bluuebunny/crossref_metadata_2025_split huggingface dataset:
TLR9-mediated inflammation drives a Ccr2-independent peripheral monocytosis through enhanced extramedullary monocytopoiesis
Authors: Weaver Lehn K. , Chu Niansheng , Behrens Edward M. 
Published: September 2016

Significance
Monocytes perpetuate inflammation during autoimmune diseases through chronic sensing of Toll-like receptor (TLR) signals. However, individual monocytes down-regulate their capacity to produce inflammation after an initial TLR-activating event. We now show that continuous TLR9 responsiveness in vivo corresponds to an accumulation of monocytes in peripherally inflamed tissues. Intriguingly, the production and positioning of monocytes occurs independent of the bone marrow, the canonical location of monocyte production during normal homeostasis. Instead, increases in peripheral monocyte numbers are dictated by the accumulation of functionally enhanced monocyte-producing cells in peripherally inflamed tissues. These novel insights into monocyte production and positioning during systemic inflammation implicate local production of TLR-responsive monocytes as a key mechanism contributing to systemic inflammation during autoimmunity.
Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy
Authors: Hammond Suzan M. , Hazell Gareth , Shabanpoor Fazel , Saleh Amer F. , Bowerman Melissa , Sleigh James N. , Meijboom Katharina E. , Zhou Haiyan , Muntoni Francesco , Talbot Kevin , Gait Michael J. , Wood Matthew J. A. 
Published: September 2016

Significance
Splice-switching oligonucleotide (SSO) treatment in spinal muscular atrophy (SMA) has quickly become a clinical reality, but without an effective delivery system, the practicalities of delivering SSO therapy efficiently might preclude its widespread use. Our peptide-conjugated SSOs are being designed for clinical trials for the treatment of Duchenne muscular dystrophy. Here, we report advanced phosphorodiamidate oligomer (PMO) internalizing peptide (Pip) peptides that effectively deliver SSOs bodywide and at doses an order-of-magnitude lower than required by naked SSOs in a mouse model of SMA. Furthermore, our peptide-SSO is able to deliver to the CNS of adult mice. This study thus presents an oligonucleotide showing activity in the CNS following a systemic route with peptide delivery.
Sound–meaning association biases evidenced across thousands of languages
Authors: Blasi Damián E. , Wichmann Søren , Hammarström Harald , Stadler Peter F. , Christiansen Morten H. 
Published: September 2016

Significance
The independence between sound and meaning is believed to be a crucial property of language: across languages, sequences of different sounds are used to express similar concepts (e.g., Russian “ptitsa,” Swahili “ndege,” and Japanese “tori” all mean “bird”). However, a careful statistical examination of words from nearly two-thirds of the world’s languages reveals that unrelated languages very often use (or avoid) the same sounds for specific referents. For instance, words for tongue tend to have l or u, “round” often appears with r, and “small” with i. These striking similarities call for a reexamination of the fundamental assumption of the arbitrariness of the sign.
Toward combined delignification and saccharification of wheat straw by a laccase-containing designer cellulosome
Authors: Davidi Lital , Moraïs Sarah , Artzi Lior , Knop Doriv , Hadar Yitzhak , Arfi Yonathan , Bayer Edward A. 
Published: September 2016

SignificanceLignocellulosic biomass is a potential major resource for renewable energy production. Plant cell-wall deconstruction, however, remains an inefficient process, mainly due to the recalcitrant nature of the lignin and cellulosic components, that requires chemical pretreatment methods prior to degradation. This study aims to overcome this barrier by combining two paradigms into a single system, by using a synthetic biology approach. The designed system integrates an engineered laccase (an oxidizing enzyme that acts on lignin) into a multienzyme cellulosome complex, thereby producing enhanced decomposition of wheat straw. These findings demonstrate the potential of introducing complementary enzymes that fail to occur together in nature into designer cellulosomes for improved lignocellulose conversion.
The investment model of volunteering in the EU-27 countries: volunteering, skills development and employability. A multi-level analysis
Authors: Souto-Otero Manuel , Shields Robin 
Published: September 2016

ABSTRACT
This article contributes to a better understanding of the social acceptance of the investment model of volunteering, that is, the view that volunteering can enhance employability through the development of professionally relevant knowledge and competences. Based on the analysis of Eurobarometer data, the article explores (1) the prevalence of the investment model of volunteering in the EU-27 countries and the extent to which this varies between individuals with the potential to make hiring decisions (IHP) and the general population, (2) the demographic factors associated with the acceptance of this model, (3) whether national differences in the acceptance of the model are better explained by variation between countries or cross-national demographic factors and (4) whether national institutional characteristics related to the competitiveness of the national labour market, the specificity of the education system, the strength of the continuing vocational training system and cultural factors influence acceptance. The results show that the acceptance of the investment model of volunteering is relatively widespread in Europe and that variation in the acceptance of the investment model among the general population is driven by both individual (age and class) and between-country differences (related to the strength of training for unemployed people), but variation is more attributable to differences between countries than cross-national demographic groups. IHP, on the other hand, tend to be more homogenous in their acceptance of the investment model than the general population.
Breaking news from the HST: the central star of the Stingray Nebula is now returning towards the AGB
Authors: Reindl Nicole , Rauch T. , Miller Bertolami M. M. , Todt H. , Werner K. 
Published: September 2016

Abstract
SAO 244567 is a rare example of a star that allows us to witness stellar evolution in real time. Between 1971 and 1990, it changed from a B-type star into the hot central star of the Stingray Nebula. This observed rapid heating has been a mystery for decades, since it is in strong contradiction with the low mass of the star and canonical post-asymptotic giant branch (AGB) evolution. We speculated that SAO 244567 might have suffered from a late thermal pulse (LTP) and obtained new observations with Hubble Space Telescope (HST)/COS to follow the evolution of the surface properties of SAO 244567 and to verify the LTP hypothesis. Our non-LTE spectral analysis reveals that the star cooled significantly since 2002 and that its envelope is now expanding. Therefore, we conclude that SAO 244567 is currently on its way back towards the AGB, which strongly supports the LTP hypothesis. A comparison with state-of-the-art LTP evolutionary calculations shows that these models cannot fully reproduce the evolution of all surface parameters simultaneously, pointing out possible shortcomings of stellar evolution models. Thereby, SAO 244567 keeps on challenging stellar evolution theory and we highly encourage further investigations.
Cosmic signatures in earth's seismic tremor?
Authors: Mulargia Francesco 
Published: September 2016

Abstract
Even in absence of earthquakes, each site on earth experiences continuous elastic vibrations which are mostly traced to the nonlinear interactions of ocean waves. However, the fine structure of the spectrum at mHz frequencies shows many persistent and highly significant narrow bandwidth peaks in surprising coincidence with solar acoustic eigenmodes. The feasibility of a common cosmic origin is evaluated through an estimate of the gravitational wave cross-section of the earth, combined with its elastic response and with the stochastic amplification produced by the interference of the cosmic signal with tremor of oceanic origin. The measured spectral peaks appear compatible with a gravitational monochromatic illumination at strains h ≳ 10−20, larger than those expected for any known gravitational stellar source. Hence, a gravitational source attribution to the tremor spectral peaks would call for a population of unknown non-luminous sources with well-defined mass–distance ratios.
Caring for breast cancer survivors in primary care
Authors: Trotter Kathryn , Stouder April 
Published: September 2016

ABSTRACT
Women with a history of breast cancer compose the largest group of cancer survivors. Physician assistants and nurse practitioners can play a key role in caring for cancer survivors in primary care settings. This article provides a brief overview and synthesis of current breast cancer guidelines, other resources, and clinical observations that may help primary care providers to translate plans developed by oncology specialists into primary care delivery.
Current Management of Patients With Diverticulosis and Diverticular Disease
Authors: Tursi Antonio , Picchio Marcello , Elisei Walter , Di Mario Francesco , Scarpignato Carmelo , Brandimarte Giovanni 
Published: September 2016

Background:
Management of diverticular disease (DD) remains a point of debate.

Goals:
To investigate the current opinion of participants of the 2nd International Symposium on Diverticular Disease, on real-life management of patients with DD of the colon.

Study:
Twelve questions were aimed at the diagnosis, treatment, and management options for diverticulosis and symptomatic DD.

Results:
In total, 115 surveys from 8 European Countries were filled out. High fiber diet was widely prescribed in diverticulosis (59.1%). Probiotics (25%) were the most frequent prescribed drug, whereas 29.8% of participants did not prescribe any treatment in diverticulosis. Colonoscopy was frequently prescribed in symptomatic patients (69.3%), whereas 72.9% of participants did not prescribe any instrumental tool in their follow-up. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs both in symptomatic patients (28.1, 14.9%, and 11.4%, respectively) and to prevent recurrence of the disease (42.5%, 12.4%, and 28.2%, respectively). With respect to laboratory exams, 57.9% of participants prescribed them during follow-up. The majority of participants (64.9%) managed suspected acute diverticulitis at home. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs to prevent recurrence of the disease (32.2%, 13.2%, and 11.4%, respectively), whereas 25.4% of participants did not prescribe any drugs. Finally, no differences were found among gastroenterologists, surgeons, and general practitioners in managing this disease.

Conclusions:
This surveys shows that current management of DD is similar between different medical specialities, generally in line with current literature.
Mesalazine for the Treatment of Symptomatic Uncomplicated Diverticular Disease of the Colon and for Primary Prevention of Diverticulitis
Authors: Picchio Marcello , Elisei Walter , Brandimarte Giovanni , Di Mario Francesco , Malfertheiner Peter , Scarpignato Carmelo , Tursi Antonio 
Published: September 2016

Background:Symptomatic uncomplicated diverticular disease (SUDD) is a common gastrointestinal disease, because it affects about one fourth of the patient harboring colonic diverticula.Goal:To assess the effectiveness of mesalazine in improving symptoms (namely abdominal pain) and in preventing diverticulitis occurrence in patients with SUDD.Study:Only randomized clinical trials (irrespective of language, blinding, or publication status) that compared mesalazine with placebo or any other therapy in SUDD were evaluated. The selected endpoints were symptom relief and diverticulitis occurrence at maximal follow-up. Absolute risk reduction (ARR, with 95% confidence interval) and the number needed to treat were used as measures of the therapeutic effect.Results:Six randomized clinical trials enrolled 1021 patients: 526 patients were treated with mesalazine and 495 with placebo or other therapies. Symptom relief with mesalazine was always larger than that with placebo and other therapies. However, absolute risk reduction was significant only when mesalazine was compared with placebo, a high-fiber diet, and low-dose rifaximin. The incidence of diverticulitis with mesalazine was lower than that observed with placebo and other treatments, being significant only when compared with placebo.Conclusions:Mesalazine is effective in achieving symptom relief and primary prevention of diverticulitis in patients with SUDD.
Primary sclerosing cholangitis in the Swiss Inflammatory Bowel Disease Cohort Study: prevalence, risk factors, and long-term follow-up
Authors: Fraga Montserrat , Fournier Nicolas , Safroneeva Ekaterina , Pittet Valérie , Godat Sébastien , Straumann Alex , Nydegger Andreas , Vavricka Stephan R. , Moradpour Darius , Schoepfer Alain M. 
Published: September 2016

Background and aim
Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD). We aimed to assess the prevalence of PSC in the Swiss Inflammatory Bowel Disease Cohort Study, to identify associated risk factors, and to describe the long-term evolution.

Patients and methods
Data of patients enrolled into the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Logistic regression modeling was performed to identify risk factors for PSC.

Results
Among 2744 patients [1188 ulcerative colitis (UC); 1556 Crohn’s disease (CD)], 57 had PSC (48 UC-PSC, nine CD-PSC). The prevalence of PSC was higher in UC compared with CD (4.04 vs. 0.58%, P<0.001). We identified the following significant independent risk factors for PSC in patients with UC: male sex [odds ratio (OR) 2.771, P=0.022], pancolitis (OR 2.855, P=0.011), nonsmoker at diagnosis (OR 9.253, P=0.030), and a history of appendicectomy (OR 4.114, P=0.019). During a median follow-up time of 74.8 months, four (7.0%) of PSC patients developed cholangiocarcinoma, six (10.5%) underwent liver transplantation, and five (8.8%) died. Survival of IBD-PSC patients was significantly worse compared with IBD patients without PSC (P=0.001). UC-PSC patients developed significantly more frequently colorectal cancer compared with UC patients without PSC (2/48 vs. 9/1440, P=0.017).

Conclusion
Approximately 4% of UC patients and 0.6% of CD patients had PSC. Male sex, pancolitis, nonsmoker status, and a history of appendicectomy were significantly associated with PSC. PSC is associated with considerable morbidity and mortality in the long term.
Iron Deficiency in Inflammatory Bowel Disease
Authors: Akkermans Marjolijn D. , Vreugdenhil Mirjam , Hendriks Daniëlle M. , van den Berg Anemone , Schweizer Joachim J. , van Goudoever Johannes B. , Brus Frank 
Published: September 2016

ABSTRACTObjectives:Iron deficiency (ID) in children with inflammatory bowel disease (IBD) is either an absolute (depleted iron stores) or a functional deficiency (caused by chronic inflammation). Differentiating between these 2 types of ID is important because they require a different therapeutic approach. Zinc protoporphyrin (ZPP) and red blood cell distribution width (RDW) are parameters of functional ID. Studies using these parameters to differentiate are nonexistent. We aimed to evaluate the prevalence of and risk factors for absolute and functional ID in paediatric IBD patients while using ZPP and RDW.Methods:We evaluated the iron status and medical charts of 59 paediatric IBD patients in a secondary hospital in the Netherlands. Absolute ID was defined as serum ferritin <15 μg/L in the absence of infection and/or acute inflammation (C‐reactive protein <10 mg/L). Iron deficiency anaemia (IDA) was defined as absolute ID in combination with anaemia. Functional ID, in patients without absolute ID, was defined as ZPP >70 μmol/mol haem and/or an RDW >14%. Anaemia of chronic disease (ACD) was defined as functional ID in combination with anaemia.Results:Absolute and functional ID were found in 19/59 (32.2%) and 32/40 (80%) patients, respectively. The prevalence of IDA and ACD was 27.1% (16/59) and 20% (8/40), respectively. Multivariate analyses showed that absolute ID and IDA were both associated with a more recent IBD‐diagnosis (both P < 0.05).Conclusions:Absolute and functional ID are common in paediatric IBD patients, and this differentiation is important because of therapeutic consequences. Furthermore, absolute ID and IDA are associated with a more recent IBD‐diagnosis.
Paediatric Gastrointestinal Endoscopy
Authors: Thomson Mike , Tringali Andrea , Dumonceau Jean‐Marc , Tavares Marta , Tabbers Merit M. , Furlano Raoul , Spaander Manon , Hassan Cesare , Tzvinikos Christos , Ijsselstijn Hanneke , Viala Jérôme , Dall'Oglio Luigi , Benninga Marc , Orel Rok , Vandenplas Yvan , Keil Radan , Romano Claudio , Brownstone Eva , Hlava Štěpán , Gerner Patrick , Dolak Werner , Landi Rosario , Huber Wolf D. , Everett Simon , Vecsei Andreas , Aabakken Lars , Amil‐Dias Jorge , Zambelli Alessandro 
Published: September 2016

ABSTRACTThis guideline refers to infants, children, and adolescents ages 0 to 18 years. The areas covered include indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; corrosive ingestion and stricture/stenosis endoscopic management; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography; and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease has been dealt with in other guidelines and are therefore not mentioned in this guideline. Training and ongoing skill maintenance are to be dealt with in an imminent sister publication to this.
What do isogamous organisms teach us about sex and the two sexes?
Authors: Lehtonen Jussi , Kokko Hanna , Parker Geoff A. 
Published: September 2016

Isogamy is a reproductive system where all gametes are morphologically similar, especially in terms of size. Its importance goes beyond specific cases: to this day non-anisogamous systems are common outside of multicellular animals and plants, they can be found in all eukaryotic super-groups, and anisogamous organisms appear to have isogamous ancestors. Furthermore, because maleness is synonymous with the production of small gametes, an explanation for the initial origin of males and females is synonymous with understanding the transition from isogamy to anisogamy. As we show here, this transition may also be crucial for understanding why sex itself remains common even in taxa with high costs of male production (the twofold cost of sex). The transition to anisogamy implies the origin of male and female sexes, kickstarts the subsequent evolution of sex roles, and has a major impact on the costliness of sexual reproduction. Finally, we combine some of the consequences of isogamy and anisogamy in a thought experiment on the maintenance of sexual reproduction. We ask what happens if there is a less than twofold benefit to sex (not an unlikely scenario as large short-term benefits have proved difficult to find), and argue that this could lead to a situation where lineages that evolve anisogamy—and thus the highest costs of sex—end up being associated with constraints that make invasion by asexual reproduction unlikely (the ‘anisogamy gateway’ hypothesis).
This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.
Living together and living apart: the sexual lives of bryophytes
Authors: Haig David 
Published: September 2016

Haploid gametophytes of bryophytes spread by clonal growth but mate locally, within an area defined by the range of sperm movement. Rarity of establishment from spores or vegetative competition can result in unisexual populations unable to reproduce sexually. Females typically outcompete males, probably because females expend fewer resources than males on the production of gametes. Extreme sexual dimorphism—tiny males growing as epiphytes on much larger females—has evolved many times. Haploid selfing is common in bryophytes with bisexual gametophytes, and results in completely homozygous sporophytes. Spores from these sporophytes recapitulate the genotype of their single haploid parent. This process can be considered analogous to ‘asexual’ reproduction with ‘sexual’ reproduction occurring after rare outcrossing between haploid parents. Ferns also produce bisexual haploid gametophytes but, unlike bryophytes, haploid outcrossing predominates over haploid selfing. This difference is probably related to clonal growth and vegetative competition occurring in the haploid but not the diploid phase in bryophytes, but the reverse in ferns. Ferns are thereby subject to stronger inbreeding depression than bryophytes.
This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.
Sexual selection in hermaphrodites, sperm and broadcast spawners, plants and fungi
Authors: Beekman Madeleine , Nieuwenhuis Bart , Ortiz-Barrientos Daniel , Evans Jonathan P. 
Published: September 2016

Darwin was the first to recognize that sexual selection is a strong evolutionary force. Exaggerated traits allow same-sex individuals to compete over access to mates and provide a mechanism by which mates are selected. It is relatively easy to appreciate how inter- and intrasexual selection work in organisms with the sensory capabilities to perceive physical or behavioural traits that signal mate quality or mate compatibility, and to assess the relative quality of competitors. It is therefore not surprising that most studies of sexual selection have focused on animals with separate sexes and obvious adaptations that function in the context of reproductive competition. Yet, many sexual organisms are both male and female at the same time, often lack sexual dimorphism and never come into direct contact at mating. How does sexual selection act in such species, and what can we learn from them? Here, we address these questions by exploring the potential for sexual selection in simultaneous hermaphrodites, sperm- and broadcast spawners, plants and fungi. Our review reveals a range of mechanisms of sexual selection, operating primarily after gametes have been released, which are common in many of these groups and also quite possibly in more familiar (internally fertilizing and sexually dimorphic) organisms.This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.
Evolutionary mysteries in meiosis
Authors: Lenormand Thomas , Engelstädter Jan , Johnston Susan E. , Wijnker Erik , Haag Christoph R. 
Published: September 2016

Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often ‘weird’ features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.