bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolating structural errors in reaction networks in systems biology
Authors: Shin Woosub , Hellerstein Joseph L 
Published: August 2020

Abstract

Motivation
The growing complexity of reaction-based models necessitates early detection and resolution of model errors. Considerable work has been done on the detection of mass balance errors, especially atomic mass analysis (AMA) (which compares the counts of atoms in the reactants and products) and Linear Programming analysis (which detects stoichiometric inconsistencies). This article extends model error checking to include: (i) certain structural errors in reaction networks and (ii) error isolation. First, we consider the balance of chemical structures (moieties) between reactants and products. This balance is expected in many biochemical reactions, but the imbalance of chemical structures cannot be detected if the analysis is done in units of atomic masses. Second, we improve on error isolation for stoichiometric inconsistencies by identifying a small number of reactions and/or species that cause the error. Doing so simplifies error remediation.

Results
We propose two algorithms that address isolating structural errors in reaction networks. Moiety analysis finds imbalances of moieties using the same algorithm as AMA, but moiety analysis works in units of moieties instead of atomic masses. We argue for the value of checking moiety balance, and discuss two approaches to decomposing chemical species into moieties. Graphical Analysis of Mass Equivalence Sets (GAMES) provides isolation for stoichiometric inconsistencies by constructing explanations that relate errors in the structure of the reaction network to elements of the reaction network. We study the effectiveness of moiety analysis and GAMES on curated models in the BioModels repository. We have created open source codes for moiety analysis and GAMES.

Availability and implementation
Our project is hosted at https://github.com/ModelEngineering/SBMLLint, which contains examples, documentation, source code files and build scripts used to create SBMLLint. Our source code is licensed under the MIT open source license.

Supplementary information
Supplementary data are available at Bioinformatics online.
Re-Imagining the Resettlement of Refugees by Engaging with an Ethic of Thriving
Authors: Vincent Kate , Baltra-Ulloa Ann Joselynn , Williams Grace 
Published: August 2020

Abstract
Learning to thrive in the context of refugee resettlement can be a difficult task to consider and sustain when so much focus is given to promoting survival, recovery from trauma and self-sufficiency. It is argued that this resettlement paradigm is rooted in notions of refugee passivity, primarily motivated by a minimalistic approach to social assimilation. We argue this resettlement paradigm suffocates thriving by imposing the government’s aim of achieving independence instead of privileging the newly arrived person, their lived experiences, dreams and aspirations. This article shares how an ethic of thriving in resettlement, with its focus on relationality, could transform the way we think about ‘integration’ and what ‘successful resettlement’ means within the Australian context. To anchor what the ethic of thriving offers the resettlement sector we share lessons learned from applying a thriving paradigm to YoungMILE—a mentorship project dedicated to launching young refugee arrived leaders in the community. This unique programme embraced relational, experimental and exploratory approaches characterised by flexibility, mutual learning, curiosity, listening to bigger goals and acknowledging the skill sets of people’s past experiences. Importantly, the project also prioritised connecting people of refugee background and the host community to promote meaningful integration.
Comparative scoping study report for the extraction of microalgae oils from two subspecies of Chlorella vulgaris
Authors: Kreft Jasmine , Moe Eric , Garcia Nicholas , Ross Andrew , Seames Wayne 
Published: August 2020

Abstract
The production of microalgae as a fatty acid oil resource for use in biofuels production is a widespread research topic at the lab scale. Microalgae contain a higher lipid content on a dry-weight basis compared to oilseeds such as soybeans. Additionally, the growth and cultivation cycle of microalgae is 15 days, in comparison to soybeans, for which the cycle occurs once or twice annually. However, to date, it has been uneconomical to produce microalgae oils in a world-scale facility due to limitations in cultivating microalgae at commercial scales. Recent developments suggest that the use of heterotrophic microalgae may be economically feasible for large-scale oil production. To assess this feasibility, a comparative scoping study was performed analysing the feasibility of an industrial-scale process plant for the growth and extraction of oil from microalgae. Processes were developed at the preliminary design level using heterotrophic subspecies and autotrophic subspecies of Chlorella vulgaris. AACE Class 4 cost estimates and economic analyses were performed. This study concludes that processes based on heterotrophic microalgae are more likely to reach economic feasibility than processes using autotrophic microalgae. However, a few barriers still remain to achieving free-market economic viability.
Household Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 in the United States
Authors: Lewis Nathaniel M , Chu Victoria T , Ye Dongni , Conners Erin E , Gharpure Radhika , Laws Rebecca L , Reses Hannah E , Freeman Brandi D , Fajans Mark , Rabold Elizabeth M , Dawson Patrick , Buono Sean , Yin Sherry , Owusu Daniel , Wadhwa Ashutosh , Pomeroy Mary , Yousaf Anna , Pevzner Eric , Njuguna Henry , Battey Katherine A , Tran Cuc H , Fields Victoria L , Salvatore Phillip , O’Hegarty Michelle , Vuong Jeni , Chancey Rebecca , Gregory Christopher , Banks Michelle , Rispens Jared R , Dietrich Elizabeth , Marcenac Perrine , Matanock Almea M , Duca Lindsey , Binder Allison , Fox Garrett , Lester Sandra , Mills Lisa , Gerber Susan I , Watson John , Schumacher Amy , Pawloski Lucia , Thornburg Natalie J , Hall Aron J , Kiphibane Tair , Willardson Sarah , Christensen Kim , Page Lindsey , Bhattacharyya Sanjib , Dasu Trivikram , Christiansen Ann , Pray Ian W , Westergaard Ryan P , Dunn Angela C , Tate Jacqueline E , Nabity Scott A , Kirking Hannah L 
Published: August 2020

Abstract

Background
The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission.

Methods
We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020–25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test.

Results
Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%–36%) overall, 42% among children (aged &lt;18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4–106.9) and 7.1 (95% CI: 1.2–42.5), respectively.

Conclusions
We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.
Clostridioides difficileInfection in Cancer and Immunocompromised Patients: Relevance of a Two-step Diagnostic Algorithm and Infecting Ribotypes on Clinical Outcomes
Authors: Yepez Guevara Eduardo A , Aitken Samuel L , Olvera Adilene V , Carlin Lily , Fernandes Kerri E , Bhatti Micah M , Garey Kevin W , Adachi Javier , Okhuysen Pablo C 
Published: August 2020

AbstractBackgroundPatients with cancer are particularly vulnerable to Clostridioides difficile infection (CDI). Guidelines recommend a two-step diagnostic algorithm to differentiate carriers from CDI; however, there are limited data for this approach while including other confounding risk factors for diarrhea such as radiation, cytotoxic chemotherapy, and adoptive cell based therapies.MethodsWe conducted a prospective, non-interventional, single center, cohort study of cancer patients with acute diarrhea and C. difficile, identified in stools by nucleic acid amplification tests (NAAT) and culture. Fecal toxin A/B was detected by enzyme immunoassay (EIA) and isolates were ribotyped using 16s rRNA fluorescent sequencing. Patients were followed for 90 days to compare outcomes according to malignancy type, infecting ribotype, and EIA status.ResultsWe followed 227 patients with a positive NAAT. Of these, 87% were hospitalized and 83% had an active malignancy. EIA was confirmed positive in 80/227 (35%) of patients. Those with EIA+ were older (60 ± 18 years vs 54 ± 19 years., P = .01), more likely to fail therapy [24/80 (30%) vs 26/147 (18%), P = .04] and experience recurrence [20/80 (25%) vs 21/147(14%), P &lt; .05]. We found a low prevalence (22%) of ribotypes historically associated with poor outcomes (002, 018, 027, 56, F078-126, 244) but their presence were associated with treatment failure [17/50 (34%) vs 33/177 (19%), P = .02].ConclusionsWhen compared to cancer patients with fecal NAAT+/EIA−, patients with NAAT+/EIA+ CDI are less likely to respond to therapy and more likely to experience recurrence, particularly when due to ribotypes associated with poor outcomes.
Anemia following acute kidney injury after noncardiac surgery and long-term outcomes: the NARA-AKI cohort study
Authors: Nishimoto Masatoshi , Murashima Miho , Kokubu Maiko , Matsui Masaru , Eriguchi Masahiro , Samejima Ken-Ichi , Akai Yasuhiro , Tsuruya Kazuhiko 
Published: August 2020

Abstract

Background
This study was conducted to investigate whether acute kidney injury (AKI) is an independent predictor of anemia and whether anemia following AKI is a mediator of mortality after AKI.

Methods
This is a retrospective cohort study. Adults with noncardiac surgery from 2007 to 2011 were included. Obstetric or urological surgery, missing data or preoperative dialysis were excluded. Subjects were followed until the end of 2015 or lost to follow-up. Exposures of interest were postoperative AKI. Outcome variables were hematocrit values at 3, 6 and 12 months postoperatively and mortality. Associations between AKI and hematocrit or association between AKI and mortality were examined by multivariable linear regression or Cox regression, respectively.

Results
Among 6692 subjects, 445 (6.6%) developed AKI. Among those with postoperative data, AKI was independently associated with lower hematocrit at 3, 6 and 12 months postoperatively, with coefficients of −0.79 [95% confidence interval (CI) −1.47 to −0.11; n = 1750], −1.35 (−2.11 to −0.60; n = 1558) and −0.91 (−1.59 to −0.22; n = 2463), respectively. Higher stages or longer duration of AKI were associated with more severe anemia. AKI was associated with higher mortality after 3 months postoperatively with a hazard ratio of 1.54 (95% CI 1.12–2.12). Further adjustment with hematocrit at 3 months attenuated the association. The mediation effect was significant (P = 0.02) by mediation analysis.

Conclusions
AKI was an independent predictor of anemia following AKI. Higher mortality associated with AKI was at least partially mediated by anemia following AKI. Whether correction of anemia following AKI improves mortality requires further research.
O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR
Authors: Tajadura-Ortega Virginia , Gambardella Gennaro , Skinner Alexandra , Halim Adnan , Van Coillie Julie , Schjoldager Katrine Ter-Borch Gram , Beatson Richard , Graham Rosalind , Achkova Daniela , Taylor-Papadimitriou Joyce , Ciccarelli Francesca D , Burchell Joy M 
Published: August 2020

Abstract
Aberrant mucin-type O-linked glycosylation is a common occurrence in cancer where the upregulation of sialyltransferases is often seen leading to the early termination of O-glycan chains. Mucin-type O-linked glycosylation is not limited to mucins and occurs on many cell surface glycoproteins including EGFR, where the number of sites can be limited. Upon EGF ligation, EGFR induces a signaling cascade and may also translocate to the nucleus where it directly regulates gene transcription, a process modulated by Galectin-3 and MUC1 in some cancers. Here, we show that upon EGF binding, breast cancer cells carrying different O-glycans respond by transcribing different gene expression signatures. MMP10, the principal gene upregulated when cells carrying sialylated core 1 glycans were stimulated with EGF, is also upregulated in ER-positive breast carcinoma reported to express high levels of ST3Gal1 and hence mainly core 1 sialylated O-glycans. In contrast, isogenic cells engineered to carry core 2 glycans upregulate CX3CL1 and FGFBP1 and these genes are upregulated in ER-negative breast carcinomas, also known to express longer core 2 O-glycans. Changes in O-glycosylation did not significantly alter signal transduction downstream of EGFR in core 1 or core 2 O-glycan expressing cells. However, striking changes were observed in the formation of an EGFR/galectin-3/MUC1/β-catenin complex at the cell surface that is present in cells carrying short core 1-based O-glycans but absent in core 2 carrying cells.
Shape–function insights into bifunctional O-GlcNActransferase of Listeria monocytogenes EGD-e
Authors: Choudhary Pravinkumar , Badmalia Maulik D ,   Ashish, Rao Alka 
Published: August 2020

Abstract
O-GlcNAcylation is an important post-translational modification of proteins. O-GlcNAcylated proteins have crucial roles in several cellular contexts both in eukaryotes and bacteria. O-GlcNActransferase (OGT) is the enzyme instrumental in O-GlcNAcylation of proteins. OGT is conserved across eukaryotes. The first bacterial OGT discovered is GmaR in Listeria monocytogenes. GmaR is a GT-2 family bifunctional protein that catalyzes glycosylation of the flagellin protein FlaA and controls transcription of flagellar motility genes in a temperature-dependent manner. Here, we provide methods for heterologous expression and purification of recombinant GmaR and FlaA, in vivo/in vitro glycosylation assays, analysis of the molecular form of recombinant GmaR and detailed enzyme kinetics. We study the structure and functional dynamics of GmaR. Using solution small-angle X-ray scattering and molecular modeling, we show that GmaR adopts an extended shape with two distinctly spaced structural units in the presence of cofactor Mg2+ and with donor UDP-GlcNAc and cofactor combined. Comparisons of restored structures revealed that in-solution binding of Mg2+ ions brings about shape rearrangements and induces structural-rigidity in hyper-variable regions at the N-terminus of GmaR protein. Taking function and shape data together, we describe that Mg2+ binding enables GmaR to adopt a shape that can bind the substrate. The manuscript provides the first 3D solution structure of a bacterial OGT of GT-2 family and detailed biochemical characterization of GmaR to facilitate its future applications.
The Strategy of Predator Evasion in Response to a Visual Looming Stimulus in Zebrafish (Danio rerio)
Authors: McKee A , McHenry M J 
Published: August 2020

SynopsisA diversity of animals survive encounters with predators by escaping from a looming visual stimulus. Despite the importance of this behavior, it is generally unclear how visual cues facilitate a prey’s survival from predation. Therefore, the aim of this study was to understand how the visual angle subtended on the eye of the prey by the predator affects the distance of adult zebrafish (Danio rerio) from predators. We performed experiments to measure the threshold visual angle and mathematically modeled the kinematics of predator and prey. We analyzed the responses to the artificial stimulus with a novel approach that calculated relationships between hypothetical values for a threshold-stimulus angle and the latency between stimulus and response. These relationships were verified against the kinematic responses of zebrafish to a live fish predator (Herichthys cyanoguttatus). The predictions of our model suggest that the measured threshold visual angle facilitates escape when the predator’s approach is slower than approximately twice the prey’s escape speed. These results demonstrate the capacity and limits to how the visual angle provides a prey with the means to escape a predator.
A Note on Semmelweis’s Animal Experiments and Their Historical Significance
Authors: Kadar Nicholas 
Published: August 2020

Abstract
This article seeks to establish what animal experiments Semmelweis conducted, and when and why he conducted them, because the Semmelweis literature contains conflicting claims about these topics or has ignored them altogether. Semmelweis first conducted animal experiments between 22 March and 20 August 1849 with Rokitansky’s assistant, Georg Maria Lautner, because his chief, Johann Klein, did not accept that by merely reducing the mortality rate from childbed fever with chlorine hand-disinfection, Semmelweis had proved his theory of the cause of childbed fever. However, Skoda concluded that the Lautner experiments did not resolve the doubts about Semmelweis’s theory they were intended to resolve, and, therefore, asked the Academy of Sciences to award Semmelweis a grant to conduct further and more varied experiments with the physiologist, Ernst Ritter von Brücke. These additional experiments were conducted in the spring and summer of 1850, but yielded only ambiguous results, and led Brücke to conclude that questions about Semmelweis’s theory could only be resolved by clinical observations, not animal experiments. This article discusses the reasoning behind these animal experiments, and Skoda’s and Brücke’s responses to them, and argues that their responses to the experiments caused Semmelweis to delay publishing his research until he had collected sufficient clinical evidence to prove his theory.
A Hinduism of their Own: Emerging Guyanese Hindu Reading Practices in New York City
Authors: Pillai Rupa 
Published: August 2020

AbstractImmigrating to New York City presents new issues for Indo--Guyanese, especially as many find themselves in lower class positions while navigating a racial structure distinct from Guyana. A subset of these Indo--Guyanese Americans, particularly middle class women as well as the 1.5-- and second generation, believes Guyanese Hinduism, the forms of Hinduism adapted to the Guyanese context, must adapt again to continue to be relevant to the community in their new home. Central to their call is questioning the religious authority of pandits. As I will discuss, pandits occupy a powerful position in Guyanese Hindu community that extends beyond the religious sphere. The key to their authority lies in their ability and skill to read and interpret Hindu scripture. However, I argue the realities of migration have resulted in a questioning of religious authority and how pandits read these texts. With some Guyanese Hindus uncertain of the reliability of their pandit’s reading of scriptural text, there is a desire to engage in a Hinduism untainted by the biases of pandits. The presumed truth held within Hindu scripture has inspired some devotees to return to the text or rather to engage the text on their own for the first time. As a result, new reading practices are appearing within the community, which encourages Guyanese Hindus to craft a Hinduism that will serve them.
Roles for the DNA-PK complex and 53BP1 in protecting ends from resection during DNA double-strand break repair
Authors: Shibata Atsushi , Jeggo Penny A 
Published: August 2020

Abstract
p53-binding protein 1 (53BP1) exerts distinct impacts in different situations involving DNA double-strand break (DSB) rejoining. Here we focus on how 53BP1 impacts upon the repair of ionising radiation-induced DSBs (IR-DSBs) and how it interfaces with Ku, the DNA end-binding component of canonical non-homologous end-joining (c-NHEJ), the major DSB repair pathway in mammalian cells. We delineate three forms of IR-DSB repair: resection-independent c-NHEJ, which rejoins most IR-DSBs with fast kinetics in G1 and G2, and Artemis and resection-dependent c-NHEJ and homologous recombination (HR), which repair IR-DSBs with slow kinetics in G1 and G2 phase, respectively. The fast component of DSB repair after X-ray exposure occurs via c-NHEJ with normal kinetics in the absence of 53BP1. Ku is highly abundant and has avid DNA end-binding capacity which restricts DNA end-resection and promotes resection-independent c-NHEJ at most IR-DSBs. Thus, 53BP1 is largely dispensable for resection-independent c-NHEJ. In contrast, 53BP1 is essential for the process of rejoining IR-DSBs with slow kinetics. This role requires 53BP1’s breast cancer susceptibility gene I (BRCA1) C-terminal (BRCT) 2 domain, persistent ataxia telangiectasia mutated (ATM) activation and potentially relaxation of compacted chromatin at heterochromatic-DSBs. In distinction, 53BP1 inhibits resection-dependent IR-DSB repair in G1 and G2, and this resection-inhibitory function can be counteracted by BRCA1. We discuss a model whereby most IR-DSBs are rapidly repaired by 53BP1-independent and resection-independent c-NHEJ due to the ability of Ku to inhibit resection, but, if delayed, then resection in the presence of Ku is triggered, the 53BP1 barrier comes into force and BRCA1 counteraction is required for resection.
Acute Myeloid Leukemia Case Harboring Unusual FLT3 Variant: Somatic vs Germline?
Authors: Singh Nirupama , Morlote Diana , Vnencak-Jones Cindy , Papadantonakis Nikolaos , Harada Shuko 
Published: August 2020

Abstract
FLT3 mutations are considered a prognostic and predictive marker. Here we report on a patient with a rare FLT3 germline variant in the context of relapsed acute myeloid leukemia (AML). A female patient aged 57 years presented with AML with mutations in the IDH2, ASXL1, and DNMT3A genes. She underwent allogenic hematopoietic stem cell transplant but relapsed 2 years posttransplant. Targeted next generation sequencing identified a new missense variant in the FLT3 tyrosine kinase domain c.2440G &gt; T (p.A814S). The treating team considered the possibility of patient eligibility for an FLT3 inhibitor. Because both somatic and germline mutations can be identified in tumor tissue with high-throughput sequencing, it becomes important to distinguish the origin of these alterations when possible—especially, in this challenging case, to define the treatment modality. Simultaneous tumor/germline sequencing allows for the identification of rare germline mutations and may help in determining their significance in the pathogenesis of disease.