bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B virus and risk of non‐Hodgkin lymphoma: An updated meta‐analysis of 58 studies
Authors: Li M. , Gan Y. , Fan C. , Yuan H. , Zhang X. , Shen Y. , Wang Q. , Meng Z. , Xu D. , Tu H.
Published: March 2018

Previous studies have focused on the relationship between hepatitis B virus (HBV) infection and non‐Hodgkin lymphoma (NHL). However, the results remain inconsistent and somehow conflicting in different subgroups. The aim of this study was to combine the findings of independent studies to comprehensively assess the association between HBV and NHL using a meta‐analysis. Relevant studies were identified through structured keyword searches in PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) database, and 58 studies with a total of 53 714 NHL cases and 1 778 591 controls were finally included. Pooled estimates indicated a significantly increased NHL risk in HBV‐infected individuals (summary odds ratio [sOR]: 2.50; 95% confidence interval [CI]: 2.20‐2.83) regardless of the study design (case–control studies: sOR: 2.47; 95% CI: 2.16‐2.82; cohort studies: sOR: 2.64; 95% CI: 1.78‐3.91). Considerable heterogeneity was observed across studies that was primarily attributed to the NHL subtypes (meta‐regression: P < .05). Overall, B‐cell NHL (sOR: 2.46; 95% CI: 1.97‐3.07) presented a stronger association with HBV infection than T‐cell NHL (sOR: 1.67; 95% CI: 1.34‐2.10). Within the B‐cell NHL subtypes, HBV infection was significantly associated with diffuse large B‐cell lymphoma (DLBCL, sOR: 2.06; 95% CI: 1.48‐2.88) and follicular lymphoma (FL, sOR: 1.54; 95% CI: 1.11‐2.12), but not with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) and Burkitt lymphoma. The results of this meta‐analysis support a positive link between HBV infection and NHL development. Further investigations for the mechanisms underlying HBV‐induced NHL are warranted.
Long‐term vegetation changes of treeless heath communities in northern Fennoscandia: Links to climate change trends and reindeer grazing
Authors: Maliniemi Tuija , Kapfer Jutta , Saccone Patrick , Skog Anu , Virtanen Risto
Published: March 2018

Question

In recent decades, high‐latitude climate has shown regionally variable trends towards warmer and moister conditions. These changes have been predicted to cause afforestation or shrubification of open tundra, increases of warmth‐demanding southern species and plant groups favoured by increased moisture, and decline of species and habitats that are dependent on snow cover. In this study, we explore temporal changes in northern tundra upland plant communities along regional gradients and in local habitats. We ask how vegetation changes are linked with long‐term trends in regional climate and grazing pressure.

Location

Northern Europe.

Methods

In 2013–2014, we resurveyed a total of 108 vegetation plots on wind‐exposed and snow‐protected tundra habitats in three subareas along a bioclimatic gradient from the northern boreal to the arctic zone. Vegetation plots were originally sampled in 1964–1967. We related observed vegetation changes to changes in temperature, precipitation and grazing pressure, which all showed regionally variable increases over the study period.

Results

We found a significant increase of the evergreen dwarf shrub Empetrum nigrum subsp. hermaphroditum in snow‐protected communities and a prominent decrease of lichens throughout the study area. No evidence for extensive tree or larger shrub (Betula spp., Salix spp. or Juniperus communis) encroachment despite climatic warming trends was found. Among studied communities, most pronounced changes in vegetation were observed in snow‐protected boreal heaths on small isolated uplands, where community composition showed low resemblance to the original composition described decades ago. Changes in plant communities correlated with changes in summer and winter temperatures, summer precipitation and reindeer grazing pressure, yet correlations varied depending on region and habitat.

Conclusions

Northern tundra uplands vary in their resistance to on‐going climate change and reindeer grazing. Isolated treeless heaths of boreal forest–tundra ecotone appear least resistant to climate change and have already shifted towards new community states.
Wandering footloose: Traditional knowledge and the “Public Domain” revisited
Authors: Oguamanam Chidi
Published: March 2018

Ongoing interdisciplinary theoretical interests over the “ownership of culture” is a complex conversation that has pitched traditional knowledge (TK) and its holders against other knowledge systems in a manner that implicates significant power relations and plural philosophical orientations over the governance of knowledge. Nowhere is the pressure on TK more pronounced than in the new‐found interest of the United States and its allies over the public domain, as evident in the work of the WIPO's special committee charged with negotiating sets of legal instruments for effective protection of TK, genetic resources, and folklore (a.ka. traditional cultural expressions). TK stakeholders are put on the defensive on the assumption that effective protection of TK would undermine the public domain. Ironically, led by the United States, countries who worked tirelessly over the decades to ratchet up intellectual property protection at the expense of the public domain have now reconstituted themselves into its later day champions when it comes to TK. However, it is not as if the Indigenous and local community custodians of TK have no approximation of the public domain in their customary laws, practices and dealings with knowledge production. There has yet to be an interest in non‐Eurocentric conceptions of the public domain. Such an interest presents an opportunity to revisit the public domain imperative in order to adumbrate an inclusive and multicultural jurisprudence of the phenomenon.
Un‐precipitated acute kidney injury is uncommon among stable patients with cirrhosis and ascites
Authors: Wong Florence , Jepsen Peter , Watson Hugh , Vilstrup Hendrik
Published: March 2018

Background & aims

Acute episodes of renal dysfunction or acute kidney injury (AKI) in cirrhotic patients with ascites are mostly precipitated by an acute event. The prevalence of un‐precipitated AKI in stable ascitic cirrhotic patients is unknown. The aims of this study were to determine (i) the prevalence of un‐precipitated AKI in stable cirrhotics with ascites and (ii) any predictive factors for its development.

Methods

A total of 1115 stable cirrhotic patients with mild liver and renal dysfunction but varying degrees of ascites severity from 3 previous satavaptan vs placebo randomized controlled trials (Group A, ascites requiring diuretics but not paracentesis; Group B, ascites requiring frequent paracentesis; Group C, refractory ascites) were included. AKI was diagnosed when there was either an increase of ≥0.3 mg/dL in ≤48 hours or a 50% increase in serum creatinine, and staged according to the fold increase of the serum creatinine. Two serum creatinine levels measured maximally 7 days apart at screening and at randomization of the satavaptan studies with no acute intervening events were used.

Results

The prevalence of un‐precipitated AKI was 1.8% overall, with the prevalence rising with increasing severity of ascites. Ninety‐five per cent of cases were stage 1, with 15% progression rate, 3 reaching the severity of type 1 acute hepatorenal syndrome. Ascites severity was the most powerful predictor for un‐precipitated AKI development, which did not predict overall mortality.

Conclusions

Increased prevalence of AKI with more severe ascites despite minimal baseline liver and renal dysfunction suggests that frequent monitoring of renal function in these patients is mandatory.
Noble gas composition, cosmic‐ray exposure age, 39Ar‐40Ar, and I‐Xe analyses of ungrouped achondrite NWA 7325
Authors: Hopp Jens , Schröter Natalie , Pravdivtseva Olga , Meyer Hans‐Peter , Trieloff Mario , Ott Ulrich
Published: March 2018

Northwest Africa (NWA) 7325 is an anomalous achondrite that experienced episodes of large‐degree melt extraction and interaction with melt under reducing conditions. Its composition led to speculations about a Mercurian origin and provoked a series of studies of this meteorite. We present the noble gas composition, and results of 40Ar/39Ar and 129I‐129Xe studies of whole rock splits of NWA 7325. The light noble gases are dominated by cosmogenic isotopes. 21Ne and 38Ar cosmic‐ray exposure ages are 25.6 and 18.9 Ma, respectively, when calculated with a nominal whole rock composition. This 38Ar age is in reasonable agreement with a cosmic‐ray exposure age of 17.5 Ma derived in our 40Ar/39Ar dating study. Due to the low K‐content of 19 ± 1 ppm and high Ca‐content of approximately 12.40 ± 0.15 wt%, no reliable 40Ar/39Ar age could be determined. The integrated age strongly depends on the choice of an initial 40Ar/36Ar ratio. An air‐like component is dominant in lower temperature extractions and assuming air 40Ar/36Ar for the trapped component results in a calculated integrated age of 3200 ± 260 (1σ) Ma. This may represent the upper age limit for a major reheating event affecting the K‐Ar system. Results of 129I‐129Xe dating give no useful chronological information, i.e., no isochron is observed. Considering the highest 129Xe*/128XeI ratio as equivalent to a lower age limit, we calculate an I‐Xe age of about 4536 Ma. In addition, elevated 129Xe/132Xe ratios of up to 1.65 ± 0.18 in higher temperature extractions indicate an early formation of NWA 7325, with subsequent disturbance of the I‐Xe system.
Chemical regulation of body feather microbiota in a wild bird
Authors: Jacob Staffan , Sallé Louis , Zinger Lucie , Chaine Alexis S. , Ducamp Christine , Boutault Léa , Russell Andrew F. , Heeb Philipp
Published: March 2018

The microbiota has a broad range of impacts on host physiology and behaviour, pointing out the need to improve our comprehension of the drivers of host–microbiota composition. Of particular interest is whether the microbiota is acquired passively, or whether and to what extent hosts themselves shape the acquisition and maintenance of their microbiota. In birds, the uropygial gland produces oily secretions used to coat feathers that have been suggested to act as an antimicrobial defence mechanism regulating body feather microbiota. However, our comprehension of this process is still limited. In this study, we for the first time coupled high‐throughput sequencing of the microbiota of both body feathers and the direct environment (i.e., the nest) in great tits with chemical analyses of the composition of uropygial gland secretions to examine whether host chemicals have either specific effects on some bacteria or nonspecific broad‐spectrum effects on the body feather microbiota. Using a network approach investigating the patterns of co‐occurrence or co‐exclusions between chemicals and bacteria within the body feather microbiota, we found no evidence for specific promicrobial or antimicrobial effects of uropygial gland chemicals. However, we found that one group of chemicals was negatively correlated to bacterial richness on body feathers, and a higher production of these chemicals was associated with a poorer body feather bacterial richness compared to the nest microbiota. Our study provides evidence that chemicals produced by the host might function as a nonspecific broad‐spectrum antimicrobial defence mechanism limiting colonization and/or maintenance of bacteria on body feathers, providing new insight about the drivers of the host's microbiota composition in wild organisms.
Anthropogenic fragmentation may not alter pre‐existing patterns of genetic diversity and differentiation in perennial shrubs
Authors: Llorens Tanya M. , Ayre David J. , Whelan Robert J.
Published: March 2018

Many plant species have pollination and seed dispersal systems and evolutionary histories that have produced strong genetic structuring. These genetic patterns may be consistent with expectations following recent anthropogenic fragmentation, making it difficult to detect fragmentation effects if no prefragmentation genetic data are available. We used microsatellite markers to investigate whether severe habitat fragmentation may have affected the structure and diversity of populations of the endangered Australian bird‐pollinated shrub Grevillea caleyi R.Br., by comparing current patterns of genetic structure and diversity with those of the closely related G. longifolia R.Br. that has a similar life history but has not experienced anthropogenic fragmentation. Grevillea caleyi and G. longifolia showed similar and substantial population subdivision at all spatial levels (global F′ST = 0.615 and 0.454; Sp = 0.039 and 0.066), marked isolation by distance and large heterozygous deficiencies. These characteristics suggest long‐term effects of inbreeding in self‐compatible species that have poor seed dispersal, limited connectivity via pollen flow and undergo population bottlenecks because of periodic fires. Highly structured allele size distributions, most notably in G. caleyi, imply historical processes of drift and mutation were important in isolated subpopulations. Genetic diversity did not vary with population size but was lower in more isolated populations for both species. Through this comparison, we reject the hypothesis that anthropogenic fragmentation has impacted substantially on the genetic composition or structure of G. caleyi populations. Our results suggest that highly self‐compatible species with limited dispersal may be relatively resilient to the genetic changes predicted to follow habitat fragmentation.
Glutamine‐rich toxic proteins GrtA, GrtB and GrtC together with the antisense RNA AsgR constitute a toxin–antitoxin‐like system in Corynebacterium glutamicum
Authors: Maeda Tomoya , Tanaka Yuya , Inui Masayuki
Published: March 2018

The Corynebacterium glutamicum R grtA (cgR_2936), grtB (cgR_2934) and grtC (cgR_2933) genes were identified as paralogs encoding glutamine‐rich toxic proteins. We also identified a new antisense small RNA AsgR (antisense sRNA for grtA) that overlaps the 3′ end of the grtA gene. Single over‐expressions of grtA, grtB and grtC resulted in complete inhibition of Escherichia coli cell growth. This growth was rescued by co‐expression of AsgR. Similar effects were observed in C. glutamicum, although the toxicities of these proteins were moderate. Inhibition of AsgR transcription resulted in increased levels and prolonged half‐lives of grtA, grtB and grtC mRNAs. We also found that the expression levels of grtA, grtB and grtC were increased in an RNase III deletion mutant. Primer extension analysis revealed the RNase III cleavage site to be in the 3′ untranslated region (3′‐UTR) of the grtA mRNA. The expression levels of grtA, grtB and grtC were increased after exposure to several stresses, including heat shock, treatment with penicillin G, lysozyme or H2O2. The deletions of grtABC and asgR genes resulted in decreased survival rate under several stresses. These results indicate that GrtABC and AsgR constitute a type I toxin–antitoxin‐like system in C. glutamicum.
Clinicopathological and genetic association between epithelioid glioblastoma and pleomorphic xanthoastrocytoma
Authors: Furuta Takuya , Miyoshi Hiroaki , Komaki Satoru , Arakawa Fumiko , Morioka Motohiro , Ohshima Koichi , Nakada Mitsutoshi , Sugita Yasuo
Published: March 2018

Epithelioid glioblastoma (eGBM) is a rare variant of GBM which was adopted in the 2016 WHO classification. eGBM and pleomorphic xanthoastrocytoma (PXA) sometimes show overlapping features histologically and genetically, such as epithelioid pattern and a highly frequent V600E mutation in the gene for vRAF murine sarcoma viral oncogene homolog B1 (BRAF), respectively. Accurate diagnosis of these rare tumors is challenging according to the new criteria in the revised 2016 WHO classification. It is an urgent task to elucidate the biological properties of the tumors and to select appropriate treatment. Twenty consecutive cases diagnosed as PXA or eGBM histologically were investigated. Twelve of the 20 cases were PXAs and eight were eGBMs. Morphologically, mitotic activity, necrosis and degenerative changes such as intracellular lipid accumulation, eosinophilic granular bodies and reticulin fiber deposits were scored. Immunohistochemical and molecular biological assessment for isocitrate dehydrogenases 1 and 2 (IDH1/2), α‐thalassemia/mental‐retardation‐syndrome‐X‐linked gene (ATRX), p53, BRAF, telomere reverse transcriptase promoter (TERT‐p), H3F3A, and integrase interactor 1 (INI1) were performed. eGBM tended to lack the degenerative changes characteristic for PXA. Of the 20 cases tested, Sanger technique showed no mutation in IDH1/2. BRAF mutation at T1799 > A (V600E) was detected in 4/12 (33.3%) PXA and 4/8 (50.0%) eGBM, while TERT‐p mutation was detected at C228 > T in 2/12 (16.7%) PXA and at C250 > T in 1/8 (12.5%) eGBM. Retained nuclear ATRX was observed in 12/12 (100%) PXA and 6/7 (85.7%) eGBM while p53 mutation was observed in 2/10 (20%) PXA and 7/7 (100%) eGBM. All tumors retained INI1 expression in their nuclei. None of the tumors harbored H3F3A mutation. One PXA without BRAF mutation acquired TERT‐p mutation at recurrence and one eGBM harbored both BRAF and TERT‐p mutation. Molecular biological similarity between eGBM and PXA was suggested in our series, while degenerative changes reflected the features of PXA. It was speculated that the common genetic alterations for development and progression of eGBM and PXA might include BRAF and TERT‐p mutations.
Walker‐256 tumor alters morphology of intestinal myenteric plexus in rats
Authors: Marega P. , Liberti E. A. , Freitas J. J. S. , Kietzer K. S.
Published: March 2018

Background

Gastrointestinal (GI) dysmotility is common in patients with cancer. There are a few studies about the myenteric plexus in the presence of anatomically remote tumors.

Methods

Forty‐eight male Wistar rats were divided into a control (CT) or Walker‐256 (TW) group. Tumor cells were subcutaneously injected and saline was injected in the CT group. After 14 days, the small and large intestines were removed for histochemical analysis. The macroscopic morphology of the intestines and the fecal excretion were also observed.

Key Results

The upper GI transit and weight of fecal pellets were reduced and the walls of the large intestine in tumor‐bearing rats showed multiple constrictions. In the capsules’ constitution of the myenteric plexus of the TW group, there were type III collagen fibers in addition to type I fibers, and the thin septa inside the capsule were absent. The large intestine in the TW group exhibited smaller neurons and the number of nitrergic‐positive neurons was also reduced in the myenteric plexus, compared to the CT group. In the TW group, the neuronal numbers and the staining intensity of acetylcholinesterase (AChE) were reduced in the large intestine. Staining was not different in the small intestine.

Conclusions and Inferences

This study showed that the Walker‐256 tumor induced alterations in the morphology of nitrergic and cholinergic neurons in the myenteric plexus and decreased the upper GI transit with the presence of multiple constrictions in the colon. Therefore, these alterations can interfere on neurotransmission and can be related to the intestinal motility alterations observed in tumor‐bearing rats.
Beer effects on postprandial digestive symptoms and gastroesophagic physiology
Authors: Serrano Falcón B. , Megía Sánchez M. , Ruiz de León A. , Rey E.
Published: March 2018

Background

Beer has been related to gastroesophageal reflux (GER) and dyspepsia, based on its alcohol and gas content. The aim of this study is to evaluate the association between moderate consumption of traditional and alcohol‐free beer and upper digestive symptoms, gastric accommodation and GER.

Methods

Healthy adults without frequent gastrointestinal symptoms and GER disease were included. The intervention involved administration of traditional beer to 10 subjects (substudy 1) and alcohol‐free beer to 20 (substudy 2); control intervention entailed administration of water. Study duration was 2 weeks (control/intervention). Postprandial gastric accommodation was assessed through the maximum tolerated volume during a nutrient drink test after the ingestion of water (day 1) and beer (day 8), in which symptoms of dyspepsia were evaluated every 5 minutes. An impedance‐pH monitoring assessed 24 hours and post‐NDT GER (days 1 and 8). Symptoms were evaluated daily during the study. The defined variables were compared between visits and weeks using a nonparametric test for paired data.

Key Results

Dyspepsia symptoms showed a progressive increase during the NDT for both interventions in the 2 substudies, though no significant differences were detected in the MTV analysis. No differences were detected in the sum of weekly symptoms. The analysis of impedance‐pH monitoring did not show any differences between intervention and control visits for both interventions.

Conclusions and Inferences

Moderate consumption of traditional and alcohol‐free beer does not increase dyspeptic symptoms or GER in healthy subjects, whether in a controlled‐intake or real‐life situation. Neither gastric accommodation nor reflux episodes are modified in this context.
Temporal regularities allow saving time for maintenance in working memory
Authors: Fanuel Lison , Portrat Sophie , Tillmann Barbara , Plancher Gaën
Published: March 2018

Recent evidence suggests that working memory (WM) performance can be enhanced in the presence of an isochronous rhythm during the retention interval because it improves refreshing. Considering the cognitive load (CL) effect as an indicator of refreshing, the present study investigated whether an isochronous rhythm might benefit memory performance under varying cognitive load. For that goal, the presence of a regular rhythm and the cognitive load of the concurrent task (i.e., reading of digits that were either same or different within a trial) were systematically varied. Recall performance was decreased by high cognitive load compared with low cognitive load but was improved in the regular rhythm condition compared with the silent condition. No interaction between cognitive load and rhythm was observed. The present results suggest that temporal regularities might speed up the reading of the digits rather than improve the efficiency of refreshing, resulting in more time available for refreshing and, consequently, improved memory performance. These findings are interpreted in the framework of the dynamic attending theory and in the scope of recent models of working memory, which are also considering the temporal components of working memory and the importance of the temporal structure of working memory tasks.
What is attentional refreshing in working memory?
Authors: Camos Valérie , Johnson Matthew , Loaiza Vanessa , Portrat Sophie , Souza Alessandra , Vergauwe Evie
Published: March 2018

Working memory is one of the most important topics of research in cognitive psychology. The cognitive revolution that introduced the computer metaphor to describe human cognitive functioning called for this system in charge of the temporary storage of incoming or retrieved information to permit its processing. In the past decades, one particular mechanism of maintenance, attentional refreshing, has attracted an increasing amount of interest in the field of working memory. However, this mechanism remains rather mysterious, and its functioning is conceived in very different ways across the literature. This article presents an up‐to‐date review on attentional refreshing through the joint effort of leading researchers in the domain. It highlights points of agreement and delineates future avenues of research.
Stability of anterior open bite treatment with bonded spurs associated with high‐pull chincup
Authors: Cassis M. A. , de Almeida R. R. , Janson G. , Aliaga‐Del Castillo A. , de Almeida M. R.
Published: March 2018

Structured Abstract

Objective

To evaluate the stability of anterior open bite (AOB) treatment with bonded spurs associated with high‐pull chincup (BS/HPCC).

Methods

The experimental group consisted of 25 Class I AOB patients (15 female, 10 male) treated with BS/HPCC for 1 year. Cephalograms were analysed at pre‐treatment (T1), post‐treatment (T2) and at the 3‐year post‐treatment (T3) stage with the patients mean ages of 8.10, 9.14 and 12.18 years, respectively. The control group consisted of 23 subjects (13 female, 10 male) with normal occlusion, with comparable ages at the 3 stages (8.45, 9.45 and 12.50 years at T1, T2 and T3, respectively). T tests were used for intergroup comparisons at T1 and to compare the changes during the 3‐year post‐treatment period (T2‐T3). Intragroup comparison in the treated group was evaluated with dependent t tests between T1 and T2. Correlations between the overbite changes in the T2‐T3 period, the pre‐treatment AOB severity and the amount of correction achieved during treatment were evaluated with Pearson′s correlation coefficient.

Results

No statistically significant relapse of the AOB was found at T3. Only 1 patient had a clinically significant AOB relapse. Neither the pre‐treatment AOB severity nor the amount of correction was related to overbite changes during the 3‐year post‐treatment period.

Conclusions

There was no statistically significant relapse of the AOB, and the clinical stability of AOB correction 3‐year post‐treatment was of 96%.
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

Background

One 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.

Methods

Clinical 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).

Results

A 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.

Conclusions

These 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

Scientific 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

A 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

One 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

Background

The 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.

Methods

We 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.

Results

Treg 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.

Conclusion

IFX 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

Background

Narrowband‐ultraviolet B (NB‐UVB) is widely used for the treatment of several dermatological diseases. A cutaneous carcinogenic effect has been hypothesized, but not proved.

Methods

We 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.

Results

In 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).

Conclusion

Despite 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

Background/Purpose

Previous 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.

Methods

A 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.

Results

A 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.

Conclusions

Photodynamic 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

Background

Solar 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.

Methods

Retrospective 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.

Results

In 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).

Conclusion

SU 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.
Drug Pricing for Competing Pharmaceutical Manufacturers Distributing through a Common PBM
Authors: Kouvelis Panos , Xiao Yixuan , Yang Nan
Published: March 2018

We study the price competition among multiple branded drug manufacturers when their drugs are distributed through a common pharmacy benefit manager (PBM). The PBM develops a drug benefit plan for its clients, which includes a formulary list that specifies the copayment for each branded drug, and a list of prices to be charged to the clients for each of the branded and generic drugs. Client organizations decide whether to contract with the PBM and pay the majority of drug costs, while the plan enrollees select which drug to consume. An important feature when multiple branded drugs are distributed through a common PBM is that the PBM's market size, measured by the number of prescriptions filled, depends on the aggregate attraction of all the drugs under the PBM's plan. Therefore, the branded drug manufacturers involuntarily cooperate in affecting the PBM's market size, while competing for the market shares under the PBM's plan, which leads to an intricate co‐opetition among the branded drug manufacturers. We characterize the PBM's optimal copayment and pricing decisions, and establish conditions for the equilibrium analysis of the price competition among the branded drug manufacturers. In particular, we provide a sufficient condition for the uniqueness of the equilibrium, and characterize the equilibrium in closed form. We apply our model to study the strategic implications of vertical integration between a branded drug manufacturer and the PBM. By comparing the pre‐ and post‐integration equilibrium outcomes, we characterize the impact of vertical integration on the branded drugs’ market shares and copayments, the non‐integrated branded drug manufacturers’ effective wholesale prices and profits, the integrated PBM's total market size and profit, the aggregate profit of all branded drug manufacturers and the PBM, consumer surplus, and social welfare. We further explore the impact of vertical integration through numerical study.
Rapid detection of Fusarium oxysporum f. sp. lactucae on soil, lettuce seeds and plants using loop‐mediated isothermal amplification
Authors: Franco Ortega S. , Tomlinson J. , Gilardi G. , Spadaro D. , Gullino M. L. , Garibaldi A. , Boonham N.
Published: March 2018

Fusarium oxysporum f. sp. lactucae (FOL) is a soil‐ and seedborne pathogen and the causal agent of fusarium wilt on lettuce. Four races have been identified within FOL, with different worldwide distribution. Several molecular techniques have been used to detect and identify this pathogen; however, not all of them have the optimal characteristics in terms of sensitivity to perform FOL detection in plant and seed material. A loop‐mediated isothermal amplification (LAMP) assay was developed based on the sequence‐characterized amplified region (SCAR) obtained in a previous rapid amplification of polymorphic DNA (RAPD) study. The LAMP assay has been validated according to the EPPO standard PM7/98. The LAMP assay was tested with lettuce seeds, soil and plant material, and can be used successfully to amplify DNA from each of these matrices. In seed lots artificially inoculated with FOL, the detection limit of the LAMP test was 0.004% infected seed.
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

Contents

Natriuretic 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.
Quantifying active and passive restoration in Central Mexico from 1986–2012: assessing the evidence of a forest transition
Authors: Honey‐Rosés Jordi , Maurer Marlene , Ramírez M. Isabel , Corbera Esteve
Published: March 2018

Recent land cover analysis reveals significant forest recovery around the world, suggesting that some countries may be in a forest transition. However, remotely sensed imagery does not reveal the driving causes of forest recovery, which may be due to active reforestation efforts or natural successional processes (passive reforestation). We aimed to distinguish these two processes in the priority temperate forests surrounding the Monarch Butterfly Biosphere Reserve (342,773 ha) in central Mexico. We combine an analysis of remotely sensed imagery with field interviews (n = 43) to examine the mechanisms and drivers of observed forest recovery. Our analysis of the satellite imagery revealed a net increase of 3,798 ha of forest between 1986 and 2012, yet the rate of recovery is slowing. Our interview data revealed that the vast majority of the recovered forests are the result of natural regrowth (passive reforestation), and most of this regrowth is observed on previously degraded forest lands. We estimate that between 58 and 429 ha have been recovered from active reforestation efforts in the 1986–2012 period. We find that reduced logging and grazing pressures are important drivers of forest recovery, while agricultural abandonment may be less influential than often believed. Our results suggest that reforestation investments might be wisely spent supporting and maintaining the natural resilience of forests rather than on costly reforestation programs.
Restoring species diversity: assessing capacity in the U.S. native plant industry
Authors: White Abigail , Fant Jeremie B. , Havens Kayri , Skinner Mark , Kramer Andrea T.
Published: March 2018

Large quantities of diverse and appropriately adapted native plant germplasm are required to facilitate restoration globally, yet shortages can prevent restorations from attaining desired species diversity and structure. An extensive native plant industry has developed in the United States to help meet these demands, yet very little is known about its capacity to support germplasm needs. To better understand current capacity and germplasm availability, we report results of the first comprehensive and quantitative assessment of the native plant industry in the United States, which includes at least 841 vendors nationwide and the species they make available for restoration. We synthesized lists of commercially available species from native plant vendors across the United States and identified gaps in species availability to inform germplasm research, development, and production. Of the approximately 25,000 vascular plant taxa native to the United States, 26% are sold commercially, with growth form, conservation status, distribution, and taxonomy significantly predicting availability. In contrast, only 0.07% of approximately 3,000 native nonvascular taxa are sold commercially. We also investigated how demand for germplasm to support high‐quality restoration efforts is met by vendors in the Midwestern tallgrass prairie region, which has been targeted extensively by restoration efforts for decades. In this well‐developed native plant market, 74% of more than 1,000 target species are commercially available, often from vendors that advertise genetically diverse, locally sourced germplasm. We make recommendations to build on the successes of regional markets like the tallgrass prairie region, and to fill identified gaps, including investing in research to support production, ensuring more consistent and clear demand, and fostering regional collaboration.
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

Background and objective

Malignant 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.

Methods

A 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.

Results

Of 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).

Conclusion

In 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.