bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary microcirculation damage in anthracycline cardiotoxicity
Authors: Galán-Arriola Carlos , Vílchez-Tschischke Jean Paul , Lobo Manuel , López Gonzalo J , de Molina-Iracheta Antonio , Pérez-Martínez Claudia , Villena-Gutiérrez Rocio , Macías Álvaro , Díaz-Rengifo Iván A , Oliver Eduardo , Fuster Valentin , Sánchez-González Javier , Ibanez Borja
Published: February 2021

Aims

The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment.

Methods and results

Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime.

Conclusion

Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.
Human immunodeficiency viral infection and differences in interstitial ventricular fibrosis and left atrial size
Authors: Wu Katherine C , Haberlen Sabina A , Plankey Michael W , Palella Frank J , Piggott Damani A , Kirk Gregory D , Margolick Joseph B , Post Wendy S
Published: February 2021

Aims

The extent to which human immunodeficiency viral (HIV) infection is independently associated with myocardial disease in the era of combination antiretroviral therapy (cART) remains understudied. We assessed differences in cardiovascular magnetic resonance imaging (CMR) metrics among people living with HIV (PLWH) and without HIV (PWOH).

Methods and results

Among 436 participants (aged 54.7 ± 6.0 years, 29% women) from three cohorts, we acquired CMR cines, late gadolinium enhancement (LGE), and T1 mapping. Multivariable linear regressions were used to evaluate associations between HIV serostatus and CMR metrics. Baseline characteristics were similar by HIV serostatus; 63% were PLWH of whom 88% received cART and 73% were virally suppressed. Median left ventricular ejection fraction was normal and similar by HIV serostatus (73%, PWOH vs. 72%, PLWH, P = 0.43) as were right ventricular function, biventricular volumes, and masses. LGE prevalence was similar (32%, PWOH vs. 36%, PLWH, P = 0.46) with low scar extents (4.1, PWOH vs. 4.9 g, PLWH, P = 0.51) and few ischaemic scars (3%, PWOH vs. 4%, PLWH, P = 0.70). Extracellular volume fraction (ECV) was higher among PLWH (29.2 ± 4.1% vs. 28.3 ± 3.7%, P = 0.04) as was indexed maximum left atrial (LA) volume (LAVI, 29.7 ± 10.3 vs. 27.8 ± 8.7 mL/m2, P = 0.05). After multivariate adjustment, ECV was 0.84% higher among PLWH (P = 0.05) and LAVI was 2.45 mL/m2 larger (P = 0.01). HIV seropositivity and higher ECV contributed to higher LAVI (P < 0.02). There were no associations between HIV disease severity and CMR metrics among PLWH.

Conclusion

HIV seropositivity was independently associated with greater diffuse non-ischaemic fibrosis and larger LA volume but no other differences in CMR metrics.
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

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

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

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

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

Mitochondrial 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

This 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

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

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

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

Objective

Routine 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 Methods

We 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.

Results

Supported documentation contained significantly more codes (incidence rate ratio [IRR] = 5.76 [4.31, 7.70] P < .001) and less free text (IRR = 0.32 [0.27, 0.40] P < .001) than baseline documentation. As expected, the proportion of diagnosis-related data was significantly lower (b = −0.08 [−0.11, −0.05] P < .001) in the supported consultations, and this was the case for both codes and free text.

Conclusions

We 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

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

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

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.
Captopril reduces lung inflammation and accelerated senescence in response to thoracic radiation in mice
Authors: Mungunsukh Ognoon , George Jeffy , McCart Elizabeth A , Snow Andrew L , Mattapallil Joseph J , Mog Steven R , Panganiban Ronald Allan M , Bolduc David L , Rittase W Bradley , Bouten Roxane M , Day Regina M
Published: February 2021

The lung is sensitive to radiation and exhibits several phases of injury, with an initial phase of radiation-induced pneumonitis followed by delayed and irreversible fibrosis. The angiotensin-converting enzyme inhibitor captopril has been demonstrated to mitigate radiation lung injury and to improve survival in animal models of thoracic irradiation, but the mechanism remains poorly understood. Here we investigated the effect of captopril on early inflammatory events in the lung in female CBA/J mice exposed to thoracic X-ray irradiation of 17–17.9 Gy (0.5–0.745 Gy min–1). For whole-body + thoracic irradiation, mice were exposed to 7.5 Gy (0.6 Gy min–1) total-body 60Co irradiation and 9.5 Gy thoracic irradiation. Captopril was administered orally (110 mg kg–1 day–1) in the drinking water, initiated 4 h through to150 days post-irradiation. Captopril treatment increased survival from thoracic irradiation to 75% at 150 days compared with 0% survival in vehicle-treated animals. Survival was characterized by a significant decrease in radiation-induced pneumonitis and fibrosis. Investigation of early inflammatory events showed that captopril significantly attenuated macrophage accumulation and decreased the synthesis of radiation-induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) pro-inflammatory cytokines in the lungs of irradiated mice. Suppression of IL-1β and TNF-α correlated with an increase of the anti-inflammatory cytokine IL-10 in the spleen with captopril treatment. We also found that captopril decreased markers for radiation-induced accelerated senescence in the lung tissue. Our data suggest that suppression of inflammation and senescence markers, combined with an increase of anti-inflammatory factors, are a part of the mechanism for captopril-induced survival in thoracic irradiated mice.
The physiology and genetics behind fruiting efficiency: a promising spike trait to improve wheat yield potential
Authors: Pretini Nicole , Alonso María P , Vanzetti Leonardo S , Pontaroli Ana C , González Fernanda G
Published: February 2021

Fruiting efficiency (FE, grains per g of spike dry weight at anthesis) was proposed as a promising spike trait to improve wheat yield potential, based on its functional relationship with grain number determination and the evidence of trait variability in elite germplasm. During the last few years, we have witnessed great advances in the understanding of the physiological and genetic basis of this trait. The present review summarizes the recent heritability estimations and the genetic gains obtained when fruiting efficiency was measured at maturity (FEm, grains per g of chaff) and used as selection criterion. In addition, we propose spike ideotypes for contrasting fruiting efficiencies based on the fertile floret efficiency (FFE, fertile florets per g of spike dry weight at anthesis) and grain set (grains per fertile floret), together with other spike fertility-related traits. We also review novel genes and quantitative trait loci available for using marker-assisted selection for fruiting efficiency and other spike fertility traits. The possible trade-off between FE and grain weight and the genes reported to alter this relation are also considered. Finally, we discuss the benefits and future steps towards the use of fruiting efficiency as a selection criterion in breeding programs.
Resolving a dusty, star-forming SHiZELS galaxy at z = 2.2 with HST, ALMA, and SINFONI on kiloparsec scales
Authors: Cochrane R K , Best P N , Smail I , Ibar E , Cheng C , Swinbank A M , Molina J , Sobral D , Dudzevičiūtė U
Published: February 2021

We present ∼0.15 arcsec spatial resolution imaging of SHiZELS-14, a massive ($M_{*}\sim 10^{11}\, \rm {M_{\odot }}$), dusty, star-forming galaxy at z = 2.24. Our rest-frame ${\sim}1\, \rm {kpc}$-scale, matched-resolution data comprise four different widely used tracers of star formation: the $\rm {H}\,\alpha$ emission line (from SINFONI/VLT), rest-frame UV continuum (from HST F606W imaging), the rest-frame far-infrared (from ALMA), and the radio continuum (from JVLA). Although originally identified by its modest $\rm {H}\,\alpha$ emission line flux, SHiZELS-14 appears to be a vigorously star-forming ($\rm {SFR}\sim 1000\, \rm {M_{\odot }\, yr^{-1}}$) example of a submillimetre galaxy, probably undergoing a merger. SHiZELS-14 displays a compact, dusty central starburst, as well as extended emission in $\rm {H}\,\alpha$ and the rest-frame optical and FIR. The UV emission is spatially offset from the peak of the dust continuum emission, and appears to trace holes in the dust distribution. We find that the dust attenuation varies across the spatial extent of the galaxy, reaching a peak of at least AH α ∼ 5 in the most dusty regions, although the extinction in the central starburst is likely to be much higher. Global star-formation rates inferred using standard calibrations for the different tracers vary from ${\sim}10\!-\!1000\, \rm {M_{\odot }\, yr^{-1}}$, and are particularly discrepant in the galaxy’s dusty centre. This galaxy highlights the biased view of the evolution of star-forming galaxies provided by shorter wavelength data.
Mitonuclear Coevolution, but not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves
Authors: Piccinini Giovanni , Iannello Mariangela , Puccio Guglielmo , Plazzi Federico , Havird Justin C , Ghiselli Fabrizio
Published: February 2021

In Metazoa, four out of five complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mitonuclear coevolution. Previous studies have supported coadaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis,” a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations due to less efficient mitochondrial selection. In this study, we analyzed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared with non-OXPHO-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared with nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.
Identification of permissive amber suppression sites for efficient non-canonical amino acid incorporation in mammalian cells
Authors: Bartoschek Michael D , Ugur Enes , Nguyen Tuan-Anh , Rodschinka Geraldine , Wierer Michael , Lang Kathrin , Bultmann Sebastian
Published: February 2021

The genetic code of mammalian cells can be expanded to allow the incorporation of non-canonical amino acids (ncAAs) by suppressing in-frame amber stop codons (UAG) with an orthogonal pyrrolysyl-tRNA synthetase (PylRS)/tRNAPylCUA (PylT) pair. However, the feasibility of this approach is substantially hampered by unpredictable variations in incorporation efficiencies at different stop codon positions within target proteins. Here, we apply a proteomics-based approach to quantify ncAA incorporation rates at hundreds of endogenous amber stop codons in mammalian cells. With these data, we compute iPASS (Identification of Permissive Amber Sites for Suppression; available at www.bultmannlab.eu/tools/iPASS), a linear regression model to predict relative ncAA incorporation efficiencies depending on the surrounding sequence context. To verify iPASS, we develop a dual-fluorescence reporter for high-throughput flow-cytometry analysis that reproducibly yields context-specific ncAA incorporation efficiencies. We show that nucleotides up- and downstream of UAG synergistically influence ncAA incorporation efficiency independent of cell line and ncAA identity. Additionally, we demonstrate iPASS-guided optimization of ncAA incorporation rates by synonymous exchange of codons flanking the amber stop codon. This combination of in silico analysis followed by validation in living mammalian cells substantially simplifies identification as well as adaptation of sites within a target protein to confer high ncAA incorporation rates.
Targeted Truth: An Experiment Testing the Efficacy of Counterindustry Tobacco Advertisements Targeted to Black Individuals and Sexual and Gender Minority Individuals
Authors: Skurka Chris , Wheldon Christopher W , Eng Nicholas
Published: February 2021

Introduction

Some groups disproportionately suffer from tobacco-related illnesses—in part, because the tobacco industry has strategically targeted these groups. To combat industry targeting, antitobacco media campaigns (eg, the truth campaign) have used analogous messaging strategies, describing the industry’s targeted marketing practices to reach these vulnerable groups. We tested the efficacy of counterindustry tobacco advertisements targeted to vulnerable groups (Black individuals and sexual and gender minority [SGM] individuals).

Aims and Methods

From March to July 2020, we recruited N = 1161 young adults in the United States, including n = 430 Black young adults and n = 452 SGM young adults (with n = 108 identifying as Black and SGM). In a web-based, between-subjects experiment, participants were randomized to watch one of four types of advertisement (“ad”): (1) ads from the truth antismoking campaign not targeted toward a specific vulnerable group, (2) Black-targeted truth ads, (3) SGM-targeted truth ads, or (4) unrelated control ads. We examined effects on support for tobacco control policies, counterindustry motivation, counterindustry beliefs, perceived effectiveness, and anger toward the industry.

Results

Relative to control, non-targeted ads increased policy support, and Black-targeted ads increased motivation and beliefs. Targeted ads elicited anger regardless of the audience targeted. However, in general, neither Black identity nor SGM identity moderated the effects of the targeted ads.

Conclusions

We offer little evidence that targeted counterindustry ads are especially influential for their intended group. However, targeted counterindustry appeals may be successful at evoking industry anger regardless of the audience targeted.

Implications

Counterindustry advertisements from the truth campaign targeting Black individuals and SGM individuals had limited effect on tobacco control policies, counterindustry motivation, and counterindustry beliefs. However, counterindustry ads evoked anger toward the industry regardless of ingroup status, which in turn was positively associated with anti-industry outcomes. These results, considered alongside the extant literature, suggest little benefit to developing targeted counterindustry tobacco campaigns for specific groups and instead point to the utility of developing campaigns that appeal to broader audiences.
COVID-19 deaths among nurses: a cross-sectional study
Authors: Keles E , Bektemur G , Baydili K N
Published: February 2021

Background

Nurses who are one of the pivotal elements of countries’ strategic responses to COVID-19 are being exposed to COVID-19.

Aims

To investigate the underlying characteristics of nurses who died due to COVID-19.

Methods

On 1 September 2020, a grey literature search was conducted. Data obtained through Medscape, Google, PubMed, government and non-government websites. The search strategy was carried out using variants and combinations of keywords related to ‘nurse’ and ‘COVID-19’ in English. Abstracted data included age, gender, type of nurse, department of nursing, country, date of death and publication characteristics.

Results

Out of reported 1518 COVID-19-related nurse deaths, details of age, gender and department of nursing were available for 766 (50%), 945 (62%) and 153 (10%) of nurses, respectively. The median age of the nurses was 56 years. The majority of deaths were reported in the 46- to 65 (32%)-year age range. While the registered nurses had the highest number of deaths according to types of nurses (680/957; 71%), they are mental health nurses (42/153; 28%) in the department of nursing. The countries with the most reported nurse deaths were USA, South Africa, Mexico and Russia.

Conclusions

The predominance of deceased mental health nurses among nursing departments can be examined in future studies. Supportive health policies can be developed to increase the motivation of nurses.
T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy
Authors: Auma Ann W N , Shive Carey , Damjanovska Sofi , Kowal Corinne , Cohen Daniel E , Bhattacharya Debika , Alston-Smith Beverly , Osborne Melissa , Kalayjian Robert , Balagopal Ashwin , Sulkowski Mark , Wyles David , Anthony Donald D
Published: February 2021

Background

Immune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection.

Methods

Peripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy.

Results

Before therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38+HLA-DR+-expressing CD4+ and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38+HLA-DR+ co-expression on CD4+ and CD8+ memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38+HLA-DR+ CD4+ and CD4+CM T-cell frequencies. Monocyte subset activation remained similar over time.

Conclusions

During HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4+ T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4+ T-cell activation to residual factors driving activation in antiretroviral therapy–controlled HIV.
Rickets and gross motor delay in a child with atopic dermatitis
Authors: Salloum Shafee , Hatcher Vishaka
Published: February 2021

We report a case of a 14-month-old boy with atopic dermatitis (AD) who presented to our hospital with hypocalcemic tetany and gross motor delay. Further laboratory and imaging confirmed the diagnosis of vitamin D deficiency and rickets. He was breastfeeding and on a restricted diet due to presumed multiple food allergies. He received calcium and vitamin D supplementation which corrected his hypocalcemia. The patient developed Staphylococcus aureus bacteremia and superficial septic thrombophlebitis for which he was treated with antibiotics and anticoagulation. An elimination diet should be avoided in AD patients as true food-induced AD is rare and management should focus on optimal skincare. AD patients have a higher rate of S. aureus skin colonization, which increases their risk for infectious complications. This case also highlights the importance of maintaining a high index of suspicion for rickets in children with isolated gross motor delay, especially in those with risk factors.
Migration and Partisan Change
Authors: Morris Irwin L.
Published: February 2021

As Democratic Party attachment and support for Democratic candidates has begun to grow in the South, existing theories designed to explain Republican growth—whether based on race relations, economic growth, or cultural conservatism—fare poorly. The author advances a new theory—Movers and Stayers theory—to explain this recent growth in Democratic support. This chapter includes a broad outline of the theory—one focused on population growth’s role in the expansion of Democratic support—and an explanation of the dynamics that boost progressivism in high-growth areas and inhibit its development in declining communities. The theory highlights the role of the distinctive progressivism of movers on the political attitudes of stayers in their new homes, and stayers in the communities they have left. The theory explains why community decline results in different political responses from whites and people of color, and it highlights the waning significance of Key’s “black belt” hypothesis.
Population Growth and Partisan Change in the South
Authors: Morris Irwin L.
Published: February 2021

The migratory mechanism at the heart of movers and stayers theory is at the local level, but the aggregation of these localized effects generate state-level dynamics as well. Over the past 20 years, the southern states have increasingly diverged into those with high population growth and those with low population growth. As movers and stayers theory predicts, these differences in population growth produce political differences. There is a substantively and statistically significant relationship between faster population growth and increased support for Democratic presidential candidates. Diverging population trajectories have also eroded the traditional political distinctions between the Rim South and the Deep South. Today, the primary sub-regional distinction is between the high-growth states and the low-growth states. Evidence from the partisan split in U.S. House delegations and both the lower and upper houses of the southern state legislatures clearly illustrates the significance of this new population-based sub-regional distinction.
Populations
Authors: Smil Vaclav
Published: February 2021

Demographic transition has been completed everywhere except for large parts of Africa. Steady decline of traditionally high fertilities and mortalities brought temporarily high rates of population growth (globally peaking during the 1960s), as the worldwide count rose from about 1 billion in 1800 to more than 7.8 billion by 2020. The new prevailing pattern of population dynamics is characterized by very low infant mortalities, fertilities well below the replacement level, increasing longevities, and aging, even decline, of many populations. Generations of high growth rates and productivity gains in agriculture and abundance of fossil fuels led to an unprecedented pace of urbanization. More than half of humanity now lives in cities, including a rising number of megacities, each with more than 10 million people.