs and Health Status among Adolescents and Young Adults with Cancer
Authors: Wu Xiao-Cheng , Prasad Pinki K. , Landry Ian , Harlan Linda C. , Parsons Helen M. , Lynch Charles F. , Smith Ashley W. , Hamilton Ann S. , Keegan Theresa H.M. 
Published: September 2015

Abstract
Background: Existing comorbidity indices were not developed for adolescent and young adults (AYA) 15 to 39 years of age. The aim of this study was to assess impact of comorbidities on health care service needs and health status among AYA cancer survivors using the newly developed AYA HOPE comorbidity index in comparison with the existing indices.
Methods: Data on comorbid conditions were obtained from medical records and service needs and health status were from a survey of AYA cancer survivors. Prevalence of comorbidities was based on the AYA HOPE index. Charlson and NCI indices were compared. Multivariable logistic regression was used.
Results: Of the 485 patients, 14.6% had ≥2 comorbidities based on the AYA HOPE Index. Prevalence of mental illness and obesity/overweight, which were not included in existing indices, were 8.2% and 5.8%, respectively. Prevalence of cardiovascular, endocrine, gastrointestinal, and neurologic conditions were higher with the AYA HOPE Index than the other two indices. Forty percent of AYA patients reported service needs, particularly for mental health services (25.2%) and support groups (17.7%). Having ≥2 comorbidities on the AYA index was associated with higher mental health service needs [OR, 2.05; 95% confidence interval (CI), 1.10–3.82] adjusting for demographic and clinical factors. Comorbidities were associated with fair/poor self-reported health status.
Conclusion: The AYA HOPE Index is a more comprehensive comorbidity index for AYA cancer patients than existing indices, and the number of comorbidities is associated with service needs and health status.
Impact: The AYA HOPE index could identify patients' additional service needs early in therapy. Cancer Epidemiol Biomarkers Prev; 24(12); 1844–9. ©2015 AACR.
Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract
Authors: Sun Yun-Yan , Peng Shiwen , Han Liping , Qiu Jin , Song Liwen , Tsai Yachea , Yang Benjamin , Roden Richard B.S. , Trimble Cornelia L. , Hung Chien-Fu , Wu T.-C. 
Published: September 2015

Abstract
Purpose: Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)–infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164).
Experimental Design: Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc).
Results: We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract.
Conclusions: Our results support future clinical translation using cervicovaginal TA-HPV vaccination. Clin Cancer Res; 22(3); 657–69. ©2015 AACR.
See related commentary by Nizard et al., p. 530
Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer
Authors: Purow Benjamin 
Published: September 2015

Abstract
Lipid kinases have largely been neglected as targets in cancer, and an increasing number of reports suggest diacylglycerol kinase alpha (DGKα) may be one with promising therapeutic potential. DGKα is one of 10 DGK family members that convert diacylglycerol (DAG) to phosphatidic acid (PA), and both DAG and PA are critical lipid second messengers in the plasma membrane. A host of important oncogenic proteins and pathways affect cancer cells in part through DGKα, including the c-Met and VEGF receptors. Others partially mediate the effects of DGKα inhibition in cancer, such as mTOR and HIF-1α. DGKα inhibition can directly impair cancer cell viability, inhibits angiogenesis, and notably may also boost T-cell activation and enhance cancer immunotherapies. Although two structurally similar inhibitors of DGKα were established decades ago, they have seen minimal in vivo usage, and it is unlikely that either of these older DGKα inhibitors will have utility for cancer. An abandoned compound that also inhibits serotonin receptors may have more translational potential as a DGKα inhibitor, but more potent and specific DGKα inhibitors are sorely needed. Other DGK family members may also provide therapeutic targets in cancer, but require further investigation. Clin Cancer Res; 21(22); 5008–12. ©2015 AACR.
A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition
Authors: Mak Milena P. , Tong Pan , Diao Lixia , Cardnell Robert J. , Gibbons Don L. , William William N. , Skoulidis Ferdinandos , Parra Edwin R. , Rodriguez-Canales Jaime , Wistuba Ignacio I. , Heymach John V. , Weinstein John N. , Coombes Kevin R. , Wang Jing , Byers Lauren Averett 
Published: September 2015

Abstract
Purpose: We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived in cancer cell lines. Given the contribution of tumor microenvironments to EMT, we extended our investigation of EMT to patient tumors from 11 cancer types to develop a pan-cancer EMT signature.
Experimental Design: Using the pan-cancer EMT signature, we conducted an integrated, global analysis of genomic and proteomic profiles associated with EMT across 1,934 tumors including breast, lung, colon, ovarian, and bladder cancers. Differences in outcome and in vitro drug response corresponding to expression of the pan-cancer EMT signature were also investigated.
Results: Compared with the lung cancer EMT signature, the patient-derived, pan-cancer EMT signature encompasses a set of core EMT genes that correlate even more strongly with known EMT markers across diverse tumor types and identifies differences in drug sensitivity and global molecular alterations at the DNA, RNA, and protein levels. Among those changes associated with EMT, pathway analysis revealed a strong correlation between EMT and immune activation. Further supervised analysis demonstrated high expression of immune checkpoints and other druggable immune targets, such as PD1, PD-L1, CTLA4, OX40L, and PD-L2, in tumors with the most mesenchymal EMT scores. Elevated PD-L1 protein expression in mesenchymal tumors was confirmed by IHC in an independent lung cancer cohort.
Conclusions: This new signature provides a novel, patient-based, histology-independent tool for the investigation of EMT and offers insights into potential novel therapeutic targets for mesenchymal tumors, independent of cancer type, including immune checkpoints. Clin Cancer Res; 22(3); 609–20. ©2015 AACR.