bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sirolimus as an alternative treatment in patients with granulomatous‐lymphocytic lung disease and humoral immunodeficiency with impaired regulatory T cells
Authors: Deyà‐Martínez Angela , Esteve‐Solé Ana , Vélez‐Tirado Natalia , Celis Veronica , Costa Jordi , Cols Maria , Jou Cristina , Vlagea Alexandru , Plaza‐Martin Ana María , Juan Manel , Alsina Laia 
Published: March 2018

AbstractBackgroundOne of the most frequent non‐infectious complications of humoral immunodeficiencies with a CVID‐like pattern is a particular form of inflammatory lung disease which is called granulomatous‐lymphocytic interstitial lung disease (GLILD). Its development worsens patient prognosis, with a significant decrease in survival. Currently, there are no unified guidelines regarding its management, and different combinations of immunosuppressants have been used with variable success.MethodsClinical and radiological data were collected from patient's medical charts. Flow cytometry was performed to characterize the immunological features with special focus in regulatory T cells (Tregs).ResultsA 16‐year‐old girl with Kabuki syndrome and a 12‐year‐old boy, both with a CVID‐like humoral immunodeficiency on immunoglobulin replacement treatment, developed during follow‐up an inflammatory complication radiologically, clinically, and histologically compatible with GLILD. They required treatment, and sirolimus was started, with very good response and no serious side effects.ConclusionsThese 2 cases provide insight into the underlying local and systemic immune anomalies involved in the development of GLILD, including the possible role of Tregs. Combined chemotherapy is commonly used as treatment for GLILD when steroids fail, but there have been some reports of successful monotherapy. As far as we know, these are the first 2 GLILD patients treated successfully with sirolimus, suggesting the advisability of further study of mTOR inhibitors as a more targeted treatment for GLILD, if impairment in Tregs is demonstrated.
Physical Magnitudes
Authors: Dees Marco 
Published: March 2018

AbstractScientific properties come in degrees: elephants aremore massivethan mice. Are facts like these fundamental or can they be explained in other terms? This article argues that the structure of physical quantities like mass reduces to facts about the role that mass plays in the laws of nature. On this view elephants are more massive than mice partly in virtue of the fact that elephants are harder to throw around.
Genetic analyses for bioactive potential in tetraploid potato (Solanum tuberosum L.)
Authors: Tierno Roberto , Ruiz de Galarreta Jose Ignacio 
Published: March 2018

AbstractA total of four traits related to bioactive potential of the tetraploid potato were studied in a North Carolina II cross‐experiment. The objectives of this study were to estimate genetic parameters for target bioactive compounds in a tetraploid potato population, to determine phenotypic and genotypic correlations and to calculate combining ability effects of cultivars and breeding lines included in the crossing scheme. Total monomeric anthocyanins, phenolics, carotenoids and hydrophilic antioxidant capacity were measured by spectrophotometric methods. The sources of variation female (GCAf), male (GCAm) and their interaction (SCA) were significant for bioactive compounds and antioxidant capacity. Narrow‐sense heritability estimates (h2) were moderate for all the traits (0.413–0.657). Both phenotypic and genotypic correlations were highly significant for phenolic compounds and antioxidant capacity. As regards combining ability, positive and negative GCA and also SCA effects have been identified for bioactive compounds and antioxidant capacity. These results indicate that hybrid breeding lines can be obtained by choosing parents with significant GCA, whose bioactive potential can also be further enhanced if the crosses have a significant SCA.
How does temperature affect splicing events? Isoform switching of splicing factors regulates splicing of LATE ELONGATED HYPOCOTYL (LHY)
Authors: James Allan B. , Calixto Cristiane P.G. , Tzioutziou Nikoleta A. , Guo Wenbin , Zhang Runxuan , Simpson Craig G. , Jiang Wenying , Nimmo Gillian A. , Brown John W.S. , Nimmo Hugh G. 
Published: March 2018

AbstractOne of the ways in which plants can respond to temperature is via alternative splicing (AS). Previous work showed that temperature changes affected the splicing of several circadian clock gene transcripts. Here, we investigated the role of RNA‐binding splicing factors (SFs) in temperature‐sensitive AS of the clock gene LATE ELONGATED HYPOCOTYL (LHY). We characterized, in wild type plants, temperature‐associated isoform switching and expression patterns for SF transcripts from a high‐resolution temperature and time series RNA‐seq experiment. In addition, we employed quantitative RT‐PCR of SF mutant plants to explore the role of the SFs in cooling‐associated AS of LHY. We show that the splicing and expression of several SFs responds sufficiently, rapidly, and sensitively to temperature changes to contribute to the splicing of the 5′UTR of LHY. Moreover, the choice of splice site in LHY was altered in some SF mutants. The splicing of the 5′UTR region of LHY has characteristics of a molecular thermostat, where the ratio of transcript isoforms is sensitive to temperature changes as modest as 2 °C and is scalable over a wide dynamic range of temperature. Our work provides novel insight into SF‐mediated coupling of the perception of temperature to post‐transcriptional regulation of the clock.
Infliximab regulates monocytes and regulatory T cells in Kawasaki disease
Authors: Koizumi Keiichi , Hoshiai Minako , Katsumata Nobuyuki , Toda Takako , Kise Hiroaki , Hasebe Yohei , Kono Yosuke , Sunaga Yuto , Yoshizawa Masashi , Watanabe Atsushi , Kagami Keiko , Abe Masako , Sugita Kanji 
Published: March 2018

AbstractBackgroundThe effect of infliximab (IFX) on immune cells has not been fully reported in Kawasaki disease (KD). To investigate the mechanism of IFX in KD, we examined changes in the abundance of CD14+CD16+ activated monocytes, regulatory T cells (Treg) cells, and T‐helper type 17 (Th17) cells following treatment with IFX.MethodsWe collected peripheral blood from patients with i.v. immunoglobulin (IVIG)‐resistant KD and analyzed absolute CD14+CD16+ monocyte, Treg (CD4+CD25+FOXP3+) and Th17 cell (CD4+IL‐17A+) counts on flow cytometry. We also measured changes in serum soluble interleukin (IL)‐2 receptor (IL‐2R), IL‐6, and tumor necrosis factor (TNF)‐α on enzyme‐linked immunosorbent assay.ResultsTreg cells and Th17 cells significantly increased after IFX treatment compared with baseline (126 ± 85 cells/μL vs 62 ± 53 cells/μL, P < 0.01; 100 ± 111 cells/μL vs 28 ± 27 cells/μL, P < 0.05, respectively). In contrast, in a subgroup of patients with CD14+CD16+ monocytes above the normal range before IFX, the CD14+CD16+ monocytes significantly decreased following IFX treatment (72 ± 51 cells/μL vs 242 ± 156 cells/μL, P < 0.05).. Serum TNF‐α did not change, but soluble IL‐2R and IL‐6 decreased after IFX treatment.ConclusionIFX could downregulate activated monocytes and upregulate Treg cells towards the normal range. IFX treatment thus contributes to the process of attenuating inflammation in KD.
Cutaneous carcinogenic risk evaluation in 375 patients treated with narrowband‐UVB phototherapy
Authors: Raone Beatrice , Patrizi Annalisa , Gurioli Carlotta , Gazzola Andrea , Ravaioli Giulia Maria 
Published: March 2018

SummaryBackgroundNarrowband‐ultraviolet B (NB‐UVB) is widely used for the treatment of several dermatological diseases. A cutaneous carcinogenic effect has been hypothesized, but not proved.MethodsWe retrospectively reviewed the data of patients treated with NB‐UVB between January 1998 and December 2013 at the Dermatology Unit of our University Hospital, to evaluate the cutaneous carcinogenic risk of NB‐UVB.ResultsIn all, 375 patients were included, each receiving a mean follow‐up of 6.9 years. Vitiligo and psoriasis were the most common diseases. In total, 19 non‐melanoma skin cancers (NMSCs) were diagnosed in eight patients, after a mean latency of 5.2 years after the first radiation. No malignant melanoma (MM) was observed. The incidence rates of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were 620.2/100 ̇000 p/y and 116.3/100 ̇000 p/y. NMSCs were more frequent in patients affected by psoriasis (P = .0232), with older age at the first radiation (mean = 68.8 years, P = .0001).ConclusionDespite the small number of patients and limited follow‐up, our data suggest that NB‐UVB may trigger cutaneous carcinogenesis, mainly in patients at risk for NMSCs, increasing their personal risk for single and multiple neoplasms, usually superficial BCCs. MM risk does not seem to be enhanced.
A dose‐finding study for hemoporfin in photodynamic therapy for port‐wine stain: A multicenter randomized double‐blind phase IIb trial
Authors: Wu Qiuju , Tu Ping , Zhou Guoyu , Yang Huilan , Zhou Zhanchao , Zhao Yi , Zheng Qingshan , Gu Ying , Tao Jining , Zhu Xuejun 
Published: March 2018

SummaryBackground/PurposePrevious studies have shown that hemoporfin‐mediated photodynamic therapy (PDT) was a treatment for port‐wine stain (PWS). Our current study aimed to identify optimal hemoporfin dose.MethodsA prospective, multicenter, double‐blind, randomized clinical trial was conducted. Patients were assigned into low‐ or high‐dose hemoporfin (2.5 mg/kg and 5 mg/kg intravenously, respectively), or control (placebo) group, at a rate of 2:2:1. Treatment efficacy was evaluated at week 8. Then, patients in control group were randomly assigned into either high‐ or low‐dose hemoporfin group. Treatment reactions and adverse events were analyzed at week 16.ResultsA total of 100 patients (40, 40, 20 in low‐, high‐dose hemoporfin, and control group, respectively) were enrolled. Compared to low dose (40%) and control group (15%), a higher proportion of patients in high‐dose group (75%) had achieved skin lesion improvements. Treatment satisfactions were graded highest in high‐dose group. Compared to low‐dose group (14.3%), high‐dose group (46.0%) had more frequent skin hyperpigmentation, which disappeared 3‐6 months after treatment. Other treatment reactions and adverse events were comparable between two groups.ConclusionsPhotodynamic therapy with 5 mg/kg hemoporfin could be an effective and safe treatment for PWS.
Solar urticaria in 145 patients: Assessment of action spectra and impact on quality of life in adults and children
Authors: Haylett Ann K. , Koumaki Dimitra , Rhodes Lesley E. 
Published: March 2018

SummaryBackgroundSolar urticaria (SU) is a rare chronic inducible urticaria triggered via uncharacterized chromophores. We detail responses of a large patient series to monochromator phototesting and broadband ultraviolet radiation (UVR); relationship to life quality is explored.MethodsRetrospective review of all SU patients undergoing standardized diagnostic photoinvestigation at a specialist centre during 2000‐2016. From 2011, patients completed dermatology life quality index (DLQI) questionnaires for the past week and year.ResultsIn 145 patients (mean: 35.8, range: 3‐69 years; 18 aged <18 years; 100 female), combined phototesting with broadband UVR and monochromator sources successfully provoked 74.5% patients, with 65.6% provoked by broadband UVR alone and 57.9% by monochromated radiation alone. The narrow wavebands most frequently eliciting wheal and flare response were between 370 and 400 nm, with 25% patients at 300 ± 5 nm, 53.6% at 320 ± 10 nm, 66.7% at 330 ± 10 nm, 77.4% at 350 ± 20 nm, 83.3% at 370 ± 20 nm, 86.9% at 400 ± 20 nm, 44% at 500 ± 20 nm and 17.8% at 600 ± 20 nm. In 62 patients, the DLQI revealed 56.1% had very to extremely large impact in the past week (all patients: mean score: 11.1, range: 0‐29) rising to 69.8% for the past year (12.5, 0‐30); adults and children were similarly affected. Patients with positive photoprovocation had higher DLQI score than those who were negative (DLQI for past week: mean: 12.6 ± SEM 1.1 vs 4.6 ± 1.4, P < .01).ConclusionSU is predominantly provoked by longer UVA‐shorter visible radiation, which penetrates window‐glass and where sunscreens are less effective; impact on life quality is considerable. Photoprotective agents effective against this spectrum are needed.
Natriuretic peptide system regulation in granulosa cells during follicle deviation and ovulation in cattle
Authors: De Cesaro MP , dos Santos JT , Ferst JG , Nóbrega JE , Rosa PRA , Rovani MT , Ilha GF , Bohrer RC , Ferreira R , Gasperin BG , Bordignon V , Gonçalves PBD 
Published: March 2018

ContentsNatriuretic peptides (NPs) are known to regulate reproductive events in polyovulatory species, but their function and regulation in monovulatory species remain to be fully characterized. Using a well‐established in vivo model, we found that bovine granulosa cells from follicles near the deviation stage express mRNA for the three NP receptors (NPR1, NPR2 and NPR3), but not for NP precursors (NPPA, NPPB and NPPC). The abundance of NPR3 mRNA was higher in dominant compared to subordinate follicles at the expected time of follicular deviation. After deviation, mRNA for all NP receptors was significantly more abundant in the dominant follicle. Intrafollicular inhibition of oestrogen receptors downregulated NPR1 mRNA in dominant follicles. In granulosa cells from preovulatory follicles, NPPC mRNA increased at 3 and 6 h after systemic GnRH treatment, but decreased at 12 and 24 h to similar levels observed in samples collected at 0 h. After GnRH treatment, NPR1 mRNA was upregulated at 24 h, NPR3 mRNA gradually decreased after 3 h, while NPR2 mRNA was not regulated. The mRNA expression of the enzyme FURIN increased at 24 h after GnRH treatment. These findings revealed that the expression of mRNA encoding important components of the NP system is regulated in bovine granulosa cells during follicular deviation and in response to GnRH treatment, which suggests a role of NP system in the modulation of these processes in monovulatory species.
External beam radiation therapy combined with airway stenting leads to better survival in patients with malignant airway obstruction
Authors: Mallow Christopher , Thiboutot Jeffrey , Semaan Roy , Hayes Margaret M. , Hales Russell , Ram Ashwin , Feller‐Kopman David , Lee Hans , Yarmus Lonny 
Published: March 2018

ABSTRACTBackground and objectiveMalignant airway obstruction (MAO), a common complication of patients with advanced lung cancer, causes debilitating dyspnoea and poor quality of life. Two common interventions used in the treatment of MAO include bronchoscopy with airway stenting and external beam radiotherapy (EBRT). Data are limited regarding their clinical effectiveness and overall effect on survival.MethodsA retrospective chart review of patients treated with airway stenting and/or EBRT at the Johns Hopkins Hospital for MAO between July 2010 and January 2017 was reviewed. Demographics, performance status, cancer histology, therapeutic intervention and date of death were recorded. Survival was calculated using cox regression analysis.ResultsOf the 606 patients who were treated for MAO, 237 were identified as having MAO and included in the study. Sixty‐eight patients underwent rigid bronchoscopy and stenting, 102 EBRT and 67 a combined approach. Patients who underwent stenting hand an increased hazard ratio (HR) of death in comparison to those who received combination therapy (HR: 2.12, 95% CI: 1.02, 4.39), while there was a trend towards significance in the EBRT alone group in comparison to the combination therapy group (HR: 1.62, 95% CI: 0.93, 2.83).ConclusionIn this retrospective analysis, combination therapy with stenting and EBRT led to better survival in comparison to stenting or EBRT alone. Prospective cohort trials are needed to confirm these results.
Consumption of Fish and Shrimp from Southeast Louisiana Poses No Unacceptable Lifetime Cancer Risks Attributable to High‐Priority Polycyclic Aromatic Hydrocarbons
Authors: Wickliffe Jeffrey K. , Simon‐Friedt Bridget , Howard Jessi L. , Frahm Ericka , Meyer Buffy , Wilson Mark J. , Pangeni Deepa , Overton Edward B. 
Published: March 2018

AbstractFollowing oil spills such as the Deepwater Horizon accident (DWH), contamination of seafood resources and possible increased health risks attributable to consumption of seafood in spill areas are major concerns. In this study, locally harvested finfish and shrimp were collected from research participants in southeast Louisiana and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs are some of the most important chemicals of concern regarding oil‐spill‐contaminated seafood resources during and following oil spills. Some PAHs are considered carcinogens for risk assessment purposes, and currently, seven of these can be combined in lifetime cancer risk assessments using EPA approaches. Most PAHs were not detected in these samples (minimum detection limits ranged from 1.2 to 2.1 PPB) and of those that were detected, they were generally below 10 PPB. The pattern of detected PAHs suggested that the source of these chemicals in these seafood samples was not a result of direct contact with crude oil. Lifetime cancer risks were assessed using conservative assumptions and models in a probabilistic framework for the seven carcinogenic PAHs. Lifetime health risks modeled using this framework did not exceed a 1/10,000 cancer risk threshold. Conservative, health‐protective deterministic estimates of the levels of concern for PAH chemical concentration and seafood intake rates were above the concentrations and intake rates modeled under this probabilistic framework. Taken together, consumption of finfish and shrimp harvested from southeast Louisiana following the DWH does not pose unacceptable lifetime cancer risks from these seven carcinogenic PAHs even for the heaviest possible consumers.
Optimizing Natural Killer Cell Doses for Heterogeneous Cancer Patients on the Basis of Multiple Event Times
Authors: Lee Juhee , Thall Peter F. , Rezvani Katy 
Published: March 2018

SummaryA sequentially adaptive Bayesian design is presented for a clinical trial of cord-blood-derived natural killer cells to treat severe haematologic malignancies. Given six prognostic subgroups defined by disease type and severity, the goal is to optimize cell dose in each subgroup. The trial has five co-primary outcomes: the times to severe toxicity, cytokine release syndrome, disease progression or response and death. The design assumes a multivariate Weibull regression model, with marginals depending on dose, subgroup and patient frailties that induce association between the event times. Utilities of all possible combinations of the non-fatal outcomes over the first 100 days following cell infusion are elicited, with posterior mean utility used as a criterion to optimize the dose. For each subgroup, the design stops accrual to doses having an unacceptably high death rate and at the end of the trial selects the optimal safe dose. A simulation study is presented to validate the design's safety, ability to identify optimal doses and robustness, and to compare it with a simplified design that ignores patient heterogeneity.
The participant roles of bullying in different grades: Prevalence and social status profiles
Authors: Pouwels J. Loes , van Noorden Tirza H. J. , Lansu Tessa A. M. , Cillessen Antonius H. N. 
Published: March 2018

AbstractThis study examined grade differences in the social status profiles and prevalence of bullying participant roles. Participants were 598 primary school students (grades 4–6), 545 students in the lower‐grades of secondary school (grades 7–8), and 1491 students in the upper‐grades of secondary school (grades 9–11). Students' participant roles, popularity, and social preference were measured with peer nominations. Bullies, assistants, and reinforcers (i.e., bullies/followers) were as popular as defenders in primary school, but more popular than defenders in secondary school. These differences depended on the gender of the reference group. Bullies/followers were more popular than defenders among other‐gender peers in the lower‐grades of secondary school but not among same‐gender peers. In the upper‐grades of secondary school, bullies/followers were more popular than defenders among all peers. Grade differences in social preference were small. The grade differences in popularity profiles of the roles were in line with grade differences in prevalence rates. Bully/follower roles were more common in secondary school than primary school among girls and the defender role was less common in secondary school among boys. This suggests that bully/follower roles are more rewarded with social status in secondary school than in primary school.
Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women
Authors: Yoshida H. , Komiya A. , Ohtsuki R. , Kusaka‐Kikushima A. , Sakai S. , Kawabata K. , Kobayashi M. , Nakamura S. , Nagaoka A. , Sayo T. , Okada Y. , Takahashi Y. 
Published: March 2018

AbstractBackgroundHyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women.MethodsThe skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID.ResultsAmong the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID‐immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high‐HYBID‐expression group compared with the low‐HYBID‐expression group, respectively.ConclusionOur data suggest that like Japanese women, HYBID‐mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.