bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic evidence for co-occurrence of antibiotic, biocide and metal resistance genes in pigs
Authors: Li Xuanji , Rensing Christopher , Vestergaard Gisle , Nesme Joseph , Gupta Shashank , Arumugam Manimozhiyan , Brejnrod Asker Daniel , Sørensen Søren Johannes
Published: January 2021

Antibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metals/biocides and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging toEnterobacteriaceaedisplayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.

Highlights

A comprehensive gut microbiome metagenomics analysis of 278 pigs

Co-selection phenomena were investigated via co-occurrence patterns as a proxy

Twenty-seven types of co-occurrences involving 131 resistance genes were detected

Regardless of use of antibiotics, AMR can be maintained by co-occurrence with MRGs/BRGs

Maintenance of AMR is not a random selection process but pertains to specific phylogenetic clades
Electrophysiological maturation and increased excitability of human iPSC-derived neurons inHTR2Avariant-related sleep bruxism
Authors: Sarkar Avijite Kumer , Nakamura Shiro , Nakai Kento , Shiga Takahiro , Abe Yuka , Hoashi Yurie , Inoue Tomio , Akamatsu Wado , Baba Kazuyoshi
Published: January 2021

Sleep bruxism (SB) is a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep. We previously found a significant association between SB and a single nucleotide polymorphism (SNP), rs6313, in the neuronal serotonin 2A receptor gene (HTR2A), and established human induced pluripotent stem cell (hiPSC)-derived neurons from SB patients with a genetic variant. To elucidate the electrophysiological characteristics of SB iPSC-derived neural cells bearing a SB-related genetic variant, we generated ventral hindbrain neurons from two SB patients and two unaffected controls and explored the intrinsic membrane properties of these neurons by patch-clamp technique. We found that the electrophysiological properties of the iPSC-derived neurons from the control line mature in a time-dependent manner in long-term cultures. In the early stage of neurogenesis, neurons from two SB lines tended to display shorter action potential (AP) half durations, which led to an increased cell capability of evoked firing. This is the firstin vitromodelling of SB using disease-specific hiPSCs. The revealed electrophysiological characteristics may serve as a benchmark for further investigation of pathogenic mechanisms underlying SB.

Summary Statement

Sleep bruxism patient-specific iPSC-derived neurons with theHTR2Avariant show altered electrophysiological characteristics, providing the foremost narration of sleep bruxism neurological phenotypesin vitrofrom any species.
tTARGIT AAVs: A sensitive and flexible method to manipulate intersectional neuronal populations
Authors: Sabatini Paul V. , Wang Jine , Rupp Alan C. , Affinati Alison H. , Flak Jonathan N. , Li Chien , Olson David P. , Myers Martin G.
Published: January 2021

While Cre-dependent viral systems permit the manipulation of many neuron types, some cell populations cannot be targeted by a single DNA recombinase. Although the combined use of Flp and Cre recombinases can overcome this limitation, insufficient recombinase activity can reduce the efficacy of existing Cre+Flp-dependent viral systems. We developed a sensitive dual recombinase-activated viral approach: tTA-driven Recombinase-Guided Intersectional Targeting (tTARGIT) AAVs. tTARGIT AAVs utilize a Flp-dependent tetracycline transactivator (tTA) “Driver” AAV and a tetracycline response element (TRE)-driven, Cre-dependent “Payload” AAV to express the transgene of interest. We employed this system inSlc17a6FlpO;LeprCremice to manipulate LepRb neurons of the ventromedial hypothalamus (VMH; LepRbVMHneurons) while omitting neighboring LepRb populations. We defined the circuitry of LepRbVMHneurons and roles for these cells in the control of food intake and energy expenditure. Thus, the tTARGIT system mediates robust recombinase-sensitive transgene expression, permitting the precise manipulation of previously intractable neural populations.
Two NLR immune receptors acquired high-affinity binding to a fungal effector through convergent evolution of their integrated domain
Authors: Białas Aleksandra , Langner Thorsten , Harant Adeline , Contreras Mauricio P , Stevenson Clare EM , Lawson David M , Sklenar Jan , Kellner Ronny , Moscou Matthew J , Terauchi Ryohei , Banfield Mark J , Kamoun Sophien
Published: January 2021

A subset of plant NLR immune receptors carry unconventional integrated domains in addition to their canonical domain architecture. One example is rice Pik-1 that comprises an integrated heavy metal–associated (HMA) domain. Here, we reconstructed the evolutionary history of Pik-1 and its NLR partner, Pik-2, and tested hypotheses about adaptive evolution of the HMA domain. Phylogenetic analyses revealed that the HMA domain integrated into Pik-1 before Oryzinae speciation over 15 million years ago and has been under diversifying selection. Ancestral sequence reconstruction coupled with functional studies showed that two Pik-1 allelic variants independently evolved from a weakly binding ancestral state to high-affinity binding of the blast fungus effector AVR-PikD. We conclude that for most of its evolutionary history the Pik-1 HMA domain did not sense AVR-PikD, and that different Pik-1 receptors have recently evolved through distinct biochemical paths to produce similar phenotypic outcomes. These findings highlight the dynamic nature of the evolutionary mechanisms underpinning NLR adaptation to plant pathogens.
Niclosamide Inhalation Powder Made by Thin-Film Freezing: Pharmacokinetic and Toxicology Studies in Rats and Hamsters
Authors: Jara Miguel O. , Warnken Zachary N. , Sahakijpijarn Sawittree , Moon Chaeho , Maier Esther Y. , Christensen Dale J. , Koleng John J. , Peters Jay I. , Hackman Sarah D. , Williams Robert O.
Published: January 2021

In this work, we have developed and testedin vivoa dry powder form of niclosamide made by thin-film freezing (TFF) and administered it by inhalation to rats and hamsters. The niclosamide dry powder, suitable for inhalation, is being developed as a therapeutic agent against COVID-19 infection. Niclosamide, a poorly water-soluble drug, is an interesting drug candidate because it was approved over 60 years ago for use as an anthelmintic medication, but recent studies demonstrated its potential as a broad-spectrum antiviral with a specific pharmacological effect against SARS-CoV-2 infection. In the past, clinical trials for other indications were terminated prior to completion due to low and highly variable oral bioavailability. In order to quickly address the current pandemic, targeting niclosamide directly to the lungs is rational to address the COVID-19 main clinical complications. Thin-film freezing technology was used to develop a niclosamide inhalation powder composition that exhibited acceptable aerosol performance with a fine particle fraction (FPF) of 86.0% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 1.11 μm and 2.84, respectively. This formulation not only proved to be safe after an acute three-day, multi-dose pharmacokinetic study in rats as evidenced by histopathology analysis, but also was able to achieve lung concentrations above the required IC50and IC90levels for at least 24 h after a single administration in a Syrian hamster model. To conclude, we successfully developed a niclosamide dry powder inhalation formulation by thin-film freezing for further scale-up and clinical testing against the COVID-19 infection. This approach overcomes niclosamide’s limitation of poor oral bioavailability by targeting the drug directly to the primary site of infection, the lungs.
Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide
Authors: Daron J. , Bravo I.G.
Published: January 2021

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus within theOrthocoronavirinaecausing an emergent infectious disease in humans, the ongoing coronavirus disease 2019 pandemic (COVID-19). Due to the high zoonotic potential of these viruses, it is critical to unravel their evolutionary history of host species shift, adaptation and emergence. Only such knowledge can guide virus discovery, surveillance and research efforts to identify viruses posing a pandemic risk in humans. We present a comprehensive analysis of the composition and codon usage bias of the 82Orthocoronavirinaemembers, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation. Further insight on the mutational equilibrium withinOrthocoronavirinaerevealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium.
Imagined speech can be decoded from low- and cross-frequency features in perceptual space
Authors: Proix Timothée , Saa Jaime Delgado , Christen Andy , Martin Stephanie , Pasley Brian N. , Knight Robert T. , Tian Xing , Poeppel David , Doyle Werner K. , Devinsky Orrin , Arnal Luc H. , Mégevand Pierre , Giraud Anne-Lise
Published: January 2021

Reconstructing intended speech from neural activity using brain-computer interfaces (BCIs) holds great promises for people with severe speech production deficits. While decodingovertspeech has progressed, decodingimaginedspeech have met limited success, mainly because the associated neural signals are weak and variable hence difficult to decode by learning algorithms. Using three electrocorticography datasets totalizing 1444 electrodes from 13 patients who performed overt and imagined speech production tasks, and based on recent theories of speech neural processing, we extracted consistent and specific neural features usable for future BCIs, and assessed their performance to discriminate speech items in articulatory, phonetic, vocalic, and semantic representation spaces. While high-frequency activity provided the best signal for overt speech, both low- and higher-frequency power and local cross-frequency contributed to successful imagined speech decoding, in particular in phonetic and vocalic, i.e. perceptual, spaces. These findings demonstrate that low-frequency power and cross-frequency dynamics contain key information for imagined speech decoding, and that exploring perceptual spaces offers a promising avenue for future imagined speech BCIs.
Does where you live influence what you are made of? Spatial correlates of chemical traits across commonly occurring boreal plants
Authors: Heckford Travis R , Leroux Shawn J. , Wal Eric Vander , Rizzuto Matteo , Balluffi-Fry Juliana , Richmond Isabella C. , Wiersma Yolanda F.
Published: January 2021

Context

Spatially explicit drivers of foliar chemical traits link plants to ecosystem processes to reveal landscape functionality. Specifically, foliar elemental, stoichiometric, and phytochemical (ESP) compositions represent key indicator traits.

Objectives

Here, we investigate the spatial drivers of foliar ESP at the species level and across species at the trait level for five commonly occurring boreal forest understory plants.

Methods

On the island of Newfoundland, Canada, we collected foliar material from four chronosequenced forest grids. Using response variables of foliar elemental (C, N, P, percent and quantity), stoichiometric (C:N, C:P, N:P), and phytochemical (terpenoids) composition, we tested multiple competing hypotheses using spatial predictors of land cover (e.g., coniferous, deciduous, mixedwood), productivity (e.g., enhanced vegetation index), biotic (e.g., stand age/height, canopy closure) and abiotic (e.g., elevation, aspect, slope) factors.

Results

We found evidence to support spatial relationships of foliar ESP for most species (mean R2= 0.22, max = 0.65). Spatial variation in elemental quantity traits of C, N, P were related to land cover along with biotic and abiotic factors for 2 of 5 focal species. Notably, foliar C, C:P, and sesquiterpene traits between different species were related to abiotic factors. Similarly, foliar terpenoid traits between different species were related to a combination of abiotic and biotic factors (mean R2= 0.26).

Conclusions

Spatial-trait relationships mainly occur at the species level, with some commonalities occurring at the trait level. By linking foliar ESP traits to spatial predictors, we can map plant chemical composition patterns that influence landscape-scale ecosystem processes.
Training with an auditory perceptual learning game transfers to speech in competition
Authors: de Larrea-Mancera E. Sebastian Lelo , Philipp Mark Allen , Stavropoulos Trevor , Carrillo Audrey Anna , Cheung Sierra , Koerner Tess , Molis Michelle R. , Gallun Frederick J. , Seitz Aaron R.
Published: January 2021

Hearing speech in competition is a major complaint in those who suffer from hearing loss. Here we investigate a novel perceptual learning game that is designed to train perceptual skills thought to underlie speech in competition, such as spectral-temporal processing and sound localization, under conditions of quiet and in noise. Thirty young normal hearing participants were assigned either to this mixed-training condition or an active control consisting of frequency discrimination training within the same gamified setting. To assess training outcomes, we examine tests of basic central auditory processing, speech in competition, and cognitive processing abilities before and after training. Results suggest modest improvements on speech in competition tests in the mixed-training but not the frequency-discrimination control condition. This data show promise for future applications in populations with hearing difficulties.
Enhancing motor learning by increasing stability of newly formed dendritic spines in motor cortex
Authors: Albarran Eddy , Raissi Aram , Jáidar Omar , Shatz Carla J. , Ding Jun B.
Published: January 2021

Dendritic spine dynamics of Layer 5 Pyramidal neurons (L5PNs) are thought to be physical substrates for motor learning and memory of motor skills and altered spine dynamics are frequently correlated with poor motor performance. Here we describe an exception to this rule by studying mice lacking Paired immunoglobulin receptor B (PirB−/−). Using chronic two-photon imaging of primary motor cortex (M1) of PirB−/−;Thy1-YFP-H mice, we found a significant increase in the survival of spines on apical dendritic tufts of L5PNs, as well as increased spine formation rates and spine density. Surprisingly and contrary to expectations, adult PirB−/− mice learn a skilled reaching task more rapidly compared to wild type (WT) littermate controls. Conditional excision of PirB from forebrain pyramidal neurons in adult mice replicated these results. Furthermore, chronic imaging of L5PN dendrites throughout the learning period revealed that the stabilization of learning-induced newly formed spines is significantly elevated in PirB−/− mice. The degree of survival of newly formed spines in M1 yielded the strongest correlation with task performance, suggesting that this increased spine stability is advantageous and can translate into enhanced acquisition and maintenance of motor skills. Notably, inhibiting PirB function acutely in M1 of adult WT mice throughout training increases the survival of spines formed during early training and enhances motor learning. These results suggest that increasing the stability of newly formed spines is sufficient to improve long-lasting learning and motor performance and demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.
Mapping South Africaʼs nationally determined contributions to the targets of the sustainable development goals
Authors: Mantlana Khanyisa B. , Maoela Malebajoa A. , Nhamo Godwell
Published: January 2021

The Paris Agreementʼs nationally determined contributions (NDCs) provide an excellent point of entry to simultaneously address climate change and the 2030 Agenda for Sustainable Development and its Sustainable Development Goals (SDGs). This study sets out to explore the connections between climate action plans (NDCs) and each of the 17 Sustainable Development Goals (SDGs). In this study, we used four levels of visibility, that is, present, generic, implied and absent to provide a broad perspective of the extent to which South Africaʼs NDC is aligned with the targets of the SDGs. Our results revealed that South Africaʼs NDC has 12% present level of visibility to the SDG targets, with SDG 7 Affordable and Clean Energy and SDG 13 Climate Action showing the highest representation of present level of visibility. By contrast, the absent level of visibility NDC showed 53% in the SDG targets, with SDG 5 Gender Equity, SDG 16 Peace, Justice and Strong Institutions and SDG 3 Good Health and Well‐Being, showing the highest representation of absent level of visibility. These results indicate that there is scope to improve the alignment of South Africaʼs NDCs with the SDG targets. To this end, we have identified areas that may benefit with further elaboration in the countryʼs second NDC.
Overcoming the impact of the COVID‐19 pandemic on oncology early phase trials and drug development in Asia—Experiences and perspectives of the Asian Oncology Early Phase 1 Consortium
Authors: Shimizu Toshio , Kim Dong‐Wan , Loong Herbert H. , Lin Chia‐Chi , Ng Matthew CH , Yamamoto Noboru , Ma Brigette , Tan Daniel SW
Published: January 2021

Aim

The significance and prioritization of early phase oncology trial continuation during a global pandemic is unknown. This study reported the outcomes, multiple challenges, and broad recommendations associated with the impact of the novel coronavirus disease 2019 (COVID‐19) on oncology early phase 1 trials—and on drug development in Asia—based on the experiences and perspectives of Asian oncology phase 1 centers.

Methods

Between March and April 2020 during the initial period of outbreak, the impact of COVID‐19 across oncology phase 1 sites in five Asian countries—China (Hong Kong), Japan, South Korea, Taiwan, and Singapore—was retrospectively analyzed.

Results

There was no trial termination or treatment discontinuation in all five countries. Although the most common impact was new patient enrollment being placed on hold, which was based on pharmaceutical sponsors’ decision‐making, the situation varied per site. Most sites had no restrictions in place that would limit their ability to fully comply with the requirements of conducting the early phase studies. The number of protocol deviations during the pandemic was largely dependent on domestic transportation status during the outbreak rather than the ability of the clinical trial centers.

Conclusion

Determining the risk to benefits ratio of patients with cancer who are enrolled in early phase 1 clinical trials under the unusual circumstances of a global pandemic is important. Specific guidance or guidelines on the conduct of early phase 1 clinical trials during public health emergencies that are based on the recent lessons learned is urgently required.
Addressing surgical inequity for Aboriginal and Torres Strait Islander people in Australia's universal health care system: a call to action
Authors: O'Brien Penny , Bunzli Samantha , Lin Ivan , Bessarab Dawn , Coffin Juli , Dowsey Michelle M. , Choong Peter F. M.
Published: January 2021

Aboriginal and Torres Strait Islander people continue to experience health inequity within the Australian health care system. Little research has examined how disparities in surgical care access and outcomes contribute to Aboriginal health. In this narrative review and call to action, we discuss five care points along the journey to high‐quality surgical care: health care seeking, primary health care services, specialist services, surgery and surgical outcomes. We highlight barriers and disparities that exist along this journey, drawing examples from the field of joint replacement surgery. Finally, we present opportunities for change at the health system, health service and clinician level, calling upon researchers, clinicians and policy makers to confront the surgical disparities experienced by Aboriginal and Torres Strait Islander people.
New Zealand and Australia emergency laparotomy mortality rates compare favourably to international outcomes: a systematic review
Authors: Fagan Georgina , Barazanchi Ahmed , Coulter Grant , Leeman Matthew , Hill Andrew G. , Eglinton Tim W.
Published: January 2021

Background

Almost 20 000 people undergo an emergency laparotomy each year in New Zealand and Australia. Common indications include small and large bowel obstruction, and intestinal perforation. Considered a high‐risk procedure, emergency laparotomy is associated with significantly high morbidity and mortality. The aim of this review was to identify and compare 30‐day, 90‐day and 1‐year mortality rates following emergency laparotomy in New Zealand and Australia.

Methods

A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Electronic searches were performed in Medline, Embase, PubMed and Scopus in April 2020.

Results

Thirty‐three papers met the inclusion criteria. Studies ranged in size from 58 to 75 280 patients. Weighted mean 30‐day mortality was 8.40% (8.39–8.41). Mortality rates increased with longer postoperative follow up with 90‐day weighted mortality rate of 14.14% (14.13–14.15) and the weighted mortality rate at 1 year of 24.60% (24.56–24.66). There was significant variability in mortality rates between countries.

Conclusion

There is a wide variability of 30‐day, 90‐day and 1‐year mortality rates internationally. Lowering postoperative mortality rates following emergency laparotomy through quality improvement initiatives could result in up to 120 lives in New Zealand and over 250 lives in Australia being saved each year. The continued work of the Australian and New Zealand Emergency Laparotomy Audit – Quality Improvement is crucial to improving emergency laparotomy mortality rates further in New Zealand and Australia.
The impact of limbus detection, arcus lipoides and limbal vessels on the primary patency of clear cornea incisions in femtosecond laser‐assisted cataract surgery
Authors: Boden Karl Thomas , Schlosser Rosemarie , Reipen Lena , Seitz Berthold , Januschowski Kai , Szurman Peter , Wakili Philip , Julich‐Haertel Henrike , Rickmann Annekatrin
Published: January 2021

Purpose

To analyse the factors influencing the primary patency of clear corneal incisions in femtosecond laser‐assisted cataract surgery (FLACS).

Methods

In this prospective single‐centre study, the graphical user interfaces of 159 patients undergoing femtosecond laser‐assisted cataract surgery were documented by video. Subsequently, the quality of limbus detection along with the incidence of vessels and an arcus lipoides were assessed by a grading system and analysed in relation to the primary patency of the incisions. In particular, the differences between a superior and a temporal main incision were analysed.

Results

The designed grading system could be applied in all cases without any problems. Limbus detection was highly inhomogeneous but had no influence on the patency of the incisions (46.3% poor, 18.4% moderate, 35.1% good). The characteristics of the arcus lipoides had little influence on the patency of the main incisions. Pronounced vascular ingrowth caused more tissue bridges but did not reduce the patency of the incisions. Temporal access was generally easier to open than a superior one (97.1% versus 88.9%).

Conclusion

We showed a patency rate of superior FLACS incisions of over 97% with the Femto LDV Z8 in our study. Temporal main incision is preferable to superior main incision in more difficult situations. The new grading system is suitable for further studies to provide information on the quality of the incision.
Predicting mortality from acetaminophen poisoning shortly after hospital presentation
Authors: Yarema Mark C. , Johnson David W. , Sivilotti Marco L.A. , Nettel‐Aguirre Alberto , DeWitt Chris , Gosselin Sophie , Murphy Nancy , Victorino Charlemagne , Bailey Benoit , Dong Kathryn , Haney Elizabeth , Purssell Roy , Thompson Margaret , Lord Jason A. , Spyker Daniel A. , Rumack Barry H.
Published: January 2021

Aims

Early identification of patients likely to die after acetaminophen (APAP) poisoning remains challenging. We sought to compare the sensitivity and time to fulfilment (latency) of established prognostic criteria.

Methods

Three physician toxicologists independently classified every in‐hospital death associated with APAP overdose from eight large Canadian cities over three decades using the Relative Contribution to Fatality scale from the American Association of Poison Control Centres. The sensitivity and latency were calculated for each of the following criteria: King's College Hospital (KCH), Model for End Stage Liver Disease (MELD) ≥33, lactate ≥3.5 mmol/L, phosphate ≥1.2 mmol/L 48+ hours post‐ingestion, as well as combinations thereof.

Results

A total of 162 in‐hospital deaths were classified with respect to APAP as follows: 26 Undoubtedly, 40 Probably, 27 Contributory, 14 Probably not, 25 Clearly not, and 30 Unknown. Cases from the first three classes (combined into n = 93 “APAP deaths”) typically presented with supratherapeutic APAP concentrations, hepatotoxicity, acidaemia, coagulopathy and/or encephalopathy, and began antidotal treatment a median of 12 hours (IQR 3.4–30 h) from the end of ingestion. Among all patients deemed “APAP deaths”, meeting either KCH or lactate criteria demonstrated the highest sensitivity (94%; 95% CI 86–98%), and the shortest latency from hospital arrival to criterion fulfilment (median 4.2 h; IQR 1.0–16 h). In comparison, the MELD criterion demonstrated a substantially lower sensitivity (55%; 43–66%) and longer latency (52 h; 4.4–∞ h, where “∞” denotes death prior to criterion becoming positive).

Conclusions

Meeting either KCH or serum lactate criteria identifies most patients who die from acetaminophen poisoning at or shortly after hospital presentation.
Targeting macrophage liver X receptors by hydrogel‐encapsulated T0901317 reduces atherosclerosis without effect on hepatic lipogenesis
Authors: Ma Chuanrui , Feng Ke , Yang Xiaoxiao , Yang Zhimou , Wang Zhongyan , Shang Yuna , Fan Guanwei , Liu Lipei , Yang Shu , Li Xiaoju , Han Jihong , Duan Yajun , Chen Yuanli
Published: January 2021

Background and Purpose

Targeting macrophage but not hepatocyte liver X receptors (LXRs) can reduce atherosclerosis without effect on hepatic lipogenesis. In this study, we encapsulated LXR ligands with D‐Nap‐GFFY to form a nanofibre hydrogel (D‐Nap‐GFFY‐T0901317 or GFFY‐T0901317) and determined its effect on atherosclerosis, hepatic lipogenesis and the underlying mechanisms involved.

Experimental Approach

D‐Nap‐GFFY‐T0901317 was subcutaneously injected to proatherogenic diet‐fed apoE‐deficient (Apoe−/−) mice, followed by determination of the development of atherosclerosis, liver steatosis and the involved mechanisms, with comparison of T0901317 oral administration.

Key Results

Subcutaneous injection of D‐Nap‐GFFY‐T0901317 to Apoe−/− mice inhibited atherosclerosis at a comparable level as T0901317 oral administration without effect on hepatic lipogenesis. More importantly, D‐Nap‐GFFY‐T0901317 regressed the advanced lesions. In arterial wall, D‐Nap‐GFFY‐T0901317 reduced macrophage/foam cells, necrotic cores and calcification and increased collagen content. It activated expression of ABCA1/G1 and smooth muscle α‐actin, while inhibiting expression of intracellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1). D‐Nap‐GFFY‐T0901317 also reduced serum pro‐inflammatory cytokines and facilitated Kupffer cell M2 polarization. Mechanistically, D‐Nap‐GFFY‐T0901317 was selectively taken up by macrophages but not hepatocytes, resulting in activation of macrophage ABCA1/G1 expression, while having no effect on lipogenic genes in hepatocytes. Moreover, the selective uptake of D‐Nap‐GFFY‐T0901317 by macrophages was mainly completed in a scavenger receptor class A‐dependent manner.

Conclusion and Implications

Our study demonstrates that D‐Nap‐GFFY‐T0901317 reduces atherosclerosis without effect on hepatic lipogenesis by targeting macrophage LXRs selectively, indicating its potential application for atherosclerosis treatment.
Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile
Authors: Heald Adrian H. , Martin Susan , Fachim Helene , Green Harry D. , Young Katherine G. , Malipatil Nagaraj , Siddals Kirk , Cortes Gabriela , Tyrrell Jessica , Wood Andrew R , Beaumont Robin N. , Frayling Timothy M. , Donn Rachelle , Narayanan Ram Prakash , Ollier William , Gibson Martin , Yaghootkar Hanieh
Published: January 2021

Aims

Change in weight, HbA1c, lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression.

Methods

We involved people with type 2 diabetes from two UK‐based cohorts: 11,914 individuals with GP follow‐up data from the UK Biobank and 723 from Salford. We generated a ‘favourable adiposity’ genetic score and conducted cross‐sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow‐up time points with 1‐year intervals.

Results

The ‘favourable adiposity’ genetic score was cross‐sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91 kg [0.59,1.23]) and BMI (0.30 kg/m2 [0.19,0.40]), but higher high‐density lipoprotein (0.02 mmol/L [0.01,0.02]) and lower triglycerides (−0.04 mmol/L [−0.07, −0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow‐up.

There was a trend for participants with higher ‘favourable adiposity’ genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62, 1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid‐lowering (0.91 [0.86, 0.97]) and anti‐hypertensive medication (0.95 [0.91, 0.99]).

Conclusions

In individuals with type 2 diabetes, having more ‘favourable adiposity’ alleles is associated with a marginally better lipid profile long‐term and having lower odds of requiring lipid‐lowering or anti‐hypertensive medication in spite of relatively higher adiposity.
Occurrence of Diaporthe species in Eucalyptus globulus, Pinus pinaster and Quercus suber in Portugal
Authors: Lopes Ana Filipa , Batista Eduardo , Hilário Sandra , Santos Liliana , Alves Artur
Published: January 2021

The genus Diaporthe is a cosmopolitan group of fungi that includes important plant pathogens, endophytes and saprobes with the ability to colonize a wide range of plant hosts. Pathogenic Diaporthe species are often reported to cause symptoms like dieback, stem canker, leaf spots, fruit rots and seed decay resulting in important economic losses on several crops. However, the occurrence of Diaporthe species associated with forest hosts and their pathogenic potential is poorly understood. We studied a collection of Diaporthe isolates obtained from a survey of forest‐related fungal diseases on Eucalyptus globulus, Pinus pinaster and Quercus suber in Portugal. Several Diaporthe species (D. eres, D. rudis, D. crousii, D. malorum and D. foeniculina) were found among the studied hosts. Pathogenicity trials were conducted to analyse the pathogenic potential and the ability to colonize putative new hosts. We report the occurrence of D. eres on P. pinaster in Portugal and a new host association with Q. suber. Additional new host reports were as follows: D. malorum and D. crousii on E. globulus, D. foeniculina on Q. suber and D. rudis on P. pinaster. Overall, Diaporthe species were shown to have low pathogenic impact on forest hosts under non‐stress conditions, despite their capability to colonize different hosts during the pathogenicity trials.
Calling activity determines male mating success in a territorial frog with parental care
Authors: Souza Jesus R. D. , Kaefer Igor L. , Lima Albertina P.
Published: January 2021

A contentious aspect in dendrobatoid frog behaviour is the recognition of the predominant factor—if any—driving male mating success. This is probably related to an extensive correlation among different male quality predictors. Here, we investigated the diurnal and territorial nurse frog Allobates subfolionidificans by means of a field study during one entire breeding season in Brazilian Amazonia. We tested the roles of two intrinsic male properties (body size and calling activity) and five territory‐related variables (territory size, vegetation cover, nesting site, perch height and food availability) on male reproductive output. A multiple regression analysis revealed calling activity as the only variable predicting male mating success in A. subfolionidificans. Vocalisation probably represents the most energetically expensive activity that a male frog undertakes during his lifetime, thus calling activity may be used by A. subfolionidificans females as a cue to mate choice that indicates competitive potential and male quality. Alternatively, non‐choosy females also should be more likely to encounter and mate with males that advertise more often throughout the breeding season.
Nursing management at a Chinese fever clinic during the COVID‐19 pandemic
Authors: Wang Y. , Qiang W.‐m. , Wang C. , Wu P.‐p. , Li M.‐m. , Kong Q.‐q. , Yu L.‐y. , Chen L.
Published: January 2021

Background

The rampant spread of the novel coronavirus disease (COVID‐19) has assumed pandemic proportions across the world. Attempts to contain its spread have entailed varying early screening and triage strategies implemented in different countries and regions.

Aim

To share the experience of scientific and standardized management of fever clinics in China, which provide the first effective checkpoint for the prevention and control of COVID‐19.

Introduction

A fever clinic was established at our hospital in Tianjin, China, for initially identifying suspected cases of COVID‐19 and controlling the spread of the disease.

Methods

The management system covered the following aspects: spatial layout; partitioning of functional zones; a work management system and associated processes; management of personnel, materials and equipment; and patient education.

Results

Within two months of introducing these measures, there was a comprehensive reduction in the number of new COVID‐19 cases in Tianjin, and zero infections occurred among medical staff at the fever clinic.

Discussion

The fever clinic plays an important role in the early detection, isolation and referral of patients presenting with fevers of unknown origin. Broad screening criteria, an adequate warning mechanism, manpower reserves and staff training at the clinic are essential for the early management of epidemics.

Conclusion

The spread of COVID‐19 has been effectively curbed through the establishment of the fever clinic, which merits widespread promotion and application.

Implications for nursing and health policies

Health managers should be made aware of the important role of fever clinics in the early detection, isolation and referral of patients, and in the treatment of infectious diseases to prevent and control their spread. In the early stage of an epidemic, fever clinics should be established in key areas with concentrated clusters of cases. Simultaneously, the health and safety of health professionals require attention.
Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City
Authors: Sieling William D. , Goldman Connor R. , Oberhardt Matthew , Phillips Matthew , Finelli Lyn , Saiman Lisa
Published: January 2021

Background

Although the burden of influenza is well characterized, the burden of community‐onset non‐influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non‐influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines.

Methods

From October 2017 to September 2019, a retrospective study was performed in a pre‐defined catchment area to estimate the population‐based incidence of community‐onset respiratory viruses associated with hospitalization. Included patients were ≥18 years old, resided in New York City, were hospitalized for ≥24 hours, and had a respiratory virus detected within 3 calendar‐days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in‐hospital mortality and compared among those with laboratory‐confirmed influenza versus those with laboratory‐confirmed non‐influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus).

Results

During the study period, 4232 eligible patients were identified of whom 50.9% were ≥65 years of age. For each virus, the population‐based incidence was highest for those ≥80 years of age. When compared to those with influenza viruses detected, those with non‐influenza respiratory viruses detected (combined) had higher population‐based incidence, significantly more ICU admissions, and higher in‐house mortality.

Conclusions

The burden of non‐influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non‐influenza respiratory viruses, particularly for older adults.
Personal protective equipment related skin reactions in healthcare professionals during COVID‐19
Authors: Abiakam Nkemjika , Worsley Peter , Jayabal Hemalatha , Mitchell Kay , Jones Michaela , Fletcher Jacqui , Spratt Fran , Bader Dan
Published: January 2021

Since the outbreak of COVID‐19 pandemic, clinicians have had to use personal protective equipment (PPE) for prolonged periods. This has been associated with detrimental effects, especially in relation to the skin health. The present study describes a comprehensive survey of healthcare workers (HCWs) to describe their experiences using PPE in managing COVID‐19 patients, with a particular focus on adverse skin reactions. A 24‐hour prevalence study and multi‐centre prospective survey were designed to capture the impact of PPE on skin health of hospital staff. Questionnaires incorporated demographics of participants, PPE type, usage time, and removal frequency. Participants reported the nature and location of any corresponding adverse skin reactions. The prevalence study included all staff in intensive care from a single centre, while the prospective study used a convenience sample of staff from three acute care providers in the United Kingdom. A total of 108 staff were recruited into the prevalence study, while 307 HCWs from a variety of professional backgrounds and demographics participated in the prospective study. Various skin adverse reactions were reported for the prevalence study, with the bridge of the nose (69%) and ears (30%) being the most affected. Of the six adverse skin reactions recorded for the prospective study, the most common were redness blanching (33%), itchiness (22%), and pressure damage (12%). These occurred predominantly at the bridge of the nose and the ears. There were significant associations (P < .05) between the adverse skin reactions with both the average daily time of PPE usage and the frequency of PPE relief. The comprehensive study revealed that the use of PPE leads to an array of skin reactions at various facial locations of HCWs. Improvements in guidelines are required for PPE usage to protect skin health. In addition, modifications to PPE designs are required to accommodate a range of face shapes and appropriate materials to improve device safety.
Drying kinetics of beef meat: Modeling by the isenthalpe mass flux method
Authors: Tom Ahmat , Bruneau Denis , Djongyang Noël
Published: January 2021

This article presents an experimental study of the drying kinetics of beef meat and a new approach of modeling these kinetics based on mass flow. Seven drying conditions, similar to those found in tropical drying processes were explored, combining three temperature values (40,50, and 60 ° C), three air velocity values (0.33, 0.66, and 1 m/s) and three relative humidity values (25, 50, and 65%). Results showed two phases of drying: a first short phase, of constant drying rate called isenthalpe phase and a second phase of decreasing drying speed. The kinetics model obtained takes into account the intrinsic characteristics of the product (equilibrium water content, initial content, and critical water content), the physical quantities of drying air related to the experimental conditions (conductivity, viscosity, and density) and the geometry of the dryer (hydraulic diameter of the pipe). The model describes the experimental values with a very good precision (residues lower than 5%).

Practical Applications

the conception, the sizing, and the manufacturing of drying equipments more suited for tropical drying processes in general and to beef meat in particular.

the optimization of solar drying processes for meat.

improving the quality of solar drying processes for meat products.
Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model
Authors: Al‐Ahmad Abraham J. , Pervaiz Iqra , Karamyan Vardan T.
Published: January 2021

Increased brain microvascular permeability and disruption of blood‐brain barrier (BBB) function are among hallmarks of several acute neurodegenerative disorders, including stroke. Numerous studies suggest the involvement of bradykinin (BK), neurotensin (NT) and substance P (SP) in BBB impairment and oedema formation after stroke; however, there is paucity of data in regard to the direct effects of these peptides on the brain microvascular endothelial cells (BMECs) and BBB. The present study aimed to evaluate the direct effects of BK, NT and SP on the permeability of BBB in an in vitro model based on human induced pluripotent stem cell (iPSC)‐derived BMECs. Our data indicate that all three peptides increase BBB permeability in a concentration‐dependent manner in an in vitro model formed from two different iPSC lines (CTR90F and CTR65M) and widely used hCMEC/D3 human BMECs. The combination of BK, NT and SP at a sub‐effective concentration also resulted in increased BBB permeability in the iPSC‐derived model indicating potentiation of their action. Furthermore, we observed abrogation of BK, NT and SP effects with pretreatment of pharmacological blockers targeting their specific receptors. Additional mechanistic studies indicate that the short‐term effects of these peptides are not mediated through alteration of tight‐junction proteins claudin‐5 and occludin, but likely involve redistribution of F‐actin and secretion of vascular endothelial growth factor. This is the first experimental study to document the increased permeability of the BBB in response to direct action of NT in an in vitro model. In addition, our study confirms the expected but not well‐documented, direct effect of SP on BBB permeability and adds to the well‐recognised actions of BK on BBB. Lastly, we demonstrate that peptidase neurolysin can neutralise the effects of these peptides on BBB, suggesting potential therapeutic implications.
Experimentally elevated testosterone shortens telomeres across years in a free‐living songbird
Authors: Heidinger Britt J. , Slowinski Samuel P. , Sirman Aubrey E. , Kittilson Jeffrey , Gerlach Nicole M. , Ketterson Ellen D.
Published: January 2021

Reproductive investment often comes at a cost to longevity, but the mechanisms that underlie these long‐term effects are not well understood. In male vertebrates, elevated testosterone has been shown to increase reproductive success, but simultaneously to decrease survival. One factor that may contribute to or serve as a biomarker of these long‐term effects of testosterone on longevity is telomeres, which are often positively related to lifespan and have been shown to shorten in response to reproduction. In this longitudinal study, we measured the effects of experimentally elevated testosterone on telomere shortening in free‐living, male dark‐eyed juncos (Junco hyemalis carolinensis), a system in which the experimental elevation of testosterone has previously been shown to increase reproductive success and reduce survival. We found a small, significant effect of testosterone treatment on telomeres, with testosterone‐treated males exhibiting significantly greater telomere shortening with age than controls. These results are consistent with the hypothesis that increased telomere shortening may be a long‐term cost of elevated testosterone exposure. As both testosterone and telomeres are conserved physiological mechanisms, our results suggest that their interaction may apply broadly to the long‐term costs of reproduction in male vertebrates.