bluuebunny/crossref_metadata_2025 huggingface dataset:
A catalog of microbial genes from the bovine rumen unveils a specialized and diverse biomass-degrading environment
Authors: Li Junhua , Zhong Huanzi , Ramayo-Caldas Yuliaxis , Terrapon Nicolas , Lombard Vincent , Potocki-Veronese Gabrielle , Estellé Jordi , Popova Milka , Yang Ziyi , Zhang Hui , Li Fang , Tang Shanmei , Chen Weineng , Chen Bing , Li Jiyang , Guo Jing , Martin Cécile , Maguin Emmanuelle , Xu Xun , Yang Huanming , Wang Jian , Madsen Lise , Kristiansen Karsten , Henrissat Bernard , Ehrlich Stanislav D. , Morgavi Diego P.
Published: February 2018

Background

The rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen.

Results

Using deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands by several folds the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e. 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes explaining the great adaptability of cattle to rapidly adjust to dietary changes.

Conclusions

These data bring new insights into functions, carbohydrate-degrading enzymes and microbes of the rumen that is complementing the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data is made available.
Converging Evidence from Electrocorticography and BOLD fMRI for a Sharp Functional Boundary in Superior Temporal Gyrus Related to Multisensory Speech Processing
Authors: Ozker Muge , Beauchamp Michael S.
Published: February 2018

Although humans can understand speech using the auditory modality alone, in noisy environments visual speech information from the talker’s mouth can rescue otherwise unintelligible auditory speech. To investigate the neural substrates of multisensory speech perception, we recorded neural activity from the human superior temporal gyrus using two very different techniques: either directly, using surface electrodes implanted in five participants with epilepsy (electrocorticography, ECOG), or indirectly, using blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) in six healthy control fMRI participants. Both ECOG and fMRI participants viewed the same clear and noisy audiovisual speech stimuli and performed the same speech recognition task. Both techniques demonstrated a sharp functional boundary in the STG, which corresponded to an anatomical boundary defined by the posterior edge of Heschl’s gyrus. On the anterior side of the boundary, cortex responded more strongly to clear audiovisual speech than to noisy audiovisual speech, suggesting that anterior STG is primarily involved in processing unisensory auditory speech. On the posterior side of the boundary, cortex preferred noisy audiovisual speech or showed no preference and showed robust responses to auditory-only and visual-only speech, suggesting that posterior STG is specialized for processing multisensory audiovisual speech. For both ECOG and fMRI, the transition between the functionally distinct regions happened within 10 mm of anterior-to-posterior distance along the STG. We relate this boundary to the multisensory neural code underlying speech perception and propose that it represents an important functional division within the human speech perception network.
Commissioning of a multi-beamline femtoslicing facility at SOLEIL
Authors: Labat Marie , Brubach Jean-Blaise , Ciavardini Alessandra , Couprie Marie-Emmanuelle , Elkaim Erik , Fertey Pierre , Ferte Tom , Hollander Philippe , Hubert Nicolas , Jal Emmanuelle , Laulhé Claire , Luning Jan , Marcouillé Olivier , Moreno Thierry , Morin Paul , Polack Francois , Prigent Pascale , Ravy Sylvain , Ricaud Jean-Paul , Roy Pascale , Silly Mathieu , Sirotti Fausto , Taleb Amina , Tordeux Marie-Agnès , Nadji Amor
Published: February 2018

The investigation of ultrafast dynamics, taking place on the few to sub-picosecond time scale, is today a very active research area pursued in a variety of scientific domains. With the recent advent of X-ray free-electron lasers (XFELs), providing very intense X-ray pulses of duration as short as a few femtoseconds, this research field has gained further momentum. As a consequence, the demand for access strongly exceeds the capacity of the very few XFEL facilities existing worldwide. This situation motivates the development of alternative sub-picosecond pulsed X-ray sources among which femtoslicing facilities at synchrotron radiation storage rings are standing out due to their tunability over an extended photon energy range and their high stability. Following the success of the femtoslicing installations at ALS, BESSY-II, SLS and UVSOR, SOLEIL decided to implement a femtoslicing facility. Several challenges were faced, including operation at the highest electron beam energy ever, and achievement of slice separation exclusively with the natural dispersion function of the storage ring. SOLEIL's setup also enables, for the first time, delivering sub-picosecond pulses simultaneously to several beamlines. This last feature enlarges the experimental capabilities of the facility, which covers the soft and hard X-ray photon energy range. In this paper, the commissioning of this original femtoslicing facility is reported. Furthermore, it is shown that the slicing-induced THz signal can be used to derive a quantitative estimate for the degree of energy exchange between the femtosecond infrared laser pulse and the circulating electron bunch.
Variability in community productivity—mediating effects of vegetation attributes
Authors: Polley H. Wayne , Wilsey Brian J.
Published: February 2018

Plant productivity varies through time in response to environmental fluctuations. Reducing variability in productivity requires an improved understanding of how plant community attributes interact with environmental fluctuations to influence plant growth dynamics. We evaluated links between two community attributes, species diversity and abundance‐weighted values of specific leaf area (SLA), and temporal variability in grassland productivity at patch (local) and aggregate (multipatch) spatial scales.

Aggregate communities were created by combining patches of spatially distinct communities of perennial plant species from grassland biodiversity experiments in Texas, USA. Interannual variability in above‐ground net primary productivity (ANPP) of aggregate communities was analysed as a function of two multiplicative components, mean temporal variability in the ANPP of patches and temporal synchrony in ANPP dynamics among patches. We used regression analyses to determine whether temporal variability in aggregate ANPP and its components were correlated with either species diversity or community‐weighted SLA over 5 years.

Temporal variability in ANPP of aggregate communities was strongly correlated with temporal variability in patch ANPP. Increasing mean SLA reduced ANPP variability of aggregate communities by increasing mean productivity. Increased temporal changes in patch‐scale SLA further reduced temporal variability in aggregate ANPP by reducing effects of precipitation fluctuations on productivity. Conversely, increasing species diversity over the narrow range measured increased temporal variability in aggregate ANPP. High diversity was associated with reduced dominance of temporally stable C4 grasses.

Our results implicate means and patch‐scale temporal dynamics in community SLA as potential indicators of variability in grassland primary productivity through time.

A plain language summary is available for this article.
Arbuscular mycorrhizal fungal communities associated with two dominant species differ in their responses to long‐term nitrogen addition in temperate grasslands
Authors: Zheng Zhi , Ma Pengfei , Li Juan , Ren Lifei , Bai Wenming , Tian Qiuying , Sun Wei , Zhang Wen‐Hao
Published: February 2018

Arbuscular mycorrhizal (AM) fungi are important components of grassland ecosystems and are sensitive to enhanced atmospheric nitrogen (N) deposition. Enhanced N deposition has been widely reported to reduce species richness and alter species composition across different types of grasslands world‐wide. Despite extensive studies on effects of N deposition on AM fungal communities of grasslands, few studies have specifically focused on effects of N deposition on AM fungi associated with dominant species in grasslands.

We investigated long‐term (12‐year) effects of N addition (80 kg ha−1 year−1) on AM fungal community richness in roots and rhizosphere biomass of two dominant plant species (forb Artemisia frigida and grass Stipa krylovii) in temperate steppes of northern China.

We found that AM fungi associated with the two dominant plant species differed in their responses to N addition. Nitrogen addition led to a significant reduction in AM fungal richness colonized in roots, and biomass in the rhizosphere of A. frigida, while N addition had little impacts on AM fungi colonized in roots and rhizosphere of S. krylovii. Nitrogen addition significantly reduced AM fungal colonization in roots and AM fungal spore density in the rhizosphere soils of A. frigida. In contrast, N addition had no effect on AM fungal colonization in roots and spore density in the rhizosphere of S. krylovii. Nitrogen addition markedly suppressed photosynthetic rates in A. frigida due to excessive foliar accumulation of manganese. The N‐induced reduction in photosynthetic rates reduced allocation of C into roots in A. frigida, leading to a lower root/shoot ratio, and suppression of AM fungal community associated with A. frigida. The inhibition of AM fungi would render A. frigida less competitive in terms of acquisition of mineral nutrients in soils, thus contributing to its loss in the steppe community under conditions of elevated N deposition.

These findings provide a mechanistic explanation for N‐evoked differential responses of AM fungal communities associated with A. frigida and S. krylovii by linking soil properties and host plants to AM fungal communities.

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Colonization across gradients of risk and reward: Nutrients and predators generate species‐specific responses among aquatic insects
Authors: Pintar Matthew R. , Bohenek Jason R. , Eveland Lauren L. , Resetarits William J.
Published: February 2018

Predation risk and resource abundance are two primary characteristics that determine species abundances and community composition. Colonizing organisms should attempt to minimize the risk of mortality and maximize growth through selection of patches with the highest expected fitness. However, maximizing fitness across multiple gradients of patch quality involves accurate cue assessment, integration and behavioural responses that consider multiple factors that affect fitness simultaneously.

Our goal was to simultaneously and factorially assess the effects of predation risk and resource abundance among an assemblage of aquatic insects to determine the relative importance of each factor, and whether the two factors interact to affect colonization, oviposition and community assembly.

We conducted a field mesocosm experiment in which we crossed predator density (0, 1, 2 fish, Fundulus chrysotus) with supplemental nutrient abundance (0, 4, 8 g rabbit chow) in a 3 × 3 factorial design. We then assayed colonization by natural populations of aquatic beetles and oviposition by natural populations of Culex mosquitoes.

We observed species‐specific responses, with many species avoiding fish and some selecting habitats with more nutrients. Nutrients and predator presence only interactively affected oviposition by Culex mosquitoes, and the effect of fish presence exceeded that of nutrients in all but one analysis.

Our results illustrate the primacy of predation risk in generating colonization patterns and structuring communities in aquatic habitats, but that colonization responses to variation in multiple components of patch quality are often species‐specific. Simultaneous assessments of multiple aspects of patch quality allow for the determination of potential interactions among cue sources and the relative importance of various patch characteristics to colonizers.

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Clinicians’ views of the training, use and maintenance of phonetic transcription in speech and language therapy
Authors: Knight Rachael‐Anne , Bandali Chandni , Woodhead Clare , Vansadia Parul
Published: February 2018

Background

The critical role of phonetic transcription in the assessment, diagnosis and management of speech disorders is well established and thus pre‐registration degrees dedicate numerous hours to phonetic training. However, this training is not always fully used in clinical work and clinicians may find it difficult to maintain their skills, suggesting a ‘theory/practice gap’.

Aims

This paper surveys speech and language therapists’ (SLTs) views of their training, practice and maintenance of transcription in order to investigate the posited theory/practice gap and to explore how education in phonetics is translated into practice.

Methods & Procedures

A total of 759 SLTs from the UK were surveyed via an online questionnaire. Multiple‐choice questions were analysed using descriptive statistics, and free‐text comments were analysed thematically.

Outcomes & Results

Thirty‐five per cent of SLTs found learning phonetics quite easy, and 30% quite difficult. Respondents suggested that more time was needed to practise transcription in and out of the classroom; nevertheless, the majority felt at least equipped to undertake transcription after their training. A total of 75% of SLTs require transcription for their role, with 61% using it often or all the time. Some 45% use a mix of broad and narrow transcription, with 41% using only broad transcription. Those not using narrow transcription attributed this to lack of confidence. A total of 57% of SLTs did not feel supported to maintain transcription skills in the workplace, and 80% had never attended a refresher course in transcription, with 75% wishing to do so.

Conclusions & Implications

As many clinicians found it difficult to learn transcription, there is an opportunity to provide more transcription practice both in and beyond the classroom. Despite most clinicians feeling equipped to undertake transcription upon completion of their training, and a large majority requiring transcription for their role, a theory/practice gap is apparent in the relatively small number of clinicians using narrow transcription exclusively, and those not using it expressing lack of confidence in their skills. Additionally, as many clinicians have never attended refresher training in transcription, and rely on their course notes to maintain their skills, more provision of opportunities for revision should be made available. With clinicians remembering a need for more practice during their training, and expressing a desire for more training opportunities in practice, there is an opportunity for clinicians, educators and regulatory bodies to work together to provide packages of transcription training material that can be used by students and practitioners to maintain and extend their skills.
A novel T4SS‐mediated DNA transfer used by pXO16, a conjugative plasmid from Bacillus thuringiensis serovar israelensis
Authors: Makart Lionel , Gillis Annika , Hinnekens Pauline , Mahillon Jacques
Published: February 2018

The entomopathogenic Bacillus thuringiensis serovar israelensis displays peculiar conjugative transfer capabilities, accounted for by the large conjugative plasmid pXO16 (350 kb). The efficient and fast conjugative transfers are accompanied by a macroscopic aggregation of bacterial partners. Moreover, pXO16 has proven capable of effective mobilization and the retro‐transfer of both mobilizable and ‘non‐mobilizable’ plasmids. In this work, the aggregation phenomenon is shown to promote pXO16 transfer while not being mandatory for transfer. Transfer of pXO16 to B. thuringiensis recipient strains that do not display aggregation is observed as well, hence enlarging the previously defined host range. The use of variant calling analysis of transconjugants allowed for observation of up to 791 kb chromosomal regions mobilization. Previous analysis of pXO16 did not reveal any Type IV Secretion System (T4SS) homologs, which suggested the presence of an unusual conjugative system. A FtsK/SpOIIIE ATPase gene proved here to be necessary for conjugative transfer. Additionally, the analysis of natural restriction‐modification systems in both conjugative partners gave credit to a ssDNA transfer mechanism. A ‘transfer israelensis plasmid’ (tip) region containing this ATPase gene was shown to code for other potential T4SS proteins, illustrating a conjugative system distantly related to the other known Gram‐positive T4SSs.
Clinical Indicators for Evaluation of Outcomes of Impaired Tissue Integrity in Orthopedic Patients: Consensus Study
Authors: da Silva Marcos Barragan , Barreto Luciana Nabinger Menna , Panato Bruna Paulsen , Engelman Bruna , Figueiredo Manoela Schmarczek , Rodríguez‐Acelas Alba Luz , Almeida Miriam de Abreu
Published: February 2018

PURPOSE

To select outcomes from the Nursing Outcomes Classification (NOC) to evaluate impaired tissue integrity in patients undergoing orthopedic surgeries, and develop conceptual and operational definitions for their indicators.

METHODS

A consensus study involving 10 nurses from clinical practice. A 100% consensus was established in the outcomes selection.

FINDINGS

Wound Healing: Primary intention (1102) with two indicators: (110214) Scar formation, and (110201) Skin approximation were selected. Four indicators were grouped to evaluate inflammatory signs together with foul wound odor and six for drainage.

CONCLUSIONS

These indicators direct the outcomes evaluation for wound healing.

IMPLICATIONS FOR NURSING PRACTICE

Support to the definition the priority interventions in nursing process documentation.
The pregnancy hormone human chorionic gonadotropin differentially regulates plasmacytoid and myeloid blood dendritic cell subsets
Authors: Sauss Karoline , Ehrentraut Stefanie , Zenclussen Ana Claudia , Schumacher Anne
Published: February 2018

Problem

Dendritic cells (DCs) are critically involved in fetal fate due to their capability to promote either immunity or tolerance to foreign fetal antigens. Our study aimed to investigate whether the hormone human chorionic gonadotropin (hCG) affects different peripheral blood DC (PBDCs) subsets.

Method of study

PBDCs were isolated from non‐pregnant women, stimulated and co‐cultured with hCG‐producing JEG‐3 or non hCG‐producing SWAN‐71 trophoblasts as well as with two different hCG preparations. The total and mature number of each PBDC subset were assessed. Additionally, the secretion of cytokines was determined in the presence or absence of hCG.

Results

We found no significant effects; neither from trophoblasts nor from the hCG preparations on PBDC cellularity. JEG‐3 cells and both hCG preparations significantly hampered the maturation of MDC1, while SWAN‐71 cells did not provoke any changes on this regard. We observed an altered ability of PBDCs to secrete cytokines in the presence of both trophoblasts and both hCG preparations.

Conclusion

Our data propose that hCG is not a key regulator of cellular alterations within PBDCs. However, under inflammatory conditions, hCG seems to keep the delicate balance between PDC and MDC and retains a tolerogenic MDC1 profile and this may contribute to tolerance maintenance.
Benzodiazepine and Z‐drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015
Authors: Cadogan Cathal A. , Ryan Cristín , Cahir Caitriona , Bradley Colin P. , Bennett Kathleen
Published: February 2018

Aims

The aim of this study was to examine prescribing trends for benzodiazepines and Z‐drugs to General Medical Services (GMS) patients in Ireland.

Methods

A repeated cross‐sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z‐drug prescribing were determined. Age (16–44, 45–64, ≥65 years) and gender trends were investigated.

Results

Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94–226.89) in 2005 to 166.07/1000 population (95% CI 165.38–166.75) in 2015 (P < 0.0001). Z‐drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73–96.00) in 2005 to 109.11/1000 population (95% CI 108.56–109.67) in 2015 (P = 0.048). Approximately one‐third of individuals dispensed either benzodiazepines or Z‐drugs were receiving long‐term prescriptions (>90 days). The proportion of those receiving >1 benzodiazepine and/or Z‐drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z‐drug prescribing rates were highest for older women (≥65 years) throughout the study period.

Conclusions

Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z‐drug prescribing. The study shows that benzodiazepine and Z‐drug prescribing is common in this population, with high proportions of individuals receiving long‐term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long‐term prescribing and use of these medications in Ireland.
Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma
Authors: Iida Shinsuke , Wakabayashi Masashi , Tsukasaki Kunihiro , Miyamoto Kenichi , Maruyama Dai , Yamamoto Kazuhito , Takatsuka Yoshifusa , Kusumoto Shigeru , Kuroda Junya , Ando Kiyoshi , Kikukawa Yoshitaka , Masaki Yasufumi , Kobayashi Miki , Hanamura Ichiro , Asai Hiroaki , Nagai Hirokazu , Shimada Kazuyuki , Tsukamoto Norifumi , Inoue Yoshiko , Tobinai Kensei
Published: February 2018

A randomized phaseIIselection design study (JCOG0904) was carried out to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex;BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal‐naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥20 and <80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) who received one or more prior therapies were randomized to receiveBD(Bor 1.3 mg/m2) orTD(Thal 200 mg/d). In both arms, 8 cycles of induction (3‐week cycle) were followed by maintenance phase (5‐week cycle) until disease progression, unacceptable toxicity, or patient refusal. The primary end‐point was 1‐year progression‐free survival (PFS). Forty‐four patients were randomized and assigned to receiveBDandTD(n = 22, each group). At a median follow‐up of 34.3 months, the 1‐yearPFSin theBDandTDarms were 45.5% (95% confidence interval (CI), 24.4%‐64.3%) and 31.8% (95%CI, 14.2%‐51.1%), respectively, and the overall response rates were 77.3% and 40.9%, respectively. The 3‐year overall survival (OS) was 70.0% (95%CI, 44.9%‐85.4%) in theBD, and 48.8% (95%CI, 25.1%‐69.0%) in theTDarm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0.0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent inBDwhen compared with theTDarm. Patients treated withBDhad better outcomes than those treated withTDwith regard to 1‐yearPFSand 3‐yearOS. Thus,BDwas prioritized overTDfor further investigations in Bor and Thal‐naïveRRMMpatients. (Clinical trial registration no.UMIN000003135.)
Roles of protein kinase R in cancer: Potential as a therapeutic target
Authors: Watanabe Takao , Imamura Takeshi , Hiasa Yoichi
Published: February 2018

Double‐stranded (ds) RNA‐dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune antiviral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor as a result of its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant disease, such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus (HCV) is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In the present review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer.
Adolescents’ Perspectives on Personal and Societal Responsibility for Childhood Obesity — The Study of Beliefs through ‘Serious’ Game (PlayDecide)
Authors: Timotijevic Lada , Acuna‐Rivera Marcela , Gemen Raymond , Kugelberg Susanna , McBarron Kate , Raats Monique M. , Zolotonosa Maria
Published: February 2018

The dominant approaches to public health policy on childhood obesity are based on the neoliberal emphasis of personal choice and individual responsibility. We study adolescents’ (N = 81) beliefs about responsibility for childhood obesity as a public health issue, through an innovative participatory method, PlayDecide, organised in two countries: the UK and Spain. There is no evidence of a blanket rejection of individual responsibility, rather, a call for renegotiation of the values that inform adolescents’ food choices. The findings suggest the need to broaden the framing of obesity‐related policy to go beyond the nutritional paradigm and include other values that signal health.
“I Learn as I Please”: The Construction of Children's Knowledge in, and about, a Buenos Aires Neighbourhood
Authors: Shabel Paula
Published: February 2018

This article summarises the findings of an ethnographic study among children of ages nine to fifteen who attend Aula Vereda, a community organisation in their neighbourhood with educational and recreational activities, once a week. On the assumption that children actively construct knowledge and do not merely repeat what adults impart, I'll identify three different ways in which these youths approach the instances of learning that the educators propose at the centre. These approaches, in turn, reveal a variety of cognitive productions and means for negotiating the spatial and generational meanings at work in the neighbourhood where they live.
Inhibition of Lats1/p‐YAP1 pathway mitigates neuronal apoptosis and neurological deficits in a rat model of traumatic brain injury
Authors: Li Di , Ji Jia‐Xuan , Xu Yi‐Tian , Ni Hai‐Bo , Rui Qin , Liu Hui‐Xiang , Jiang Feng , Gao Rong , Chen Gang
Published: February 2018

Aims

To investigate the roles of Lats1/p‐YAP1 pathway in TBI‐induced neuronal apoptosis and neurological deficits in rats.

Results

We found that Lats1 and YAP1 were expressed in cerebral cortex neurons of Sprague‐Dawley rats, and the phosphorylation levels of Lats1 and YAP1 in injured regions were significantly increased after TBI. Furthermore, inhibition of Lats1 not only decreased the level of p‐YAP1, but also attenuated neuronal apoptosis and neurological impairment.

Conclusions

Our work demonstrates that inhibition of Lats1/p‐YAP1 pathway mitigates neuronal apoptosis and neurological deficits in a rat model of TBI.
Histopathology of 460 liver allografts removed at retransplantation: A shift in disease patterns over 27 years
Authors: Neves Souza Lara , de Martino Rodrigo Bronze , Sanchez‐Fueyo Alberto , Rela Mohamed , Dhawan Anil , O'Grady John , Heaton Nigel , Quaglia Alberto
Published: February 2018

Background and aim

Approximately 10%‐19% of liver transplant recipients develop irreversible graft failure requiring retransplantation. We reviewed the histology of failed grafts removed at retransplantation in our center over 27 years.

Methods

Two hundred and seventy‐six adults and 118 children underwent retransplantation from 1987 to 2014, receiving 321 and 139 liver grafts, respectively. We analyzed graft histology, recipient demographics, indications and time interval to retransplantation. We divided retransplantation in 3 eras: A (1987‐1994), B (1995‐2001), and C (2002‐2014).

Results

A total of 3298 adult and 938 pediatric primary liver transplants were conducted in our center, and 8.4% of adults and 12.6% of children experienced retransplantation. Considering the changes throughout the eras, the proportion of chronic rejection declined, while that of unexplained chronic fibrosing hepatitis increased steadily, representing the main reason for retransplantation conducted >10 years after primary transplant in children, and second in adults in the most recent era. This chronic hepatitis of the graft might correspond to a slowly evolving form of rejection, possibly with a humoral component, associated with progressive graft fibrosis and eventually failure.

Conclusions

We observed a shift in histopathology of failed liver grafts, with increasing relevance of chronic idiopathic hepatitis associated with progressive fibrosis and graft failure.
Trends in the use of illicit substances in Thailand: Results from national household surveys
Authors: Angkurawaranon Chaisiri , Jiraporncharoen Wichuda , Likhitsathian Surinporn , Thaikla Kanittha , Kanato Manop , Perngparn Usaneya , Assanangkornchai Sawitri , Aramrattana Apinun
Published: February 2018

Introduction and Aims

Thailand borders some of the world’s largest methamphetamine and opioid producing countries and trafficking routes. Thailand’s ‘War on Drugs’ campaign was launched in 2003. This study reports trends in illicit substance use in Thailand over the period 2001–2011.

Design and Methods

National Household surveys on illicit drug use were conducted in 2001, 2003, 2007, 2008 and 2011. A stratified multi‐stage cluster random sampling technique was implemented for each survey. Provinces in four regions were systematically selected using a probability proportionate to the size of the targeted population. Participants were interviewed using structured questionnaires on their history of substance use.

Results

The prevalence of illicit drug use within the past drastically decreased from 4.5% in 2001 to 1.0% in 2003 (P < 0.05). Since 2003, the prevalence of illicit use within the past year varied between 1.0% and 1.3%. By 2011, it was estimated that 0.84% have used kratom (a substance derived from Mitragyna speciosa) within the past year. Around 0.20% and 0.19% reported using cannibis and yaba (metamphetamine tablet) within a year of the 2011 survey. Other types of illicit drugs were less commonly used in Thailand.

Discussion and Conclusions

There was a decrease in prevalence of illicit drug use within the past year between 2001 and 2003 in Thailand. Since 2003, the past year prelavence of illicit drug use has remained relatively stable. From 2001 to 2011, cannabis, kratom and yaba have remained the three most commonly reported types of illicit drugs used in Thailand.
Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET‐DD) study, a collaborative study carried out in 14 countries
Authors: Lloyd C. E. , Nouwen A. , Sartorius N. , Ahmed H. U. , Alvarez A. , Bahendeka S. , Basangwa D. , Bobrov A. E. , Boden S. , Bulgari V. , Burti L. , Chaturvedi S. K. , Cimino L. C. , Gaebel W. , de Girolamo G. , Gondek T. M. , de Braude M. Guinzbourg , Guntupalli A. , Heinze M. G. , Ji L. , Hong X. , Khan A. , Kiejna A. , Kokoszka A. , Kamala T. , Lalic N. M. , Lecic Tosevski D. , Mankovsky B. , Li M. , Musau A. , Müssig K. , Ndetei D. , Rabbani G. , Srikanta S. S. , Starostina E. G. , Shevchuk M. , Taj R. , Vukovic O. , Wölwer W. , Xin Y.
Published: February 2018

Aims

To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries.

Methods

People with diabetes aged 18–65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected.

Results

A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non‐existent in many countries (0–29.6%).

Conclusions

Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.
Alternative test models for skin ageing research
Authors: Nakamura Motoki , Haarmann‐Stemmann Thomas , Krutmann Jean , Morita Akimichi
Published: February 2018

Increasing ethical concerns regarding animal experimentation have led to the development of various alternative methods based on the 3Rs (Refinement, Reduction and Replacement), first described by Russell and Burch in 1959. Cosmetic research and skin ageing research are particularly susceptible to concerns related to animal testing. In addition to animal welfare reasons, there are scientific and economic reasons to reduce and avoid animal experiments. Importantly, animal experiments may not reflect findings in humans mainly because of the differences in architectures and immune responses between animal skin and human skin. Here, we review the shift from animal testing to the development and application of alternative non–animal‐based methods and the necessity and benefits of this shift. Some specific alternatives to animal models are discussed, including biochemical approaches, 2‐dimensional and 3‐dimensional cell cultures and volunteer studies, as well as future directions, including genome‐based research and the development of in silico computer simulations of skin models. Among the in vitro methods, 3‐dimensional reconstructed skin models are highly popular and useful alternatives to animal models however still have many limitations. With careful selection and skilful handling, these alternative methods will become indispensable for modern dermatology and skin ageing research.
Seasonal, interannual and decadal drivers of tree and grass productivity in an Australian tropical savanna
Authors: Moore Caitlin E. , Beringer Jason , Donohue Randall J. , Evans Bradley , Exbrayat Jean‐François , Hutley Lindsay B. , Tapper Nigel J.
Published: February 2018

Tree–grass savannas are a widespread biome and are highly valued for their ecosystem services. There is a need to understand the long‐term dynamics and meteorological drivers of both tree and grass productivity separately in order to successfully manage savannas in the future. This study investigated the interannual variability (IAV) of tree and grass gross primary productivity (GPP) by combining a long‐term (15 year) eddy covariance flux record and model estimates of tree and grassGPPinferred from satellite remote sensing. On a seasonal basis, the primary drivers of tree and grassGPPwere solar radiation in the wet season and soil moisture in the dry season. On an interannual basis, soil water availability had a positive effect on treeGPPand a negative effect on grassGPP. No linear trend in the tree–grassGPPratio was observed over the 15‐year study period. However, the tree–grassGPPratio was correlated with the modes of climate variability, namely the Southern Oscillation Index. This study has provided insight into the long‐term contributions of trees and grasses to savanna productivity, along with their respective meteorological determinants ofIAV.
Myocardial infarction stabilization by cell‐based expression of controlled Vascular Endothelial Growth Factor levels
Authors: Melly Ludovic , Cerino Giulia , Frobert Aurélien , Cook Stéphane , Giraud Marie‐Noëlle , Carrel Thierry , Tevaearai Stahel Hendrik T. , Eckstein Friedrich , Rondelet Benoît , Marsano Anna , Banfi Andrea
Published: February 2018

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.
Papulopustular rosacea and rosacea‐like demodicosis: two phenotypes of the same disease?
Authors: Forton F.M.N. , De Maertelaer V.
Published: February 2018

Background

Papulopustular rosacea and rosacea‐like demodicosis have numerous similarities, but they are generally considered as two distinct entities, mainly because the causal role of the Demodex mite in the development of rosacea is not yet widely accepted. Several clinical characteristics are traditionally considered to differentiate the two conditions; for example, papulopustular rosacea is typically characterized by central facial papulopustules and persistent erythema, whereas small superficial papulopustules and follicular scales rather suggest rosacea‐like demodicosis. However, none of these characteristics is exclusive to either entity.

Objective

To explore differences in Demodex densities according to clinical characteristics traditionally associated with these two conditions.

Methods

Retrospective, observational, case–control study of 242 patients with central face papulopustules. Demodex densities were measured on two consecutive standardized skin surface biopsies.

Results

In the whole cohort, Demodex densities were greater in patients with persistent erythema than in those without. In 132 patients without recent treatment or other facial dermatoses, 120 (91%) had persistent erythema, 119 (90%) small superficial papulopustules and 124 (94%) follicular scales; 116 (88%) simultaneously had clinical characteristics traditionally associated with both papulopustular rosacea and rosacea‐like demodicosis. Higher Demodex densities were linked to the presence of follicular scales, but not to papulopustules size, nor to the presence/absence of persistent erythema.

Conclusion

Our observations highlight the difficulty differentiating between these entities and suggest that rosacea‐like demodicosis and papulopustular rosacea should no longer be considered as two separate entities, but rather as two phenotypes of the same disease.
Altered epigenetic pathways and cell cycle dysregulation in healthy appearing skin of patients with koebnerized squamous cell carcinomas following skin surgery
Authors: Gambichler T. , Rüddel I. , Hessam S. , Bechara F.G. , Stockfleth E. , Schmitz L.
Published: February 2018

Background

Koebnerized non‐melanoma skin cancer following skin trauma represents a rare and obscure event.

Objectives

To study molecular pathological parameters in koebnerized squamous cell carcinomas (K‐SCCs) occurring after complete tumour removal.

Methods

We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long‐term azathioprine therapy. Both patients rapidly developed several K‐SCCs following histopathologically proven complete excision of cutaneous SCCs. We performed immunohistochemistry for p53, p16, Ki‐67, TET‐2, IDH‐2, 5‐hmc and 5‐mc. PCR was carried out for the detection of human papilloma viruses. Mutation analysis was performed for BRAF, K‐RAS and EGFR.

Results

All lesions investigated were negative for HPV DNA. Mutations were not detected. Healthy appearing skin of both patients showed relatively high Ki‐67, p16 and p53 expression which was comparable to the expression observed in primary SCCs as well as K‐SCCs. Protein expression of Ki‐67, p16 and mutant p53 was barely detected in the specimens of the healthy controls. A decreased protein expression of TET‐2 enzyme was seen in all tumours and healthy appearing skin when compared to the skin of healthy controls.

Conclusions

We observed two patients with K‐SCCs developing under DMF treatment. In healthy appearing skin of patients with K‐SCCs, wound healing processes, including induction of proliferation and growth factor release, might promote the growth of preneoplastic keratinocytes and cancer formation on the basis of pre‐existing altered epigenetic pathways and cell cycle dysregulation. Although fumarates can reduce TET‐2 expression, the role of DMF intake in the development of K‐SCCs remains unclear.
The measurement of drug‐induced interferon γ‐releasing cells and lymphocyte proliferation in severe cutaneous adverse reactions
Authors: Suthumchai N. , Srinoulprasert Y. , Thantiworasit P. , Rerknimitr P. , Tuchinda P. , Chularojanamontri L. , Rerkpattanapipat T. , Chanprapaph K. , Disphanurat W. , Chakkavittumrong P. , Tovanabutra N. , Srisuttiyakorn C. , Sukasem C. , Klaewsongkram J. ,   the ThaiSCAR study group
Published: February 2018

Background

The lymphocyte transformation test (LTT) is a standard laboratory method to identify culprit drugs in patients with a history of drug‐induced non‐immediate hypersensitivity and is mainly performed during the recovery phase. The measurement of drug‐specific interferon γ (IFN‐γ)‐releasing cells has been introduced to confirm culprit drugs, even during the acute phase of drug allergy.

Objectives

This study aimed to evaluate the capability of the enzyme‐linked immunospot assay (ELISpot) to detect drug‐specific IFN‐γ‐releasing cells during the acute phase and the capability of LTT to identify culprit drugs during the recovery phase in patients presenting with severe cutaneous adverse reactions (SCARs).

Methods

Peripheral blood mononuclear cells (PBMCs) from 23 SCAR patients were collected during the acute and recovery phases and assayed for drug‐specific IFN‐γ‐releasing cells and lymphocyte proliferation, respectively.

Results

Drug‐specific IFN‐γ‐releasing cells were detectable in 73.9% of SCAR subjects (55.6% and 85.7% in patients who were and were not taking systemic steroids, respectively), whereas LTT results were positive in 52.2% of SCAR subjects. The frequencies of drug‐specific IFN‐γ‐releasing cells were significantly higher in patients with positive LTT than in those with negative LTT (260.1 ± 110.0 and 46.6 ± 20.7 cells/106 PBMCs, P = 0.01). A significant correlation between the results of the IFN‐γ ELISpot assay and LTT was demonstrated (r = 0.65, P value <0.01).

Conclusion

The IFN‐γ ELISpot assay could be a useful tool to identify culprit drugs in SCAR patients when culprit drug identification is urgently needed during the acute phase of drug allergy.