bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of piperacillin in combination with novel β-lactamase inhibitor IID572 against β-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models
Authors: Growcott E J , Gamboa L , Roth T , Lopez S , Osborne C S 
Published: January 2020

Abstract

Objectives
The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel β-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various β-lactamase enzymes.

Methods
Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of β-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated.

Results
In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D β-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing β-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested.

Conclusions
In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with β-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.
Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals
Authors: Lepore Luciana , Fabrizio Claudia , Bavaro Davide Fiore , Milano Eugenio , Volpe Anna , Lagioia Antonella , Angarano Gioacchino , Saracino Annalisa , Monno Laura 
Published: January 2020

Abstract

Objectives
Fostemsavir, a novel attachment inhibitor targeting the HIV-1 gp120, has demonstrated wide in vitro activity. However, the high rate of HIV gp120 substitutions could jeopardize its efficacy. We investigated envelope (env) substitutions at positions associated with resistance to fostemsavir in patients with a new HIV-1 diagnosis according to HIV subtype and tropism.

Methods
Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H/M/T, M426L, M434I and M475I mutations was evaluated. Other amino acid changes at the same positions were also recorded. The variability at each amino acid position was evaluated using Shannon entropy.

Results
The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)/M (0.8%) and L116P (0.31%). Statistically significant differences were found at positions 375 (R5/non-R5 strains and B/non-B subtypes) and 426 (B/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B/non-B, P &lt; 0.00001). The variability of env constant domains appeared to be more relevant in the non-B virus population.

Conclusions
In conclusion, gp120 substitutions were detected in different subtypes and in both R5 and non-R5 variants. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial.
Challenges of improving treatment outcomes for colorectal and anal cancers in Japan: the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG)
Authors: Ouchi Akira , Shida Dai , Hamaguchi Tetsuya , Takashima Atsuo , Ito Yoshinori , Ueno Hideki , Ishiguro Megumi , Takii Yasumasa , Ikeda Satoshi , Ohue Masayuki , Fujita Shin , Shiozawa Manabu , Kataoka Kozo , Ito Masaaki , Tsukada Yuichiro , Akagi Tomonori , Inomata Masafumi , Shimada Yasuhiro , Kanemitsu Yukihide 
Published: January 2020

Abstract
Colorectal cancer is a major public health concern in Japan. While early-stage colorectal adenocarcinoma treatment entails radical resection of the primary tumor, the importance of perioperative treatment is growing as physicians seek to further improve treatment outcomes. For anal squamous cell carcinoma, definitive chemoradiotherapy is superior to radical surgery in terms of improved patient quality of life. The Colorectal Cancer Study Group of the Japanese Clinical Oncology Group was established in 2001 and has worked to provide answers to common clinical questions and improve treatment outcomes for colorectal and anal cancers through 15 large-scale prospective clinical trials. Here, we discuss the current state of perioperative treatment for early-stage colon, rectal and anal cancers in Japan and approaches taken by the Colorectal Cancer Study Group/the Japanese Clinical Oncology Group to improve treatment outcomes for these cancers.
What Difference do Mayors Make? The Role of Municipal Authorities in Turkey and Lebanon’s Response to Syrian Refugees
Authors: Betts Alexander , MemiŞoĞlu Fulya , Ali Ali 
Published: January 2020

AbstractWith the majority of refugees now in urban areas, mayors and municipal authorities have been recognized as increasingly important policy actors in the global refugee regime. This trend is acknowledged in the policy literature. However, there has been little systematic academic research exploring the conditions under which mayors make a difference to refugee-policy outcomes. Theoretically, we outline a heuristic framework aimed at disaggregating key variables, including the independent influence of mayors, in shaping municipal-level outcomes. Empirically, the article assesses the role of municipal authorities and mayors in the two most numerically significant host countries for Syrian refugees: Turkey and Lebanon. It comparatively examines variation across six metropolitan municipalities, three from each country: Izmir, Adana and Gaziantep (Turkey), and Qalamoun, Anjar and Zahle (Lebanon). We show that mayors matter because they may mediate the implementation of national policies and because they sometimes adopt supplementary refugee policies and practices at the municipal level, which may be more or less proactive or more or less restrictive than central-government policy.
Perspective: The History and Afterlife of Darwin’s Childhood Garden
Authors: Piesse Jude 
Published: January 2020

Abstract
This article examines the history and significance of Charles Darwin’s childhood garden at The Mount in Shrewsbury. Unlike the mature Darwin’s garden at Down House, Kent, his childhood garden at The Mount has only recently begun to be restored and it is not well known outside of local or specialist circles. The first part of the article aims to recover the story of the garden for a wider interdisciplinary readership. It builds upon research in the fields of garden history and biography to make a case for the garden’s importance to Darwin’s life and scientific work while also revealing the site’s afterlife as a lost garden and challenging restoration project. The second part of the article argues that the garden can be viewed as an enchanted space that enables us to connect more closely with a positive vision of a romantic, ecologically conscious Darwin who is of particular relevance to our times. I conclude by briefly outlining how these ideas were tested at the Darwin’s Childhood Garden Study Day, organized with Shropshire Wildlife Trust in 2016 following its purchase of part of the site in 2013.
Glycosyltransferase OsUGT90A1 helps protect the plasma membrane during chilling stress in rice
Authors: Shi Yao , Phan Huy , Liu Yaju , Cao Shouyun , Zhang Zhihua , Chu Chengcai , Schläppi Michael R 
Published: January 2020

Abstract
Due to its subtropical origins, rice (Oryza sativa) is sensitive to low-temperature stress. In this study, we identify LOC_Os04g24110, annotated to encode the UDP-glycosyltransferase enzyme UGT90A1, as a gene associated with the low-temperature seedling survivability (LTSS) quantitative trait locus qLTSS4-1. Differences between haplotypes in the control region of OsUGT90A1 correlate with chilling tolerance phenotypes, and reflect differential expression between tolerant and sensitive accessions rather than differences in protein sequences. Expression of OsUGT90A1 is initially enhanced by low temperature, and its overexpression helps to maintain membrane integrity during cold stress and promotes leaf growth during stress recovery, which are correlated with reduced levels of reactive oxygen species due to increased activities of antioxidant enzymes. In addition, overexpression of OsUGT90A1 in Arabidopsis improves freezing survival and tolerance to salt stress, again correlated with enhanced activities of antioxidant enzymes. Overexpression of OsUGT90A1 in rice decreases root lengths in 3-week-old seedlings while gene-knockout increases the length, indicating that its differential expression may affect phytohormone activities. We conclude that higher OsUGT90A1 expression in chilling-tolerant accessions helps to maintain cell membrane integrity as an abiotic stress-tolerance mechanism that prepares plants for the resumption of growth and development during subsequent stress recovery.
Planet Hunters TESS I: TOI 813, a subgiant hosting a transiting Saturn-sized planet on an 84-day orbit
Authors: Eisner N L , Barragán O , Aigrain S , Lintott C , Miller G , Zicher N , Boyajian T S , Briceño C , Bryant E M , Christiansen J L , Feinstein A D , Flor-Torres L M , Fridlund M , Gandolfi D , Gilbert J , Guerrero N , Jenkins J M , Jones K , Kristiansen M H , Vanderburg A , Law N , López-Sánchez A R , Mann A W , Safron E J , Schwamb M E , Stassun K G , Osborn H P , Wang J , Zic A , Ziegler C , Barnet F , Bean S J , Bundy D M , Chetnik Z , Dawson J L , Garstone J , Stenner A G , Huten M , Larish S , Melanson L D , Mitchell T , Moore C , Peltsch K , Rogers D J , Schuster C , Smith D S , Simister D J , Tanner C , Terentev I , Tsymbal A 
Published: January 2020

ABSTRACT
We report on the discovery and validation of TOI 813 b (TIC 55525572 b), a transiting exoplanet identified by citizen scientists in data from NASA’s Transiting Exoplanet Survey Satellite (TESS) and the first planet discovered by the Planet Hunters TESS project. The host star is a bright (V = 10.3 mag) subgiant ($R_\star =1.94\, R_\odot$, $M_\star =1.32\, M_\odot$). It was observed almost continuously by TESS during its first year of operations, during which time four individual transit events were detected. The candidate passed all the standard light curve-based vetting checks, and ground-based follow-up spectroscopy and speckle imaging enabled us to place an upper limit of $2\, M_{\rm Jup}$ (99 per cent confidence) on the mass of the companion, and to statistically validate its planetary nature. Detailed modelling of the transits yields a period of $83.8911 _{ - 0.0031 } ^ { + 0.0027 }$ d, a planet radius of 6.71 ± 0.38 R⊕ and a semimajor axis of $0.423 _{ - 0.037 } ^ { + 0.031 }$ AU. The planet’s orbital period combined with the evolved nature of the host star places this object in a relatively underexplored region of parameter space. We estimate that TOI 813 b induces a reflex motion in its host star with a semi-amplitude of ∼6 m s−1, making this a promising system to measure the mass of a relatively long-period transiting planet.
Decision Making in Retroperitoneal Nerve Sheath and Nerve-Associated Tumors: A Modular Approach
Authors: Heinen Christian , Schmidt Thomas , Kretschmer Thomas 
Published: January 2020

Abstract

BACKGROUND
Surgical treatment of retroperitoneal nerve and nerve-associated tumors is challenging, especially in cases with large extent. A single surgical access may have limitations and jeopardize patients.

OBJECTIVE
To present a series of patients to illustrate our individually tailored treatment concept and decision pathway.

METHODS
Retrospectively, clinical findings and imaging were related to surgical features and outcome. An algorithm for choice of approach was established.

RESULTS
From 2012 to 2017, we operated on n = 13 patients with retroperitoneal tumors, of these n = 9 were included (n = 6 female, n = 3 male). Histological findings included n = 2 schwannomas, n = 2 malignant peripheral nerve sheath tumors, n = 1 non-origin sarcoma, n = 1 perineurioma, n = 1 intraneural ganglion cyst, n = 1 lymphoma, and n = 1 paraganglioma.
In n = 6 patients, we used a monoportal (retroperitoneal/transperitoneal) approach; in n = 2 patients, a biportal retroperitoneal to inguinal/transperitoneal to dorsal approach; and in n = 1 patient, a triportal transperitoneal to dorsal to gluteal approach.
In n = 2 patients, we performed an open biopsy only; in n = 2 patients, a tumor enucleation; in n = 3 patients, a subtotal function-sparing resection; in n = 1 patient, a complete resection; and in n = 1 patient, intraneural decompression.
In n = 1 patient, a new motor deficit appeared. n = 4 patients required further radio-oncological treatment. n = 8/9 patients are alive without tumor progress or recurrence.

CONCLUSION
Retroperitoneal nerve or nerve-associated tumors encompass multiple entities. Depending on suspected histology and tumor extension, extensile or combined surgical approaches may be necessary. We present our algorithm for assessment and decision-making regarding surgical access ports and pathways.
Molecular profiling-based decision for targeted therapies in IDH wild-type glioblastoma
Authors: Kessler Tobias , Berberich Anne , Casalini Belen , Drüschler Katharina , Ostermann Hannah , Dormann Andrea , Walter Sandy , Hai Ling , Schlesner Matthias , Herold-Mende Christel , Jungk Christine , Unterberg Andreas , Bendszus Martin , Sahm Katharina , von Deimling Andreas , Winkler Frank , Platten Michael , Wick Wolfgang , Sahm Felix , Wick Antje 
Published: January 2020

Abstract

Background
Molecular profiling allows tumor classification as well as assessment of diagnostic, prognostic, and treatment-related molecular changes. Translation into clinical practice and relevance for patients has not been demonstrated yet.

Methods
We analyzed clinical and molecular data of isocitrate dehydrogenase wild-type glioblastoma patients with sufficient clinical follow-up from the Heidelberg Neuro-Oncology Center and with molecular analysis of tumor tissue that consisted of DNA methylation array data, genome-scale copy number variations, gene panel sequencing, and partly mTOR immunohistochemistry between October 2014 and April 2018.

Results
Of 536 patients screened, molecular assessment was performed in 253 patients (47%) in a prospective routine clinical setting with further clinical appointments. Therapy decision was directly based on the molecular assessment in 97 (38%) patients. Of these, genetic information from MGMT (n = 68), EGFR (n = 7), CDKN2A/B (n = 8), alterations of the PI3K–AKT–mTOR pathway (n = 5), and BRAF (n = 3) have been the most frequently used for decision making with a positive overall survival signal for patients with glioblastoma harboring an unmethylated MGMT promoter treated according to the molecular assignment. Based on detected molecular alterations and possible targeted therapies, we generated an automated web-based prioritization algorithm.

Conclusion
Molecular decision making in clinical practice was mainly driven by MGMT promoter status in elderly patients and study inclusion criteria. A reasonable number of patients have been treated based on other molecular aberrations. This study prepares for complex molecular decisions in a routine clinical decision making.
Decrease in Resting Heart Rate Measured Using Smartphone Apps to Verify Abstinence From Smoking: An Exploratory Study
Authors: Herbec Aleksandra , Parker Ella , Ubhi Harveen Kaur , Raupach Tobias , West Robert 
Published: January 2020

Abstract

Introduction
Verifying self-reports of smoking abstinence is challenging in studies that involve remote data collection. Resting heart rate (HR) decreases during smoking abstinence. This study assessed whether a decrease in resting HR measured using freely available smartphone apps could potentially be used to verify smoking abstinence.

Methods
This study involved a repeated measures experimental design, with data collection in natural setting. Participants were 18 adult, daily smokers. They recorded resting HR in beats per minute (bpm) using freely available smartphone apps during five timepoints (two in the morning and three postnoon) on each of 3 days. The outcome measure was the mean of the postnoon HR recordings. The experimental condition for each of the 3 days (counterbalanced order) was as follows: (1) smoking as usual, (2) not smoking without nicotine replacement therapy (NRT), or (3) not smoking but using NRT. Abstinence was verified using expired-air carbon monoxide (CO) concentration.

Results
Compared with the smoking as usual condition, mean HR was 13.4 bpm lower (95% confidence interval [CI] = 5.4 to 21.4, p = .001) in the not smoking without NRT condition and 10.4 bpm lower (95% CI = 3.1 to 17.8, p = 0.004) in the not smoking with NRT condition. There was no statistically significant difference in HR between the two not smoking conditions (p = .39). Abstinence during not smoking days without and with NRT was CO-verified in 18/18 and in 16/18 cases, respectively.

Conclusions
Self-recording of resting HR in natural setting using smartphone apps shows a reliable decrease in response to smoking abstinence and may provide a basis for remote verification in smoking cessation studies.

Implications
Remote verification of self-reported abstinence in smoking cessation studies remains challenging. Smoking abstinence has been shown to decrease resting HR under laboratory conditions. This study demonstrated that self-recording using freely available smartphone apps shows reliable decreases in resting HR during smoking abstinence and may provide a basis for inexpensive remote verification of smoking abstinence.
The Relation between the Treatise and the Enquiry
Authors: Qu Hsueh M. 
Published: January 2020

Abstract
This chapter outlines two critical interpretive issues: the relationship between Hume’s scepticism and his naturalism; and the relationship between the Treatise of Human Nature and the Enquiry concerning Human Understanding. In particular, it makes a preliminary case that these two interpretive issues are intimately connected: Hume changes his epistemology between the Treatise and the Enquiry due to a dissatisfaction with his treatment of scepticism in the former work. The chapter offers a preliminary investigation of Hume’s characterisation of the relationship between the Treatise and the Enquiry. It outlines a case for Hume’s motivation in writing the Advertisement and the Enquiry being a concern for his intellectual legacy. In particular, it is suggested that the Enquiry and the Advertisement are meant to rectify Hume’s treatment of scepticism in the Treatise.
Hume’s Aims
Authors: Qu Hsueh M. 
Published: January 2020

Abstract
This chapter compares Hume’s characterisation of his aims and methodologies in the Introduction to the Treatise of Human Nature and Section 1 of the Enquiry concerning Human Understanding. It finds that key among the differences between the two is that EHU 1 stresses the taxonomic project of ‘mental geography’ (EHU 1.13), and also a negative project of rejecting false metaphysics, both of which are absent from the Introduction to the Treatise. This ‘mental geography’ will prove crucial to the negative project of rejecting false metaphysics, and foreshadows Hume’s more comprehensive presentation of his epistemology in EHU 12. The chapter argues that these differences suggest that the Enquiry is a more normatively focused work than the Treatise.
Battling for the Story
Authors: Callison Candis , Young Mary Lynn 
Published: January 2020

Abstract
Social media has shifted the terrain for journalism, and offers platforms for counter-narratives, alternative views, and broader expertise. In Chapter 2, we focus on the social media response in three specific cases: (1) two separate trials for the murders of two Indigenous youth, Colten Boushie and Tina Fontaine, in central Canada, in which the two white men accused in their homicides were acquitted within a month of each other in early 2018; (2) the 2015 civil trial and discrimination case brought by Ellen Pao, a Silicon Valley venture capitalist, who was forced out of her job; (3) a 2016 #MeToo related moment in which writer Kelly Oxford asked women to share their stories through #notokay. In all three cases, we find a “battle for the story” that plays out in a range of ways from a refusal to participate, to talking back and resisting journalism’s habit of “hoarding the mic.”
Dominant Crisis Narratives and Changing Infrastructures
Authors: Callison Candis , Young Mary Lynn 
Published: January 2020

Abstract
In Chapter 4, we examine efforts to address reckoning at one of Canada’s most respected legacy journalism organizations: the Toronto Star. Methodologically, we draw on a number of sets of data: public and policy discourse about the journalism crisis in Canada, recent events related to race and gender at the Star, and ethnographic fieldwork and interviews with Star journalists regarding the development of data journalism. Our analysis generates questions about how news organizations are wrestling concurrently with structural critique, economic challenges, and technological transformation. The gender, race, and colonial reckoning that we find in other chapters, we see internally at the Star where long-standing issues with “the view from nowhere,” the challenge of closed systems of journalism, and legacy organizations’ openness to change are conjoined with issues such as methodological interpretation, journalism’s colonial history and its systematic whiteness, and exclusion of Indigenous and minority journalists.
Indigenous Journalisms
Authors: Callison Candis , Young Mary Lynn 
Published: January 2020

Abstract
Chapter 6 draws on ethnographic fieldwork and interviews with Indigenous journalists in Canada and the United States who have been addressing colonialism, race, and gender in their journalism all along. Indigenous journalists articulate the challenges of working in and among mainstream media that has largely erased and misrepresented Indigenous voices, communities, and concerns on a range of issues. They undertake a differentiated set of approaches that draw on journalism ideals and get at deeper problems structurally such that transformation within journalism as profession, identity, and method might be possible. As a result, Indigenous journalists are using digital media to transform journalism methods, decolonizing journalism ideals like “fairness and balance” by drawing from Indigenous knowledge, histories, and relational frameworks. This chapter provides a bookend to Chapter 1 by offering a pathway into discussing not only new bases for ethical consideration but also provides examples of some of the multiple journalisms available through digital media.