bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Activation of α7-Nicotinic Receptors by Nicotine Improves Rodent Skin Flap Survival Through Nitrergic System
Authors: Abbaszadeh-kasbi Ali , Haddadi Nazgol-Sadat , Dehdashtian Amir , Afshari Khashayar , Jazaeri Seyedeh Zarifeh , Khodaei Naser , Momeni Majid , Dehpour Ahmad-Reza 
Published: March 2019

Background
Recent reports have identified angiogenic, anti-inflammatory, and antioxidant properties of acute treatment with nicotine via activation of nicotinic acetylcholine receptors (nAChRs). In addition, the nitric oxide (NO) pathway is involved in ischemic reperfusion injuries.

Objectives
We investigated the effects of acute pretreatment with nicotine in a rat model of random-pattern skin flap and the potential role of the NO pathway.

Methods
The Sprague-Dawley rats received increasing doses of (−)-nicotine (0.5, 1, 1.5, 2, and 3 mg/kg) before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline, and flap survival was evaluated 7 days after surgery. In addition, animals received an α7-nAChR antagonist, methyllycaconitine, with nicotine. Quantitative reverse transcription polymerase chain reaction was also applied to measure the dermal expression of α7-nAChR. Next, a nonselective NO synthase inhibitor, N-nitro-l-arginine methyl ester hydrochloride; a selective inducible NO synthase inhibitor, aminoguanidine; and an NO precursor, l-arginine, were administered with nicotine.

Results
Nicotine at doses of 1, 1.5, and 2 mg/kg significantly increased flap survival, whereas the protective effects of nicotine disappeared at higher doses. Methyllycaconitine completely reversed the protective effects of nicotine and the elevated cutaneous expression of α7-nAChR in nicotine-pretreated rats. In addition, systemic administration of N-nitro-l-arginine methyl ester hydrochloride or aminoguanidine with an effective dose of nicotine caused a significant decrease in flap survival. Conversely, coinjection of a subeffective dose of l-arginine with the subeffective dose of nicotine significantly boosted its protective effects.

Conclusions
Acute pretreatment with nicotine by stimulating the expression and activation of cutaneous α7-nAChR improves skin flap survival, which is partially mediated through modulation of the NO pathway.
The Pattern of Residual Tumor After Neoadjuvant Chemotherapy for Locally Advanced Esophageal Cancer and Its Clinical Significance
Authors: Hashimoto Tadayoshi , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuhiro , Takahashi Tsuyoshi , Kurokawa Yukinori , Motoori Masaaki , Kimura Yutaka , Nakajima Kiyokazu , Morii Eiichi , Mori Masaki , Doki Yuichiro 
Published: March 2019

Objectives:
To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance.

Background:
NAC is a standard treatment for locally advanced esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown.

Methods:
One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin-eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis.

Results:
Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types.

Conclusions:
After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis.
Benchmarks in Pancreatic Surgery
Authors: Sánchez-Velázquez Patricia , Muller Xavier , Malleo Giuseppe , Park Joon-Seong , Hwang Ho-Kyoung , Napoli Niccolò , Javed Ammar A. , Inoue Yosuke , Beghdadi Nassiba , Kalisvaart Marit , Vigia Emanuel , Walsh Carrie D. , Lovasik Brendan , Busquets Juli , Scandavini Chiara , Robin Fabien , Yoshitomi Hideyuki , Mackay Tara M. , Busch Olivier R. , Hartog Hermien , Heinrich Stefan , Gleisner Ana , Perinel Julie , Passeri Michael , Lluis Nuria , Raptis Dimitri A , Tschuor Christoph , Oberkofler Christian E. , DeOliveira Michelle L. , Petrowsky Henrik , Martinie John , Asbun Horacio , Adham Mustapha , Schulick Richard , Lang Hauke , Koerkamp Bas Groot , Besselink Marc G. , Han Ho-Seong , Miyazaki Masaru , Ferrone Cristina R. , Fernández-del Castillo Carlos , Lillemoe Keith D. , Sulpice Laurent , Boudjema Karim , Del Chiaro Marco , Fabregat Joan , Kooby David A. , Allen Peter , Lavu Harish , Yeo Charles J. , Barroso Eduardo , Roberts Keith , Muiesan Paolo , Sauvanet Alain , Saiura Akio , Wolfgang Christopher L. , Cameron John L. , Boggi Ugo , Yoon Dong-Sup , Bassi Claudio , Puhan Milo A. , Clavien Pierre-Alain 
Published: March 2019

Objective:
To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD).

Background:
Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative.

Methods:
This multicenter study analyzes consecutive patients (2012–2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches.

Results:
Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%–93%) and minimally invasive (11%–62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases.

Conclusion:
The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.
A core microbiota of the plant-earthworm interaction conserved across soils
Authors: Jacquiod Samuel , Puga-Freitas Ruben , Spor Aymé , Mounier Arnaud , Monard Cécile , Mougel Christophe , Philippot Laurent , Blouin Manuel 
Published: March 2019

AbstractMicroorganisms participate in most crucial soil functions and services benefiting human activities, such as biogeochemical cycles, bioremediation and food production. Their activity happens essentially in hotspots created by major soil macroorganisms, like rhizosphere and cast shaped by plants and earthworms respectively1. While effects of individual macroorganism on soil microbes are documented, no studies attempted to decipher how the mosaic of microhabitats built by multiple macroorganisms and their interaction determine the structure of microbial communities. Here we show a joint shaping of soil bacterial communities by these two macroorganisms, with a prevalent role of plants over earthworms. In a controlled microcosm experiment with three contrasted soils and meticulous microhabitat sampling, we found that the simultaneous presence of barley and endogeic earthworms resulted in non-additive effects on cast and rhizosphere bacterial communities. Using a source-sink approach derived from the meta-community theory2,3, we found specific cast and rhizospherecore microbiota4,5of the plant-eartworm interaction, detected in all soils only when both macroorganisms are present. We also evidenced acore networkof the plant-earthworm interaction, with cosmopolitan OTUs correlated both in cast and rhizosphere of all soils. Our study provides a new framework to explore aboveground-belowground interactions through the prism of microbial communities. This multiple-macroorganisms shaping of bacterial communities also affects fungi and archaea, while being strongly influenced by soil type. Further functional investigations are needed to understand how thesecore microbiotaandcore networkcontribute to the modulation of plant adaptive response to local abiotic and biotic conditions.
Expression of ppsD, a gene involved in synthesis of Mycobacterium tuberculosis virulence factor PDIM, reflects treatment response in pulmonary tuberculosis patients
Authors: Sriraman Kalpana , Kekane Rupali , Shah Daksha , Saranath Dhananjaya , Mistry Nerges 
Published: March 2019

AbstractDrug resistant tuberculosis (TB) cases are primarily driven by transmission, however, treatment failure and acquisition of drug resistance are still significant issues in drug sensitive TB cases. Study of gene expression in Mycobacterium tuberculosis (Mtb) isolated from poor outcome patients may offer clues towards prediction of treatment response. In the current study, expression of five non-drug target genes (ppsD, embC, Rv1457c, Rv1687c and recB) previously identified to be associated with drug resistance was studied in clinical isolates from patients with different treatment outcomes to examine its correlation to treatment response and acquisition of drug resistance in Mtb. Our results show that expression of ppsD, a gene involved in synthesis of cell wall lipid PDIM, was significantly increased in patients who developed drug resistance during treatment and patients who were drug resistant at diagnosis. On the other hand in longitudinal isolates collected during treatment, ppsD expression decreased consistently in patients who responded to treatment and became culture negative, while it increased in patients who did not respond to treatment as indicated by their culture positive status towards the end of treatment. These results demonstrate that ppsD expression reflects treatment response in TB patients and hence can be potentially used as a marker for predicting treatment response. Additional longitudinal studies with a larger cohort of patients are required to establish application of ppsD expression as a marker of treatment response.
Botswana’s wildlife losing ground as Kalahari Wildlife Management Areas (WMAs) are dezoned for livestock expansion
Authors: Keeping Derek , Kashe Njoxlau , Langwane Horekwe (Karoha) , Sebati Panana , Molese Nicholas , Gielen Marie-Charlotte , Keitsile-Barungwi Amo , Xhukwe Quashe (/Uase) , Brahman !Nate (Shortie) 
Published: March 2019

AbstractBotswana is rightfully lauded for maintaining 42% of its land base for conservation, and ranking top in the world for effort to conserve megafauna. Yet during the recent preservationist political climate characterized by a hunting moratorium and deterioration of CBNRM, changes to the national land use map suggest Botswana is losing grip on its lofty status. While conservation attention is turned to elephants and KAZA, discussion about the official dezoning of 8,268 km2of free-ranging wildlife estate in the Kalahari ecosystem has been notably absent. Using track-based methods we quantified wildlife populations inhabiting this relinquished wilderness now awaiting imminent conversion to fenced and private livestock holdings. We find that the affected areas contain approximately 3,900 free-ranging large herbivores and 50 large carnivores, all of which will become consumed, displaced or potential conflict animals. Erstwhile publicly-owned wildlife particularly important for local communities will effectively become de facto private property for an elite minority. The land use changes spell negative consequences for wildlife not only via mechanisms of habitat loss and edge effects but also reduced landscape connectivity between protected areas that limits seasonal movements and gene flow thus eroding long-term population resilience in a drought-prone environment. As Botswana’s agricultural lobby continues to exert pressure on the Kalahari ecosystem, we suggest that ground surveys conducted by Kalahari trackers be implemented to inform decision-making rather than relying on the inadequate coarse-grained aerial survey record only.
Land-use and related pressures have reduced biotic integrity more on islands than on mainlands
Authors: Sanchez-Ortiz Katia , Gonzalez Ricardo E. , De Palma Adriana , Newbold Tim , Hill Samantha L. L. , Tylianakis Jason M. , Börger Luca , Lysenko Igor , Purvis Andy 
Published: March 2019

ABSTRACTTracking progress towards biodiversity targets requires indicators that are sensitive to changes at policy-relevant scales, can easily be aggregated to any spatial scale and are simple to understand. The Biodiversity Intactness Index (BII), which estimates the average abundance of a diverse set of organisms in a given area relative to their reference populations, was proposed in 2005 in response to this need. A new implementation of BII was developed as part of the PREDICTS project in 2016 and has been adopted by GEO BON, IPBES and CBD. The previous global models for BII estimation could not account for pressures having different effects in different settings. Islands are a setting of particular interest: many are home to a disproportionate number of endemic species; oceanic islands may have relatively low overall species diversity because of their isolation; and the pattern and timing of human pressures can be very different from that seen on mainlands. Here, we test whether biotic integrity – as estimated by BII – has decreased more severely on islands than mainlands. We update methods previously used to estimate BII globally (Newbold et al., 2016) to allow pressure effects to differ between islands and mainlands, while also implementing some other recent improvements in modelling. We estimate BII for islands and mainlands by combining global models of how two aspects of biodiversity – overall abundance, and compositional similarity to minimally-impacted sites – have been affected by human pressures. We use these models to project high-resolution (∼1km2) global maps of BII for the year 2005. We calculate average BII for island and mainland biomes, countries, IPBES regions and biodiversity hotspots; and repeat our analyses using a richness-based version of BII. BII on both islands and mainlands has fallen below the values proposed as safe limits across most regions, biomes and biodiversity hotspots. Our BII estimates are lower than those published in 2016, globally, within all biodiversity hotspots and within most biomes, and show greater spatial heterogeneity; detailed analysis of these differences shows that they arise mostly from a combination of improvements to the modelling framework. Average BII does not strongly differ between islands and mainlands, but richness-based BII has fallen by more on islands. It seems native species are more negatively affected by rising human population density and road development on islands than mainlands, and islands have seen more land conversion. Our results highlight the parlous state of biodiversity native to islands.
Diversification of the type IV filament super-family into machines for adhesion, secretion, DNA transformation and motility
Authors: Denise Rémi , Abby Sophie S , Rocha Eduardo PC 
Published: March 2019

AbstractProcesses of molecular innovation require tinkering and co-option of existing genes. How this occurs in terms of molecular evolution at long evolutionary scales remains poorly understood. Here, we analyse the natural history of a vast group of membrane-associated molecular systems in Bacteria and Archaea – type IV filament super-family (TFF-SF) – that diversified in systems involved in flagellar or twitching motility, adhesion, protein secretion, and DNA natural transformation. We identified such systems in all phyla of the two domains of life, and their phylogeny suggests that they may have been present in the last universal common ancestor. From there, two lineages, a Bacterial and an Archaeal, diversified by multiple gene duplications of the ATPases, gene fission of the integral membrane platform, and accretion of novel components. Surprisingly, we find that the Tad systems originated from the inter-kingdom transfer from Archaea to Bacteria of a system resembling the Epd pilus. The phylogeny and content of ancestral systems suggest that initial bacterial pili were engaged in cell motility and/or DNA transformation. In contrast, specialized protein secretion systems arose much later, and several independent times, in natural history. All these processes of functional diversification were accompanied by genetic rearrangements with implications for genetic regulation and horizontal gene transfer: systems encoded in fewer loci were more frequently exchanged between taxa. Overall, the evolutionary history of the TFF-SF by itself provides an impressive catalogue of the variety of molecular mechanisms involved in the origins of novel functions by tinkering and co-option of cellular machineries.
Common variants associated withOSMRexpression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans
Authors: van Keulen D. , van Koeverden I.D. , Boltjes A. , Princen H.M.G. , van Gool A.J. , de Borst G.J. , Asselbergs F.W. , Tempel D. , Pasterkamp G. , van der Laan S.W. 
Published: March 2019

AbstractBackground and aimsOncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in OSM and its receptors,OSMRandLIFR, on overall plaque vulnerability, plaque phenotype, intraplaqueOSMRandLIFRexpression, coronary artery calcification burden and cardiovascular disease susceptibility.Methods and resultsWe queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreasedOSMRexpression and that rs10491509 (A allele) was associated with increasedLIFRexpression in arterial tissues. No variant was significantly associated withOSMexpression.We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β=0.118 ± s.e.=0.040,p=3.00×10-3, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β=0.248 ± s.e.=0.088, p=4.66 × 10-3, C allele) and collagen content (β=-0.259 ± s.e.=0.095, p=6.22 × 10-3, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaqueOSMRexpression. Neither was intraplaqueOSMRexpression associated with plaque vulnerability and no knownOSMReQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in theLIFRlocus.ConclusionsOur study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.
Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
Authors: Hafemeister Christoph , Satija Rahul 
Published: March 2019

AbstractSingle-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity with technical effects. To address this, we present a modeling framework for the normalization and variance stabilization of molecular count data from scRNA-seq experiments. We propose that the Pearson residuals from ’regularized negative binomial regression’, where cellular sequencing depth is utilized as a covariate in a generalized linear model, successfully remove the influence of technical characteristics from downstream analyses while preserving biological heterogeneity. Importantly, we show that an unconstrained negative binomial model may overfit scRNA-seq data, and overcome this by pooling information across genes with similar abundances to obtain stable parameter estimates. Our procedure omits the need for heuristic steps including pseudocount addition or log-transformation, and improves common downstream analytical tasks such as variable gene selection, dimensional reduction, and differential expression. Our approach can be applied to any UMI-based scRNA-seq dataset and is freely available as part of the R packagesctransform, with a direct interface to our single-cell toolkitSeurat.