bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Communicating Uncertainty on Public Responses to Precision Medicine Research
Authors: Ratcliff Chelsea L , Wong Bob , Jensen Jakob D , Kaphingst Kimberly A 
Published: July 2021

AbstractBackgroundPrecision medicine research depends upon recruiting large and diverse participant cohorts to provide genetic, environmental, and lifestyle data. How prospective participants react to information about this research, including depictions of uncertainty, is not well understood.PurposeThe current study examined public responses to precision medicine research, focusing on reactions toward (a) uncertainty about the scientific impact of sharing data for research, and (b) uncertainty about the privacy, security, or intended uses of participant data.MethodsU.S. adults (N = 674; 51.9% male; 50% non-Hispanic white; Mage = 42.23) participated in an online experimental survey. Participants read a manipulated news article about precision medicine research that conveyed either certainty or uncertainty of each type (scientific, data). Participants then rated their attitudes toward the research, trust in the researchers, and willingness to join a cohort. We tested direct and mediated paths between message condition and outcomes and examined individual characteristics as moderators.ResultsOverall attitudes were positive and a majority of participants (65%) reported being somewhat or very likely to participate in precision medicine research if invited. Conveying uncertainty of either type had no overall main effect on outcomes. Instead, those who reported perceiving greater uncertainty had lower attitudes, trust, and willingness to join, while those with more tolerance for uncertainty, support for science, and scientific understanding responded favorably to the scientific uncertainty disclosure.ConclusionsFindings suggest responses to precision medicine research uncertainty are nuanced and that successful cohort enrollment may be well-supported by a transparent approach to communicating with prospective participants.
Effect of rapid methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction screening on vancomycin use in the intensive care unit
Authors: Diep Calvin , Meng Lina , Pourali Samaneh , Hitchcock Matthew M , Alegria William , Swayngim Rebecca , Ran Ran , Banaei Niaz , Deresinski Stan , Holubar Marisa 
Published: July 2021

Abstract

Purpose
To determine the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screen on vancomycin duration in critically ill patients with suspected pneumonia.

Methods
This was a retrospective, quasi-experimental study at a 613-bed academic medical center with 67 intensive care beds. Adult patients admitted to the intensive care unit (ICU) between 2017 and 2019 for 24 hours or longer and empirically started on intravenous vancomycin for pneumonia were included. The primary intervention was the implementation of a MRSA nasal PCR screen protocol. The primary outcome was duration of empiric vancomycin therapy. Secondary outcomes included the rate of acute kidney injury (AKI), the number of vancomycin levels obtained, the rate of resumption of vancomycin for treatment of pneumonia, ICU length of stay, hospital length of stay, the rate of ICU readmission, and the rate of in-hospital mortality.

Results
A total of 418 patients were included in the final analysis. The median vancomycin duration was 2.59 days in the preprotocol group and 1.44 days in the postprotocol group, a reduction of approximately 1.00 day (P &lt; 0.01). There were significantly fewer vancomycin levels measured in the postprotocol group than in the preprotocol group. Secondary outcomes were similar between the 2 groups, except that there was a lower rate of AKI and fewer vancomycin levels obtained in the postprotocol group (despite implementation of area under the curve–based vancomycin dosing) as compared to the preprotocol group.

Conclusion
The implementation of a pharmacist-driven MRSA nasal PCR screen was associated with a decrease in vancomycin duration and the number of vancomycin levels obtained in critically ill patients with suspected pneumonia.
Differential responses of thesunn4andrdn1-1super-nodulation mutants ofMedicago truncatulato elevated atmospheric CO2
Authors: Qiao Yunfa , Miao Shujie , Jin Jian , Mathesius Ulrike , Tang Caixian 
Published: July 2021

AbstractBackground and AimsNitrogen fixation in legumes requires tight control of carbon and nitrogen balance. Thus, legumes control nodule numbers via an autoregulation mechanism. ‘Autoregulation of nodulation’ mutants super-nodulate are thought to be carbon-limited due to the high carbon-sink strength of excessive nodules. This study aimed to examine the effect of increasing carbon supply on the performance of super-nodulation mutants.MethodsWe compared the responses of Medicago truncatula super-nodulation mutants (sunn-4 and rdn1-1) and wild type to five CO2 levels (300–850 μmol mol−1). Nodule formation and nitrogen fixation were assessed in soil-grown plants at 18 and 42 d after sowing.Key ResultsShoot and root biomass, nodule number and biomass, nitrogenase activity and fixed nitrogen per plant of all genotypes increased with increasing CO2 concentration and reached a maximum at 700 μmol mol−1. While the sunn-4 mutant showed strong growth retardation compared with wild-type plants, elevated CO2 increased shoot biomass and total nitrogen content of the rdn1-1 mutant up to 2-fold. This was accompanied by a 4-fold increase in nitrogen fixation capacity in the rdn1-1 mutant.ConclusionsThese results suggest that the super-nodulation phenotype per se did not limit growth. The additional nitrogen fixation capacity of the rdn1-1 mutant may enhance the benefit of elevated CO2 for plant growth and N2 fixation.
Drug repositioning based on the heterogeneous information fusion graph convolutional network
Authors: Cai Lijun , Lu Changcheng , Xu Junlin , Meng Yajie , Wang Peng , Fu Xiangzheng , Zeng Xiangxiang , Su Yansen 
Published: July 2021

AbstractIn silico reuse of old drugs (also known as drug repositioning) to treat common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked drugs, with potentially lower overall development costs and shorter development timelines. Therefore, there is a pressing need for computational drug repurposing methodologies to facilitate drug discovery. In this study, we propose a new method, called DRHGCN (Drug Repositioning based on the Heterogeneous information fusion Graph Convolutional Network), to discover potential drugs for a certain disease. To make full use of different topology information in different domains (i.e. drug–drug similarity, disease–disease similarity and drug–disease association networks), we first design inter- and intra-domain feature extraction modules by applying graph convolution operations to the networks to learn the embedding of drugs and diseases, instead of simply integrating the three networks into a heterogeneous network. Afterwards, we parallelly fuse the inter- and intra-domain embeddings to obtain the more representative embeddings of drug and disease. Lastly, we introduce a layer attention mechanism to combine embeddings from multiple graph convolution layers for further improving the prediction performance. We find that DRHGCN achieves high performance (the average AUROC is 0.934 and the average AUPR is 0.539) in four benchmark datasets, outperforming the current approaches. Importantly, we conducted molecular docking experiments on DRHGCN-predicted candidate drugs, providing several novel approved drugs for Alzheimer’s disease (e.g. benzatropine) and Parkinson’s disease (e.g. trihexyphenidyl and haloperidol).
Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma
Authors: Lee K F , Lo E Y J , Wong K K C , Fung A K Y , Chong C C N , Wong J , Ng K K C , Lai P B S 
Published: July 2021

Abstract

Background
Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC).

Methods
This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC.

Results
The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis.

Conclusion
AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72–77 mmHg) during hepatectomy is important.
Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination
Authors: Chen Lin-Lei , Lu Lu , Choi Charlotte Yee-Ki , Cai Jian-Piao , Tsoi Hoi-Wah , Chu Allen Wing-Ho , Ip Jonathan Daniel , Chan Wan-Mui , Zhang Ricky Ruiqi , Zhang Xiaojuan , Tam Anthony Raymond , Lau Daphne Pui-Ling , To Wing-Kin , Que Tak-Lun , Yip Cyril Chik-Yan , Chan Kwok-Hung , Cheng Vincent Chi-Chung , Yuen Kwok-Yung , Hung Ivan Fan-Ngai , To Kelvin Kai-Wang 
Published: July 2021

Abstract

Background
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively.

Methods
The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay.

Results
The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding.

Conclusions
P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “nonvariant” strains.
Conservative, surgical, and percutaneous treatment for mitral regurgitation shortly after acute myocardial infarction
Authors: Haberman Dan , Estévez-Loureiro Rodrigo , Benito-Gonzalez Tomas , Denti Paolo , Arzamendi Dabit , Adamo Marianna , Freixa Xavier , Nombela-Franco Luis , Villablanca Pedro , Krivoshei Lian , Fam Neil , Spargias Konstantinos , Czarnecki Andrew , Pascual Isaac , Praz Fabien , Sudarsky Doron , Kerner Arthur , Ninios Vlasis , Gennari Marco , Beeri Ronen , Perl Leor , Wasserstrum Yishay , Danenberg Haim , Poles Lion , George Jacob , Caneiro-Queija Berenice , Scianna Salvatore , Moaraf Igal , Schiavi Davide , Scardino Claudia , Corpataux Noé , Echarte-Morales Julio , Chrissoheris Michael , Fernández-Peregrina Estefanía , Di Pasquale Mattia , Regueiro Ander , Vergara-Uzcategui Carlos , Iñiguez-Romo Andres , Fernández-Vázquez Felipe , Dvir Danny , Maisano Francesco , Taramasso Maurizio , Shuvy Mony 
Published: July 2021

Abstract

Aims
Severe mitral regurgitation (MR) following acute myocardial infarction (MI) is associated with high mortality rates and has inconclusive recommendations in clinical guidelines. We aimed to report the international experience of patients with secondary MR following acute MI and compare the outcomes of those treated conservatively, surgically, and percutaneously.

Methods and results
Retrospective international registry of consecutive patients with at least moderate-to-severe MR following MI treated in 21 centres in North America, Europe, and the Middle East. The registry included patients treated conservatively and those having surgical mitral valve repair or replacement (SMVR) or percutaneous mitral valve repair (PMVR) using edge-to-edge repair. The primary endpoint was in-hospital mortality. A total of 471 patients were included (43% female, age 73 ± 11 years): 205 underwent interventions, of whom 106 were SMVR and 99 PMVR. Patients who underwent mitral valve intervention were in a worse clinical state (Killip class ≥3 in 60% vs. 43%, P &lt; 0.01), but yet had lower in-hospital and 1-year mortality compared with those treated conservatively [11% vs. 27%, P &lt; 0.01 and 16% vs. 35%, P &lt; 0.01; adjusted hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.18–0.46, P &lt; 0.01]. Surgical mitral valve repair or replacement was performed earlier than PMVR [median of 12 days from MI date (interquartile range 5–19) vs. 19 days (10–40), P &lt; 0.01]. The immediate procedural success did not differ between SMVR and PMVR (92% vs. 93%, P = 0.53). However, in-hospital and 1-year mortality rates were significantly higher in SMVR than in PMVR (16% vs. 6%, P = 0.03 and 31% vs. 17%, P = 0.04; adjusted HR 3.75, 95% CI 1.55–9.07, P &lt; 0.01).

Conclusions
Early intervention may mitigate the poor prognosis associated with conservative therapy in patients with post-MI MR. Percutaneous mitral valve repair can serve as an alternative for surgery in reducing MR for high-risk patients.
Development of a yoghurt alternative, based on plant-adapted lactic acid bacteria, soy drink and the liquid fraction of brewers’ spent grain
Authors: Madsen Sanne Kjærulf , Priess Camilla , Wätjen Anders Peter , Øzmerih Süleyman , Mohammadifar Mohammad Amin , Heiner Bang-Berthelsen Claus 
Published: July 2021

ABSTRACT
With consumers becoming more aware of sustainability, healthier lifestyles and animal welfare, plant-based food products as alternatives to dairy products have become a fast-growing industry in the last decade, and an increasing number of plant-based products are showing up on the markets. With over 88 million tons of food wasted in Europe annually, a sustainable alternative to dairy could be to use side streams for new products. Here, we tried to develop a plant-based yogurt alternative based on three ingredients: commercial soy drink and a liquid fraction of brewers’ spent grain fermented with plant-adapted lactic acid bacteria. Analysis of the content and properties of the fermented product were compared to a commercial plant-based yoghurt-like product and a commercial dairy yoghurt. Results from the project show that fermentation of a commercial soy drink containing 20% of the liquid fraction of brewers’ spent grain results in a product with texture and sensory characteristics that mimics a dairy yogurt.
From effectiveness to sustainability: understanding the impact of CARE’s Community Score Card© social accountability approach in Ntcheu, Malawi
Authors: Mgoli Mwale Patience , Msiska Thumbiko , Chinkhota Kriss , Munthali Tapiwa , Wako Etobssie , Rodriguez Mariela , Laterra Anne , Shato Thembekile , Sebert Kuhlmann Anne 
Published: July 2021

Abstract
We evaluated the sustainability of CARE’s Community Score Card© (CSC) social accountability approach in Ntcheu, Malawi, approximately 2.5 years after the end of formal intervention activities. Using a cross-sectional, exploratory design, we conducted 41 focus groups with members of Community Health Advisory Groups (CHAGs) and youth groups and 19 semi-structured interviews with local and district government officials, project staff, and national stakeholders to understand how and in what form CSC activities are continuing. Focus groups and interviews were audio-recorded, transcribed and translated into English. Thematic coding was done using Dedoose software. Most groups were continuing to meet and implement the CSC, although some made modifications. CHAGs, youth and local government officials all attributed their continued implementation to the value that they saw in the process that allows marginalized groups within the community, including women and youth, a safe space for sharing their ideas and issues and the initial results this generated. However, lack of access to resources for implementation and challenges in convening and facilitating the interface meeting phase created barriers to continued sustainability. The CSC is sustainable by communities 2.5 years after the end of formal intervention activities. For future interventions, health systems and non-governmental organizations should plan for a transition phase with periodic refresher trainings and a small fund to support implementation, such as refreshments and transportation, to increase the likelihood of community-driven sustainability.
CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during humanin vitromyogenesis
Authors: Mérien Antoine , Tahraoui-Bories Julie , Cailleret Michel , Dupont Jean-Baptiste , Leteur Céline , Polentes Jérôme , Carteron Alexandre , Polvèche Hélène , Concordet Jean-Paul , Pinset Christian , Jarrige Margot , Furling Denis , Martinat Cécile 
Published: July 2021

AbstractAlternative splicing has emerged as a fundamental mechanism for the spatiotemporal control of development. A better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of muscleblind-like (MBNL) proteins, a family of tissue-specific splicing regulators whose loss of function is associated with myotonic dystrophy type 1 (DM1), an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the consequences of their losses on the generation of skeletal muscle cells. Our results suggested that MBNL proteins are required for the late myogenic maturation. In addition, loss of MBNL1 and MBNL2 recapitulated the main features of DM1 observed in hiPSC-derived skeletal muscle cells. Comparative transcriptomic analyses also revealed the muscle-related processes regulated by these proteins that are commonly misregulated in DM1. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope with the loss of function of these MBNL proteins.
North American and Norwegian Chronic Wasting Disease Prions Exhibit Different Potential for Interspecies Transmission and Zoonotic Risk
Authors: Pritzkow Sandra , Gorski Damian , Ramirez Frank , Telling Glenn C , Benestad Sylvie L , Soto Claudio 
Published: July 2021

Abstract

Background
Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting various species of wild and captive cervids. The risk that CWD poses to cohabiting animals or more importantly to humans is largely unknown.

Methods
In this study, we investigated differences in the capacity of CWD isolates obtained from 6 different cervid species to induce prion conversion in vitro by protein misfolding cyclic amplification. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at expenses of normal prion proteins from various mammals and human, respectively.

Results
Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro.

Conclusions
Our results suggest that Norway and North American CWD prions correspond to different strains with distinct spillover and zoonotic potentials.
Gendered Honor: How Mass Common Sense Shaped India's Foreign Policy in Jammu and Kashmir, 1947–1950
Authors: Julka Amit 
Published: July 2021

Abstract
How do the masses shape foreign policy? This question has been examined through various conceptual lenses—national identity, public opinion, and popular culture. At the core of all these approaches is an argument that “taken for granted” ideas matter because they constitute a society's mass common sense, in turn influencing assorted political possibilities. What remains to be theorized is how and why such influence occurs. This paper argues that mass common sense sets the limits of legitimacy within societal discourse, thus shaping all political and policy discourses, including foreign policy. The paper evaluates this argument in the case of India's decision to militarily intervene in the princely state of Jammu and Kashmir in 1947. This is done in two steps. The first is to reconstruct India's common sense circa 1947, and this is done from popular Hindi–Urdu language sources such as children's literature and films. The second is to trace possible ways through which commonsensical notions of gender, beauty, and honor influenced the Nehru government toward intervention. The study's conclusions have relevance for interpretivist theories of foreign policy as well as for Indian foreign policy, specifically the persistence of India's tendency to prioritize certain “regions” over others—and the Kashmir Valley and Jammu above all—over most if not all other foreign policy issue areas.