bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis
Authors: Lee Kun-Han , Chen Ying-Fan , Yeh Wan-Yu , Yeh Jiunn-Tyng , Yang Tzu-Han , Chou Chian-Ying , Chang Yuh-Lih , Wang Wei-Ting , Chiang Chern-En , Chen Chen-Huan , Cheng Hao-Min
Published: December 2022

Background

An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive.

Objective

Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies.

Methods

We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated.

Results

Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73–0.99) and ICH (RR: 0.38; 95% CI: 0.28–0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results.

Conclusions

In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.
Ontogenetic changes in root and shoot respiration, fresh mass and surface area of Fagus crenata
Authors: Kurosawa Yoko , Mori Shigeta , Wang Mofei , Pedro Ferrio Juan , Nishizono Tomohiro , Yamaji Keiko , Koyama Kohei , Haruma Toshikatsu , Doyama Kohei
Published: December 2022

Background and Aims

To date, studies on terrestrial plant ecology and evolution have focused primarily on the trade-off patterns in the allocation of metabolic production to roots and shoots in individual plants and the scaling of whole-plant respiration. However, few empirical studies have investigated the root : shoot ratio by considering scaling whole-plant respiration at various sizes throughout ontogeny.

Methods

Here, using a whole-plant chamber system, we measured the respiration rates, fresh mass and surface area of entire roots and shoots from 377 Fagus crenata individuals, from germinating seeds to mature trees, collected from five different Japanese provenances. Non-linear regression analysis was performed for scaling of root and shoot respiration, fresh mass and surface area with body size.

Key Results

Whole-plant respiration increased rapidly in germinating seeds. In the seedling to mature tree size range, the scaling of whole-plant respiration to whole-plant fresh mass was expressed as a linear trend on the log–log coordinates (exponent slightly greater than 0.75). In the same body size range, root and shoot respiration vs. whole-plant fresh mass were modelled by upward-convex (exponent decreased from 2.35 to 0.638) and downward-convex trends (exponent increased from –0.918 to 0.864), respectively. The root fraction in whole-plant respiration, fresh mass and surface area shifted continuously throughout ontogeny, increasing in smaller seedlings during early growth stages and decreasing in larger trees.

Conclusions

Our results suggest a gradual shift in allocation priorities of metabolic energy from roots in seedlings to shoots in mature trees, providing insights into how roots contribute to shoot and whole-plant growth during ontogeny. The models of root : shoot ratio in relation to whole-plant physiology could be applied in tree growth modelling, and in linking the different levels of ecological phenomena, from individuals to ecosystems.
Defence plasticity in the spiny plant Aralia elata (Miq.) Seem. in response to light and soil fertility
Authors: Yamawo Akira , Tomlinson Kyle W
Published: December 2022

Background and Aims

Plants have evolved various defences against herbivores, including direct chemical and structural defences and co-opted biological defences by predatory insects. However, the effects of abiotic habitat conditions on the quantitative expression of defence traits of spiny species have not been elucidated.

Methods

Here, we investigated whether a spiny deciduous tree, Aralia elata (Miq.) Seem., changes its defence expression across light and nutrient gradients. We measured allocation to spines and C-based secondary metabolites (condensed tannins and total phenols) on A. elata plants growing across light and nutrient gradients in situ in natural landscapes in Japan. Second, we examined the effects of light and soil nutrient condition on allocation to shoot organs, spines and chemical defences of juveniles of two genotypes of the species, respectively spiny (mainland population) and non-spiny (island population), grown in a glasshouse.

Key Results

In the field investigation, absolute spine mass, spine mass fraction, total phenols and condensed tannins all responded positively to canopy openness. Total phenol content was also negatively related to soil N. In the glasshouse, spiny genotype individuals had less total biomass, had lower stem allocation and were shorter than non-spiny genotype individuals. In spiny genotype trees, both spine mass fraction and total phenols decreased under low light conditions. Nutrient additions had negative effects on spine mass fraction and total phenols, but no effect on absolute spine mass.

Conclusions

These results suggest that development of spines is costly for A. elata and receives greater allocation when carbohydrate supply is more plentiful. Thus, light is a more important determinant of spine allocation than soil nutrients for A. elata.
Specificity in root domain accumulation of Phytoglobin1 and nitric oxide (NO) determines meristematic viability in water-stressedBrassica napusroots
Authors: Mira Mohammed M , Ibrahim Shimaa , So Kenny , Kowatsch Ralph , Duncan Robert W , Hill Robert D , Stasolla Claudio
Published: December 2022

Background and Aims

Drought reduces plant productivity, especially in the susceptible species Brassica napus. Water stress, mimicked by applications of 10 % polyethylene glycol (PEG), elevates nitric oxide (NO) in root cells after a few hours, contributing to degradation of the root apical meristems (RAMs), the function of which relies on auxin and brassinosteroids (BRs). Phytoglobins (Pgbs) are effective NO scavengers induced by this stress. This study examines the effects of BnPgb1 dysregulation in dehydrating B. napus roots, and the spatiotemporal relationship between Pgb1 and activities of auxin and BRs in the regulation of the RAM.

Methods

Brassica napus lines over-expressing [BnPgb1(S)] or down-regulating [BnPgb1(RNAi)] BnPgb1 were exposed to PEG-induced water stress. The localization of BnPgb1, NO, auxin and PIN1 were analysed during the first 48 h, while the expression level of biosynthetic auxin and BR genes was measured during the first 24 h. Pharmacological treatments were conducted to assess the requirement of auxin and BR in dehydrating roots.

Key Results

During PEG stress, BnPgb1 protein accumulated preferentially in the peripheral domains of the root elongation zone, exposing the meristem to NO, which inhibits polar auxin transport (PAT), probably by interfering with PIN1 localization and the synthesis of auxin. Diminished auxin at the root tip depressed the synthesis of BR and caused the degradation of the RAMs. The strength of BnPgb1 signal in the elongation zone was increased in BnPgb1(S) roots, where NO was confined to the most apical cells. Consequently, PAT and auxin synthesis were retained, and the definition of RAMs was maintained. Auxin preservation of the RAM required BRs, although BRs alone was not sufficient to fully rescue drought-damaged RAMs in auxin-depleted environments.

Conclusions

The tissue-specific localization of BnPgb1 and NO determine B. napus root responses to water stress. A model is proposed in which auxin and BRs act as downstream components of BnPgb1 signalling in the preservation of RAMs in dehydrating roots.
Grain protein function prediction based on self-attention mechanism and bidirectional LSTM
Authors: Liu Jing , Tang Xinghua , Guan Xiao
Published: December 2022

With the development of genome sequencing technology, using computing technology to predict grain protein function has become one of the important tasks of bioinformatics. The protein data of four grains, soybean, maize, indica and japonica are selected in this experimental dataset. In this paper, a novel neural network algorithm Chemical-SA-BiLSTM is proposed for grain protein function prediction. The Chemical-SA-BiLSTM algorithm fuses the chemical properties of proteins on the basis of amino acid sequences, and combines the self-attention mechanism with the bidirectional Long Short-Term Memory network. The experimental results show that the Chemical-SA-BiLSTM algorithm is superior to other classical neural network algorithms, and can more accurately predict the protein function, which proves the effectiveness of the Chemical-SA-BiLSTM algorithm in the prediction of grain protein function. The source code of our method is available at https://github.com/HwaTong/Chemical-SA-BiLSTM.
screenwerk: a modular tool for the design and analysis of drug combination screens
Authors: Hanes Robert , Ayuda-Durán Pilar , Rønneberg Leiv , Nakken Sigve , Hovig Eivind , Zucknick Manuela , Enserink Jorrit M
Published: December 2022

Motivation

There is a rapidly growing interest in high-throughput drug combination screening to identify synergizing drug interactions for treatment of various maladies, such as cancer and infectious disease. This creates the need for pipelines that can be used to design such screens, perform quality control on the data and generate data files that can be analyzed by synergy-finding bioinformatics applications.

Results

screenwerk is an open-source, end-to-end modular tool available as an R-package for the design and analysis of drug combination screens. The tool allows for a customized build of pipelines through its modularity and provides a flexible approach to quality control and data analysis. screenwerk is adaptable to various experimental requirements with an emphasis on precision medicine. It can be coupled to other R packages, such as bayesynergy, to identify synergistic and antagonistic drug interactions in cell lines or patient samples. screenwerk is scalable and provides a complete solution for setting up drug sensitivity screens, read raw measurements and consolidate different datasets, perform various types of quality control and analyze, report and visualize the results of drug sensitivity screens.

Availability and implementation

The R-package and technical documentation is available at https://github.com/Enserink-lab/screenwerk; the R source code is publicly available at https://github.com/Enserink-lab/screenwerk under GNU General Public License v3.0; bayesynergy is accessible at https://github.com/ocbe-uio/bayesynergy. Selected modules are available through Galaxy, an open-source platform for FAIR data analysis at https://oncotools.elixir.no

Supplementary information

Supplementary data are available at Bioinformatics online.
Mental Health Family Carer Experiences during COVID-19: A Rapid Scoping Review of the International Literature
Authors: Walters Caroline , Petrakis Melissa
Published: December 2022

Internationally, people experiencing mental health challenges and psychosocial distress faced service disruptions, increased uncertainties and isolation, during the COVID-19 pandemic. Mental health family carers in turn experienced high levels of demand to fill gaps in service responses within a context of fear and uncertainty. A scoping narrative review methodology was undertaken to account for the varying methodologies of studies and the recency of the COVID-19 pandemic. Six databases were searched: Proquest, Ovid, Psych Info, CINAHL, Scopus, WHO COVID-19 database in January 2022. A total of 147 articles were identified, with 19 included in the final review. Findings revealed few studies focused on the experiences of mental health family carers during the pandemic. Studies that elevated mental health family voices identified they were more likely to provide emotional support than other carers, and less likely to receive government income support. Higher distress was present in family carers who lived with people with low independence, supported more than one person and provided higher levels of care. Family carers experienced concerns about—family members becoming infected during hospitalisations, accessing services, inappropriate and early discharges, care provision if family carers became unwell and the need for targeted responses and quality for online services.
Vascular endothelial cells: a fundamental approach for brain waste clearance
Authors: Wei Huimin , Jiang Huimin , Zhou Yifan , Xiao Xuechun , Zhou Chen , Ji Xunming
Published: December 2022

Accumulation of neurotoxic protein aggregates is the pathological hallmark of neurodegenerative disease. Proper clearance of these waste metabolites is an essential process for maintaining brain microenvironment homeostasis and may delay or even halt the onset and progression of neurodegeneration. Vascular endothelial cells regulate the molecular exchange between the circulation and brain parenchyma, thereby protecting the brain against the entry of xenobiotics and decreasing the accumulation of neurotoxic proteins.

In this review, we provide an overview of cerebrovascular endothelial cell characteristics and their impact on waste metabolite clearance. Lastly, we speculate that molecular changes in cerebrovascular endothelial cells are the drivers of neurodegenerative diseases.
The evidence against somatotopic organization of function in the primate corticospinal tract
Authors: Lemon Roger N , Morecraft Robert J
Published: December 2022

We review the spatial organization of corticospinal outputs from different cortical areas and how this reflects the varied functions mediated by the corticospinal tract. A long-standing question is whether the primate corticospinal tract shows somatotopical organization. Although this has been clearly demonstrated for corticofugal outputs passing through the internal capsule and cerebral peduncle, there is accumulating evidence against somatotopy in the pyramidal tract in the lower brainstem and in the spinal course of the corticospinal tract. Answering the question on somatotopy has important consequences for understanding the effects of incomplete spinal cord injury.

Our recent study in the macaque monkey, using high-resolution dextran tracers, demonstrated a great deal of intermingling of fibres originating from primary motor cortex arm/hand, shoulder and leg areas. We quantified the distribution of fibres belonging to these different projections and found no significant difference in their distribution across different subsectors of the pyramidal tract or lateral corticospinal tract, arguing against somatotopy. We further demonstrated intermingling with corticospinal outputs derived from premotor and supplementary motor arm areas.

We present new evidence against somatotopy for corticospinal projections from rostral and caudal cingulate motor areas and from somatosensory areas of the parietal cortex. In the pyramidal tract and lateral corticospinal tract, fibres from the cingulate motor areas overlap with each other. Fibres from the primary somatosensory cortex arm area completely overlap those from the leg area. There is also substantial overlap of both these outputs with those from posterior parietal sensorimotor areas.

We argue that the extensive intermingling of corticospinal outputs from so many different cortical regions must represent an organizational principle, closely related to its mediation of many different functions and its large range of fibre diameters.

The motor sequelae of incomplete spinal injury, such as central cord syndrome and ‘cruciate paralysis’, include much greater deficits in upper than in lower limb movement. Current teaching and text book explanations of these symptoms are still based on a supposed corticospinal somatotopy or ‘lamination’, with greater vulnerability of arm and hand versus leg fibres. We suggest that such explanations should now be finally abandoned. Instead, the clinical and neurobiological implications of the complex organization of the corticospinal tract need now to be taken into consideration. This leads us to consider the evidence for a greater relative influence of the corticospinal tract on upper versus lower limb movements, the former best characterized by skilled hand and digit movements.
miR-132-3p regulates antibody-mediated complement-dependent cytotoxicity in colon cancer cells by directly targeting CD55
Authors: Fan Yu , Liao Juan , Wang Yu , Wang Zhu , Zheng Hong , Wang Yanping
Published: December 2022

The overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour cells helps them survive complement attacks by suppressing antibody-mediated complement-dependent cytotoxicity (CDC). Consequently, mCRP overexpression limits monoclonal antibody drug immune efficacy. CD55, an mCRP, plays an important role in inhibiting antibody-mediated CDC. However, the mechanisms regulating CD55 expression in tumour cells remain unclear. Here, the aim was to explore CD55-targeting miRNAs. We previously constructed an in vitro model comprising cancer cell lines expressing α-gal and serum containing natural antibodies against α-gal and complement. This was used to simulate antibody-mediated CDC in colon cancer cells. We screened microRNAs that directly target CD55 using LoVo and Ls-174T colon cell lines, which express CD55 at low and high levels, respectively. miR-132-3p expression was dramatically lower in Ls-174T cells than in LoVo cells. miR-132-3p overexpression or inhibition transcriptionally regulated CD55 expression by specifically targeting its mRNA 3ʹ-untranslated regions. Further, miR-132-3p modulation regulated colon cancer cell sensitivity to antibody-mediated CDC through C5a release and C5b-9 deposition. Moreover, miR-132-3p expression was significantly reduced, whereas CD55 expression was increased, in colon cancer tissues compared to levels in adjacent normal tissues. CD55 protein levels were negatively correlated with miR-132-3p expression in colon cancer tissues. Our results indicate that miR-132-3p regulates colon cancer cell sensitivity to antibody-mediated CDC by directly targeting CD55. In addition, incubating the LoVo human tumour cell line, stably transfected with the xenoantigen α-gal, with human serum containing natural antibodies comprises a stable and cheap in vitro model to explore the mechanisms underlying antibody-mediated CDC.
Gingival transcriptomic patterns of macrophage polarization during initiation, progression, and resolution of periodontitis
Authors: Gonzalez Octavio A , Kirakodu Sreenatha S , Nguyen Linh M , Ebersole Jeffrey L
Published: December 2022

Phenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for M0, M1, and M2 macrophages in healthy tissues with the younger animals showing the least expression. M0 gene expression increased with disease in all but the aged group, while M1 was increased in adult and young animals, and M2 in all age groups, as early as disease initiation (within 0.5 months). Numerous histocompatibility genes were increased with disease, except in the aged samples. An array of cytokines/chemokines representing both M1 and M2 cells were increased with disease showing substantial increases with disease initiation (e.g. IL1A, CXCL8, CCL19, CCL2, CCL18), although the aged tissues showed a more limited magnitude of change across these macrophage genes. The analytics of macrophage genes at sites of gingival health, disease, and resolution demonstrated distinct profiles of host response interactions that may help model the disease mechanisms occurring with the formation of a periodontal lesion.
Estimating the relationship between liquid- and vapor-phase odorant concentrations using a photoionization detector (PID)-based approach
Authors: Jennings Liam , Williams Ellie , Caton Samuel , Avlas Marta , Dewan Adam
Published: December 2022

Olfactory studies frequently utilize odor stimuli consisting of volatiles created from liquid dilutions of various chemicals. A problem arises if the researcher relies on these liquid dilutions to extrapolate vapor concentrations based on ideal gas behavior. For most chemicals, the relationship between liquid and vapor concentration deviates from these laws of proportionality due to interactions between the chemical and the solvent. Here, we describe a method to estimate vapor-phase concentrations of diluted odorants using a photoionization detector. To demonstrate the utility of this method, we assessed the relationship between liquid-/vapor-phase concentrations for 14 odorants (7 alcohols, 1 ester, and 6 aldehydes) in 5 different solvents (water, mineral oil, diethyl phthalate, dipropylene glycol, and propylene glycol). An analysis of 7 additional esters is also included to assess how carbon chain length and functional group, interacts with these solvents (for a total of 105 odorant/solvent pairs). Our resulting equilibrium equations successfully corrected for behavioral sensitivity differences observed in mice tested with the same odorant in different solvents and were overall similar to published measurements using a gas chromatography-based approach. In summary, this method should allow researchers to determine the vapor-phase concentration of diluted odorants and will hopefully assist in more accurate comparisons of odorant concentrations across olfactory studies.
Bartonella quintanaTransmitted by Head Lice: An Outbreak of Trench Fever in Senegal
Authors: Hammoud Alissa , Louni Meriem , Fenollar Florence , Bassene Hubert , Sambou Masse , Duclos Nathalie , Diatta Georges , Sokhna Cheikh , Levasseur Anthony , Raoult Didier , Mediannikov Oleg
Published: December 2022

Background

Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse feces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood.

Methods

In Senegal, the implementation of a permanent local surveillance system in a point-of-care laboratory (POC) allows the monitoring of emerging diseases. Here we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of 2 isolated strains of B. quintana were sequenced and analyzed.

Results

A total of 2289 blood samples were collected in the 2010–2015 period. From 2010–2013, B. quintana DNA was detected by polymerase chain reaction (PCR) in 0.25% (4/1580). In 2014, 228 blood samples were collected, along with 161 head lice from 5 individuals. B. quintana DNA was detected in 4.4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61.7%, 50/81) and non-febrile patients (61.4%, 43/70). Two B. quintana strains were isolated from blood and head lice from 2 different patients. Genomic sequence analysis showed 99.98% overall similarity between both strains.

Conclusions

The presence of live B. quintana in head lice, and the genetic identity of strains from patients’ blood and head lice during a localized outbreak in Senegal, supports the evidence of head lice vectorial capacity.
The use of Vaccinia Immune Globulin in the Treatment of Severe Mpox. Virus Infection in Human Immunodeficiency Virus/AIDS
Authors: Thet Andrea K , Kelly Paul J , Kasule Sabirah N , Shah Anish K , Chawala Arpan , Latif Amber , Chilimuri Sridhar S , Zeana Cosmina B
Published: December 2022

We report a case of progressive, severe mpox virus (MPXV) infection in a patient with AIDS despite a standard course of tecovirimat. He significantly improved after administration of vaccinia immune globulin intravenous (VIGIV) highlighting its use as an adjunct for severe disease in immunocompromised hosts.
Three Cases of Non-compliance: Challenges of Trust and Governmental Response Strategies
Authors: Liang Bin
Published: December 2022

This study examines three noncompliant cases occurred in Wuhan, China during the outbreak of the COVID-19 in 2020, including the Li Wenliang (李文亮) case, the Chen Qiushi (陈秋实) case, and the Huang Dengying (黄登英) case. These cases, albeit with different natures, broke out during the early stage of Wuhan ™s epidemic and posted threat and challenges to the Chinese authorities to different degrees. Based on open source information, this study focuses on the issues of trust and examines trust at three different levels (interpersonal trust, public trust, and political trust) among interactions by three groups of actors, including individuals involved in each case, the general public (e.g., how the public perceived and evaluated each case), and the authorities (e.g., how governments at the local and central levels perceived and handled each case). Two research questions are addressed: 1) How did trust at different levels play out in each case? 2) How did Chinese authorities respond to and handle threat and public trust challenges? Policy implications are drawn.
UpStreAm doxycycline in ST-eLeVation myocArdial infarction: targetinG infarct hEaling and ModulatIon (SALVAGE-MI trial)
Authors: Noaman Samer , Neil Christopher , O’Brien Jessica , Frenneaux Michael , Hare James , Wang Bing , Yee Tai Tsin , Theuerle James , Shaw James , Stub Dion , Bloom Jason , Walton Antony , Duffy Stephen J , Peter Karl-Heinz , Cox Nicholas , Kaye David M , Taylor Andrew , Chan William
Published: December 2022

Aims

Experimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling.

Methods and results

In this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo. The primary outcome was final IS adjusted for area-at-risk (fIS/AAR) measured on two cardiac magnetic resonance scans ∼6 months apart. Of 103 participants, 50 were randomized to doxycycline and 53 to placebo and were matched for age (59 ± 12 vs. 60 ± 10 years), male sex (92% vs. 79%), diabetes mellitus (26% vs. 11%) and left anterior descending artery occlusion (50% vs. 49%), all P > 0.05. Patients treated with doxycycline had a trend for larger fIS/AAR [0.79 (0.5–0.9) vs. 0.61 (0.47–0.76), P = 0.06], larger fIS at 6 months [18.8% (12–26) vs. 13.6% (11–21), P = 0.08], but similar acute IS [21.7% (17–34) vs. 19.4% (14–27), P = 0.19] and AAR [26% (20–36) vs. 24.7% (16–31), P = 0.22] compared with placebo. Doxycycline did not ameliorate adverse LV remodelling [%Δend-diastolic volume index, 1.1% (−3.8–8.4) vs. −1.34% (−6.1–5.8), P = 0.42] and was independently associated with larger fIS (regression coefficient = 0.175, P = 0.03).

Conclusion

Doxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety concerns regarding doxycycline use in STEMI for infarct modulation and healing.
Lower testosterone levels are associated with higher risk of death in men
Authors: Muehlenbein Michael P , Gassen Jeffrey , Shattuck Eric C , Sparks Corey S
Published: December 2022

Background and Objectives

Testosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men.

Methodology

Relationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer’s disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries.

Results

Results of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality—which included deaths from any known disease—also revealed greater general risk for those with lower testosterone levels. For most disease categories, the hazard associated with low testosterone was especially evident at older ages when mortality from that particular ailment was already elevated. Notably, testosterone levels were not related to mortality risk for deaths unrelated to chronic disease (i.e. accidents and injuries).

Conclusions and Implications

While the causal direction of relationships between testosterone and mortality risk remains unclear, these results may reflect the decline in testosterone that accompanies many disease states. Accordingly, the relationship between testosterone and male mortality may be indirect; ill individuals are expected to have both lower testosterone and higher mortality risk.
Eigenvalue bounds for double saddle-point systems
Authors: Bradley Susanne , Greif Chen
Published: December 2022

We derive bounds on the eigenvalues of a generic form of double saddle-point matrices. The bounds are expressed in terms of extremal eigenvalues and singular values of the associated block matrices. Inertia and algebraic multiplicity of eigenvalues are considered as well. The analysis includes bounds for preconditioned matrices based on block diagonal preconditioners using Schur complements, and it is shown that in this case the eigenvalues are clustered within a few intervals bounded away from zero. Analysis for approximations of Schur complements is included. Some numerical experiments validate our analytical findings.
The Self-Assembled Skin Substitute History: Successes, Challenges, and Current Treatment Indications
Authors: Dagher Jason , Arcand Charles , Auger François A , Germain Lucie , Moulin Véronique J
Published: December 2022

The self-assembled skin substitute (SASS) is an autologous bilayered skin substitute designed by our academic laboratory, the Laboratoire d’Organogenèse Expérimentale (LOEX) to offer definitive treatment for patients lacking donor sites (unwounded skin) to cover their burn wounds. This product shows skin-like attributes, such as an autologous dermal and epidermal layer, and is easily manipulable by the surgeon. Its development stems from the need for skin replacement in high total body surface area burned survivors presenting few donor sites for standard split-thickness skin grafting. This review aims to present the history, successes, challenges, and current therapeutic indications of this skin substitute. We review the product’s development history, before discussing current production techniques, as well as clinical use. The progression observed since the initial SASS production technique described in 1999, up to the most recent technique expresses significant advances made in the technical aspect of our product, such as the reduction of the production time. We then explore the efficacy and benefits of SASS over existing skin substitutes and discuss the outcomes of a recent study focusing on the successful treatment of 14 patients. Moreover, an ongoing cross-Canada study is further assessing the product’s safety and efficacy. The limitations and technical challenges of SASS are also discussed.
A Brief History of RECELL® and Its Current Indications
Authors: Holmes James H
Published: December 2022

A concise history of the development of the RECELL® device and the seminal work of Dr. Fiona Wood will be provided, as well as the current indications and potential future prospects for the use of RECELL® in the United States.
Skin Tissue Engineering Advances in Burns: A Brief Introduction to the Past, the Present, and the Future Potential
Authors: Chogan Faraz , Chen Yufei , Wood Fiona , Jeschke Marc G
Published: December 2022

Burn injuries are a severe form of skin damage with a significant risk of scarring and systemic sequelae. Approximately 11 million individuals worldwide suffer burn injuries annually, with 180,000 people dying due to their injuries. Wound healing is considered the main determinant for the survival of severe burns and remains a challenge. The surgical treatment of burn wounds entails debridement of necrotic tissue, and the wound is covered with autologous skin substitutes taken from healthy donor areas. Autologous skin transplantation is still considered to be the gold standard for wound repair. However, autologous skin grafts are not always possible, especially in cases with extensive burns and limited donor sites. Allografts from human cadaver skin and xenografts from pig skin may be used in these situations to cover the wounds temporarily. Alternatively, dermal analogs are used until permanent coverage with autologous skin grafts or artificial skins can be achieved, requiring staged procedures to prolong the healing times with the associated risks of local and systemic infection. Over the last few decades, the wound healing process through tissue-engineered skin substitutes has significantly enhanced as the advances in intensive care ensuring early survival have led to the need to repair large skin defects. The focus has shifted from survival to the quality of survival, necessitating accelerated wound repair. This special volume of JBCR is dedicated to the discoveries, developments, and applications leading the reader into the past, present, and future perspectives of skin tissue engineering in burn injuries.
The Role of Cell-Based Therapies in Acute Burn Wound Skin Repair: A Review
Authors: Wood Fiona M
Published: December 2022

Tissue engineering solutions for skin have been developed over the last few decades with a focus initially on a two-layered structure with epithelial and dermal repair. An essential element of skin restoration is a source of cells capable of differentiating into the appropriate phenotype. The need to repair areas of skin when traditional techniques were not adequate addressed led to cell based therapies being developed initially as a laboratory-based tissue expansion opportunity, both as sheets of cultured epithelial autograft and in composite laboratory-based skin substitutes. The time to availability of the cell-based therapies has been solved in a number of ways, from using allograft cell-based solutions to the use of point of care skin cell harvesting for immediate clinical use. More recently pluripotential cells have been explored providing a readily available source of cells and cells which can express the broad range of phenotypes seen in the mature skin construct. The lessons learnt from the use of cell based techniques has driven the exploration of the use of 3D printing technology, with controlled accurate placement of the cells within a specific printed construct to optimise the phenotypic expression and tissue generation.
Observations of nemaline bodies in muscle biopsies of critically ill patients infected with SARS-CoV-2
Authors: Vandenabeele Frank , Stevens Sjoerd , Snijders Tim , Stessel Björn , Dubois Jasperina , van Loon Luc J C , Lambrichts Ivo , Agten Anouk
Published: December 2022

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1–3 and days 5–8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5–8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.
Access to non-prescription medicines via vending machines: key considerations to help transfer the self-care concept to the next generation while managing safety risks
Authors: Jairoun Ammar Abdulrahman , Al-Hemyari Sabaa Saleh , Shahwan Moyad , El-Dahiyat Faris , Jairoun Maimona , Godman Brian , Kurdi Amanj , Zyoud Samer H
Published: December 2022

Objectives

Non-prescription vending machines are automated self-service systems that are increasingly used to dispense these medicines. Whilst regulatory health academics have devoted considerable attention to non-pharmacy medication outlets in Gulf Cooperation Council countries and others, the public health literature on these vending machines remains lacking. Whilst non-prescription vending machines undoubtedly provide a number of benefits, they are not without their risks, which include polypharmacy and medication interactions.

Methods

The purpose of this article is to provide a framework for further investigation of the function, advantages, and practical constraints of non-prescription vending machines.

Key findings

Overall, more research is required to determine the optimal balance between achieving the benefits of non-prescription vending machines whilst avoiding unnecessary constraints on regulatory bodies and vending machine providers but minimizing patient harm.

Conclusions

Further studies are also required to assess the consequences of these policy experiments. Specifically, there is a need to better understand the extent to which vending machines can provide beneficial and reasonable access to non-prescription medicines to enhance the quality of life of the population especially during pandemics.
ThePhytophthora capsiciRxLR effectorCRISIS2triggers cell death via suppressing plasma membrane H+-ATPase in the host plant
Authors: Seo Ye-Eun , Lee Hye-Young , Kim Haeun , Yan Xin , Park Sang A , Kim Myung-Shin , Segonzac Cécile , Choi Doil , Mang Hyunggon
Published: December 2022

Pathogen effectors can suppress various plant immune responses, suggesting that they have multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we screened the Phytophthora capsici RxLR cell death-inducer suppressing immune system (CRISIS). We found that the cell death induced by the CRISIS2 effector in Nicotiana benthamiana was inhibited by the irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin. Biochemical and gene-silencing analyses revealed that CRISIS2 physically and functionally associated with PMAs and induced host cell death independent of immune receptors. CRISIS2 induced apoplastic alkalization by suppressing PMA activity via its association with the C-terminal regulatory domain. In planta expression of CRISIS2 significantly enhanced the virulence of P. capsici, whereas host-induced gene-silencing of CRISIS2 compromised the disease symptoms and the biomass of the pathogen. Thus, our study has identified a novel RxLR effector that plays multiple roles in the suppression of plant defense and in the induction of cell death to support the pathogen hemibiotrophic life cycle in the host plant.
Buyers versus borrowers: a look at the finances of Shakespeare and Company
Authors: Benedict Nora
Published: December 2022

Sylvia Beach is known for her ‘imperfect record keeping’ and often indecipherable business accounts (Fitch, N. R. (1985). Sylvia Beach and the Lost Generation: A History of Literary Paris in the Twenties and Thirties. New York: Norton, p. 161). That said, data from her lending library cards and logbooks provide key insight into Shakespeare and Company’s cash flow. While this financial information is not always presented in a systematic or exhaustive manner, it can still be used to develop a more nuanced understanding of the inner workings of Beach’s literary enterprise. To that end, in this article, I use the Shakespeare and Company Project data sets to examine the exchange of books in Beach’s bookshop. More specifically, my analysis centers on the details surrounding purchases and borrows of books from the events data set. By limiting the scope of my study to only those records that contain transactional data—whether in the form of membership fees or actual book purchases—I provide a case study of how to approach incomplete data that unearths a new array of networks that were central to the daily operations of Shakespeare and Company. As a result, in contrast with the common focus on solely the most notable lending library members (or members of the Lost Generation in general), this financial approach brings to light invisible networks and underexplored figures whose monetary contributions were essential to keeping Beach’s business afloat.
Acceptability and feasibility of cognitive assessments with adults with primary brain cancer and brain metastasis: A systematic review
Authors: Carlson Melissa A , Fradgley Elizabeth A , Yates Della , Morris Sarah , Tait Jordan , Paul Christine L
Published: December 2022

Routine cognitive assessment for adults with brain cancers is seldom completed but vital for guiding daily living, maintaining quality of life, or supporting patients and families. This study aims to identify cognitive assessments which are pragmatic and acceptable for use in clinical settings. MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane were searched to identify studies published in English between 1990 and 2021. Publications were independently screened by two coders and included if they: (1) were peer-reviewed; (2) reported original data relating to adult primary brain tumor or brain metastases; (3) used objective or subjective assessments; (4) reported assessment acceptability or feasibility. The Psychometric And Pragmatic Evidence Rating Scale was used. Consent, assessment commencement and completion, and study completion were extracted along with author-reported acceptability and feasibility data. PROSPERO Registration: CRD42021234794. Across 27 studies, 21 cognitive assessments had been assessed for feasibility and acceptability; 15 were objective assessments. Acceptability data were limited and heterogeneous, particularly consent (not reported in 23 studies), assessment commencement (not reported in 19 studies), and assessment completion (not reported in 21 studies). Reasons for non-completion could be grouped into patient-factors, assessment-factors, clinician-factors, and system-factors. The three cognitive assessments with the most acceptability and feasibility data reported were the MMSE, MoCA, and NIHTB-CB. Further acceptability and feasibility data are needed including consent, commencement and completion rates. Cost, length, time, and assessor burden are needed for the MMSE, MoCA, and NIHTB-CB, along with potentially new computerized assessments suited for busy clinical settings.
Sympatric or micro-allopatric speciation in a glacial lake? Genomic islands support neither
Authors: Sun Ning , Yang Liandong , Tian Fei , Zeng Honghui , He Ziwen , Zhao Kai , Wang Cheng , Meng Minghui , Feng Chenguang , Fang Chengchi , Lv Wenqi , Bo Jing , Tang Yongtao , Gan Xiaoni , Peng Zuogang , Chen Yiyu , He Shunping
Published: December 2022

Apparent cases of sympatric speciation may actually be due to micro-allopatric or micro-parapatric speciation. One way to distinguish between these models is to examine the existence and nature of genomic islands of divergence, wherein divergent DNA segments are interspersed with low-divergence segments. Such islands should be rare or absent under micro-allopatric speciation but common in cases of speciation with gene flow. Sympatric divergence of endemic fishes is known from isolated saline, crater, postglacial, and ancient lakes. Two morphologically distinct cyprinid fishes, Gymnocypris eckloni scoliostomus (GS) and G. eckloni eckloni (GE), in a small glacial lake on the Qinghai–Tibet Plateau, Lake Sunmcuo, match the biogeographic criteria of sympatric speciation. In this study, we examined genome-wide variation in 46 individuals from these two groups. The divergence time between the GS and GE lineages was estimated to be 20–60 Kya. We identified 54 large genomic islands (≥100 kb) of speciation, which accounted for 89.4% of the total length of all genomic islands. These islands harboured divergent genes related to olfactory receptors and olfaction signals that may play important roles in food selection and assortative mating in fishes. Although the genomic islands clearly indicated speciation with gene flow and rejected micro-allopatric speciation, they were too large to support the hypothesis of sympatric speciation. Theoretical and recent empirical studies suggested that continual gene flow in sympatry should give rise to many small genomic islands (as small as a few kilobases in size). Thus, the observed pattern is consistent with the extensive evidence on parapatric speciation, in which adjacent habitats facilitate divergent selection but also permit gene flow during speciation. We suggest that many, if not most, of the reported cases of sympatric speciation are likely to be micro-parapatric speciation.