bluuebunny/crossref_metadata_2025 huggingface dataset:
A Charity of Mutuality and Hospitality: L'Arche's Witness to Catholic Theology
Authors: Little Brent
Published: May 2020

Through the writings of Jean Vanier, this paper encourages Catholic theologians to examine critically their theological sources and their own rhetoric for the context of developmental disabilities. Specifically, this thought experiment is an invitation for the Catholic academy to consider how its theologies of charity can assist the church to reflect on its pastoral ministry to people with developmental disabilities. Some Catholic discourse is built on an assumed one-directional concept of charity that emphasizes the agency and gifts of the giver over the receiver. Such a one-sided model of hospitality tends to emphasize the giver as the person without developmental disabilities, whereas the person with disabilities is described as the receiver of hospitality; their own gifts and agency thereby are either unacknowledged or downplayed. This paper argues, instead, that Catholic theologies of charity, particularly regarding developmental disabilities, should be built on a mutuality that affirms each person's agency to be both a giver and a receiver of charity.
I. Pastor Aeternus in Its Context
Authors: von Arx Jeffrey
Published: May 2020

How has Pastor Aeternus stood the test of time in the face of Vatican II, the great social leveling brought about by democracy and the mass media, and the severe erosion of confidence in hierarchical institutions, including the Catholic Church?
III. Pastor Aeternus, Liberalism, and the Limits of Papal Authority
Authors: Washburn Christian D.
Published: May 2020

Two dogmatic constitutions from the First Vatican Council, Dei Filius and Pastor Aeternus, are worth revisiting today. These documents were in part a response to the challenge of liberalism. Although such a retrieval of the wisdom of Dei Filius and Pastor Aeternus is necessary as a means of protecting Christ's revelation, this is not sufficient. The doctrine of Pastor Aeternus should also be developed to make more clear the limits of papal authority.
IV. Pastor Aeternus at 150
Authors: Ross Susan A.
Published: May 2020

Kristin Colberg's fine essay in the December 2019 issue of Horizons clearly lays out the social, historical, and theological context for Pastor Aeternus. The year 1870 was a tumultuous, difficult, even dangerous, time for the Roman Catholic Church as it dealt with rationalism, challenges to secular as well as religious authority, new scientific ideas, and the loss of its own political power. When I have taught historical survey courses, I always stress the significance of context, and Pastor Aeternus is no exception. I also ask my students, when reading about controversial issues, to ask the question: “What is each position trying to protect?” Clearly, Pastor Aeternus is trying to protect the church's independence from secular powers, from perceived errors, and from forces of disunity both in society and in the church itself.
I. Teaching and Theologizing about Religion and Genocide: Some Reflections
Authors: Barnett Victoria
Published: May 2020

A quarter of a century has passed since the 1994 genocide against the Tutsi in Rwanda and the 1995 genocide in Bosnia and Herzegovina. The anniversaries of these tragedies beckon us to reflect on the responsibility of theologians, scholars of religion, and religious educators to confront genocide. How should scholars use the tools of these disciplines to educate about genocide responsibly and promote peace and respect for human dignity and rights in the wake of such tragedy? How might they utilize their intellectual, spiritual, and material resources to help prevent violent extremism and genocide? Four scholars who have profoundly engaged these questions in their academic work generously agreed to contribute to this roundtable. One of them writes directly from his context of Rwanda, while another writes from her homeland in Bosnia and Herzegovina. The two scholars based in the United States have also systematically confronted the problem of ethnic and religious hatred and genocide, focusing on the Holocaust and the Bosnian genocide, respectively. All four contributors serve as remarkable examples of theologians and scholars of religion who have used their training and skills to promote a world where “never again” is not merely a slogan.
III. After the War: The Responsibility and Competence of Academics
Authors: Maros Zorica
Published: May 2020

Twenty-five years after the end of the war, the political and social scene of Bosnia and Herzegovina is still characterized by the mentality of the 1990s. In recent months, we have witnessed political rhetoric that is very much reminiscent of the time before, at the beginning, and during the war. In the first part of this essay, I will try to present some of the reasons for this situation. In the second part, I will point out the responsibility of intellectuals for such a condition. In this concluding section, I will discuss how we have used our academic resources in an attempt to change the situation and strengthen social responsibility.
From Aesthetics to Experience: How Changing Conceptions of Prayer Changed the Sound of Jewish Worship
Authors: Kelman Ari Y. , Lockwood Jeremiah
Published: May 2020

This article tracks changes in conceptions of American Jewish congregational prayer music during the second half of the twentieth century, paying specific attention to the late 1960s and early 1970s. During those years, more than fifty albums of new American Jewish synagogue music were released. These drew on the sounds of folk and rock music, and they represented a shift from the sounds of classical cantorial synagogue music. These changes have largely been understood as a shift away from cantorial styles, which emphasized performance and virtuosity, and toward more accessible and more participatory forms of prayer. This article contributes to our understanding of the sounds of American Jewish prayer practices by attending to the larger discourses in which the musical changes were situated. By listening to the music, reading album liner notes, and contemporaneous writings about Jewish prayer music, we discover a shift in descriptions and expectations of how Jewish prayer ought to work, from one that emphasizes the aesthetics of the music to one that emphasizes the experience of the music. We argue that music is one element of a larger shift in how people who made music for congregational prayer understood prayer and how best to engage congregations in that practice.
Risk of bloodstream infection in patients with renal dysfunction: a population-based cohort study
Authors: Dagasso Gabrielle , Conley Joslyn , Steele Lisa , Parfitt Elizabeth E. C. , Pasquill Kelsey , Laupland Kevin B.
Published: May 2020

Although patients with end-stage renal disease (ESRD) are known to be at high risk for developing bloodstream infections (BSI), the risk associated with lesser degrees of renal dysfunction is not well defined. We sought to determine the risk for acquiring and dying from community-onset BSIs among patients with renal dysfunction. A retrospective, population-based cohort study was conducted among adult residents without ESRD in the western interior of British Columbia. Estimated glomerular filtration rates (eGFR) were determined for cases and incidence rate ratios (IRR) were calculated using prevalence estimates. Overall, 1553 episodes of community-onset BSI were included of which 39%, 32%, 17%, 9%, 2% and 1% had preceding eGFRs of ≥90, 60–89, 45–59, 30–44, 15–29 and <15 ml/min/m2, respectively. As compared to those with eGFR ≥60 ml/min/m2, patients with eGFR 30–59 ml/min/m2(IRR 4.4; 95% confidence interval (CI) 3.9–4.9) and eGFR <30 ml/min/m2(IRR 7.0; 95% CI 5.0–9.5) were at significantly increased risk for the development of community-onset BSI. An eGFR <30 ml/min/m2was an independent risk factor for death (odds ratio 2.3; 95% CI 1.01–5.15). Patients with renal dysfunction are at increased risk for developing and dying from community-onset BSI that is related to the degree of dysfunction.
An evaluation of direct PCR assays for the detection and quantification of Porphyromonas gingivalis
Authors: Gu B. L. , Qi Y. J. , Kong J. Y. , Li Z. T. , Wang J. P. , Yuan X. , Gao S. G.
Published: May 2020

Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.
Parfit on Act Consequentialism
Authors: de Lazari-Radek Katarzyna , Singer Peter
Published: May 2020

In the first two volumes of On What Matters, Derek Parfit argues that three major normative theories – Kantianism, Contractualism and Rule Consequentialism – are, in their most defensible forms, compatible, and can be reconciled in what he calls ‘Triple Theory’. This has led many to assume that Parfit does not believe that Act Consequentialism is a defensible form of Consequentialism. We draw on correspondence with Parfit to show that this assumption is incorrect. We then consider Parfit's efforts, in the third volume of On What Matters, to narrow the differences between Act Consequentialism and the triple theory, in part by treating impartial rationality as an external rival to morality, in much the same way that egoism is an external rival to morality. We argue that Parfit's attempts to bridge the gap between Act Consequentialism and Triple Theory meet with only limited success.
Queering the Nation: Hegemonic Masculinity, Negative Sovereignty and the Great War in Sebastian Barry’sA Long Long Way
Authors: Meneses Juan
Published: May 2020

This article examines how Sebastian Barry’s 2005 novelA Long Long Wayexplores the impact of the First World War in the construction of a sovereignty that is, against the grain of a teleological understanding of history, not incorporated in the official chronicle of the Irish independence from the British Empire. Through the lens of what I call ‘negative sovereignty’, which describes a form of agency that amounts to something less than nothing and is located in the obverse of the official historical record, I argue that the novel thematises the disruption caused by the war as a crisis in the hegemonic masculinity at the core of the national imagination. This article, thus, reads the novel’s protagonist, Willie Dunne, as a ‘queering’ subjectivity that embodies this kind of sovereignty, provoking a suspension in the patriarchal foundation of nation-building as symbolised by the severance of his relationship with his father.
A long-term, open-label study of valbenazine for tardive dyskinesia
Authors: Lindenmayer Jean-Pierre , Verghese Cherian , Marder Stephen R. , Burke Joshua , Jimenez Roland , Siegert Scott , Liang Grace S. , O’Brien Christopher F.
Published: May 2020

Background

Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.

Methods

Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs).

Results

At study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4).

Conclusions

Valbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.
Dietary intake and processes of behaviour change in a nutrition education intervention for pregnant women in rural Malawi: a cluster-randomised controlled trial
Authors: Ziyenda Katenga-Kaunda Lillian , Iversen Per Ole , Holmboe-Ottesen Gerd , Fjeld Heidi , Mdala Ibrahimu , Kamudoni Penjani Rhoda
Published: May 2020

Objective:

To examine if increased intake of locally available nutrient-dense foods among pregnant women improved the quality of their dietary intake and if use of the Theory of Planned Behaviour could explain changes in their dietary behaviour.

Design:

We used data from a randomised controlled trial where the intervention group received nutrition education and dietary counselling. We promoted the use of recipes that utilised powders to enhance dietary diversity. We examined how the intervention achieved changes in dietary intakes and used mixed effects logistic regression models with random effects at village level to explore changes over time of the outcomes, adjusted for selected explanatory variables.

Setting:

The study was conducted in twenty villages in rural Malawi.

Participants:

Data from 257 pregnant women who were enrolled during late first trimester and followed until birth.

Results:

The intervention achieved improvements in the Dietary Diversity Score (DDS) and the Six Food Group Pyramid (SFG) score, especially in intakes of micronutrient-rich foods. A third of the women in the intervention group attained optimal DDS, whereas about 50 % attained optimal SFG. The theorised behaviour mediators (i.e. nutrition attitudes, nutrition behaviour control and subjective norm) that had improved were also significantly associated with high DDS.

Conclusions:

Improved dietary intakes were achieved through promoting the use of locally available nutrient-dense foods. Attainment of high DDS was a consequence of the women’s belief in the effectiveness of the proposed nutrition recommendations. We identified critical personal and environmental constraints related to dietary intakes during pregnancy in a low-resource setting.
Preconception nutrition: building advocacy and social movements to stimulate action
Authors: Vogel Christina , Kriznik Natasha , Stephenson Judith , Barker Mary
Published: May 2020

Action to improve preconception nutrition is a collective, societal responsibility. We believe that the Developmental Origins of Health and Disease (DOHaD) society is ideally placed to facilitate the development of a global agenda for preconception nutrition which recognises the societal importance of nutrition for young women and men, and supports them in optimising their nutritional status for the benefit of the next generation. In this paper, we outline four key actions that can be taken by the members of DOHaDʼs international society located across 67 countries, and nine regional societies, to demonstrate this leadership role. The recommended actions to place preconception nutrition at the top of national and regional agendas include (i) continuing to build the scientific evidence, (ii) monitoring of progress made by governments and commercial companies, (iii) developing advocacy coalitions that unite individuals and organisations around common policy options and (iv) working with partners to develop an emotive and empowering preconception nutrition awareness campaign. Collectively, these actions hold the potential to develop into a preconception nutrition social movement to invoke high-level government support and across-sector policy action, while raising public demand for action and engaging corporate actors.
Rechtliche Anforderungen und organisatorische Herausforderungen
Authors: Gottlob Melanie , Holzke Martin , Längle Gerhard
Published: May 2020

Zusammenfassung. Viele Kliniken stehen aktuell vor der Frage, ob und wie sie die stationsäquivalente Behandlung in ihr Versorgungsangebot aufnehmen können. Aufgrund der gesetzlichen Anforderungen gibt es eine Reihe an Vorgaben, die hierzu erfüllt werden müssen. Der Beitrag erläutert die wesentlichen Aspekte der vorgegebenen Rahmenbedingungen und die daraus resultierenden organisatorischen Herausforderungen.
Authentisch, mit Wertschätzung und Offenheit
Authors: Stähli Alexandra , Metzenthin Petra
Published: May 2020

Zusammenfassung. Sinnfragen sind oftmals Ausdruck vermeintlich unüberwindbarer Diskrepanzen zwischen „innen“ und „außen“, zwischen Person und Umwelt, zwischen Vergangenheit, Gegenwart und Zukunft. Sinnfragen lösen Gefühle der Ohnmacht, Hoffnungslosigkeit und Verzweiflung aus. Dahinter finden sich die Emotionen Angst, Trauer und Wut. In der therapeutischen Arbeit mit Patientinnen und Patienten in Sinnkrisen gilt es eine erhöhte Sensibilität für diese Verflechtungen zu entwickeln, die Betroffenen im Umgang mit diesen Emotionen zu unterstützen und somit dem urmenschlichen Bedürfnis nach Integrität nachzukommen.
Solar Irradiance Variability: Modeling the Measurements
Authors: Lean J. L. , Coddington O. , Marchenko S. V. , Machol J. , DeLand M. T. , Kopp G.
Published: May 2020

New models of the Sun's irradiance variability are developed from 15 years of direct observations made by the Solar Radiation and Climate Experiment (SORCE) spacecraft from 2003 to 2017 (inclusive). Multiple linear regression parameterizes the observations in terms of facular brightening and sunspot darkening, which are the primary sources of solar irradiance variability. The facular influence is specified as a combination of a linear and nonlinear solar ultraviolet (UV) index; the addition of the nonlinear term allows better reproduction of concurrent solar cycle and rotational variability. The sunspot darkening index is calculated using sunspot observations from both the Debrecen catalog and Air Force Solar Observing Optical Network (SOON) operational sites, the former providing superior model performance. The new model of total solar irradiance variability, NRLTSI3, with the Debrecen sunspot index reproduces the direct Total Irradiance Monitor (TIM) observations better than does the NRLTSI2 model that currently specifies irradiance for the NOAA Climate Data Record (CDR); the correlation of the model and observations increases from 0.956 to 0.971, and the standard deviation of the residuals decreases from 0.124 to 0.100 W m−2. The new model of solar spectral irradiance variability, NRLSSI3, which extends from 115 to 100,000 nm, reproduces rotational modulation in independent Ozone Monitoring Instrument (OMI) observations at near‐UV and visible wavelengths. The SATIRE model overestimates rotational modulation of near‐UV Fraunhofer spectral features because of excess facular brightness; the EMPIRE model overestimates rotational modulation at all near‐UV wavelengths.
Evaluation of the OPTRAM Model to Retrieve Soil Moisture in the Sanjiang Plain of Northeast China
Authors: Chen Mingxing , Zhang Yuhu , Yao Yunjun , Lu Jing , Pu Xiao , Hu Tao , Wang Peng
Published: May 2020

Soil moisture is a key factor affecting crop growth and crop yield. Information on soil moisture is critical for crop growth monitoring and yield estimation. This study evaluated the OPtical TRApezoid Model (OPTRAM) on soil moisture estimates in the Sanjiang Plain, China, using Moderate Resolution Imaging Spectroradiometer (MODIS) data and in situ soil moisture data acquired from May to September in 2016 and 2017. This model was empirically calculated by parameterizing the relationship between the normalized difference vegetation index (NDVI) and shortwave infrared transformed reflectance (STR). In addition, the precipitation data were collected and used for verification of the results. According to the scatterplots of STR and NDVI, OPTRAM can estimate soil moisture from July to September, while it's inapplicable in May and June. Evaluation results indicated that OPTRAM‐based soil moisture estimates provide overall RMSE from 0.05 to 0.13 cm3/cm3, bias from −0.11 to 0.06 cm3/cm3, and R2 from 0.10 to 0.50, respectively, for all investigated sites. The performance of OPTRAM compared with the precipitation data showed good agreement. In conclusion, OPTRAM could be used to estimate soil moisture with reasonable accuracy in most areas from July to September in Sanjiang Plain.
Contribution of Secondary Particles to Wintertime PM2.5 During 2015–2018 in a Major Urban Area of the Sichuan Basin, Southwest China
Authors: Du X. X. , Shi G. M. , Zhao T. L. , Yang F. M. , Zheng X. B. , Zhang Y. J. , Tan Q. W.
Published: May 2020

A novel method, noted as approximate envelope method (AEM), was developed to estimate the secondary PM2.5 concentrations based on the air quality monitoring data. This approach made it possible to obtain the long‐term characteristics of the secondary PM2.5 using only conventional observations. The secondary PM2.5 concentrations and their variation characteristics under different PM2.5 pollution levels during wintertime of 2015 to 2018 in Chengdu, a major urban area of Sichuan Basin over Southwest China, were analyzed. The results showed that the secondary PM2.5 concentrations ranged from 52.3 to 122.8 μg·m−3 and accounted for 56.3%, 63.6%, and 67.4% of the total PM2.5 in slight, moderate, and heavy pollution status, respectively. Additionally, the concentrations of secondary PM2.5 increased year by year, while the concentrations of primary PM2.5 performed significant decreasing trends from 2015 to 2018. The diurnal variations of primary and secondary PM2.5 presented a significantly unimodal patterns but with maximum at morning and noon, respectively. Specific meteorological conditions such as high (low) relative humidity and temperature (wind speed and air pressure) aggravated the secondary particulate pollution in wintertime of Chengdu, reflecting an influence of regional climate change over the Sichuan Basin of Southwest China on the urban air pollution.
Abundant Spontaneous and Dynamically Triggered Submarine Landslides in the Gulf of Mexico
Authors: Fan Wenyuan , McGuire Jeffrey J. , Shearer Peter M.
Published: May 2020

Submarine landslides that occur offshore are common along the U.S. continental margins. These mass wasting events can trigger tsunamis and hence potentially devastate coastal communities and damage offshore infrastructure. However, the initiation and failure processes of submarine landslides are poorly understood. Here, we identify and locate 85 previously unknown submarine landslides in the Gulf of Mexico from 2008 to 2015. Ten of these landslides failed spontaneously while the remaining 75 were dynamically triggered by passing seismic surface waves from distant earthquakes with magnitudes as small as ∼5. Our observations demonstrate ongoing submarine landslide activity in the Gulf of Mexico where dense energy industry infrastructure is present and that the region is prone to secondary seismic hazard despite the low local seismicity rate. Our results should facilitate future investigations to identify unstable offshore slopes, to illuminate dynamic processes of landslides, and perhaps to apply remote detection technology in tsunami warning systems.
The Response in Air Quality to the Reduction of Chinese Economic Activities During the COVID‐19 Outbreak
Authors: Shi Xiaoqin , Brasseur Guy P.
Published: May 2020

During the COVID‐19 outbreak that took place in early 2020, the economic activities in China were drastically reduced and accompanied by a strong reduction in the emission of primary air pollutants. On the basis of measurements made at the monitoring stations operated by the China National Environmental Monitoring Center, we quantify the reduction in surface PM2.5, NO2, CO, and SO2 concentrations in northern China during the lockdown, which started on 23 January 2020. We find that, on the average, the levels of surface PM2.5 and NO2 have decreased by approximately 35% and 60%, respectively, between the period 1 and 22 January 2020 and the period 23 January and 29 February 2020. At the same time, the mean ozone concentration has increased by a factor 1.5–2. In urban area of Wuhan, where drastic measures were adopted to limit the spread of the coronavirus, similar changes in the concentrations of PM2.5, NO2, and ozone are found.
Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice
Authors: Kuniishi Hiroshi , Yamada Daisuke , Wada Keiji , Yamada Mitsuhiko , Sekiguchi Masayuki
Published: May 2020

Stress increases the risk of neuropsychiatric disorders, such as major depression. Exposure to stress has been reported to induce various neuronal changes, such as alterations in synaptic transmission and structure. However, a causal link between stress-induced neural circuit alterations and changes in emotional behaviours is not well understood. In the present study, we focused on a projection pathway from the orbitofrontal cortex (OFC) to the basolateral nucleus of the amygdala (BLA) as a crucial circuit for negative emotions and examined the effect of stress on OFC–BLA excitatory synaptic transmission using optogenetic and whole-cell patch-clamp methods in mice. As a stress-inducing procedure, we used repeated tail-shock, which increased stress-related behaviours. We found greater α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-d-aspartate current ratios and insertion of calcium-permeable AMPA receptors (AMPARs) in the OFC–BLA synapse after stress. These stress-induced synaptic and behavioural changes were reduced by a blockade of protein kinase A, which plays a principal role in stress-induced targeting of AMPARs into the synaptic membrane. To examine a possible causal relationship between alterations in synaptic transmission in the OFC–BLA pathway and stress-related behaviour, we performed optogenetic activation or chemogenetic inactivation of OFC–BLA transmission in mice. We found that optogenetic activation and chemogenetic inactivation of OFC–BLA transmission increased and decreased stress-related behaviour, respectively. In conclusion, we have demonstrated that stress altered the postsynaptic properties of the OFC–BLA pathway. These synaptic changes might be one of the underlying mechanisms of stress-induced behavioural alterations.
The Pan-Immune-Inflammation Value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials
Authors: Fucà Giovanni , Guarini Vincenzo , Antoniotti Carlotta , Morano Federica , Moretto Roberto , Corallo Salvatore , Marmorino Federica , Lonardi Sara , Rimassa Lorenza , Sartore-Bianchi Andrea , Borelli Beatrice , Tampellini Marco , Bustreo Sara , Claravezza Matteo , Boccaccino Alessandra , Murialdo Roberto , Zaniboni Alberto , Tomasello Gianluca , Loupakis Fotios , Adamo Vincenzo , Tonini Giuseppe , Cortesi Enrico , de Braud Filippo , Cremolini Chiara , Pietrantonio Filippo
Published: May 2020

Background

Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy.

Methods

In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan–Meier method and Cox hazards regression models were used for survival analyses.

Results

A total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36–2.03, P < 0.001) and worse OS (HR, 2.01; 95% CI, 1.57–2.57; P < 0.001) compared to patients with low PIV. PIV outperformed the other IIBs in the GBR model and in the multivariable models.

Conclusion

PIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.
LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2
Authors: Yu Hua , Ding Jun , Zhu Hongwen , Jing Yao , Zhou Hu , Tian Hengli , Tang Ke , Wang Gang , Wang Xiongjun
Published: May 2020

The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical significance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. LOXL1 was found to exhibit antiapoptotic activity by interacting with multiple antiapoptosis modulators, especially BAG family molecular chaperone regulator 2 (BAG2). LOXL1-D515 interacted with BAG2-K186 through a hydrogen bond, and its lysyl oxidase activity prevented BAG2 degradation by competing with K186 ubiquitylation. Then, we discovered that LOXL1 expression was specifically upregulated through the VEGFR-Src-CEBPA axis. Clinically, the patients with higher LOXL1 levels in their blood had much more abundant BAG2 protein levels in glioma tissues. Conclusively, LOXL1 functions as an important mediator that increases the antiapoptotic capacity of tumor cells, and approaches targeting LOXL1 represent a potential strategy for treating glioma. In addition, blood LOXL1 levels can be used as a biomarker to monitor glioma progression.
Determinants of transcription factor regulatory range
Authors: Chen Chen-Hao , Zheng Rongbin , Tokheim Collin , Dong Xin , Fan Jingyu , Wan Changxin , Tang Qin , Brown Myles , Liu Jun S. , Meyer Clifford A. , Liu X. Shirley
Published: May 2020

Characterization of the genomic distances over which transcription factor (TF) binding influences gene expression is important for inferring target genes from TF chromatin immunoprecipitation followed by sequencing (ChIP-seq) data. Here we systematically examine the relationship between thousands of TF and histone modification ChIP-seq data sets with thousands of gene expression profiles. We develop a model for integrating these data, which reveals two classes of TFs with distinct ranges of regulatory influence, chromatin-binding preferences, and auto-regulatory properties. We find that the regulatory range of the same TF bound within different topologically associating domains (TADs) depend on intrinsic TAD properties such as local gene density and G/C content, but also on the TAD chromatin states. Our results suggest that considering TF type, binding distance to gene locus, as well as chromatin context is important in identifying implicated TFs from GWAS SNPs.
A Cas9 with PAM recognition for adenine dinucleotides
Authors: Chatterjee Pranam , Lee Jooyoung , Nip Lisa , Koseki Sabrina R. T. , Tysinger Emma , Sontheimer Erik J. , Jacobson Joseph M. , Jakimo Noah
Published: May 2020

CRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme through identification of the natural 5$$^{\prime}$$′-NAAN-3$$^{\prime}$$′ PAM preference of Streptococcus macacae Cas9 (SmacCas9). To achieve efficient editing activity, we graft the PAM-interacting domain of SmacCas9 to its well-established ortholog from Streptococcus pyogenes (SpyCas9), and further engineer an increased efficiency variant (iSpyMac) for robust genome editing activity. We establish that our hybrids can target all adenine dinucleotide PAM sequences and possess robust and accurate editing capabilities in human cells.
Adaptation of the master antioxidant response connects metabolism, lifespan and feather development pathways in birds
Authors: Castiglione Gianni M. , Xu Zhenhua , Zhou Lingli , Duh Elia J.
Published: May 2020

Birds (Aves) display high metabolic rates and oxygen consumption relative to mammals, increasing reactive oxygen species (ROS) formation. Although excess ROS reduces lifespan by causing extensive cellular dysfunction and damage, birds are remarkably long-lived. We address this paradox by identifying the constitutive activation of the NRF2 master antioxidant response in Neoaves (~95% of bird species), providing an adaptive mechanism capable of counterbalancing high ROS levels. We demonstrate that a KEAP1 mutation in the Neoavian ancestor disrupted the repression of NRF2 by KEAP1, leading to constitutive NRF2 activity and decreased oxidative stress in wild Neoaves tissues and cells. Our evidence suggests this ancient mutation induced a compensatory program in NRF2-target genes with functions beyond redox regulation—including feather development—while enabling significant metabolic rate increases that avoid trade-offs with lifespan. The strategy of NRF2 activation sought by intense clinical investigation therefore appears to have also unlocked a massively successful evolutionary trajectory.
Mottness versus unit-cell doubling as the driver of the insulating state in 1T-TaS2
Authors: Butler C. J. , Yoshida M. , Hanaguri T. , Iwasa Y.
Published: May 2020

If a material with an odd number of electrons per unit-cell is insulating, Mott localisation may be invoked as an explanation. This is widely accepted for the layered compound 1T-TaS2, which has a low-temperature insulating phase comprising charge order clusters with 13 unpaired orbitals each. But if the stacking of layers doubles the unit-cell to include an even number of orbitals, the nature of the insulating state is ambiguous. Here, scanning tunnelling microscopy reveals two distinct terminations of the charge order in 1T-TaS2, the sign of such a double-layer stacking pattern. However, spectroscopy at both terminations allows us to disentangle unit-cell doubling effects and determine that Mott localisation alone can drive gap formation. We also observe the collapse of Mottness at an extrinsically re-stacked termination, demonstrating that the microscopic mechanism of insulator-metal transitions lies in degrees of freedom of inter-layer stacking.
Experimental violation of n-locality in a star quantum network
Authors: Poderini Davide , Agresti Iris , Marchese Guglielmo , Polino Emanuele , Giordani Taira , Suprano Alessia , Valeri Mauro , Milani Giorgio , Spagnolo Nicolò , Carvacho Gonzalo , Chaves Rafael , Sciarrino Fabio
Published: May 2020

The launch of a satellite capable of distributing entanglement through long distances and the first loophole-free violation of Bell inequalities are milestones indicating a clear path for the establishment of quantum networks. However, nonlocality in networks with independent entanglement sources has only been experimentally verified in simple tripartite networks, via the violation of bilocality inequalities. Here, by using a scalable photonic platform, we implement star-shaped quantum networks consisting of up to five distant nodes and four independent entanglement sources. We exploit this platform to violate the chained n-locality inequality and thus witness, in a device-independent way, the emergence of nonlocal correlations among the nodes of the implemented networks. These results open new perspectives for quantum information processing applications in the relevant regime where the observed correlations are compatible with standard local hidden variable models but are non-classical if the independence of the sources is taken into account.
Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination
Authors: Kelliher Jessica L. , West Kirk L. , Gong Qingguo , Leung Justin W. C.
Published: May 2020

Histone ubiquitination plays an important role in the DNA damage response (DDR) pathway. RNF168 catalyzes H2A and H2AX ubiquitination on lysine 13/15 (K13/K15) upon DNA damage and promotes the accrual of downstream repair factors at damaged chromatin. Here, we report that RNF168 ubiquitinates the non-canonical H2A variants H2AZ and macroH2A1/2 at the divergent N-terminal tail lysine residue. In addition to their evolutionarily conserved nucleosome acidic patch, we identify the positively charged alpha1-extension helix as essential for RNF168-mediated ubiquitination of H2A variants. Moreover, mutation of the RNF168 UMI (UIM- and MIU-related UBD) hydrophilic acidic residues abolishes RNF168-mediated ubiquitination as well as 53BP1 and BRCA1 ionizing radiation-induced foci formation. Our results reveal a juxtaposed bipartite electrostatic interaction utilized by the nucleosome to direct RNF168 orientation towards the target lysine residues in proximity to the H2A alpha1-extension helix, which plays an important role in the DDR pathway.
Structural basis for assembly and function of a diatom photosystem I-light-harvesting supercomplex
Authors: Nagao Ryo , Kato Koji , Ifuku Kentaro , Suzuki Takehiro , Kumazawa Minoru , Uchiyama Ikuo , Kashino Yasuhiro , Dohmae Naoshi , Akimoto Seiji , Shen Jian-Ren , Miyazaki Naoyuki , Akita Fusamichi
Published: May 2020

Photosynthetic light-harvesting complexes (LHCs) play a pivotal role in collecting solar energy for photochemical reactions in photosynthesis. One of the major LHCs are fucoxanthin chlorophyll a/c-binding proteins (FCPs) present in diatoms, a group of organisms having important contribution to the global carbon cycle. Here, we report a 2.40-Å resolution structure of the diatom photosystem I (PSI)-FCPI supercomplex by cryo-electron microscopy. The supercomplex is composed of 16 different FCPI subunits surrounding a monomeric PSI core. Each FCPI subunit showed different protein structures with different pigment contents and binding sites, and they form a complicated pigment–protein network together with the PSI core to harvest and transfer the light energy efficiently. In addition, two unique, previously unidentified subunits were found in the PSI core. The structure provides numerous insights into not only the light-harvesting strategy in diatom PSI-FCPI but also evolutionary dynamics of light harvesters among oxyphototrophs.
Direct observation of dual-step twinning nucleation in hexagonal close-packed crystals
Authors: He Yang , Li Bin , Wang Chongmin , Mao Scott X.
Published: May 2020

Design and processing of advanced lightweight structural alloys based on magnesium and titanium rely critically on a control over twinning that remains elusive to date and is dependent on an explicit understanding on the twinning nucleation mechanism in hexagonal close-packed (HCP) crystals. Here, by using in-situ high resolution transmission electron microscopy, we directly show a dual-step twinning nucleation mechanism in HCP rhenium nanocrystals. We find that nucleation of the predominant {1 0 −1 2} twinning is initiated by disconnections on the Prismatic│Basal interfaces which establish the lattice correspondence of the twin with a minor deviation from the ideal orientation. Subsequently, the minor deviation is corrected by the formation of coherent twin boundaries through rearrangement of the disconnections on the Prismatic│Basal interface; thereafter, the coherent twin boundaries propagate by twinning dislocations. The findings provide high-resolution direct evidence of the twinning nucleation mechanism in HCP crystals.
Author Correction: The Genome Sequences of 90 Mushrooms
Authors: Li Huiying , Wu Surui , Ma Xiao , Chen Wei , Zhang Jing , Duan Shengchang , Gao Yun , Kui Ling , Huang Wenli , Wu Peng , Shi Ruoyu , Li Yifan , Wang Yuanzhong , Li Jieqing , Guo Xiang , Luo Xiaoli , Li Qiang , Xiong Chuan , Liu Honggao , Gui Mingying , Sheng Jun , Dong Yang
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Stepwise PathNet: a layer-by-layer knowledge-selection-based transfer learning algorithm
Authors: Imai Shunsuke , Kawai Shin , Nobuhara Hajime
Published: May 2020

Some neural network can be trained by transfer learning, which uses a pre-trained neural network as the source task, for a small target task’s dataset. The performance of the transfer learning depends on the knowledge (i.e., layers) selected from the pre-trained network. At present, this knowledge is usually chosen by humans. The transfer learning method PathNet automatically selects pre-trained modules or adjustable modules in a modular neural network. However, PathNet requires modular neural networks as the pre-trained networks, therefore non-modular pre-trained neural networks are currently unavailable. Consequently, PathNet limits the versatility of the network structure. To address this limitation, we propose Stepwise PathNet, which regards the layers of a non-modular pre-trained neural network as the module in PathNet and selects the layers automatically through training. In an experimental validation of transfer learning from InceptionV3 pre-trained on the ImageNet dataset to networks trained on three other datasets (CIFAR-100, SVHN and Food-101), Stepwise PathNet was up to 8% and 10% more accurate than finely tuned and from-scratch approaches, respectively. Also, some of the selected layers were not supported by the layer functions assumed in PathNet.
Ikaite nucleation at 35 °C challenges the use of glendonite as a paleotemperature indicator
Authors: Tollefsen Elin , Balic-Zunic Tonci , Mörth Carl-Magnus , Brüchert Volker , Lee Cheng Choo , Skelton Alasdair
Published: May 2020

Glendonites have been found worldwide in marine sediments from the Neoproterozoic Era to the Quaternary Period. The precursor of glendonite, ikaite (CaCO3 · 6H2O), is metastable and has only been observed in nature at temperatures <7 °C. Therefore, glendonites in the sedimentary record are commonly used as paleotemperature indicators. However, several laboratory experiments have shown that the mineral can nucleate at temperatures>7 °C. Here we investigate the nucleation range for ikaite as a function of temperature and pH. We found that ikaite precipitated at temperatures of at least 35 °C at pH 9.3 −10.3 from a mixture of natural seawater and sodium carbonate rich solution. At pH 9.3, we observed pseudomorphic replacement of ikaite by porous calcite during the duration of the experiment (c. 5 hours). These results imply that ikaite can form at relatively high temperatures but will then be rapidly replaced by a calcite pseudomorph. This finding challenges the use of glendonites as paleotemperature indicators.
Surgery for Radiologically Normal-Appearing Temporal Lobe Epilepsy in a Centre with Limited Resources
Authors: Arifin Muhamad Thohar , Bakhtiar Yuriz , Andar Erie B. P. S. , Kurnia B. Happy , Priambada Dody , Risdianto Ajid , Kusnarto Gunadi , Tsaniadi Krisna , Bunyamin Jacob , Hanaya Ryosuke , Arita Kazunori , Bintoro Aris Catur , Iida Koji , Kurisu Kaoru , Askoro Rofat , Briliantika Surya P. , Muttaqin Zainal
Published: May 2020

Approximately 26–30% of temporal lobe epilepsy (TLE) cases display a normal-appearing magnetic resonance image (MRI) leading to difficulty in determining the epileptogenic focus. This causes challenges in surgical management, especially in countries with limited resources. The medical records of 154 patients with normal-appearing MRI TLE who underwent epilepsy surgery between July 1999 and July 2019 in our epilepsy centre in Indonesia were examined. The primary outcome was the Engel classification of seizures. Anterior temporal lobectomy was performed in 85.1% of the 154 patients, followed by selective amygdalo-hippocampectomy and resection surgery. Of 82 patients (53.2%), Engel Class I result was reported in 69.5% and Class II in 25.6%. The median seizure-free period was 13 (95% CI,12.550–13.450) years, while the seizure-free rate at 5 and 12 years follow-up was 96.3% and 69.0%, respectively. Patients with a sensory aura had better seizure-free outcome 15 (11.575–18.425) years. Anterior temporal lobectomy and selective amygdala-hippocampectomy gave the same favourable outcome. Despite the challenges of surgical procedures for normal MRI TLE, our outcome has been favourable. This study suggests that epilepsy surgery in normal MRI TLE can be performed in centres with limited resources.
Odor Mixtures in Identification Testing Using Sniffin’ Sticks: The SSomix Test
Authors: Liu David Tianxiang , Besser Gerold , Lang Miriam , Sharma Gunjan , Pablik Eleonore , Renner Bertold , Mueller Christian Albert
Published: May 2020

Clinical tests assessing olfactory performance have become indispensable for diagnosing olfactory dysfunction. As time and personnel resources are limited, it would be advantageous to have shorter protocols focusing on singular aspects of olfactory performance, such as odor identification. However, such a unidimensional approach is often inconclusive and needs further tests (and tools). Hence, new testing methods with high levels of sensitivity, specificity, and reproducibility are required for clinical practice. Here, we developed a Sniffin’ Sticks odor mixture identification test method (SSomix), with emphasis on resource efficiency and simplicity of administration. SSomix consists of mixtures of two and three odors applied onto a piece of paper using 11 out of 16 items from the original Sniffin’ Sticks identification test kit. A total of 66 healthy subjects and 22 patients with olfactory dysfunction were included in the study. SSomix showed good to excellent test-retest reliability and validity. The area under the receiver operating characteristics curves indicated good diagnostic accuracy in identifying patients with reduced and severely impaired olfactory function. SSomix was a suitable downsizing of the original kit, especially regarding resource efficiency.