bluuebunny/crossref_metadata_2025_split huggingface dataset:
One Health compartmental analysis of ESBL-producing Escherichia coli on Reunion Island reveals partitioning between humans and livestock
Authors: Miltgen Guillaume , Martak Daniel , Valot Benoit , Kamus Laure , Garrigos Thomas , Verchere Guillaume , Gbaguidi-Haore Houssein , Ben Cimon Céline , Ramiandrisoa Mahery , Picot Sandrine , Lignereux Anne , Masson Geoffrey , Jaffar-Bandjee Marie-Christine , Belmonte Olivier , Cardinale Eric , Hocquet Didier , Mavingui Patrick , Bertrand Xavier 
Published: February 2022

Abstract

Background
Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) is a major cause of infections worldwide. An understanding of the reservoirs and modes of transmission of these pathogens is essential, to tackle their increasing frequency.

Objectives
We investigated the contributions of various compartments (humans, animals, environment), to human colonization or infection with ESBL-Ec over a 3 year period, on an island.

Methods
The study was performed on Reunion Island (Southwest Indian Ocean). We collected ESBL-Ec isolates prospectively from humans, wastewater and livestock between April 2015 and December 2018. Human specimens were recovered from a regional surveillance system representative of the island’s health facilities. These isolates were compared with those from livestock and urban/rural wastewater, by whole-genome sequencing.

Results
We collected 410 ESBL-Ec isolates: 161 from humans, 161 from wastewater and 88 from animals. Phylogenomic analysis demonstrated high diversity (100 STs), with different STs predominating among isolates from humans (ST131, ST38, ST10) and animals (ST57, ST156). The large majority (90%) of the STs, including ST131, were principally associated with a single compartment. The CTX-M-15, CTX-M-27 and CTX-M-14 enzymes were most common in humans/human wastewater, whereas CTX-M-1 predominated in animals. Isolates of human and animal origin had different plasmids carrying blaCTX-M genes, with the exception of a conserved IncI1-ST3 blaCTX-M-1 plasmid.

Conclusions
These molecular data suggest that, despite their high level of contamination, animals are not a major source of the ESBL-Ec found in humans living on this densely populated high-income island. Public health policies should therefore focus primarily on human-to-human transmission, to prevent human infections with ESBL-Ec.
Management of elderly patients with early gastric cancer in Japan
Authors: Sekiguchi Masau , Oda Ichiro , Morita Shinji , Katai Hitoshi , Yano Tomonori , Terashima Masanori , Kataoka Tomoko , Muto Manabu 
Published: February 2022

Abstract
Management of elderly patients with early gastric cancer is an important issue in an aging society such as Japan. While endoscopic resection is recommended as the standard treatment for early gastric cancers with extremely low risk of lymph node metastasis (&lt;1%), gastrectomy with lymphadenectomy is recommended for the other early gastric cancers as the standard treatment even in elderly patients. Endoscopic submucosal dissection is the most recommended endoscopic resection procedure because of its high ability for ‘en bloc’ resection. Endoscopic submucosal dissection can reportedly provide favorable short-term outcomes in elderly patients. In terms of patient prognosis, the importance of considering patients’ physical and nutritional conditions before endoscopic submucosal dissection has recently attracted attention. With respect to gastrectomy, the nationwide data in Japan have demonstrated relatively low 5-year overall survival and non-negligible post-operative 90-day mortality in men aged ≥75 years and women aged ≥80 years compared with those in younger patients. Among these elderly patients, 20% or more reportedly died within 5 years after gastrectomy mostly due to other diseases. These facts suggested the necessity of a less invasive management option for the elderly patients. Efforts are being made to provide a non-invasive follow-up option without gastrectomy following endoscopic resection in elderly patients. To avoid the increase in gastric cancer-related deaths, the selection of patients with relatively low lymph node metastasis risk is essential, and several tools to estimate the lymph node metastasis risk from early gastric cancers have been developed. To avoid overtreatment with gastrectomy in more elderly early gastric cancer patients, new endoscopic submucosal dissection indications for them are also warranted.
Management of elderly patients with bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group
Authors: Tanaka Kazuhiro , Ozaki Toshifumi 
Published: February 2022

Abstract
Approximately, 40% of bone sarcomas and 60% of soft tissue sarcoma arise in patients aged ≥65 years. However, because sarcoma is very rare, there is little evidence regarding the management of elderly patients with sarcoma. Age has been reported as a prognostic factor in patients with sarcomas. The standard therapy for all localized bone and soft tissue sarcomas is surgical resection, even in elderly patients. Radiation or ion-beam therapy can be considered for unresectable sarcomas. Although adjuvant chemotherapy is standard for osteosarcoma, the usefulness of adjuvant chemotherapy for elderly patients has not been verified; therefore, it may not be recommended for elderly patients with osteosarcoma. For elderly patients with advanced osteosarcoma, if general conditions permit, doxorubicin- and/or ifosfamide-based regimens as well as molecular-targeted therapies, including sorafenib, regorafenib and everolimus, may be considered, although these drugs have not been approved for sarcoma in Japan. Adjuvant chemotherapy with doxorubicin plus ifosfamide is recommended for patients with high-risk localized soft tissue sarcoma if they are aged ≤70 years. For first-line treatment of advanced soft tissue sarcoma in elderly patients, doxorubicin monotherapy is considered to be the standard regimen, and pazopanib can be an alternative. For second-line treatment, gemcitabine-based regimens, pazopanib, trabectedin and eribulin may be options for elderly patients with advanced soft tissue sarcoma.
Cellular Telephone Use and the Risk of Brain Tumors: Update of the UK Million Women Study
Authors: Schüz Joachim , Pirie Kirstin , Reeves Gillian K , Floud Sarah , Beral Valerie ,   for the Million Women Study Collaborators
Published: February 2022

Abstract

Background
The ongoing debate of whether use of cellular telephones increases the risk of developing a brain tumor was recently fueled by the launch of the fifth generation of wireless technologies. Here, we update follow-up of a large-scale prospective study on the association between cellular telephone use and brain tumors.

Methods
During 1996-2001, 1.3 million women born in 1935-1950 were recruited into the study. Questions on cellular telephone use were first asked in median year 2001 and again in median year 2011. All study participants were followed via record linkage to National Health Services databases on deaths and cancer registrations (including nonmalignant brain tumors).

Results
During 14 years follow-up of 776 156 women who completed the 2001 questionnaire, a total of 3268 incident brain tumors were registered. Adjusted relative risks for ever vs never cellular telephone use were 0.97 (95% confidence interval = 0.90 to 1.04) for all brain tumors, 0.89 (95% confidence interval = 0.80 to 0.99) for glioma, and not statistically significantly different to 1.0 for meningioma, pituitary tumors, and acoustic neuroma. Compared with never-users, no statistically significant associations were found, overall or by tumor subtype, for daily cellular telephone use or for having used cellular telephones for at least 10 years. Taking use in 2011 as baseline, there were no statistically significant associations with talking for at least 20 minutes per week or with at least 10 years use. For gliomas occurring in the temporal and parietal lobes, the parts of the brain most likely to be exposed to radiofrequency electromagnetic fields from cellular telephones, relative risks were slightly below 1.0.

Conclusion
Our findings support the accumulating evidence that cellular telephone use under usual conditions does not increase brain tumor incidence.
Phenotyping methods to assess heat stress resilience in grapevine
Authors: Pettenuzzo Silvia , Cappellin Luca , Grando Maria Stella , Costantini Laura 
Published: February 2022

AbstractGlobal warming has become an issue in recent years in viticulture, as increasing temperatures have a negative impact on grapevine (Vitis vinifera) production and on wine quality. Phenotyping for grapevine response to heat stress is, therefore, important to understand thermotolerance mechanisms, with the aim of improving field management strategies or developing more resilient varieties. Nonetheless, the choice of the phenotypic traits to be investigated is not trivial and depends mainly on the objectives of the study, but also on the number of samples and on the availability of instrumentation. Moreover, the grapevine literature reports few studies related to thermotolerance, generally assessing physiological responses, which highlights the need for more holistic approaches. In this context, the present review offers an overview of target traits that are commonly investigated in plant thermotolerance studies, with a special focus on grapevine, and of methods that can be employed to evaluate those traits. With the final goal of providing useful tools and references for future studies on grapevine heat stress resilience, advantages and limitations of each method are highlighted, and the available or possible implementations are described. In this way, the reader is guided in the choice of the best approaches in terms of speed, complexity, range of application, sensitivity, and specificity.
The effects of self-interacting dark matter on the stripping of galaxies that fall into clusters
Authors: Sirks Ellen L , Oman Kyle A , Robertson Andrew , Massey Richard , Frenk Carlos 
Published: February 2022

ABSTRACT
We use the Cluster-EAGLE (c-eagle) hydrodynamical simulations to investigate the effects of self-interacting dark matter (SIDM) on galaxies as they fall into clusters. We find that SIDM galaxies follow similar orbits to their cold dark matter (CDM) counterparts, but end up with ∼25 per cent less mass by the present day. One in three SIDM galaxies is entirely disrupted, compared to one in five CDM galaxies. However, the excess stripping will be harder to observe than suggested by previous DM-only simulations because the most stripped galaxies form cores and also lose stars: The most discriminating objects become unobservable. The best test will be to measure the stellar-to-halo mass relation (SHMR) for galaxies with stellar mass $10^{10}\!-\!10^{11}\, \mathrm{M}_{\odot }$. This is 8 times higher in a cluster than in the field for a CDM universe, but 13 times higher for an SIDM universe. Given intrinsic scatter in the SHMR, these models could be distinguished with noise-free galaxy–galaxy strong lensing of ∼32 cluster galaxies.
The intracluster light on Frontier Fields clusters Abell 370 and Abell S1063
Authors: de Oliveira Nícolas O L , Jiménez-Teja Yolanda , Dupke Renato 
Published: February 2022

ABSTRACT
We analysed the contribution of the intracluster light (ICL) to the total luminosity of two massive galaxy clusters observed by the Hubble Space Telescope within the Frontier Fields program, Abell 370 (z ∼ 0.375) and Abell S1063 (z ∼ 0.348), in order to correlate it with the dynamical stage of these systems. We applied an algorithm based on the Chebyshev–Fourier functions called CICLE, specially developed to disentangle the ICL from the light of galaxies and measure the ICL fraction. We measured the ICL fraction in three broad-band optical filters, F435W, F606W, and F814W, without assuming any prior hypothesis about the ICL physical properties or morphology. The results obtained from the ICL fraction vary between $\sim 7\!-\!25{{\ \rm per\ cent}}$, and $\sim 3\!-\!22{{\ \rm per\ cent}}$ for both A370 and AS1063, respectively, which are consistent with theoretical predictions for the total amount of ICL obtained by ICL formation and evolution simulations. We found enhanced ICL fractions in the intermediate filter F606W for both clusters and we suggest that this is due to the presence of an excess of younger/lower metallicity stars in the ICL compared to the cluster galaxies. We conclude that both Abell 370 and Abell S1063 are merging systems since they exhibit a similar feature as merging CLASH and Frontier Fields clusters sub-sample previously analysed. We compare these results to the dynamical indicators obtained through different methods and we reinforce the use of ICL as a new and independent method to determine the dynamical state of clusters of galaxies.
Seasonal exacerbation of rheumatoid arthritis detected by big claims data analysis: A retrospective population study
Authors: Ando Fumihiko , Takabayashi Katsuhiko , Fujita Shinsuke , Nakajima Hiroshi , Hanaoka Hideki , Suzuki Takahiro 
Published: February 2022

ABSTRACT

Objectives
The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data.

Methods
We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender, and ages.

Results
The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender, and age groups particularly when the number was on the higher side.

Conclusion
We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data.
Rituximab in the real-world treatment of lupus nephritis: A retrospective cohort study in Japan
Authors: Tanaka Yoshiya , Nakayamada Shingo , Yamaoka Kunihiro , Ohmura Koichiro , Yasuda Shinsuke 
Published: February 2022

ABSTRACT

Objectives
Although recommended in established international guidelines for lupus nephritis (LN), rituximab is not officially approved for LN treatment, making all such use off-label. The Japan College of Rheumatology (JCR) conducted a retrospective observational study on real-world efficacy and safety of rituximab treatment for LN in Japan.

Methods
Clinical data were collected from 47 hospitals for LN patients treated with rituximab to retrospectively investigate dosing schedule, efficacy, and safety.

Results
This retrospective analysis included 115 patients: 84 (73%) received 375 mg/m2 weekly up to four doses, and 31 (27%) received 1000 mg/body in one or two doses 2 weeks apart. Rituximab significantly improved findings for urinalysis, systemic lupus erythematosus serology, and systemic lupus erythematosus disease activity and was assessed as ‘extremely effective’ in 24.8% of patients and ‘effective’ in 60.2%. The renal response by the JCR-I criteria was 52.5% for overall response rate (ORR) (complete renal response rate 20.8% and partial renal response rate 31.7%) and that by the JCR-II criteria was 49.5% (21.8% and 27.7%, respectively). Corticosteroid dose was significantly reduced. Rituximab was well tolerated, with frequent but manageable adverse events of infusion reaction and infection.

Conclusions
Rituximab is effective for the treatment of Japanese patients with LN refractory to conventional therapy.
Spacer2PAM: A computational framework to guide experimental determination of functional CRISPR-Cas system PAM sequences
Authors: Rybnicky Grant A , Fackler Nicholas A , Karim Ashty S , Köpke Michael , Jewett Michael C 
Published: February 2022

AbstractRNA-guided nucleases from CRISPR-Cas systems expand opportunities for precise, targeted genome modification. Endogenous CRISPR-Cas systems in many prokaryotes are attractive to circumvent expression, functionality, and unintended activity hurdles posed by heterologous CRISPR-Cas effectors. However, each CRISPR-Cas system recognizes a unique set of protospacer adjacent motifs (PAMs), which requires identification by extensive screening of randomized DNA libraries. This challenge hinders development of endogenous CRISPR-Cas systems, especially those based on multi-protein effectors and in organisms that are slow-growing or have transformation idiosyncrasies. To address this challenge, we present Spacer2PAM, an easy-to-use, easy-to-interpret R package built to predict and guide experimental determination of functional PAM sequences for any CRISPR-Cas system given its corresponding CRISPR array as input. Spacer2PAM can be used in a ‘Quick’ method to generate a single PAM prediction or in a ‘Comprehensive’ method to inform targeted PAM libraries small enough to screen in difficult to transform organisms. We demonstrate Spacer2PAM by predicting PAM sequences for industrially relevant organisms and experimentally identifying seven PAM sequences that mediate interference from the Spacer2PAM-informed PAM library for the type I-B CRISPR-Cas system from Clostridium autoethanogenum. We anticipate that Spacer2PAM will facilitate the use of endogenous CRISPR-Cas systems for industrial biotechnology and synthetic biology.
8-oxodG accumulation within super-enhancers marks fragile CTCF-mediated chromatin loops
Authors: Scala Giovanni , Gorini Francesca , Ambrosio Susanna , Chiariello Andrea M , Nicodemi Mario , Lania Luigi , Majello Barbara , Amente Stefano 
Published: February 2022

Abstract
8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a major product of the DNA oxidization process, has been proposed to have an epigenetic function in gene regulation and has been associated with genome instability. NGS-based methodologies are contributing to the characterization of the 8-oxodG function in the genome. However, the 8-oxodG epigenetic role at a genomic level and the mechanisms controlling the genomic 8-oxodG accumulation/maintenance have not yet been fully characterized. In this study, we report the identification and characterization of a set of enhancer regions accumulating 8-oxodG in human epithelial cells. We found that these oxidized enhancers are mainly super-enhancers and are associated with bidirectional-transcribed enhancer RNAs and DNA Damage Response activation. Moreover, using ChIA-PET and HiC data, we identified specific CTCF-mediated chromatin loops in which the oxidized enhancer and promoter regions physically associate. Oxidized enhancers and their associated chromatin loops accumulate endogenous double-strand breaks which are in turn repaired by NHEJ pathway through a transcription-dependent mechanism. Our work suggests that 8-oxodG accumulation in enhancers–promoters pairs occurs in a transcription-dependent manner and provides novel mechanistic insights on the intrinsic fragility of chromatin loops containing oxidized enhancers-promoters interactions.
Responsibility for Acts and Omissions
Authors: Clarke Randolph 
Published: February 2022

Abstract
Accounts of moral responsibility commonly focus on responsibility for actions and their consequences. But we can be responsible as well for omitting to act or refraining from acting, and for consequences of these. And since omitting and refraining are not in every case performing an action, an account of responsibility for actions will not apply straightforwardly to these cases. This paper advances proposals concerning responsibility for omitting, refraining, and their consequences. Providing such an account is complicated by the fact that cases of omitting or refraining are quite varied.
Instrumentalist Theories of Moral Responsibility
Authors: Vargas Manuel 
Published: February 2022

Abstract
In both the historical and contemporary literature on moral responsibility, there are accounts of responsibility that appeal to instrumentalist considerations in accounting for, variously, the nature, structure, and justification of moral responsibility. On the face of it, instrumentalist approaches can seem ill-suited for delivering an adequate theory of responsibility. For example, if one thinks that the hallmark of moral responsibility is its retrospective or “backward-looking” focus, that it involves some notion of desert, or that it somehow invokes or justifies retributive attitudes, instrumentalist theories of responsibility can seem to be nonstarters. Even so, instrumentalist (or “consequentialist”) approaches to responsibility have a storied pedigree within analytic philosophy. In recent years, the approach has enjoyed renewed attention and rehabilitation. This chapter provides an overview of instrumentalist theories of responsibility, including their history, recent developments, and ongoing disputes.
Ethics Is Hard! What Follows? On Moral Ignorance and Blame
Authors: Harman Elizabeth 
Published: February 2022

Abstract
When someone acts morally wrongly because they are caught in the grip of a false moral view, although they have thought a reasonable amount about morality, are they thereby blameless for so acting? Recently, a number of philosophers have embraced the view that moral ignorance does exculpate in such cases. This chapter outlines an attractive line of thought according to which moral ignorance exculpates. This line of thought is mistaken: Being caught in the grip of a false moral view is not exculpatory. Ethics is hard, that’s true. But this doesn’t have the implications for blameworthiness that some people think it does.
Group Responsibility
Authors: List Christian 
Published: February 2022

Abstract
Are groups ever capable of bearing responsibility, over and above their individual members? This chapter discusses and defends the view that certain organized collectives—namely, those that qualify as group moral agents—can be held responsible for their actions, and that group responsibility is not reducible to individual responsibility. The view has important implications. It supports the recognition of corporate civil and even criminal liability in our legal systems, and it suggests that, by recognizing group agents as loci of responsibility, we may be able to avoid “responsibility gaps” in some cases of collectively caused harms for which there is a shortfall of individual responsibility. The chapter also asks whether the view that certain groups are responsible agents commits us to the view that those groups should also be given rights of their own and gives a qualified negative answer.
Forgiveness
Authors: Milam Per-Erik 
Published: February 2022

Abstract
The responsibility and forgiveness literatures have only recently begun to influence one another in a significant way. The aim of this chapter is to introduce a common model of forgiveness and some recent challenges to it, each of which highlights potential connections between forgiveness and responsibility. According to the Standard View, to forgive is to overcome one’s blame toward a culpable wrongdoer. One of the most compelling alternatives to this view is the Norm Changing View, which understands forgiving as the exercise of a normative power that changes what the offender owes the victim. Which of these views one prefers has implications for how one understands the various features of forgiveness, including who can forgive, the difficulty of forgiving, and the possibility of withdrawing forgiveness.