bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150 000 Mexican adults
Authors: Gnatiuc Louisa , Tapia-Conyer Roberto , Wade Rachel , Ramirez-Reyes Raúl , Aguilar-Ramirez Diego , Herrington William , Hill Michael , Lewington Sarah , Torres Jason , Trichia Eirini , Collins Rory , Peto Richard , Clarke Robert , Kuri-Morales Pablo , Emberson Jonathan R , Alegre-Díaz Jesus 
Published: February 2021

Abstract

Aims
Results of previous studies of abdominal adiposity and risk of vascular-metabolic mortality in Hispanic populations have been conflicting. We report results from a large prospective study of Mexican adults with high levels of abdominal adiposity.

Methods and results
A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist–hip ratio, and waist–height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35–74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40–74 years were 2.32 [95% confidence interval (CI) 1.84–2.94] for waist circumference, 2.22 (1.71–2.88) for the waist–hip ratio, 2.63 (2.06–3.36) for the waist–height ratio, and 1.58 (1.29–1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27–1.41), 1.31 (1.23–1.39), 1.38 (1.31–1.45), and 1.18 (1.13–1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75–0.86).

Conclusions
In this study of Mexican adults, abdominal adiposity (and in particular the waist–height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.
Residents’ and Relatives’ Experiences of Acute Situations: A Qualitative Study to Inform a Care Model
Authors: Basinska Kornelia , Künzler-Heule Patrizia , Guerbaai Raphaëlle Ashley , Zúñiga Franziska , Simon Michael , Wellens Nathalie I H , Serdaly Christine , Nicca Dunja 
Published: February 2021

Abstract

Background and Objectives
As new models of care aiming to reduce hospitalizations from nursing homes emerge, their implementers must consider residents’ and relatives’ needs and experiences with acute changes in the residents’ health situations. As part of the larger INTERCARE implementation study, we explored these persons’ experiences of acute situations in Swiss nursing homes.

Research Design and Methods
3 focus groups were conducted with residents and their relatives and analyzed via reflexive thematic analysis.

Results
The first theme, the orchestra plays its standards, describes experiences of structured everyday care in nursing homes, which functions well despite limited professional and competency resources. The second theme, the orchestra reaches its limits, illustrates accounts of acute situations in which resources were insufficient to meet residents’ needs. Interestingly, participants’ perceptions of acute situations went well beyond our own professional view, that is, changes in health situations, and included situations best summarized as “changes that might have negative consequences for residents if not handled adequately by care workers.” Within the third theme, the audience compensates for the orchestra’s limitations, participants’ strategies to cope with resource limitations in acute situations are summarized.

Discussion and Implications
Our findings suggest differences between care providers’ and participants’ perspectives regarding acute situations and care priority setting. Alongside efforts to promote staff awareness of and responsiveness to acute situations, care staff must commit to learning and meeting individual residents’ and relatives’ needs. Implications for the development and implementation of a new nurse-led model of care are discussed.
long-read-tools.org: an interactive catalogue of analysis methods for long-read sequencing data
Authors: Amarasinghe Shanika L , Ritchie Matthew E , Gouil Quentin 
Published: February 2021

Abstract

Background
The data produced by long-read third-generation sequencers have unique characteristics compared to short-read sequencing data, often requiring tailored analysis tools for tasks ranging from quality control to downstream processing. The rapid growth in software that addresses these challenges for different genomics applications is difficult to keep track of, which makes it hard for users to choose the most appropriate tool for their analysis goal and for developers to identify areas of need and existing solutions to benchmark against.

Findings
We describe the implementation of long-read-tools.org, an open-source database that organizes the rapidly expanding collection of long-read data analysis tools and allows its exploration through interactive browsing and filtering. The current database release contains 478 tools across 32 categories. Most tools are developed in Python, and the most frequent analysis tasks include base calling, de novo assembly, error correction, quality checking/filtering, and isoform detection, while long-read single-cell data analysis and transcriptomics are areas with the fewest tools available.

Conclusion
Continued growth in the application of long-read sequencing in genomics research positions the long-read-tools.org database as an essential resource that allows researchers to keep abreast of both established and emerging software to help guide the selection of the most relevant tool for their analysis needs.
Identification of LRRK2 missense variants in the accelerating medicines partnership Parkinson’s disease cohort
Authors: Bryant Nicole , Malpeli Nicole , Ziaee Julia , Blauwendraat Cornelis , Liu Zhiyong ,   AMP PD Consortium, West Andrew B 
Published: February 2021

Abstract
Pathogenic missense variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified through linkage analysis in familial Parkinson disease (PD). Subsequently, other missense variants with lower effect sizes on PD risk have emerged, as well as non-coding polymorphisms (e.g. rs76904798) enriched in PD cases in genome-wide association studies. Here we leverage recent whole-genome sequences from the Accelerating Medicines Partnership-Parkinson’s Disease (AMP-PD) and the Genome Aggregation (gnomAD) databases to characterize novel missense variants in LRRK2 and explore their relationships with known pathogenic and PD-linked missense variants. Using a computational prediction tool that successfully classifies known pathogenic LRRK2 missense variants, we describe an online web-based resource that catalogs characteristics of over 1200 LRRK2 missense variants of unknown significance. Novel high-pathogenicity scoring variants, some identified exclusively in PD cases, tightly cluster within the ROC-COR-Kinase domains. Structure–function predictions support that some of these variants exert gain-of-function effects with respect to LRRK2 kinase activity. In AMP-PD participants, all p.R1441G carriers (N = 89) are also carriers of the more common PD-linked variant p.M1646T. In addition, nearly all carriers of the PD-linked p.N2081D missense variant are also carriers of the LRRK2 PD-risk variant rs76904798. These results provide a compendium of LRRK2 missense variants and how they associate with one another. While the pathogenic p.G2019S variant is by far the most frequent high-pathogenicity scoring variant, our results suggest that ultra-rare missense variants may have an important cumulative impact in increasing the number of individuals with LRRK2-linked PD.
Combinatorial glucose, nicotinic acid and N-acetylcysteine therapy has synergistic effect in preclinicalC. elegansand zebrafish models of mitochondrial complex I disease
Authors: Guha Sujay , Mathew Neal D , Konkwo Chigoziri , Ostrovsky Julian , Kwon Young Joon , Polyak Erzsebet , Seiler Christoph , Bennett Michael , Xiao Rui , Zhang Zhe , Nakamaru-Ogiso Eiko , Falk Marni J 
Published: February 2021

AbstractMitochondrial respiratory chain disorders are empirically managed with variable antioxidant, cofactor and vitamin ‘cocktails’. However, clinical trial validated and approved compounds, or doses, do not exist for any single or combinatorial mitochondrial disease therapy. Here, we sought to pre-clinically evaluate whether rationally designed mitochondrial medicine combinatorial regimens might synergistically improve survival, health and physiology in translational animal models of respiratory chain complex I disease. Having previously demonstrated that gas-1(fc21) complex I subunit ndufs2−/− C. elegans have short lifespan that can be significantly rescued with 17 different metabolic modifiers, signaling modifiers or antioxidants, here we evaluated 11 random combinations of these three treatment classes on gas-1(fc21) lifespan. Synergistic rescue occurred only with glucose, nicotinic acid and N-acetylcysteine (Glu + NA + NAC), yielding improved mitochondrial membrane potential that reflects integrated respiratory chain function, without exacerbating oxidative stress, and while reducing mitochondrial stress (UPRmt) and improving intermediary metabolic disruptions at the levels of the transcriptome, steady-state metabolites and intermediary metabolic flux. Equimolar Glu + NA + NAC dosing in a zebrafish vertebrate model of rotenone-based complex I inhibition synergistically rescued larval activity, brain death, lactate, ATP and glutathione levels. Overall, these data provide objective preclinical evidence in two evolutionary-divergent animal models of mitochondrial complex I disease to demonstrate that combinatorial Glu + NA + NAC therapy significantly improved animal resiliency, even in the face of stressors that cause severe metabolic deficiency, thereby preventing acute neurologic and biochemical decompensation. Clinical trials are warranted to evaluate the efficacy of this lead combinatorial therapy regimen to improve resiliency and health outcomes in human subjects with mitochondrial disease.
An evolutionary perspective on economic catch-up by latecomers
Authors: Malerba Franco , Lee Keun 
Published: February 2021

AbstractThis paper proposes an evolutionary view of economic catch-up by latecomers, considered as a long-run process of closing the gap in capabilities by promoting learning and innovation in interaction with innovation systems (national, sectoral or regional). According to this perspective, catch-up is viewed as a dynamic evolutionary process which is not deterministic and cannot be planned in details because it faces uncertainty and continuous change; is associated with a variety of exogenous events (windows of opportunity) and is the result of the idiosyncratic behavior of heterogeneous actors characterized by different understanding, views and experiences. This process leads to a variety of responses and strategies by latecomer firms and countries, even in the presence of similar external technological or market conditions. One major point that emerges from this perspective is that there is a strong complementarity between learning and capabilities by domestic firms and the national, sectoral, and regional systems in which firms operate. The paper also discusses various strategies, such as detours and leapfrogging, along the stages and the different paths and trajectories that this long-term evolutionary process of countries and sectors follows.
Parabolic Frequency on Manifolds
Authors: Holck Colding Tobias , Minicozzi II William P 
Published: February 2021

Abstract
We prove monotonicity of a parabolic frequency on static and evolving manifolds without any curvature or other assumptions. These are parabolic analogs of Almgren’s frequency function. When the static manifold is Euclidean space and the drift operator is the Ornstein–Uhlenbeck operator, this can been seen to imply Poon’s frequency monotonicity for the ordinary heat equation. When the manifold is self-similarly evolving by the Ricci flow, we prove a parabolic frequency monotonicity for solutions of the heat equation. For the self-similarly evolving Gaussian soliton, this gives directly Poon’s monotonicity. Monotonicity of frequency is a parabolic analog of the 19th century Hadamard three-circle theorem about log convexity of holomorphic functions on C. From the monotonicity, we get parabolic unique continuation and backward uniqueness.
Activity of cefepime/zidebactam (WCK 5222) against ‘problem’ antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory
Authors: Mushtaq Shazad , Garello Paolo , Vickers Anna , Woodford Neil , Livermore David M 
Published: February 2021

Abstract

Background
Triple-action diazabicyclooctanes, e.g. zidebactam, combine β-lactamase inhibition, antibacterial activity, and ‘enhancement’ of PBP3-targeted β-lactams.

Objectives
To examine the activity of cefepime/zidebactam against consecutive ‘problem’ Gram-negative bacteria referred to the UK national reference laboratory.

Methods
MICs were determined by BSAC agar dilution for 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, categorized by carbapenemase detection and interpretive reading.

Results
Universal susceptibility to cefepime/zidebactam 8 + 8 mg/L was seen for otherwise multidrug-resistant Enterobacterales with AmpC, extended-spectrum, K1, KPC and OXA-48-like β-lactamases, or with impermeability and ‘unassigned’ mechanisms. Unlike ceftazidime/avibactam and all other comparators, cefepime/zidebactam 8 + 8 mg/L also inhibited most (190/210, 90.5%) Enterobacterales with MBLs. Resistance in the remaining minority of MBL producers, and in 13/24 with both NDM MBLs and OXA-48-like enzymes, was associated with Klebsiella pneumoniae ST14. For Pseudomonas aeruginosa, MICs of cefepime/zidebactam rose with efflux grade, but exceeded 8 + 8 mg/L for only 11/85 isolates even in the highly-raised efflux group. Among 103 P. aeruginosa with ESBLs or MBLs, 97 (94.5%) were inhibited by cefepime/zidebactam 8 + 8 mg/L whereas fewer than 15% were susceptible to any comparator. MICs for Acinetobacter baumannii with acquired OXA carbapenemases clustered around 8 + 8 to 32 + 32 mg/L, with higher values for MBL producers. A strong enhancer effect augmented activity against many isolates that were highly resistant to cefepime and zidebactam alone and which had mechanisms not inhibited by zidebactam.

Conclusions
Assuming successful clinical trials, cefepime/zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters.
CON: Testing for ESBL production is unnecessary for ceftriaxone-resistant Enterobacterales
Authors: Mathers Amy J , Lewis James S 
Published: February 2021

Abstract
Phenotypic testing for Enterobacterales that harbour ESBLs is not additive to accurate in vitro β-lactam MICs for clinical decision-making. ESBL testing is an outdated practice established in an era of higher cephalosporin breakpoints to prevent resistant Enterobacterales carrying Ambler class A β-lactamases with affinity for later-generation β-lactams from being reported as susceptible to later-generation cephalosporins, leading to clinical failures. ESBL testing is problematic because of inaccuracies when multiple classes of β-lactamases are produced by the same organism, thus limiting the testing application to specific species and resistance types. Clinical laboratories should instead focus finite resources on accurate susceptibility testing using contemporary interpretative criteria to help guide therapeutic decisions. With continued emergence of antimicrobial resistance and in the setting of accurate susceptibility testing and current breakpoints the use of ESBL phenotypic testing is not helpful in clinical decision-making.
Can decision support combat incompleteness and bias in routine primary care data?
Authors: Kostopoulou Olga , Tracey Christopher , Delaney Brendan C 
Published: February 2021

AbstractObjectiveRoutine primary care data may be used for the derivation of clinical prediction rules and risk scores. We sought to measure the impact of a decision support system (DSS) on data completeness and freedom from bias.Materials and MethodsWe used the clinical documentation of 34 UK general practitioners who took part in a previous study evaluating the DSS. They consulted with 12 standardized patients. In addition to suggesting diagnoses, the DSS facilitates data coding. We compared the documentation from consultations with the electronic health record (EHR) (baseline consultations) vs consultations with the EHR-integrated DSS (supported consultations). We measured the proportion of EHR data items related to the physician’s final diagnosis. We expected that in baseline consultations, physicians would document only or predominantly observations related to their diagnosis, while in supported consultations, they would also document other observations as a result of exploring more diagnoses and/or ease of coding.ResultsSupported documentation contained significantly more codes (incidence rate ratio [IRR] = 5.76 [4.31, 7.70] P &lt; .001) and less free text (IRR = 0.32 [0.27, 0.40] P &lt; .001) than baseline documentation. As expected, the proportion of diagnosis-related data was significantly lower (b = −0.08 [−0.11, −0.05] P &lt; .001) in the supported consultations, and this was the case for both codes and free text.ConclusionsWe provide evidence that data entry in the EHR is incomplete and reflects physicians’ cognitive biases. This has serious implications for epidemiological research that uses routine data. A DSS that facilitates and motivates data entry during the consultation can improve routine documentation.
Impact of Background Fruit Odors on Attraction of Drosophila suzukii (Diptera: Drosophilidae) to Its Symbiotic Yeast
Authors: Huang Juan , Gut Larry J 
Published: February 2021

Abstract
Background odors produced by plants in the environment can interfere with the response of insects to a point-releasing attractant, especially when their compositions overlap. In this study, a series of binary choice tests was conducted in a wind tunnel to investigate whether background odors emitted from cherry, blueberry, blackberry, or raspberry fruits would affect the level of Drosophila suzukii (Matsumura) attraction to its symbiotic yeast, Hanseniaspora uvarum (Niehaus) (Saccharomycetales: Saccharomycetaceae). Whether an increase in the intensity of background odors would affect the attractiveness of H. uvarum to D. suzukii was also investigated, either by increasing the number of cherry or raspberry fruit per cup or by increasing the number of fruit cups surrounding the cup baited with the yeast. In wind tunnel assays, background fruit odors interfering with D. suzukii attraction to the yeast varied among fruit types. Raspberry odor inhibited the attractiveness of H. uvarum to the fly the most, followed by blackberry odor, whereas cherry and blueberry odors had no significant impact on the attraction. An increase in the intensity of odors by adding more cherry or raspberry fruit per cup did not increase the impact of fruit odor on the attraction; however, adding more raspberry cups around H. uvarum linearly decreased its attractiveness, suggesting that background host fruit abundance and likely increase in host odor may influence D. suzukii attraction to yeast odor depending on host species.
Incompetence of the Asian Longhorned Tick (Acari: Ixodidae) in Transmitting the Agent of Human Granulocytic Anaplasmosis in the United States
Authors: Levin Michael L , Stanley Hannah M , Hartzer Kris , Snellgrove Alyssa N 
Published: February 2021

Abstract
The Asian longhorned tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae), was recently introduced into the United States and is now established in at least 15 states. Considering its ability for parthenogenetic propagation and propensity for creating high-density populations, there is concern that this tick may become involved in transmission cycles of endemic tick-borne human pathogens. Human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum is one of the more common tick-borne diseases in the United States, especially in the northeastern and midwestern states. There is considerable geographical overlap between HGA cases and the currently known distribution of H. longicornis, which creates a potential for this tick to encounter A. phagocytophilum while feeding on naturally infected vertebrate hosts. Therefore, we evaluated the ability of H. longicornis to acquire and transmit the agent of HGA under laboratory conditions and compared it to the vector competence of I. scapularis. Haemaphysalis longicornis nymphs acquired the pathogen with the bloodmeal while feeding on infected domestic goats, but transstadial transmission was inefficient and PCR-positive adult ticks were unable to transmit the pathogen to naïve goats. Results of this study indicate that the Asian longhorned tick is not likely to play a significant role in the epidemiology of HGA in the United States.
ReMOT Control Delivery of CRISPR-Cas9 Ribonucleoprotein Complex to Induce Germline Mutagenesis in the Disease Vector Mosquitoes Culex pipiens pallens (Diptera: Culicidae)
Authors: Li Xixi , Xu Yang , Zhang Hongbo , Yin Haitao , Zhou Dan , Sun Yan , Ma Lei , Shen Bo , Zhu Changliang 
Published: February 2021

Abstract
The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes—14 µl injection mixture was required, and no precipitation occurred with ≤1 µl of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G0 progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G0 progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.