bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing the oligomeric re-assembling of bacterial fimbriae in vitro: a small-angle X-ray scattering and analytical ultracentrifugation study
Authors: Solovyova Alexandra S. , Peters Daniel T. , Dura Gema , Waller Helen , Lakey Jeremy H. , Fulton David A. 
Published: May 2021

AbstractCapsular antigen fragment 1 (Caf1) is an oligomeric protein consisting of 15 kDa monomeric subunits that are non-covalently linked through exceptionally strong and kinetically inert interactions into a linear polymer chain. It has been shown that after its thermal depolymerisation into unfolded monomeric subunits, Caf1 is able to efficiently repolymerise in vitro to reform its polymeric structure. However, little is known about the nature of the repolymerisation process. An improved understanding of this process will lead to the development of methods to better control the lengths of the repolymerised species, and ultimately, to better design of the properties of Caf1-based materials. Here we utilize small-angle X-ray scattering to estimate the size of Caf1 polymers during the first 24 h of the re-polymerisation process. Analytical ultracentrifugation measurements were also used to investigate the process post-24 h, where the rate of repolymerisation becomes considerably slower. Results show that in vitro polymerisation proceeds in a linear manner with no evidence observed for the formation of a lateral polymer network or uncontrolled aggregates. The rate of Caf1 in vitro repolymerisation was found to be concentration-dependent. Importantly, the rate of polymer growth was found to be relatively fast over the first few hours, before continuing at a dramatically slower rate. This observation is not consistent with the previously proposed step-growth mechanism of in vitro polymerisation of Caf1, where a linear increase in polymer length would be expected with time. We speculate how our observations may support the idea that the polymerisation process may be occurring at the ends of the chains with monomers adding sequentially. Our findings will contribute towards the development of new biomaterials for 3D cell culture and bio-printing.
Admission blood glucose level and outcome in patients requiring venoarterial extracorporeal membrane oxygenation
Authors: Bemtgen Xavier , Rilinger Jonathan , Jäckel Markus , Zotzmann Viviane , Supady Alexander , Benk Christoph , Bode Christoph , Wengenmayer Tobias , Lother Achim , Staudacher Dawid L. 
Published: May 2021

Abstract
Background
Patients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO.

Methods
We conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80–140 mg/dl), to mild (141-240 mg/dl), moderate (241–400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups.

Results
392 patients met inclusion criteria. Median age was 62 years (51.5–70.0), SAPS II at admission was 54 (43.5–63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups.

Conclusion
Arterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies.

Graphical Abstract
Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland
Authors: Zirpel Johanna J. , Pfister Isabel B. , Gerhardt Christin , Garweg Justus G. 
Published: May 2021

Abstract
Objective
To assess the long-term visual outcomes in eyes with symptomatic diabetic macular oedema (DME) under intravitreal treatment (IVT) in a clinical routine setting.

Methods
Patients with newly diagnosed DME were included in this retrospective study if they had received at least three IVTs and a follow-up period ≥ 2 years. Due to altered treatment patterns since the approval of ranibizumab for DME in 2012, patients were subdivided according to their first IVT before 2013 (group 1) or thereafter (group 2). The primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time.

Results
Of 217 eyes (191 patients) with DME, 151 eyes (117 patients) fulfilled the inclusion criteria (63 eyes in the first period, 88 in the second period). Mean follow-up time was 7.9 ± 3.1 (group 1) and 4.1 ± 1.4 years (group 2; p < 0.001). Visual gains were similar in the first year (group 1: + 5.3 ± 15.5, group 2: + 7.3 ± 12.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; p = 0.44), but not thereafter (after 2 years in group 1: + 4.4 ± 15.0, group 2: + 8.3 ± 13.0 ETDRS letters; p = 0.038). During the first year, group 1 patients received less clinical examinations (group 1: 6.6 ± 3.3, group 2: 7.5 ± 2.1; p = 0.007) and less injections (group 1: 3.6 ± 2.7, group 2: 6.1 ± 2.7; p < 0.001).

Conclusion
A greater visual gain, in response to more intensive treatment during the first year, was maintained for at least 5 years in group 2 subjects. Our data confirm that in a real-world setting, early intensive treatment results in satisfying long-term visual outcomes.
Apoptosis-mediated anticancer activity in prostate cancer cells of a chestnut honey (Castanea sativa L.) quinoline–pyrrolidine gamma-lactam alkaloid
Authors: Beretta Giangiacomo , Moretti Roberta Manuela , Nasti Rita , Cincinelli Raffaella , Dallavalle Sabrina , Montagnani Marelli Marina 
Published: May 2021

AbstractProstate cancer (PCa) is the most common malignancy in men and represents the second leading cause of cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived endogenous metabolite kynurenic acid (KYNA) and of the lactam form of 3–2′-pyrrilonidinyl-kynurenic acid (3-PKA-L), alkaloids usually present in combination in chestnut honey. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell colony formation assay, and Western blot analysis of the major mediator proteins involved in apoptotic processes. In all experiments, KYNA was scarcely or not active while 3-PKA-L showed anticancer activity in the high concentration range (0.01 mM – 1 mM) from 24 to 72 h. The results obtained showed that cell death was induced by extrinsic apoptotic pathway, by cell morphological changes and reduction of cell colonies number. These novel results represent the first promising step to the accurate description of 3-PKA-L cytotoxic effect, not observed with KYNA, paving the way to the search of new anticancer agents, as well as to the better understanding of the physiopathological role of this interesting natural product.
Anxiety, depression, and worries in advanced Parkinson disease during COVID-19 pandemic
Authors: Montanaro Elisa , Artusi Carlo Alberto , Rosano Cristina , Boschetto Carlotta , Imbalzano Gabriele , Romagnolo Alberto , Bozzali Marco , Rizzone Mario Giorgio , Zibetti Maurizio , Lopiano Leonardo 
Published: May 2021

Abstract
Background
The psychological impact of the COVID-19 outbreak and lockdown on frail populations with advanced Parkinson disease (APD) and their caregivers may present with peculiar features and require specific interventions.

Methods
We enrolled here 100 APD patients and 60 caregivers. Seventy-four patients were treated with device-aided therapies (DAT) and 26 with standard medical treatment (SMT). Through a telephonic interview, subjects underwent the Hospital Anxiety and Depression Scale (HADS-A; HADS-D), and an ad hoc questionnaire to explore thoughts and emotions related to the pandemic.

Results
Depression was observed in 35% of APD patients and anxiety in 39%, with a significant reduction of the latter after the lockdown (p= 0.023). We found a significant correlation between the type of therapy and the HADS-A score (p= 0.004). Patients’ main worries were as follows: a possible higher risk of COVID-19 infection (25%), interruption of non-pharmacological treatments (35%), interruption of outpatient clinics (38%), PD complications related to COVID-19 (47%). Patients treated with DAT manifested worries about device-related issues and risk for caregivers’ infection. The 40% of caregivers showed anxiety, while the 21.7% of them showed depression.

Conclusion
Our study reveals a higher prevalence of anxiety and the presence of peculiar worries and needs in APD patients during the pandemic alongside psychological sequelae of their caregivers. These findings are important for neurologists and healthcare services to foster strategies for the management of psychological distress in both patients and caregivers.
Automatic classification of landslide kinematics using acoustic emission measurements and machine learning
Authors: Deng Lizheng , Smith Alister , Dixon Neil , Yuan Hongyong 
Published: May 2021

AbstractFounded on understanding of a slope’s likely failure mechanism, an early warning system for instability should alert users of accelerating slope deformation behaviour to enable safety-critical decisions to be made. Acoustic emission (AE) monitoring of active waveguides (i.e. a steel tube with granular internal/external backfill installed through a slope) is becoming an accepted monitoring technology for soil slope stability applications; however, challenges still exist to develop widely applicable AE interpretation strategies. The objective of this study was to develop and demonstrate the use of machine learning (ML) approaches to automatically classify landslide kinematics using AE measurements, based on the standard landslide velocity scale. Datasets from large-scale slope failure simulation experiments were used to train and test the ML models. In addition, an example field application using data from a reactivated landslide at Hollin Hill, North Yorkshire, UK, is presented. The results show that ML can automatically classify landslide kinematics using AE measurements with the accuracy of more than 90%. The combination of two AE features, AE rate and AE rate gradient, enable both velocity and acceleration classifications. A conceptual framework is presented for how this automatic approach would be used for landslide early warning in the field, with considerations given to potentially limited site-specific training data.
Community structure of environmental microorganisms associated with COVID-19 affected patients
Authors: Zhang Weihua , Mo Guoxin , Yang Jie , Hu Xingshuo , Huang Hujie , Zhu Jing , Zhang Pei , Xia Han , Xie Lixin 
Published: May 2021

AbstractTo clarify the characteristics and distribution of hospital environmental microbiome associated with confirmed COVID-19 patients. Environmental samples with varying degrees of contamination which were associated with confirmed COVID-19 patients were collected, including 13 aerosol samples collected near eight patients in different wards, five swabs from one patient’s skin and his personal belongings, and two swabs from the surface of positive pressure respiratory protective hood and the face shield from a physician who had close contact with one patient. Metagenomic next-generation sequencing (mNGS) was used to analyze the composition of the microbiome. One of the aerosol samples (near patient 4) was detected positive for COVID-19, and others were all negative. The environmental samples collected in different wards possessed protean compositions and community structures, the dominant genera including Pseudomonas, Corynebacterium, Neisseria, Staphylococcus, Acinetobacter, and Cutibacterium. Top 10 of genera accounted for more than 76.72%. Genera abundance and proportion of human microbes and pathogens radiated outward from the patient, while the percentage of environmental microbes increased. The abundance of the pathogenic microorganism of medical supplies is significantly higher than other surface samples. The microbial compositions of the aerosol collected samples nearby the patients were mostly similar to those from the surfaces of the patient's skin and personal belongings, but the abundance varied greatly. The positive rate of COVID-19 RNA detected from aerosol around patients in general wards was quite low. The ward environment was predominantly inhabited by species closely related to admitted patients. The spread of hospital microorganisms via aerosol was influenced by the patients’ activity.
A case study of a conservation flagship species: the monarch butterfly
Authors: Preston Stephanie D. , Liao Julia D. , Toombs Theodore P. , Romero-Canyas Rainer , Speiser Julia , Seifert Colleen M. 
Published: May 2021

AbstractWhat makes a flagship species effective in engaging conservation donors? Large, charismatic mammals are typically selected as ambassadors, but a few studies suggest butterflies—and monarchs in particular—may be even more appealing. To gather more information about people’s responses to monarchs, we conducted an empirical study of member submissions to a successful conservation campaign, the Monarch Story Campaign, conducted by the Environmental Defense Fund (EDF). The set of 691 stories along with their associated demographic and donation data was analyzed in a mixed-methods study using qualitative analysis and tests of association. The results showed that people often described encounters with monarchs in childhood and as adults. They expressed strong, positive emotions, and lauded the monarch’s beauty and other “awe-inspiring” qualities and expressed wonder at their lifecycle (i.e., metamorphosis and migration). They also raised conservation themes of distress at monarch loss, calls for action, and caretaking, such as being “fragile” and “in need.” Sharing personal encounters was associated with current efforts to save the species and more past financial donations, while a second pattern tied more donations to awe at the monarch’s mass migration. These results imply that conservation campaigns built around species people encounter may build lifelong awareness, concern, and actions towards conservation.
Pathologic response of ductal carcinoma in situ to neoadjuvant systemic treatment in HER2-positive breast cancer
Authors: Groen Emma J. , van der Noordaa Marieke E. M. , Schaapveld Michael , Sonke Gabe S. , Mann Ritse M. , van Ramshorst Mette S. , Lips Esther H. , Vrancken Peeters Marie-Jeanne T. F. D. , van Duijnhoven Frederieke H. , Wesseling Jelle 
Published: May 2021

Abstract
Purpose
The presence of extensive ductal carcinoma in situ (DCIS) adjacent to HER2-positive invasive breast cancer (IBC) is often a contra-indication for breast-conserving surgery, even in case of excellent treatment response of the invasive component. Data on the response of DCIS to neoadjuvant systemic treatment (NST) are limited. Therefore, we estimated the response of adjacent DCIS to NST-containing HER2-blockade in HER2-positive breast cancer patients and assessed the association of clinicopathological and radiological factors with response.

Methods
Pre-NST biopsies were examined to determine presence of DCIS in all women with HER2-positive IBC treated with trastuzumab-containing NST ± pertuzumab between 2004 and 2017 in a comprehensive cancer center. When present, multiple DCIS factors, including grade, calcifications, necrosis, hormone receptor, and Ki-67 expression, were scored. Associations of clinicopathological and radiological factors with complete response were assessed using logistic regression models.

Results
Adjacent DCIS, observed in 138/316 patients with HER2-positive IBC, was eradicated after NST in 46% of patients. Absence of calcifications suspicious for malignancy on pre-NST mammography (odds ratio (OR) 3.75; 95% confidence interval (95% CI) 1.72–8.17), treatment with dual HER2-blockade (OR 2.36; 95% CI 1.17–4.75), a (near) complete response on MRI (OR 3.55; 95% CI 1.31–9.64), and absence of calcifications (OR 3.19; 95% CI 1.34–7.60) and Ki-67 > 20% in DCIS (OR 2.74; 95% CI 1.09–6.89) on pre-NST biopsy were significantly associated with DCIS response.

Conclusions
As DCIS can respond to NST containing HER2-blockade, the presence of extensive DCIS in HER2-positive breast cancer before NST should not always indicate a mastectomy. The predictive factors we found could be helpful when considering breast-conserving surgery in these patients.
Evaluating process-based integrated assessment models of climate change mitigation
Authors: Wilson Charlie , Guivarch Céline , Kriegler Elmar , van Ruijven Bas , van Vuuren Detlef P. , Krey Volker , Schwanitz Valeria Jana , Thompson Erica L. 
Published: May 2021

AbstractProcess-based integrated assessment models (IAMs) project long-term transformation pathways in energy and land-use systems under what-if assumptions. IAM evaluation is necessary to improve the models’ usefulness as scientific tools applicable in the complex and contested domain of climate change mitigation. We contribute the first comprehensive synthesis of process-based IAM evaluation research, drawing on a wide range of examples across six different evaluation methods including historical simulations, stylised facts, and model diagnostics. For each evaluation method, we identify progress and milestones to date, and draw out lessons learnt as well as challenges remaining. We find that each evaluation method has distinctive strengths, as well as constraints on its application. We use these insights to propose a systematic evaluation framework combining multiple methods to establish the appropriateness, interpretability, credibility, and relevance of process-based IAMs as useful scientific tools for informing climate policy. We also set out a programme of evaluation research to be mainstreamed both within and outside the IAM community.
Assessing genetic diversity and connectivity in a tule elk (Cervus canadensis nannodes) metapopulation in Northern California
Authors: Batter Thomas J. , Bush Joshua P. , Sacks Benjamin N. 
Published: May 2021

AbstractThe tule elk (Cervus canadensis nannodes) is a California endemic subspecies that experienced an extreme bottleneck (potentially two individuals) in the mid-1800s. Through active management, including reintroductions, the subspecies has grown to approximately 6000 individuals spread across 22 recognized populations. The populations tend to be localized and separated by unoccupied intervening habitat, prompting targeted translocations to ensure gene flow. However, little is known about the genetic status or connectivity among adjacent populations in the absence of active translocations. We used 19 microsatellites and a sex marker to obtain baseline data on the genetic effective population sizes and functional genetic connectivity of four of these populations, three of which were established since the 1980s and one of which was established ~ 100 years ago. A Bayesian assignment approach suggested the presence of 5 discrete genetic clusters, which corresponded to the four primary populations and two subpopulations within the oldest of them. Effective population sizes ranged from 15 (95% CI 10–22) to 51 (95% CI 32–88). We detected little or no evidence of gene flow among most populations. Exceptions were a signature of unidirectional gene flow to one population founded by emigrants of the other 30 years earlier, and bidirectional gene flow between subpopulations within the oldest population. We propose that social cohesion more than landscape characteristics explained population structure, which developed over many generations corresponding to population expansion. Whether or which populations can grow and reach sufficient effective population sizes on their own or require translocations to maintain genetic diversity and population growth is unclear. In the future, we recommend pairing genetic with demographic monitoring of these and other reintroduced elk populations, including targeted monitoring following translocations to evaluate their effects and necessity.
High angular resolution gravitational wave astronomy
Authors: Baker John , Baker Tessa , Carbone Carmelita , Congedo Giuseppe , Contaldi Carlo , Dvorkin Irina , Gair Jonathan , Haiman Zoltan , Mota David F. , Renzini Arianna , Buis Ernst-Jan , Cusin Giulia , Ezquiaga Jose Maria , Mueller Guido , Pieroni Mauro , Quenby John , Ricciardone Angelo , Saltas Ippocratis D. , Shao Lijing , Tamanini Nicola , Tasinato Gianmassimo , Zumalacárregui Miguel 
Published: May 2021

AbstractSince the very beginning of astronomy the location of objects on the sky has been a fundamental observational quantity that has been taken for granted. While precise two dimensional positional information is easy to obtain for observations in the electromagnetic spectrum, the positional accuracy of current and near future gravitational wave detectors is limited to between tens and hundreds of square degrees, which makes it extremely challenging to identify the host galaxies of gravitational wave events or to detect any electromagnetic counterparts. Gravitational wave observations provide information on source properties that is complementary to the information in any associated electromagnetic emission. Observing systems with multiple messengers thus has scientific potential much greater than the sum of its parts. A gravitational wave detector with higher angular resolution would significantly increase the prospects for finding the hosts of gravitational wave sources and triggering a multi-messenger follow-up campaign. An observatory with arcminute precision or better could be realised within the Voyage 2050 programme by creating a large baseline interferometer array in space and would have transformative scientific potential. Precise positional information of standard sirens would enable precision measurements of cosmological parameters and offer new insights on structure formation; a high angular resolution gravitational wave observatory would allow the detection of a stochastic background and resolution of the anisotropies within it; it would also allow the study of accretion processes around black holes; and it would have tremendous potential for tests of modified gravity and the discovery of physics beyond the Standard Model.