bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic role of nutritional status in elderly patients hospitalized for COVID-19: a monocentric study
Authors: Recinella Guerino , Marasco Giovanni , Serafini Giovanni , Maestri Lorenzo , Bianchi Giampaolo , Forti Paola , Zoli Marco
Published: October 2020

Background

Symptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection incidence is higher in the elderly patients. Pre-existing geriatric conditions such as comorbidity and frailty seem related to worse hospital outcomes.

Aims

To assess the role of nutritional status as an independent prognostic factor for in-hospital death in elderly patients.

Methods

Consecutive elderly patients (age > 65 years) hospitalized for novel coronavirus disease (COVID-19) were enrolled. Demographics, laboratory and comorbidity data were collected. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Uni- and multivariate Cox regression analyses to evaluate predictors for in-hospital death were performed.

Results

One hundred and nine hospitalized elderly patients (54 male) were consecutively enrolled. At univariate analysis, age (HR 1.045 [CI 1.008–1.082]), cognitive impairment (HR 1.949 [CI 1.045–3.364]), C-reactive protein (HR 1.004 [CI 1.011–1.078]), lactate dehydrogenases (HR 1.003 [CI 1.001–1.004]) and GNRI moderate–severe risk category (HR 8.571 [CI 1.096–67.031]) were risk factors for in-hospital death, while albumin (HR 0.809 [CI 0.822–0.964]), PaO2/FiO2 ratio (HR 0.996 [CI 0.993–0.999]) and body mass index (HR 0.875 [CI 0.782–0.979]) were protective factors. Kaplan–Meier survival curves showed a significative higher survival in patients without GNRI moderate or severe risk category (p = 0.0013).

At multivariate analysis, PaO2/FiO2 ratio (HR 0.993 [CI 0.987–0.999], p = 0.046) and GNRI moderate–severe risk category (HR 9.285 [1.183–72.879], p = 0.034) were independently associated with in-hospital death.

Conclusion

Nutritional status assessed by GNRI is a significative predictor of survival in elderly patients hospitalized for COVID-19. The association between GNRI and PaO2/FiO2 ratio is a good prognostic model these patients.
Endodontic retreatment of curved root canals using the dual wavelength erbium, chromium:yttrium, scandium, gallium, garnet, and diode 940-nm lasers and the XP-Endoshaper/finisher technique
Authors: Nasher Riman , Hilgers Ralf-Dieter , Gutknecht Norbert
Published: October 2020

Purpose

The aim of this quantitative study was to compare between a dual-wavelength laser (Er,Cr:YSGG, diode 940 nm) to the XP-Endoshaper/finisher combined with ethylenediaminetetraacetic acid (EDTA) 17% technique in removing secondary smear layer created during endodontic retreatment of curved canals.

Methods

Twenty-four human curved root canals were endodontically prepared and filled with AH-sealer and Reciproc® Gutta percha cones. The fillings were removed after 6 weeks, and the samples were randomly divided into 3 groups: A, negative control: irrigated with distilled water; B, XP-Endoshaper/finisher with EDTA 17%; and C Er,Cr:YSGG (2 W, 20 Hz, 50 μs) and diode 940 nm (2 W, 50% duty cycle). The canals were split longitudinally, and a laser scanning microscope (VK-X100K, VK-X200K, Keyence, Osaka, Japan) was used to capture images with the magnification of × 1000 from the canals. The images were scored by three blinded dentists using the Hülsmann scoring system, and a statistical analysis was carried out.

Results

A significant difference between the apical regions of groups B and C (p = 0.0010) was observed, with group C showing a cleaner apical region. However, this difference is cancelled out when comparing all areas of the canals (t = 1.43, df 21 p = 0.1663).

Conclusion

Within the limitations of this study, it can be concluded that a dual laser wavelength protocol (Er,Cr:YSGG (2 W, 20 Hz, 50 μs) and diode 940 nm (2 W, 50% duty cycle) may be positive in removing the secondary smear layer formed during endodontic retreatment cases of curved root canals.
Rules and Practices of International Investment Law and Arbitration
Authors: Radi Yannick
Published: October 2020

International investment law and arbitration is its own 'galaxy', made up of thousands of treaties to be read in relation to hundreds of awards. It is also diverse, as treaty and arbitration practices display nuances and differences on a number of issues. While it has been expanding over the past few decades in quantitative terms, this galaxy is now developing new traits as a reaction to the criticisms formulated across civil society in relation to the protection of public interest. This textbook enables readers to master and make sense of this galaxy in motion. It offers an up-to-date, comprehensive and detailed analysis of the rules and practices which form international investment law and arbitration, covering its substantive, institutional and procedural aspects. Using analytical and practice-oriented approaches, it provides analyses accessible to readers discovering this field anew, while it offers a wealth of in-depth studies to those who are already familiar with it.
Refugees, Evacuees, and Repatriates: Biafran Children, UNHCR, and the Politics of International Humanitarianism in the Nigerian Civil War
Authors: Ibhawoh Bonny
Published: October 2020

The Nigeria-Biafra war contributed to the rise of post-colonial moral interventionism, ushering in a new form of human rights politics. During the war, relief agencies evacuated 4,000 children from the conflict zones to Gabon and Côte d’Ivoire to protect them from the conflict. This was part of a broader international humanitarian airlift operation that brought relief supplies to the besieged Biafra territory. At the end of the war, most of the children were returned to their homes in Nigeria through an international humanitarian repatriation effort. Ibhawoh examines how state interests and the politics of international humanitarian interventionism manifested in debates about classifying and protecting displaced children, the most vulnerable victims of the conflict.
“To give light where He made all dark”: Educating the Blind about the Natural World and God in Nineteenth-Century North America
Authors: Pearce Joanna L.
Published: October 2020

Nineteenth-century educators worried that blind children were particularly susceptible to moral apathy, religious decay, and atheism because they could not see the beauty of nature. These educators used instruction in biology, zoology, and natural history to teach blind children about the beauty of the natural world and the breadth of God's creation. Instruction techniques included innovative but expensive apparatuses and tactile models. Despite cost challenges, educators of the blind devoted time and ingenuity to expand the science curriculum, particularly nature study programs, to help their students become successful, productive, and pious citizens equal to their sighted peers. Teaching blind students about nature ensured the blind would not become burdens on society but could be brought into the proper, civilized, religious sphere of the sighted.
w-Stackingw-projection hybrid algorithm for wide-field interferometric imaging: implementation details and improvements
Authors: Pratley Luke , Johnston-Hollitt Melanie , McEwen Jason D.
Published: October 2020

We present a detailed discussion of the implementation strategies for a recently developedw-stackingw-projection hybrid algorithm used to reconstruct wide-field interferometric images. In particular, we discuss the methodology used to deploy the algorithm efficiently on a supercomputer via use of a Message Passing Interface (MPI)k-means clustering technique to achieve efficient construction and application of non-coplanar effects. Additionally, we show that the use of conjugate symmetry can increase thew-stacking efficiency, decrease the time required to construction, and applyw-projection kernels for large data sets. We then demonstrate this implementation by imaging an interferometric observation of Fornax A from the Murchison Widefield Array (MWA). We perform an exact non-coplanar wide-field correction for 126.6 million visibilities using 50 nodes of a computing cluster. Thew-projection kernel construction takes only 15 min prior to reconstruction, demonstrating that the implementation is both fast and efficient.
The effect of flaxseed on physical and mental fatigue in children and adolescents with overweight/obesity: a randomised controlled trial
Authors: Gholami Zohreh , Akhlaghi Masoumeh
Published: October 2020

Anti-inflammatory agents such as long-chain n-3 fatty acids have been recognised to improve disease-related fatigue. We hypothesised that α-linolenic acid may also benefit in reduction of fatigue in low-grade inflammation such as overweight/obesity. Seventy-two healthy children and adolescents with BMI > 25 kg/m2 were randomised to flaxseed (n 38) and puffed wheat (n 34) groups. Participants consumed isoenergetic amounts of either 20 g/d flaxseed or 25 g/d puffed wheat for 4 weeks. Fatigue, mood feelings (depression, anxiety and stress), appetite, energy intake, weight, height and waist circumference were measured. Analysis was performed based on per-protocol and intention-to-treat (ITT) approaches. Consumption of flaxseed decreased mental fatigue and caused a significant between-group difference (P < 0·001). Although no significant change in physical and total score of fatigue was observed in either group, a significant between-group difference occurred due to a more remarkable change in these parameters in the flaxseed group. General fatigue, motivation, activity and mood feelings did not change significantly between groups. Flaxseed showed less benefit than puffed wheat on anthropometric measures as it caused a smaller increase in height (0·53 (sd 0·89) v. 1·09 (sd 0·87) cm, P = 0·03) and reduction in BMI (–0·25 (sd 0·63) v. −0·67 (sd 0·56) kg/m2, P = 0·01) than puffed wheat. Appetite and waist circumference decreased in both groups, but no significant difference was observed between groups. In ITT analysis, only alteration in mental fatigue was significant. In conclusion, consumption of flaxseed may improve mental fatigue in children with overweight/obesity. However, because of smaller increase in height, it is better to hinder administration of flaxseed during periods of growth.
Prevalence and predictors of vitamin D deficiency in a nationally representative sample of Australian Aboriginal and Torres Strait Islander adults
Authors: Black Lucinda J. , Dunlop Eleanor , Lucas Robyn M. , Pearson Glenn , Farrant Brad , Shepherd Carrington C. J.
Published: October 2020

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/l) is recognised as a public health problem globally. The present study details the prevalence and predictors of vitamin D deficiency in a nationally representative sample (n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012–2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS. Survey-weighted logistic regression models were used to determine the independent predictors of vitamin D deficiency. Approximately 27 % of adult AATSIHS participants were vitamin D deficient. Vitamin D deficiency was more prevalent in remote areas (39 %) than in non-remote areas (23 %). Independent predictors of vitamin D deficiency included assessment during winter (men, adjusted OR (aOR) 5·7; 95 % CI 2·2, 14·6; women, aOR 2·2; 95 % CI 1·3, 3·8) and spring (men, aOR 3·3; 95 % CI 1·4, 7·5; women, aOR 2·6; 95 % CI 1·5, 4·5) compared with summer, and obesity (men, aOR 2·6; 95 % CI 1·2, 5·4; women, aOR 4·3; 95 % CI 2·8, 6·8) compared with healthy weight. Statistically significant associations were evident for current smokers (men only, aOR 2·0; 95 % CI 1·2, 3·4), remote-dwelling women (aOR 2·0; 95 % CI 1·4, 2·9) and university-educated women (aOR 2·4; 95 % CI 1·2, 4·8). Given the high prevalence of vitamin D deficiency in this population, strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches are needed.
Higher egg consumption associated with increased risk of diabetes in Chinese adults – China Health and Nutrition Survey
Authors: Wang Yue , Li Ming , Shi Zumin
Published: October 2020

The association between egg consumption and diabetes is inconclusive. We aimed to examine the association between long-term egg consumption and its trajectory with diabetes in Chinese adults. A total of 8545 adults aged ≥18 years old who attended the China Health and Nutrition Survey from 1991 to 2009 were included in this analysis. Egg consumption at each survey was assessed by a 3-d 24-h recall and weighed food record methods. The consumption trajectories of eggs were modelled with the latent class group approach. Diabetes was diagnosed based on fasting blood glucose in 2009. Logistic regression was used to examine the association. The mean age of the study population was 50·9 (sd 15·1) years. About 11·1 % had diabetes in 2009. Egg consumption nearly doubled in 2009 from 16 g/d in 1991. Compared with the first quartile of egg consumption (0–9·0 g/d), the adjusted OR of diabetes for the second (9·1–20·6 g/d), third (20·7–37·5 g/d) and fourth (≥37·6 g/d) quartiles were 1·29 (95 % CI 1·03, 1·62), 1·37 (95 % CI 1·09, 1·72) and 1·25 (95 % CI 1·04, 1·64), respectively (Pfor trend = 0·029). Three trajectory groups of egg consumption were identified. Compared with group 1 (30·7 %, low baseline intake and slight increase), both group 2 (62·2 %, medium baseline intake and increase) and group 3 (7·1 %, high baseline intake and decrease) were associated with an increased OR for diabetes. The results suggested that higher egg consumption was positively associated with the risk of diabetes in Chinese adults.
A predictive model for Covid-19 spread – with application to eight US states and how to end the pandemic
Authors: Khan Z. S. , Van Bussel F. , Hussain F.
Published: October 2020

A compartmental model is proposed to predict the coronavirus 2019 (Covid-19) spread. It considers: detected and undetected infected populations, social sequestration, release from sequestration, plus reinfection. This model, consisting of seven coupled equations, has eight coefficients which are evaluated by fitting data for eight US states that make up 43% of the US population. The evolution of Covid-19 is fairly similar among the states: variations in contact and undetected recovery rates remain below 5%; however, variations are larger in recovery rate, death rate, reinfection rate, sequestration adherence and release rate from sequestration. Projections based on the current situation indicate that Covid-19 will become endemic. If lockdowns had been kept in place, the number of deaths would most likely have been significantly lower in states that opened up. Additionally, we predict that decreasing contact rate by 10%, or increasing testing by approximately 15%, or doubling lockdown compliance (from the current ~15% to ~30%) will eradicate infections in Texas within a year. Extending our fits for all of the US states, we predict about 11 million total infections (including undetected), and 8 million cumulative confirmed cases by 1 November 2020.
In Between: Cultural Exchange and Competing Systems
Authors: SCHMIDT DÖRTE
Published: October 2020

After the Second World War, cultural politics has become a central medium for international relations. Owing to the particular conditions of their development, the relations between Latin America and Europe constituted an interesting case study in which the positioning of different nations in the realm of two competing political systems and the politics of memory concerning the recent war are intertwined. This article highlights five ‘moments’ in West Germany with respect to the relationship between Europe and Latin America in the field of music: the papers of the German Federal Foreign Office, the Berlin Festival week, the Darmstadt summer courses, the DAAD Berlin Artists Program, and the Horizonte Festival in Berlin. These sources invite an observation as to how – from the perspective of cultural politics – contrasting notions of the ‘international’ have tended to ‘fade out’ after the end of Cold War polarizations, leading to a more or less common acceptance of a notion of the ‘global’ as a privileged concept in contemporary cultural debates.
Ausentes presentes: Art Music from the Chilean Exile in the Anacrusa Festivals at the Goethe-Institute Santiago (1985–89)
Authors: FUGELLIE DANIELA
Published: October 2020

Created in 1984, the Anacrusa Music Association organized concerts, workshops, and festivals of contemporary music in Chile during the last years of Pinochet's military dictatorship. Crucial for these events was the collaboration with the Goethe-Institute Santiago, which enabled a space for free expression within the repressive context of the dictatorship. This article explores the circulation and reception of musical works by Chilean composers living in exile performed in the 1985, 1987, and 1989 Anacrusa festivals. The trajectories of the pieces by three main figures of the politically engaged avant-garde of the 1960s – Gustavo Becerra-Schmidt, Sergio Ortega, and Fernando García – can be seen as a transfer process that involved the goals of West German cultural diplomacy in Chile, as well as the interaction between Anacrusa organizers, Latin American colleagues, and performers who returned from exile.
Evaluation of yield of safflower (Carthamus tinctoriusL.) genotypes under semi-arid conditions
Authors: Mousavi Ojaq Seyed Mojtaba , Mozafari Hamid , Jabbari Hamid , Sani Behzad
Published: October 2020

To identify appropriate genotypes for breeding varieties suitable for semi-arid areas, yield components, as well as morphophonological traits of 127 safflower genotypes, were assessed at the Seed and Plant Improvement Institute, Iran. Cluster analysis revealed four distinct groups. The largest group (third cluster) includes 48 genotypes with characteristics such as mostly yellow-coloured flowers, mostly thorny with few thistle genotypes, relatively early-flowering, relatively high number of heads and grains per plant, highest 1000-grain weight with the highest grain yields. In contrast, the smallest group (second cluster) contains 13 genotypes with characteristics such as yellow florets, semi-dwarf, thorny, moderately late-flowering, low number of heads per plant and number of grains per head, low 1000-grain weight, and low grain yield. Principal component analysis results showed that the three components accounted for 29.5, 15.9 and 11.1% of the total variation, respectively. Graphic representation of the biplots based on the first and second principal components showed that the experimental genotypes were classified into four groups. The results also indicated that stem diameter, the number of branches, heads per plant and grains per head had the highest correlation with the first component, and grain yield, flower colour, flowering initiation and plant height had the highest correlation with the second component. These traits can be considered as an appropriate index for the selection of elite safflower genotypes for breeding varieties suited to cultivation in semi-arid conditions.
Autonomy Support, Life Satisfaction, and Quality of Life of Cancer	Patients
Authors: Kaya Cahit , Bezyak Jill , Chan Fong , Bengtson Kevin , Hsu Sharon
Published: October 2020

Abstract. Previous research shows that perceived autonomy support is significantly associated with positive health outcomes for different clinical populations. However, there is not a standardized measurement tool that assesses perceived autonomy support for the Turkish population. This study translated the Health Care Climate Questionnaire (HCCQ), a perceived autonomy support measurement tool, into Turkish and investigated the factorial structure of the questionnaire with a group of patients with cancer. This study used a convenience-sampling method with 192 people with cancer. The participants were recruited from a major cancer institute and a non-profit organization in Turkey by research partners. Volunteer participants either filled out a hard copy of a survey packet or completed the survey packet through a secured online survey tool website (i.e., https://www.surveymonkey.com ). In addition, a closed Facebook group for cancer survivors in Turkey was used to advertise the study’s link. The results indicated the participants perceived a moderate level of autonomy support. In comparison to German and US populations, perceived autonomy support was low among Turkish cancer patients. The results also indicated that the HCCQ has a two-factor measurement structure. Correlations with external variables indicated that the scores of HCCQ were significantly positively associated with life satisfaction and quality of life of cancer patients and negatively associated with cancer related symptoms (e.g., fatigue).
Associations of Police Officer Health Behaviors and Subjective Well-Being
Authors: Baker Lucas D. , Berghoff Christopher R. , Kuo Jennifer L. , Quevillon Randal P.
Published: October 2020

Abstract. Background: Law enforcement officers (LEOs) are responsible for maintaining public order and safety within communities. As a consequence of this obligation, LEOs are repeatedly exposed to a myriad of unavoidable occupational stressors, known to affect health behaviors and well-being. Importantly, LEO well-being has public safety implications as those reporting higher well-being exhibit more equitable police behavior relative to those reporting lower well-being. Aims: The present study aimed to identify factors that may be leveraged to enhance LEO well-being by investigating the indirect relation of health behaviors to well-being through psychological flexibility. Method: Path-analytic regression models were used to analyze cross-sectional data provided by LEOs recruited from three geographically dispersed police agencies ( N = 459; Male = 84.7%, White = 64.2%). Results: Results indicated psychological flexibility accounted for the relations of chronic pain and quality sleep to well-being. Regular exercise accounted for the largest proportion of well-being variance, though the indirect effect through psychological flexibility was not significant. Limitations: Inclusion of more comprehensive measures of well-being and health behaviors may further clarify the strength of relations reported herein. Conclusion: Enhancing flexible response styles may support high well-being in LEO populations who report poor sleep quality and chronic pain.
Mechanical Amorphization of Synthetic Fault Gouges During Rotary‐Shear Friction Experiments at Subseismic to Seismic Slip Velocities
Authors: Kaneki S. , Oohashi K. , Hirono T. , Noda H.
Published: October 2020

Although the effects of mechanical amorphization by fault motion on fault rocks have been investigated both in nature and experiments, the relationship between slip processes and the amount of amorphous materials produced remains unclear. We performed rotary‐shear friction experiments on synthetic quartz and kaolinite gouges at room temperature, normal stresses of 1 or 3 MPa, slip velocities of 0.001 or 1 m s−1, and displacements of 1–101 m. X‐ray diffraction and microscopic observation data revealed that mechanical amorphization in both materials was accompanied by grain‐size reduction, particle rounding, and the formation of ultrafine particles. The amount of amorphous materials produced was strongly dependent on mineralogy and total frictional work regardless of slip velocity. Therefore, mechanical amorphization can occur during both coseismic and subseismic slip. Amorphization of ~7 wt% of quartz gouge required 30.33 MJ kg−1 of frictional work, whereas for kaolinite gouge, only 0.77 MJ kg−1 was required, which is consistent with observed preferential amorphization of clay minerals in faults. For kaolinite, up to 6% of frictional work can be used for mechanical amorphization, indicating its potential importance for faulting energetics. Because some kinds of amorphous phyllosilicates release water at lower temperature than crystalline, mechanical amorphization of fault rocks may influence thermochemical pressurization. Gradual weakening of quartz gouge at 0.001 m s−1 slip velocity suggested that <4 wt% of amorphous silica can weaken a fault by amorphous silica‐related lubrication. Mechanical amorphization may accelerate pressure solution healing of faults if dissolution can occur under high porous conditions.
Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer
Authors: Morotti Matteo , Zois Christos E. , El-Ansari Rokaya , Craze Madeleine L. , Rakha Emad A. , Fan Shih-Jung , Valli Alessandro , Haider Syed , Goberdhan Deborah C. I. , Green Andrew R. , Harris Adrian L.
Published: October 2020

Background

Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.

Methods

The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.

Results

SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).

Conclusions

These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.
AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma
Authors: Yao Catherine D. , Haensel Daniel , Gaddam Sadhana , Patel Tiffany , Atwood Scott X. , Sarin Kavita Y. , Whitson Ramon J. , McKellar Siegen , Shankar Gautam , Aasi Sumaira , Rieger Kerri , Oro Anthony E.
Published: October 2020

Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies.
Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy
Authors: Woodcock D. J. , Riabchenko E. , Taavitsainen S. , Kankainen M. , Gundem G. , Brewer D. S. , Ellonen P. , Lepistö M. , Golubeva Y. A. , Warner A. C. , Tolonen T. , Jasu J. , Isaacs W. B. , Emmert-Buck M. R. , Nykter M. , Visakorpi T. , Bova G. S. , Wedge D. C.
Published: October 2020

The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease, and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. Substantial evolution occurs within the prostate, resulting in branching into multiple spatially intermixed lineages. One dominant lineage emerges that initiates and drives systemic metastasis, where polyclonal seeding between sites is common. Routes to metastasis differ between patients, and likely genetic drivers of metastasis distinguish the metastatic lineage from the lineage that remains confined to the prostate within each patient. Body fluids capture features of the dominant lineage, and subclonal expansions that occur in the metastatic phase are non-uniformly represented. Cerebrospinal fluid analysis reveals lineages not detected in blood-borne DNA, suggesting possible clinical utility.
SARS-CoV-2 exposure, symptoms and seroprevalence in healthcare workers in Sweden
Authors: Rudberg Ann-Sofie , Havervall Sebastian , Månberg Anna , Jernbom Falk August , Aguilera Katherina , Ng Henry , Gabrielsson Lena , Salomonsson Ann-Christin , Hanke Leo , Murrell Ben , McInerney Gerald , Olofsson Jennie , Andersson Eni , Hellström Cecilia , Bayati Shaghayegh , Bergström Sofia , Pin Elisa , Sjöberg Ronald , Tegel Hanna , Hedhammar My , Phillipson Mia , Nilsson Peter , Hober Sophia , Thålin Charlotte
Published: October 2020

SARS-CoV-2 may pose an occupational health risk to healthcare workers. Here, we report the seroprevalence of SARS-CoV-2 antibodies, self-reported symptoms and occupational exposure to SARS-CoV-2 among healthcare workers at a large acute care hospital in Sweden. The seroprevalence of IgG antibodies against SARS-CoV-2 was 19.1% among the 2149 healthcare workers recruited between April 14th and May 8th 2020, which was higher than the reported regional seroprevalence during the same time period. Symptoms associated with seroprevalence were anosmia (odds ratio (OR) 28.4, 95% CI 20.6–39.5) and ageusia (OR 19.2, 95% CI 14.3–26.1). Seroprevalence was also associated with patient contact (OR 2.9, 95% CI 1.9–4.5) and covid-19 patient contact (OR 3.3, 95% CI 2.2–5.3). These findings imply an occupational risk for SARS-CoV-2 infection among healthcare workers. Continued measures are warranted to assure healthcare workers safety and reduce transmission from healthcare workers to patients and to the community.
Two distinct immunopathological profiles in autopsy lungs of COVID-19
Authors: Nienhold Ronny , Ciani Yari , Koelzer Viktor H. , Tzankov Alexandar , Haslbauer Jasmin D. , Menter Thomas , Schwab Nathalie , Henkel Maurice , Frank Angela , Zsikla Veronika , Willi Niels , Kempf Werner , Hoyler Thomas , Barbareschi Mattia , Moch Holger , Tolnay Markus , Cathomas Gieri , Demichelis Francesca , Junt Tobias , Mertz Kirsten D.
Published: October 2020

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+T cells and macrophages. ISGhighpatients die significantly earlier after hospitalization than ISGlowpatients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses
Authors: Perez-Alvarez Alberto , Yin Shuting , Schulze Christian , Hammer John A. , Wagner Wolfgang , Oertner Thomas G.
Published: October 2020

In hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms a spine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but long-term depression (LTD) was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both long-term potentiation (LTP) and LTD are possible.
GABAergic motor neurons bias locomotor decision-making in C. elegans
Authors: Liu Ping , Chen Bojun , Wang Zhao-Wen
Published: October 2020

Proper threat-reward decision-making is critical to animal survival. Emerging evidence indicates that the motor system may participate in decision-making but the neural circuit and molecular bases for these functions are little known. We found in C. elegans that GABAergic motor neurons (D-MNs) bias toward the reward behavior in threat-reward decision-making by retrogradely inhibiting a pair of premotor command interneurons, AVA, that control cholinergic motor neurons in the avoidance neural circuit. This function of D-MNs is mediated by a specific ionotropic GABA receptor (UNC-49) in AVA, and depends on electrical coupling between the two AVA interneurons. Our results suggest that AVA are hub neurons where sensory inputs from threat and reward sensory modalities and motor information from D-MNs are integrated. This study demonstrates at single-neuron resolution how motor neurons may help shape threat-reward choice behaviors through interacting with other neurons.
A spinal neural circuitry for converting touch to itch sensation
Authors: Chen Sihan , Gao Xiao-Fei , Zhou Yuxi , Liu Ben-Long , Liu Xian-Yu , Zhang Yufen , Barry Devin M. , Liu Kun , Jiao Yingfu , Bardoni Rita , Yu Weifeng , Chen Zhou-Feng
Published: October 2020

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressingTachykinin 2-Cre(Tac2Cre) receive direct Aβ low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition ofTac2Creneurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch.
Titrating bacterial growth and chemical biosynthesis for efficient N-acetylglucosamine and N-acetylneuraminic acid bioproduction
Authors: Tian Rongzhen , Liu Yanfeng , Cao Yanting , Zhang Zhongjie , Li Jianghua , Liu Long , Du Guocheng , Chen Jian
Published: October 2020

Metabolic engineering facilitates chemical biosynthesis by rewiring cellular resources to produce target compounds. However, an imbalance between cell growth and bioproduction often reduces production efficiency. Genetic code expansion (GCE)-based orthogonal translation systems incorporating non-canonical amino acids (ncAAs) into proteins by reassigning non-canonical codons to ncAAs qualify for balancing cellular metabolism. Here, GCE-based cell growth and biosynthesis balance engineering (GCE-CGBBE) is developed, which is based on titrating expression of cell growth and metabolic flux determinant genes by constructing ncAA-dependent expression patterns. We demonstrate GCE-CGBBE in genome-recoded Escherichia coli Δ321AM by precisely balancing glycolysis and N-acetylglucosamine production, resulting in a 4.54-fold increase in titer. GCE-CGBBE is further expanded to non-genome-recoded Bacillus subtilis to balance growth and N-acetylneuraminic acid bioproduction by titrating essential gene expression, yielding a 2.34-fold increase in titer. Moreover, the development of ncAA-dependent essential gene expression regulation shows efficient biocontainment of engineered B. subtilis to avoid unintended proliferation in nature.
Publisher Correction: Age and life expectancy clocks based on machine learning analysis of mouse frailty
Authors: Schultz Michael B. , Kane Alice E. , Mitchell Sarah J. , MacArthur Michael R. , Warner Elisa , Vogel David S. , Mitchell James R. , Howlett Susan E. , Bonkowski Michael S. , Sinclair David A.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Straightforward preparation of supramolecular Janus nanorods by hydrogen bonding of end-functionalized polymers
Authors: Han Shuaiyuan , Pensec Sandrine , Yilmaz Dijwar , Lorthioir Cédric , Jestin Jacques , Guigner Jean-Michel , Niepceron Frédérick , Rieger Jutta , Stoffelbach François , Nicol Erwan , Colombani Olivier , Bouteiller Laurent
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Detection of genomic alterations in breast cancer with circulating tumour DNA sequencing
Authors: Kleftogiannis Dimitrios , Ho Danliang , Liew Jun Xian , Poon Polly S. Y. , Gan Anna , Ng Raymond Chee-Hui , Tan Benita Kiat-Tee , Tay Kiang Hiong , Lim Swee H. , Tan Gek San , Shih Chih Chuan , Lim Tony Kiat-Hon , Lee Ann Siew-Gek , Tan Iain Beehuat , Yap Yoon-Sim , Ng Sarah B.
Published: October 2020

Analysis of circulating cell-free DNA (cfDNA) has opened new opportunities for characterizing tumour mutational landscapes with many applications in genomic-driven oncology. We developed a customized targeted cfDNA sequencing approach for breast cancer (BC) using unique molecular identifiers (UMIs) for error correction. Our assay, spanning a 284.5 kb target region, is combined with a novel freely-licensed bioinformatics pipeline that provides detection of low-frequency variants, and reliable identification of copy number variations (CNVs) directly from plasma DNA. We first evaluated our pipeline on reference samples. Then in a cohort of 35 BC patients our approach detected actionable driver and clonal variants at low variant frequency levels in cfDNA that were concordant (77%) with sequencing of primary and/or metastatic solid tumour sites. We also detected ERRB2 gene CNVs used for HER2 subtype classification with 80% precision compared to immunohistochemistry. Further, we evaluated fragmentation profiles of cfDNA in BC and observed distinct differences compared to data from healthy individuals. Our results show that the developed assay addresses the majority of tumour associated aberrations directly from plasma DNA, and thus may be used to elucidate genomic alterations in liquid biopsy studies.
Ceritinib in Japanese patients with anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer: interim analysis results of a post-marketing surveillance study
Authors: Kaneda Hiroyasu , Kizaki Minako , Ochi Masami , Shiraiwa Naoko , Akatsu Shigemi
Published: October 2020

Ceritinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with unresectable advanced and/or recurrent ALK fusion gene-positive non-small cell lung cancer (NSCLC). As per the approval condition in Japan, this post-marketing surveillance (PMS) study evaluated the clinical safety (including adverse events [AEs], adverse drug reactions [ADRs] and priority investigation items) and efficacy (including ORR and PFS) of ceritinib in Japanese patients. Interim analysis was conducted ~ 2 years after the start of this non-interventional, multicentre, uncontrolled, open-label, special drug-use investigation and results are reported from March 28, 2016 to April 28, 2018. Each patient was followed up for 1 year. Most patients started treatment with 750 mg ceritinib. Safety profile was similar to that observed at the time of approval. No new AEs or ADRs with incidences higher than that at approval were identified. The rate of gastrointestinal ADRs (nausea, vomiting and diarrhoea) was 73.64%. Meaningful efficacy was observed in both post-crizotinib and post-alectinib settings, with ORR of 29.55% (95% CI 20.29–40.22) and disease control rate of 53.41% (95% CI 42.46–64.12). No concerns regarding the safety and efficacy of ceritinib were identified. No new measures, including modification of the PMS study protocol, are considered necessary.
Author Correction: Perceived match between own and observed models’ bodies: influence of face, viewpoints, and body size
Authors: De Coster Lize , Sánchez-Herrero Pablo , Aliaga Carlos , Otaduy Miguel A. , López-Moreno Jorge , Tajadura-Jiménez Ana
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Beaver dam capacity of Canada’s boreal plain in response to environmental change
Authors: Stoll Nichole-Lynn , Westbrook Cherie J.
Published: October 2020

Environmental changes are altering the water cycle of Canada’s boreal plain. Beaver dams are well known for increasing water storage and slowing flow through stream networks. For these reasons beavers are increasingly being included in climate change adaptation strategies. But, little work focuses on how environmental changes will affect dam building capacity along stream networks. Here we estimate the capacity of the stream network in Riding Mountain National Park, Manitoba, Canada to support beaver dams under changing environmental conditions using a modelling approach. We show that at capacity, the park’s stream network can support 24,690 beaver dams and hold between 8.2 and 12.8 million m3 of water in beaver ponds. Between 1991 and 2016 the park’s vegetation composition shifted to less preferred beaver forage, which led to a 13% decrease in maximum dam capacity. We also found that dam capacity is sensitive to the size of regularly-occurring floods—doubling the 2-year flood reduces the park’s dam capacity by 21%. The results show that the potential for beaver to offset some expected climatic-induced changes to the boreal water cycle is more complex than previously thought, as there is a feedback wherein dam capacity can be reduced by changing environmental conditions.
Author Correction: Potential role of compost mixed biochar with rhizobacteria in mitigating lead toxicity in spinach
Authors: Zafar-ul-Hye Muhammad , Tahzeeb-ul-Hassan Muhammad , Abid Muhammad , Fahad Shah , Brtnicky Martin , Dokulilova Tereza , Datta Rahul , Danish Subhan
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Cooperative rescue of a juvenile capuchin (Cebus imitator) from a Boa constrictor
Authors: Jack Katharine M. , Brown Michaela R. , Buehler Margaret S. , Cheves Hernadez Saul , Ferrero Marín Nuria , Kulick Nelle K. , Lieber Sophie E.
Published: October 2020

The threat of predation by snakes is considered to have played a significant role in the evolution of primate sensory systems and behavior. However, we know relatively little about individual and group responses given the rarity of observed predation events. Here we report an observed (filmed) predation attempt by an adult Boa constrictor (~ 2 m) on a juvenile white-faced capuchin (Cebus imitator) in the Sector Santa Rosa of the Área de Conservación Guanacaste, Costa Rica. The snake caught the juvenile monkey on the ground during a terrestrial play session. When the victim screamed, the alpha male, alpha female, and another adult female ran to the scene, physically attacked the snake (with bites and hits), and pulled the victim to safety. Most group members participated in the vocal mobbing of the snake both during and after the attack. Based on the outcomes of this predation attempt and published reports of other B. constrictor attacks on primates, the coordinated efforts of ≥ 2 group members is needed for a successful rescue. This observation adds to our growing knowledge of cooperative group behavior and its importance in predator defense.
Author Correction: GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs
Authors: Gao Bo , Huang Qiang , Jie Qiang , Lu Wei-Guang , Wang Long , Li Xiao-Jie , Sun Zhen , Hu Ya-Qian , Chen Li , Liu Bao-Hua , Liu Jian , Yang Liu , Luo Zhuo-Jing
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: A new treatment strategy for end-stage hepatic alveolar echinococcosis: IVC resection without reconstruction
Authors: Du Qiancheng , Wang Yanyan , Zhang Mengzhao , Chen Yichong , Mei Xuepeng , Li Yanfei , Zhou Ying , Fan Haining
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
High fidelity defines the temporal consistency of host-parasite interactions in a tropical coastal ecosystem
Authors: Lopes V. L. , Costa F. V. , Rodrigues R. A. , Braga É. M. , Pichorim M. , Moreira P. A.
Published: October 2020

Host-parasite interactions represent a selective force that may reduce hosts’ lifespan, their reproductive success and survival. Environmental conditions can affect host-parasite communities, leading to distinct patterns of interactions with divergent ecological and evolutionary consequences for their persistence. Here, we tested whether climatic oscillation shapes the temporal dynamics of bird-haemosporidian associations, assessing the main mechanisms involved in the temporal dissimilarity of their interactions’ networks. For two years, we monthly sampled birds in a tropical coastal ecosystem to avian malaria molecular diagnosis. The studied networks exhibited high specialization, medium modularity, with low niche overlap among parasites lineages. Moreover, alpha and β-diversity of hosts, parasites and their interactions, as well as the structure of their networks were temporally consistent, i.e., stable under fluctuations in temperature or precipitation over seasons. The structure and temporal consistency of the studied antagonistic networks suggest a high fidelity between partners, which is likely relevant for their evolutionary persistence.