bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verification of Harmonization of Serum Total and Free Prostate-Specific Antigen (PSA) Measurements and Implications for Medical Decisions
Authors: Ferraro Simona , Bussetti Marco , Rizzardi Sara , Braga Federica , Panteghini Mauro 
Published: October 2020

Abstract

Background
Previous studies have shown that the harmonization of prostate-specific antigen (PSA) assays remained limited even after the introduction of WHO International Standards. This information needs updating for current measuring systems (MS) and reevaluation according to established analytical performance specifications (APS) and the characteristics of antibodies used.

Methods
Total (tPSA) and free (fPSA) PSA were measured in 135 and 137 native serum samples, respectively, by Abbott Alinity i, Beckman Access Dxl, Roche Cobas e801, and Siemens Atellica IM MSs. Passing–Bablok regression and difference plots were used to compare results from each MS to the all-method median values. Agreement among methods was evaluated against APS for bias derived from biological variation of the 2 measurands.

Results
The median interassay CV for tPSA MSs (11.5%; 25–75th percentiles, 9.2–13.4) fulfilled the minimum APS goal for intermethod bias (15.9%), while the interassay CV for fPSA did not [20.4% (25–75th percentiles, 18.4–22.7) vs goal 17.6%]. Considering the all-method median value of each sample as reference, all tPSA MSs exhibited a mean percentage bias within the minimum goal. On the other hand, Alinity (+21.3%) and Access (−24.2%) were out of the minimum bias goal for fPSA, the disagreement explained only in minimal part by the heterogeneity of employed antibodies.

Conclusions
The harmonization among tPSA MSs is acceptable only when minimum APS are applied and necessitates further improvement. The marked disagreement among fPSA MSs questions the use of fPSA as a second-level test for biopsy referral.
Titin-truncating mutations associated with dilated cardiomyopathy alter length-dependent activation and its modulation via phosphorylation
Authors: Vikhorev Petr G , Vikhoreva Natalia N , Yeung WaiChun , Li Amy , Lal Sean , dos Remedios Cristobal G , Blair Cheavar A , Guglin Maya , Campbell Kenneth S , Yacoub Magdi H , de Tombe Pieter , Marston Steven B 
Published: October 2020

Abstract

Aims
Dilated cardiomyopathy (DCM) is associated with mutations in many genes encoding sarcomere proteins. Truncating mutations in the titin gene TTN are the most frequent. Proteomic and functional characterizations are required to elucidate the origin of the disease and the pathogenic mechanisms of TTN-truncating variants.

Methods and results
We isolated myofibrils from DCM hearts carrying truncating TTN mutations and measured the Ca2+ sensitivity of force and its length dependence. Simultaneous measurement of force and adenosine triphosphate (ATP) consumption in skinned cardiomyocytes was also performed. Phosphorylation levels of troponin I (TnI) and myosin binding protein-C (MyBP-C) were manipulated using protein kinase A and λ phosphatase. mRNA sequencing was employed to overview gene expression profiles. We found that Ca2+ sensitivity of myofibrils carrying TTN mutations was significantly higher than in myofibrils from donor hearts. The length dependence of the Ca2+ sensitivity was absent in DCM myofibrils with TTN-truncating variants. No significant difference was found in the expression level of TTN mRNA between the DCM and donor groups. TTN exon usage and splicing were also similar. However, we identified down-regulation of genes encoding Z-disk proteins, while the atrial-specific regulatory myosin light chain gene, MYL7, was up-regulated in DCM patients with TTN-truncating variants.

Conclusion
Titin-truncating mutations lead to decreased length-dependent activation and increased elasticity of myofibrils. Phosphorylation levels of TnI and MyBP-C seen in the left ventricles are essential for the length-dependent changes in Ca2+ sensitivity in healthy donors, but they are reduced in DCM patients with TTN-truncating variants. A decrease in expression of Z-disk proteins may explain the observed decrease in myofibril passive stiffness and length-dependent activation.
Cryoablation vs. radiofrequency ablation of the atrioventricular node in patients with His-bundle pacing
Authors: Zweerink Alwin , Bakelants Elise , Stettler Carine , Burri Haran 
Published: October 2020

Abstract

Aims
Radiofrequency ablation (RFA) of the atrioventricular node (AVN) with His-bundle pacing (HBP) can cause rise in capture thresholds. Cryoablation (CRYO) may offer reversibility in case of threshold rise but has never been tested for AVN ablation in this setting. Our aim was to compare procedural characteristics and outcome of CRYO compared with RFA for AVN ablation in patients with HBP.

Methods and results
Forty-four patients with HBP underwent AVN ablation for an ‘ablate and pace’ indication. Cryoablation was performed in the first 22 patients and RFA in the following 22 patients. Procedural characteristics, success rates, and change in His capture thresholds were compared between groups. Distance from the ablation site to the His lead was measured using biplane fluoroscopy. Acute success was 100% with both strategies. Median procedural duration was significantly longer for CRYO {50 [interquartile range (IQR) 38–63] min} compared with RFA [36 (IQR, 30–41) min; P = 0.027]. An acute threshold rise of ≥1 V was observed in four CRYO (one complete loss of capture) and three RFA patients (P = 0.38), with all of the applications being within 6 mm of the His lead tip. During follow-up, nine patients had AVN re-conduction (six CRYO vs. three RFA; P = 0.58), but only four patients required a redo procedure (all CRYO; P = 0.09).

Conclusion
Cryoablation does not offer any advantage over RFA for AVN ablation in patients with HBP and tended to require more redo procedures. If possible, a distance of ≥6 mm should be maintained from the His lead tip to avoid a rise in capture thresholds.
Are Older Populations at a Disadvantage? County-Level Analysis of Confirmed COVID-19 Cases in Urban and Rural America
Authors: Choi Seung-won Emily , Yang Tse-Chuan 
Published: October 2020

Abstract

Objectives
This study examines how areas with different older population compositions are affected by Coronavirus Disease 2019 (COVID-19) and whether urban and rural counties face different challenges.

Methods
Applying negative binomial regression to a data set of U.S. counties (N = 3,042), we estimated the relationship between older population ratios and the number of confirmed COVID-19 cases, and how this relationship changes over time in urban and rural counties, respectively.

Results
Although low-ratio counties show the highest number of confirmed cases of COVID-19 at the beginning of the pandemic, confirmed cases in high-ratio counties (&gt;25% of the total population is aged 65 and older) increase exponentially with time in urban areas. High-ratio rural counties hit their peak later and recover more slowly compared to low- and medium-ratio rural counties.

Discussion
Both urban and rural counties with larger older populations are more vulnerable and their disadvantages in COVID-19 infections are more rapidly exacerbated over time in urban areas. This underscores the importance of early action in those counties for effective intervention and prevention.
‘We had to manage what we had on hand, in whatever way we could’: adaptive responses in policy for decentralized drug-resistant tuberculosis care in South Africa
Authors: Kielmann Karina , Dickson-Hall Lindy , Jassat Waasila , Le Roux Sacha , Moshabela Mosa , Cox Helen , Grant Alison D , Loveday Marian , Hill Jeremy , Nicol Mark P , Mlisana Koleka , Black John 
Published: October 2020

Abstract
In 2011, the South African National TB Programme launched a policy of decentralized management of drug-resistant tuberculosis (DR-TB) in order to expand the capacity of facilities to treat patients with DR-TB, minimize delays to access care and improve patient outcomes. This policy directive was implemented to varying degrees within a rapidly evolving diagnostic and treatment landscape for DR-TB, placing new demands on already-stressed health systems. The variable readiness of district-level systems to implement the policy prompted questions not only about differences in health systems resources but also front-line actors’ capacity to implement change in resource-constrained facilities. Using a grounded theory approach, we analysed data from in-depth interviews and small group discussions conducted between 2016 and 2018 with managers (n = 9), co-ordinators (n = 15), doctors (n = 7) and nurses (n = 18) providing DR-TB care. Data were collected over two phases in district-level decentralized sites of three South African provinces. While health systems readiness assessments conventionally map the availability of ‘hardware’, i.e. resources and skills to deliver an intervention, a notable absence of systems ‘hardware’ meant that systems ‘software’, i.e. health care workers (HCWs) agency, behaviours and interactions provided the basis of locally relevant strategies for decentralized DR-TB care. ‘Software readiness’ was manifest in four areas of DR-TB care: re-organization of service delivery, redressal of resource shortages, creation of treatment adherence support systems and extension of care parameters for vulnerable patients. These strategies demonstrate adaptive capacity and everyday resilience among HCW to withstand the demands of policy change and innovation in stressed systems. Our work suggests that a useful extension of health systems ‘readiness’ assessments would include definition and evaluation of HCW ‘software’ and adaptive capacities in the face of systems hardware gaps.
Neurostructural Correlates of Cannabis Use in Adolescent Bipolar Disorder
Authors: Sultan Alysha A , Kennedy Kody G , Fiksenbaum Lisa , MacIntosh Bradley J , Goldstein Benjamin I 
Published: October 2020

Abstract

Background
Little is known regarding the association of cannabis use with brain structure in adolescents with bipolar disorder (BD). This subject is timely, given expanded availability of cannabis contemporaneously with increased social acceptance and diminished societal constraints to access. Therefore, we set out to examine this topic in a sample of adolescents with BD and healthy control (HC) adolescents.

Methods
Participants included 144 adolescents (47 BD with cannabis use [BDCB+; including 13 with cannabis use disorder], 34 BD without cannabis use [BDCB−], 63 HC without cannabis use) ages 13–20 years. FreeSurfer-processed 3T MRI with T1-weighted contrast yielded measures of cortical thickness, surface area (SA), and volume. Region of interest (amygdala, hippocampus, ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) analyses and exploratory vertex-wise analysis were undertaken. A general linear model tested for between-group differences, accounting for age, sex, and intracranial volume.

Results
Vertex-wise analysis revealed significant group effects in frontal and parietal regions. In post-hoc analyses, BDCB+ exhibited larger volume and SA in parietal regions, and smaller thickness in frontal regions, relative to HC and BDCB−. BDCB− had smaller volume, SA, and thickness in parietal and frontal regions relative to HC. There were no significant region of interest findings after correcting for multiple comparisons.

Conclusion
This study found that cannabis use is associated with differences in regional brain structure among adolescents with BD. Future prospective studies are necessary to determine the direction of the observed association and to assess for dose effects.
Projection Effects and the Role of Political Ambiguity
Authors: Martin Danielle , Banducci Susan , Stevens Daniel , Coan Travis 
Published: October 2020

AbstractScholars studying political perceptions find evidence of the presence of projection effects. Yet several questions still need to be explored as to the time frame of the effect and the factors affecting projection. In particular, although the effect of ambiguity on projection has often been assumed and has been tested in a formal model (Jensen, 2009), no empirical evidence supports the idea that ambiguity fosters projection. We analyze an online survey conducted before and after the 2017 UK General Election. In addition to testing for the presence of projection effects on four different policy issues, we show that ambiguity fosters projection. This result suggests that ambiguity is not always necessarily a good strategy for political parties.
Molecular Epidemiology of Mansonella Species in Gabon
Authors: Sandri Thaisa Lucas , Kreidenweiss Andrea , Cavallo Simon , Weber David , Juhas Sascha , Rodi Miriam , Woldearegai Tamirat Gebru , Gmeiner Markus , Veletzky Luzia , Ramharter Michael , Tazemda-Kuitsouc Gildas B , Matsiegui Pierre Blaise , Mordmüller Benjamin , Held Jana 
Published: October 2020

Abstract
Mansonella perstans, a filarial nematode, infects large populations in Africa and Latin America. Recently, a potential new species, Mansonella sp “DEUX,” was reported. Carriage of endosymbiotic Wolbachia opens treatment options for Mansonella infections. Within a cross-sectional study, we assessed the prevalence of filarial infections in 834 Gabonese individuals and the presence of the endosymbiont Wolbachia. Almost half of the participants (400/834 [48%]) were infected with filarial nematodes, with Mansonella sp “DEUX” being the most frequent (295/400 [74%]), followed by Loa loa (273/400 [68%]) and Mansonella perstans (82/400 [21%]). Being adult/elderly, male, and living in rural areas was associated with a higher risk of infection. Wolbachia carriage was confirmed in M. perstans and Mansonella sp “DEUX.” In silico analysis revealed that Mansonella sp “DEUX” is not detected with currently published M. perstans–specific assays. Mansonella infections are highly prevalent in Gabon and might have been underreported, likely also beyond Gabon.
Malta’s only acute public hospital service during COVID-19: a diary of events from the first wave to transition phase
Authors: Cuschieri Sarah , Falzon Celia , Janulova Lina , Aguis Steve , Busuttil Walter , Psaila Noel , Farrugia Karl , Debono Joseph , Grech Victor 
Published: October 2020

Abstract

Introduction
COVID-19 has challenged healthcare systems worldwide. Some countries collapsed under surge conditions, while others (such as Malta) showed resilience. Public health measures in Malta quickly reined in COVID-19 spread. This review summarizes pandemic preparedness measures in Malta and the impact on routine services.

Methods
A literature search was conducted using Google, Google Scholar and PubMed and by reviewing Maltese online newspapers. A comprehensive summary of internal operations conducted at Mater Dei Hospital (MDH) was made available.

Results
A hospital ‘Incident Command Group’ was set up to plan an optimal COVID-19 response strategy. A ‘rapid response team’ was also created to cater for the logistics and management of supplies. A ‘COVID-19 Emergency Operation Centre’ simulated different COVID-19 scenarios. All elective services were suspended and all staff were mandatorily trained in wearing personal protective equipment. Staff were also retrained in the care of COVID-19 patients. In preparation for potential admission surges, MDH underwent rapid expansion of normal and intensive care beds. Swabbing was ramped up to one of the highest national rates worldwide. The cost for hospital COVID-19 preparedness exceeded €100 million for Malta’s half a million population.

Conclusion
Malta and its sole acute hospital coped well with the first wave with 680 cases and 9 deaths. The increased ability to deal with COVID-19 (a principally respiratory pathogen) will serve well for the anticipated combined annual influenza and the COVID-19 second wave this coming winter.
Restoring carbapenem efficacy: a novel carbapenem companion targeting metallo-β-lactamases in carbapenem-resistant Enterobacterales
Authors: Ooi Nicola , Lee Victoria E , Chalam-Judge Nathan , Newman Rebecca , Wilkinson Andrew J , Cooper Ian R , Orr David , Lee Sally , Savage Victoria J 
Published: October 2020

AbstractBackgroundThe dissemination of MBLs compromises effective use of many β-lactams in the treatment of patients with life-threatening bacterial infections. Predicted global increases in the prevalence of MBL-producing carbapenem-resistant Enterobacterales (CRE) are being realized, yielding infections that are untreatable with existing therapies including newly approved β-lactam/β-lactamase inhibitor combinations. Developing MBL inhibitors (MBLIs) now is essential to address the growing threat that MBL-producing CRE pose to patients.MethodsA novel MBLI series was assessed by susceptibility testing and time–kill assays. Target activity and selectivity was evaluated using bacterial NDM, VIM and IMP enzyme assays and human matrix metallopeptidase enzyme assays, respectively, and cytotoxicity was assessed in HepG2 cells. In vivo efficacy of meropenem/MBLI combinations was evaluated in a mouse thigh infection model using an NDM-1-producing Escherichia coli strain.ResultsCombination of MBLIs with carbapenems reduced MICs for NDM/IMP/VIM-producing Enterobacterales by up to 128-fold compared with the carbapenems alone. Supplementation of meropenem with the promising compound 272 reduced the MIC90 from 128 to 0.25 mg/L in a panel of MBL-producing CRE clinical isolates (n = 115). Compound 272 restored the bactericidal activity of meropenem and was non-cytotoxic, potentiating the antimicrobial action of meropenem through specific inhibition of NDM, IMP and VIM. In vivo efficacy was achieved in a mouse thigh infection model with meropenem/272 dosed subcutaneously.ConclusionsWe have developed a series of rationally designed MBLIs that restore activity of carbapenems against NDM/IMP/VIM-producing Enterobacterales. This series warrants further development towards a novel combination therapy that combats antibiotic-resistant organisms, which pose a critical threat to human health.
Correlation of SARS-CoV-2 Neutralizing Antibodies to an Automated Chemiluminescent Serological Immunoassay
Authors: Grenache David G , Ye Chunyan , Bradfute Steven B 
Published: October 2020

Abstract

Introduction
Neutralizing antibodies (NAbs) are capable of binding to a virus to render it incapable of infection. The ability of commercially available SARS-CoV-2 serological tests to detect NAbs has not been widely reported. We sought to correlate the antibodies detected by an automated chemiluminescent immunoassay with NAbs.

Methods
Residual serum samples from 35 patients that had a positive antibody test using the LIAISON® SARS-CoV-2 S1/S2 IgG chemiluminescent immunoassay and 2 antibody-negative control sera were tested for NAbs using a plaque reduction neutralization test (PRNT).

Results
NAbs were detected in 66% (23/35) of the antibody-positive samples. The immunoassay signal value ranged from 21.7 to 131.3 AU/mL (median, 90.5) with significant correlation between it and the PRNT (r = 0.61, P = 0.002). In the samples without NAbs, the immunoassay signal ranged from 16.3 to 66.2 AU/mL (median, 27.2). An immunoassay signal cutoff of &gt;41 AU/mL was 91% sensitive and 92% specific for the detection of NAbs.

Discussion
It is important that correlates of immunity to SARS-CoV-2 be identified and NAbs are considered to be central indicators of such. PRNT is the gold-standard test for identifying NAbs but it cannot be used for large-scale testing of populations. It is necessary to establish relationships between it and widely used commercial serological assays for SARS-CoV-2.
Towards a Right to Sustainable Security of Person in Times of Terrorism? Assessing Possibilities and Limitations Through a Critical Evaluation of Citizenship Stripping and Non-Repatriation Policies
Authors: Paulussen Christophe 
Published: October 2020

Abstract
On the basis of the case studies of deprivation of nationality and the non-repatriation and possible prosecution of foreign fighters and their families, this article will argue that some counter-terrorism measures, adopted under the justification of protecting national security, will not make these countries, and thus also the individuals under its jurisdiction, safer. Hence, it is wondered whether the notion of national security is both spatially and temporally still in sync with the hyperconnected world in which we live and in which terrorists operate—and whether it is not better to move to the adoption of the broader concept of sustainable security. This article will then turn to the question of whether ordinary citizens (or NGOs litigating on their behalf) could use their existing right to security of person to block those inefficient measures and if not, whether they should be able to operationalise the concept of sustainable security in the human rights context. The article will assert that while the general concept of sustainable security can certainly help at the policy level in encouraging governments to move away from mere national security thinking and thus assist in adopting counter-terrorism measures that provide true, durable security, the situation is different at the level of human rights. The existing right to security of person arguably does not go that far to be able to block the inefficient counter-terrorism measures as discussed in this article and an extension of this right, to a right to sustainable security of person, should not be pursued.
Dark Energy Survey Year 1 results: the lensing imprint of cosmic voids on the cosmic microwave background
Authors: Vielzeuf P , Kovács A , Demirbozan U , Fosalba P , Baxter E , Hamaus N , Huterer D , Miquel R , Nadathur S , Pollina G , Sánchez C , Whiteway L , Abbott T M C , Allam S , Annis J , Avila S , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Cawthon R , Costanzi M , da Costa L N , De Vicente J , Desai S , Diehl H T , Doel P , Eifler T F , Everett S , Flaugher B , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , March M , Marshall J L , Melchior P , Menanteau F , Palmese A , Paz-Chinchón F , Plazas A A , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Suchyta E , Tarle G , Thomas D , Weller J , Zuntz J ,   The DES Collaboration
Published: October 2020

ABSTRACT
Cosmic voids gravitationally lens the cosmic microwave background (CMB) radiation, resulting in a distinct imprint on degree scales. We use the simulated CMB lensing convergence map from the Marenostrum Institut de Ciencias de l’Espai (MICE) N-body simulation to calibrate our detection strategy for a given void definition and galaxy tracer density. We then identify cosmic voids in Dark Energy Survey (DES) Year 1 data and stack the Planck 2015 lensing convergence map on their locations, probing the consistency of simulated and observed void lensing signals. When fixing the shape of the stacked convergence profile to that calibrated from simulations, we find imprints at the 3σ significance level for various analysis choices. The best measurement strategies based on the MICE calibration process yield S/N ≈ 4 for DES Y1, and the best-fitting amplitude recovered from the data is consistent with expectations from MICE (A ≈ 1). Given these results as well as the agreement between them and N-body simulations, we conclude that the previously reported excess integrated Sachs–Wolfe (ISW) signal associated with cosmic voids in DES Y1 has no counterpart in the Planck CMB lensing map.