bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Association of Working From Home on Work Functioning Impairment in Desk Workers During COVID-19 Pandemic
Authors: Takayama Atsushi , Yoshioka Takashi , Ishimaru Tomohiro , Yoshida Satomi , Kawakami Koji , Tabuchi Takahiro
Published: April 2023

Objective

This study clarifies the longitudinal association between working from home and work functioning impairment among desk workers.

Methods

Nationwide surveys were conducted from 2020 to 2022, analyzing 3532 desk workers who never worked from home before the COVID-19 pandemic.

Results

The adjusted hazard ratio (95% confidence intervals) of working from home at least once a month or more with the composite result (incidence of work functioning or reduced work participation) was 1.22 (1.04–1.43). The cause-specific hazard ratios of work functioning impairment and reduced work participation were 1.30 (1.04–1.61) and 1.13 (0.86–1.47).

Conclusions

Working from home could be longitudinally associated with work functioning impairment, especially for workers who are in higher positions. Workers and policy makers should be aware of the potential risk of working from home regarding presenteeism.
Fluorescence confocal microscopy on liver specimens for full digitization of transplant pathology
Authors: Kinzler Maximilian N. , Schulze Falko , Reitz Alexandra , Gretser Steffen , Ziegler Paul , Shmorhun Oleksandr , Friedrich-Rust Mireen , Bojunga Jörg , Zeuzem Stefan , Schnitzbauer Andreas A. , Bechstein Wolf Otto , Reis Henning , Barreiros Ana Paula , Wild Peter J.
Published: April 2023

Fluorescence confocal microscopy (FCM) is a rapidly evolving tool that provides real-time virtual HE images of native tissue. Data about the potential of FCM as an alternative to frozen sections for the evaluation of donor liver specimens are lacking so far. The aim of the current study was to determine the value of FCM in liver specimens according to the criteria of the German Society for Organ Procurement. In this prospective study, conventional histology and FCM scans of 50 liver specimens (60% liver biopsies, 26% surgical specimens, and 14% donor samples) were evaluated according to the German Society for Organ Procurement. A comparison of FCM scans and conventional frozen sections revealed almost perfect levels of agreement for cholangitis (κ = 0.877), fibrosis (κ = 0.843), and malignancy (κ = 0.815). Substantial levels of agreement could be obtained for macrovesicular steatosis (κ = 0.775), inflammation (κ = 0.763), necrosis (κ = 0.643), and steatohepatitis (κ = 0.643). Levels of agreement were moderate for microvesicular steatosis (κ = 0.563). The strength of agreement between frozen sections and FCM was superior to the comparison of conventional HE and FCM imaging. We introduce FCM as a potential alternative to the frozen section that may represent a novel approach to liver transplant pathology where timely feedback is crucial and the deployment of human resources is becoming increasingly difficult.
Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Alshimali Hussain , Kuckelman John , Seethala Raghu , Sharma Nirmal S. , Coppolino Antonio , Keshk Mohamed , Young John S. , Mallidi Hari R.
Published: April 2023

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan–Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement (p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group (p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.
Endothelium-biomarkers for postthrombotic syndrome: a case–control study
Authors: Ranero Sabrina , Silveira Gonzalo , Trias Natalia , Brugnini Andreina , Lens Daniela , Guillermo Cecilia , Grille Sofía
Published: April 2023

Background

The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase.

Methods

A case–control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry.

Results

Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/μl (0.34–1.5) vs. 0.20/μl (0.11–0.77); P = 0.04) and EPC (0.75/μl (0.38–1.52) vs. 0.09/μl (0.05–0.82); P = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30–597.90) vs. 98.00 pg/ml (82.30–193.02); P = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r = 0.86, P < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups.

Conclusions

The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.
Coexpression of factor VIII and factor von Willebrand variants in a woman with heavy menstrual bleeding
Authors: Casini Alessandro , Yaron Michal , Couzens Alexander , Fontana Pierre , Neerman-Arbez Marguerite
Published: April 2023

Heavy menstrual bleeding is one of the most common causes of consultation in haematology. We present the clinical case of a 20-year-old woman referred by her gynaecologist due to heavy menstrual bleeding since menarche, complicated by iron deficiency anaemia. Haemostasis work-up was initially suggestive of a von Willebrand disease type 1. Genetic analyses by whole exome sequencing lead to a fortuitous discovery of haemophilia by identifying a heterozygous missense mutation in F8, exon 8 c.1127T>G:p.Val376Gly, previously reported in a patient with mild haemophilia A. The bleeding phenotype worsened by concomitant low von Willebrand factor (VWF) due to VWF variants influencing VWF levels. Our case highlights how whole exome sequencing can help to correct an erroneous diagnosis and identify polymorphisms that eventually contribute to the overall haemostatic balance.
Mendelian randomization and the association of fibroblast growth factor-23 with heart failure with preserved ejection fraction
Authors: Akwo Elvis A. , Robinson-Cohen Cassianne
Published: April 2023

Purpose of review

Observational data provide compelling evidence for elevated fibroblast growth factor-23 (FGF23) as a risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Given the limitations of observational studies, uncertainties persist regarding the causal role of FGF23 in the pathogenesis of HF and HFpEF. Recently, Mendelian randomization (MR) studies have been performed to examine causal associations between FGF23 and HF phenotypes.

Recent findings

The current review describes the methodological basis of the MR techniques used to examine the causal role of FGF23 on HF phenotypes, highlighting the importance of large-scale multiomics data. The findings from most of the MR studies indicate an absence of evidence of a causal effect of FGF23 on the risk of HF in general population settings. However, analysis using individual-level data showed a strong association between genetically-predicted FGF23 and HFpEF in individuals with a genetic predisposition to low estimated glomerular filtration (eGFR).

Evidence from MR analysis suggests a causal role of FGF23 in the pathogenesis of HFpEF in low eGFR settings – a finding supported by experimental, clinical, and epidemiological data. While future MR studies of FGF23 and HFpEF could provide further evidence, randomized trials of FGF23-lowering agents could provide the most definitive answers on the association in chronic kidney disease populations.
Sexual Satisfaction of Midlife Women Living With HIV in Canada: A Prospective Cohort Analysis
Authors: King Elizabeth M. , Carter Allison , Loutfy Mona , Webster Kathleen , Muchenje Marvelous , Murray Melanie C.M. , de Pokomandy Alexandra , Ding Erin , Li Jenny , Kaida Angela
Published: April 2023

Background:

Although sexual activity and function decline in older women living with HIV, positive dimensions of sexual health, such as satisfaction, are relatively unexplored. We evaluated the prevalence of sexual satisfaction for midlife women with HIV and assessed its relation to women's physical, mental, and sociostructural experiences.

Setting:

We studied women in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) over 3 survey waves (2013–2018).

Methods:

We included women living with HIV aged ≥45 years who reported ever having consensual sex. Sexual satisfaction was assessed using an item from the Sexual Satisfaction Scale for Women and was dichotomized into satisfactory (“completely/very/reasonably satisfactory”) and not satisfactory (“not very/not at all satisfactory”). Probable depression was based on CES-D ≥10. Multivariable logistic regression and fixed effects models determined correlates of sexual satisfaction. Reasons for sexual inactivity and alternate forms of sexual expression were also explored.

Results:

Among 508 midlife women, 61% were satisfied with their sexual lives at baseline. Women with probable depression had lower odds of sexual satisfaction than those without (aOR: 0.44; 95% CI: 0.27 to 0.71) and worsening depressive symptoms over time were associated with poorer sexual satisfaction (P = 0.001). Increased sexual activity was associated with higher sexual satisfaction (aOR: 2.75; 95% CI: 1.54 to 4.91); however, 51% of women reporting sexual satisfaction were sexually inactive. Sexually inactive women engaged in alternate forms of sexual expression such as self-pleasure (37%) and intimate relationships without sex (13%).

Conclusion:

Midlife women with HIV have high rates of sexual satisfaction, even in the absence of sexual activity. Depressive symptoms were closely associated with sexual dissatisfaction, alerting providers to the importance of screening for depression and sexual health together.
Magnetic Resonance Imaging of Pediatric Lungs and Airways
Authors: Liszewski Mark C. , Ciet Pierluigi , Winant Abbey J. , Lee Edward Y.
Published: April 2023

Disorders of the lungs and airways are among the most common indications for diagnostic imaging in infants and children. Traditionally, chest radiograph has been the first-line imaging test for detecting these disorders and when cross-sectional imaging is necessary, computed tomography (CT) has typically been the next step. However, due to concerns about the potentially harmful effects of ionizing radiation, pediatric imaging in general has begun to shift away from CT toward magnetic resonance imaging (MRI) as a preferred modality. Several unique technical challenges of chest MRI, including motion artifact from respiratory and cardiac motion as well as low signal-to-noise ratios secondary to relatively low proton density in the lung have slowed this shift in thoracic imaging. However, technical advances in MRI in recent years, including developments in non-Cartesian MRI data sampling methods such as radial, spiral, and PROPELLER imaging and the development of ultrashort TE and zero TE sequences that render CT-like high-quality imaging with minimal motion artifact have allowed for a shift to MRI for evaluation of lung and large airways in centers with specialized expertise. This article presents a practical approach for radiologists in current practice to begin to consider MRI for evaluation of the pediatric lung and large airways and begin to implement it in their practices. The current role for MRI in the evaluation of disorders of the pediatric lung and large airways is reviewed, and example cases are presented. Challenges for MRI of the lung and large airways in children are discussed, practical tips for patient preparation including sedation are described, and imaging techniques suitable for current clinical practice are presented.
RESPIRATORY MECHANICS AND NEURAL RESPIRATORY DRIVE OF UNTREATED GASPING DURING CARDIAC ARREST IN A PORCINE MODEL
Authors: Lin Lin , Wang Pengfei , Zheng Houzhen , Zhong Zheye , Zhuansun Yongxun , Yang Zhengfei , Chen Rui
Published: April 2023

Introduction: Although the effects on hemodynamics of gasping during cardiac arrest (CA) have received a lot of attention, less is known about the respiratory mechanics and physiology of respiration in gasping. This study aimed to investigate the respiratory mechanics and neural respiratory drive of gasping during CA in a porcine model. Method: Pigs weighing 34.9 ± 5.7 kg were anesthetized intravenously. Ventricular fibrillation (VF) was electrically induced and untreated for 10 min. Mechanical ventilation (MV) was ceased immediately after the onset of VF. Hemodynamic and respiratory parameters, pressure signals, diaphragmatic electromyogram data, and blood gas analysis data were recorded. Results: Gasping was observed in all the animals at a significantly lower rate (2–5 gaps/min), with higher tidal volume (V
T; 0.62 ± 0.19 L, P < 0.01), and with lower expired minute volume (2.51 ± 1.49 L/min, P < 0.001) in comparison with the baseline. The total respiratory cycle time and the expiratory time tended to be lengthened. Statistically significant elevations in transdiaphragmatic pressure, the pressure-time product of diaphragmatic pressure, and the mean of root mean square diaphragmatic electromyogram values (RMSmean) were observed (P < 0.05, P < 0.05, and P < 0.001, respectively); however, V
T/RMSmean and transdiaphragmatic pressure/RMSmean were reduced at all time points. The partial pressure of oxygen showed a continuous decline after VF to reach statistical significance in the 10th minute (9.46 ± 0.96 kPa, P < 0.001), whereas the partial pressure of carbon dioxide tended to first rise and then fall. Conclusions: Gasping during CA was characterized by high V
T, extremely low frequency, and prolonged expiratory time, which may improve hypercapnia. During gasping, increased work of breathing and insufficient neuromechanical efficacy of neural respiratory drive suggested the necessity of MV and appropriate management strategies for MV during resuscitation after CA.
Rewilding soil-disturbing vertebrates to rehabilitate degraded landscapes: benefits and risks
Authors: Eldridge David J. , Soliveres Santiago
Published: April 2023

Soil-disturbing animals are common globally and play important roles in creating and maintaining healthy functional soils and landscapes. Yet many of these animals are threatened or locally extinct due to habitat loss, predation by non-native animals or poaching and poisoning. Some reintroduction and rewilding programmes have as their core aims to increase animal populations and reinstate processes that have been lost due to their extirpation. Here we use a meta-analytical approach to review the effects of soil-disturbing vertebrates on ecosystem processes, and advance the argument that they can be used to rehabilitate degraded ecosystems by altering mainly composition and function, but with fewer positive effects on structure. We describe four examples where the loss or reintroduction of soil-disturbing vertebrates leads to ecosystem state changes and highlight the role of spatial scale, covarying management changes, and species co-occurrence in modulating their effects. We discuss the advantages and disadvantages of using soil-disturbing vertebrates over mechanized engineering approaches such as pitting and furrowing, considering some advantages to include more self-sustainable and heterogeneous disturbances, creation of new habitats and added recreational values. Finally, we identify key knowledge gaps in our understanding of the use of soil-disturbing vertebrates for rehabilitating degraded ecosystems.
The use of social media in assessing the impact of war on cetaceans
Authors: Węgrzyn Ewa , Rusev Ivan , Tańska Natalia , Miedviedieva Iryna , Kagalo Alexander A. , Leniowski Konrad
Published: April 2023

War has always brought millions of silent non-human victims but the scale of this suffering is often either unknown, neglected or difficult to quantify. Further, the complexities associated with long-term and large-scale monitoring of marine species make it difficult to assess the impacts of war and the mortality of cetaceans resulting from warfare has not been investigated. Here we propose the use of a modified form of citizen science, namely gathering the information from social media. Dolphin stranding is such a poignant incident for most people, that the probability of eyewitness posting information on social media appears high. We test this idea by collecting data on cetacean strandings along the Black Sea published on the Internet over the three months of Russia's invasion of Ukraine in 2022. We also validate this method with a small-scale scientific study on cetacean mortality during the same period of time, conducted in ‘Tuzlivski lymany’ Nature National Park in Ukraine. Our dual approach has produced similar results, indicating a dramatic increase in cetacean mortality due to war operations in the Black Sea. We advocate the future use of social media to bridge the knowledge gap on the impacts of war on animals, in particular cetaceans.
Alfred Russel Wallace's Unrealized Last Book: Insights from the Plan for
Darwin and Wallace
Authors: Costa James T. , Beccaloni George
Published: April 2023

In honour of the two hundredth birthday of naturalist Alfred Russel Wallace (1823–1913) we present a transcription and analysis of the plan for Wallace's unrealized final book. Recently come to light,
Darwin and Wallace
was to have been a volume of eight chapters published by the well-known London publishing house of John Murray in the spring of 1915, a project derailed by Wallace's death at the age of 90 in November 1913. Drawing on letters, manuscripts and contemporary published works, we show how the chapter outlines illuminate Wallace's late-life thinking about his and Darwin's working methods, the factors contributing to their independent discovery of natural selection and contemporary challenges to Darwin–Wallace evolutionary gradualism and natural selection by the neo-Lamarckian, mutationist and early Mendelian schools during the period dubbed the ‘eclipse of Darwinism’. Wallace's planned book provides insight into how the co-founder of modern evolutionary biology saw his legacy in relation to Darwin's, and his role as fierce and eloquent defender of his and Darwin's theory during a fascinating period in the history of evolutionary biology. In the emergence of neo-Darwinism in the ‘Modern Synthesis’ period, Wallace's contributions were largely omitted, an oversight that
Darwin and Wallace
may have prevented had it been realized.
Judgement bias may be explained by shifts in stimulus response curves
Authors: Strang Caroline , Muth Felicity
Published: April 2023

Judgement bias, or ‘optimism’ and ‘pessimism’, has been demonstrated across many taxa, yet the cognitive mechanisms underlying this behaviour remain unclear. In an optimism paradigm, animals are trained to an association, and, if given a positive experience, behave more favourably towards ‘ambiguous’ stimuli. We tested whether this effect could be explained by changes to stimulus response gradients by giving bees a task where their response was tested across a wider gradient of stimuli than typically tested. In line with previous work, we found that bees given a positive experience demonstrated judgement bias, being more likely to visit ambiguous stimuli. However, bees were also less likely to visit a stimulus on the other side of the rewarded stimulus (S+), and as such had a shifted stimulus response curve, showing a diminished peak shift response. In two follow-up experiments we tested the hypothesis that our manipulation altered bees’ stimulus response curves via changes to the peak shift response by reducing peak shift in controls. We found that, in support of our hypothesis, elimination of peak shift also eliminated differences between treatments. Our results point towards a cognitive explanation of ‘optimistic’ behaviour in non-human animals and offer a new paradigm for considering emotion-like states.
Wide-gamut structural colours on oakblue butterflies by naturally tuned photonic nanoarchitectures
Authors: Piszter Gábor , Kertész Krisztián , Bálint Zsolt , Biró László Péter
Published: April 2023

The iridescent structural colours of butterflies, generated by photonic nanoarchitectures, often function as species-specific sexual signals; therefore, they are reproduced precisely from generation to generation. The wing scales of oakblue hairstreak butterflies (genus
Arhopala
, Theclinae, Lycaenidae, Lepidoptera) contain multi-layer photonic nanoarchitectures, which can generate a wide range of structural colours, from violet to green. By scanning (SEM) and cross-sectional transmission electron microscopy (TEM) investigation, the colour tuning mechanism of the cover scales was explored. We revealed that the characteristic size change of structural elements in similar photonic nanoarchitectures led to different structural colours that were examined by various reflectance spectrophotometry techniques. The measured structural properties of the naturally tuned photonic nanoarchitectures were used to calculate wing reflectances, which were compared with the measurement results. We found that the simulated structural colours were systematically redshifted by 95–126 nm as compared with the measured normal-incidence reflectance results. This is attributed to the swelling of the chitinous multi-layer structures during the standard TEM sample preparation and the tilt of the cover scales, which both affect the apparent layer thicknesses in the TEM cross-sections. We proposed a simulation correction and compared the results with the layer thicknesses measured on cryogenically prepared non-embedded SEM cross-sections.
Bacterial community dynamics and associated genes in hydrocarbon contaminated soil during bioremediation using brewery spent grain
Authors: Nnadi Mabel Owupele , Bingle Lewis , Thomas Keith
Published: April 2023

Brewery spent grain (BSG) has previously been exploited in bioremediation. However, detailed knowledge of the associated bacterial community dynamics and changes in relevant metabolites and genes over time, is limited. This study investigated the bioremediation of diesel contaminated soil amended with BSG. We observed the complete degradation of three Total Petroleum Hydrocarbon (TPH C10 – C28) fractions in amended treatments as compared to one fraction in the unamended treatments. The biodegradation rate constant was higher in amended treatments (0.1021 k) than in unamended (0.059 k) and bacterial CFUs increased significantly in amended treatments. The degradation compounds observed fitted into the elucidated diesel degradation pathways and quantitative PCR results showed that the gene copy numbers of all three associated degradation genes, alkB , catA and xylE, were significantly higher in amended treatments. High-throughput sequencing of 16S rRNA gene amplicons showed that amendment with BSG enriched autochthonous hydrocarbon degraders. Also, community shifts of the genera Acinetobacter and Pseudomonas correlated with the abundance of catabolic genes and degradation compounds observed. This study showed that these two genera are present in BSG and thus, may be associated with the enhanced biodegradation observed in amended treatments. The results suggest that the combined evaluation of TPH, microbiological, metabolite and genetic analysis provides a useful wholistic approach to assessing bioremediation.
The role of sand flies as vectors of viruses other than phleboviruses
Authors: Jancarova Magdalena , Polanska Nikola , Volf Petr , Dvorak Vit
Published: April 2023

Sand flies (Diptera: Phlebotominae) are proven vectors of various pathogens of medical and veterinary importance. Although mostly known for their pivotal role in the transmission of parasitic protists of the genusLeishmaniathat cause leishmaniases, they are also proven or suspected vectors of many arboviruses, some of which threaten human and animal health, causing disorders such as human encephalitis (Chandipura virus) or serious diseases of domestic animals (vesicular stomatitis viruses). We reviewed the literature to summarize the current published information on viruses detected in or isolated from phlebotomine sand flies, excluding the familyPhenuiviridaewith the genusPhlebovirus, as these have been well investigated and up-to-date reviews are available. Sand fly-borne viruses from four other families (Rhabdoviridae,Flaviviridae,ReoviridaeandPeribunyaviridae) and one unclassified group (Negevirus) are reviewed for the first time regarding their distribution in nature, host and vector specificity, and potential natural transmission cycles.
Transcriptional landscape of Burkholderia pseudomallei cultured under environmental and clinical conditions
Authors: Kong Cin , Wong Rui-Rui , Ghazali Ahmad-Kamal , Hara Yuka , Tengku Aziz Tengku Nurfarhana , Nathan Sheila
Published: April 2023

Burkholderia pseudomallei

, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of

B. pseudomallei

pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium’s large genome encodes an array of factors that support the pathogen’s ability to survive under stressful conditions, including the host’s internal milieu. In this study, we performed comparative transcriptome analysis of

B. pseudomallei

cultured in human plasma versus soil extract media to provide insights into

B. pseudomallei

gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in

B. pseudomallei

grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of

B. pseudomallei

virulence potential when present in human plasma. This ex vivo gene expression profile provides comprehensive information on

B. pseudomallei

’s adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.
Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa
Authors: Dubern Jean-Frédéric , Halliday Nigel , Cámara Miguel , Winzer Klaus , Barrett David A. , Hardie Kim R. , Williams Paul
Published: April 2023

In

Pseudomonas aeruginosa

, quorum sensing (QS) depends on an interconnected regulatory hierarchy involving the Las, Rhl and Pqs systems, which are collectively responsible for the co-ordinated synthesis of a diverse repertoire of N-acylhomoserine lactones (AHLs) and 2-alkyl-4-quinolones (AQs). Apparent population density-dependent phenomena such as QS may, however, be due to growth rate and/or nutrient exhaustion in batch culture. Using continuous culture, we show that growth rate and population density independently modulate the accumulation of AHLs and AQs such that the highest concentrations are observed at a slow growth rate and high population density. Carbon source (notably succinate), nutrient limitation (C, N, Fe, Mg) or growth at 25 °C generally reduces AHL and AQ levels, except for P and S limitation, which result in substantially higher concentrations of AQs, particularly AQ N-oxides, despite the lower population densities achieved. Principal component analysis indicates that ~26 % variation is due to nutrient limitation and a further 30 % is due to growth rate. The formation of N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) turnover products such as the ring opened form and tetramic acid varies with the limiting nutrient limitation and anaerobiosis. Differential ratios of N-butanoyl-homoserine lactone (C4-HSL), 3OC12-HSL and the AQs as a function of growth environment are clearly apparent. Inactivation of QS by mutation of three key genes required for QS signal synthesis (lasI, rhlI and pqsA) substantially increases the concentrations of key substrates from the activated methyl cycle and aromatic amino acid biosynthesis, as well as ATP levels, highlighting the energetic drain that AHL and AQ synthesis and hence QS impose on

P. aeruginosa

.
Extracellular Domains of CAR Reprogram T-Cell Metabolism Without Antigen Stimulation
Authors: Lakhani Aliya , Chen Ximin , Chen Laurence C. , Khericha Mobina , Chen Yvonne Y. , Park Junyoung O.
Published: April 2023

Metabolism is an indispensable part of T-cell proliferation, activation, and exhaustion, yet the metabolism of chimeric antigen receptor (CAR)-T cells remains incompletely understood. CARs are comprised of extracellular domains that determine cancer specificity, often using single-chain variable fragments (scFvs), and intracellular domains that trigger signaling upon antigen binding. Here we show that CARs differing only in the scFv reprogram T-cell metabolism differently. Even in the absence of antigens, some CARs increase proliferation and nutrient uptake in T cells. Using stable isotope tracers and mass spectrometry, we observe basal metabolic fluxes through glycolysis doubling and amino acid uptake overtaking anaplerosis in CAR-T cells harboring rituximab scFv, unlike other similar anti-CD20 scFvs. Disparate rituximab and 14g2a-based anti-GD2 CAR-T cells are similarly hypermetabolic and channel excess nutrients to nitrogen overflow metabolism. Since CAR-dependent metabolic reprogramming alters cellular energetics, nutrient utilization, and proliferation, metabolic profiling should be an integral part of CAR-T cell development.
Mast fruiting in a large tropical African legume tree provides evidence for the nutrient resource limitation hypothesis
Authors: Newbery David M. , Schwan Sarah , Chuyong George B. , Neba Godlove A. , Etta Culbertson E. , Norghauer Julian M. , Worbes Martin
Published: April 2023

The large grove-forming tropical treeMicroberlinia bisulcata(Fabaceae subfamily Detarioideae) at Korup, Cameroon, shows strong mast fruiting. Reproductive allocation is considerable. The site has very nutrient-poor soil. To test the nutrient resource limitation hypothesis, phenological recordings between 1989 and 2017 were matched with climate variables, and analyzed using logistic time-series regression. Masting happened mostly on 2- or 3-year cycles. A strong predictor was mean daily rainfall in the dry season: low in the current year of masting and high in the year prior. Less strongly predictive was the increase in dry season radiation between prior and mast years. Masting events showed no relationship to annual stem increment, nor with local plantation yields. Later, the normally heavy mastings became moderate after two attacks by caterpillars. Collated studies of fallen leaf nutrient concentrations showed that P increased markedly, K rose and fell, but N and Mg changed little, in the inter-mast interval. P and K were likely being accumulated and stored, and then triggered masting events when internal thresholds were crossed. The drier season prior to masting enabled a rise in C, and the wetter season the year before, with higher soil moisture, enabled better acquisition and uptake of nutrients by roots and mycorrhizas. The main storage of P may be in bark and branches, that for K on soil organic-colloids. A rooting-fruiting trade-off in C allocated over a minimal 2-year cycle is implied. Hypothesized is that synchrony among masting trees may be achieved, in part, by an equilibration of P across the mycorrhizal network. The long-term driver appears to be the inherent year-to-year stochasticity of dry-season rainfall, realization of which leads to an important refinement of the hypothesis. Life history strategy linked to nutrient resource dynamics provides a plausible explanation and more advanced hypothesis for the masting events observed.
The genetic legacy of the expansion of Bantu-speaking peoples in Africa
Authors: Fortes-Lima Cesar A. , Burgarella Concetta , Hammarén Rickard , Eriksson Anders , Vicente Mário , Jolly Cecile , Semo Armando , Gunnink Hilde , Pacchiarotti Sara , Mundeke Leon , Matonda Igor , Muluwa Joseph Koni , Coutros Peter , Nyambe Terry S. , Cikomola Cirhuza , Coetzee Vinet , de Castro Minique , Ebbesen Peter , Delanghe Joris , Stoneking Mark , Barham Lawrence , Lombard Marlize , Meyer Anja , Steyn Maryna , Malmström Helena , Rocha Jorge , Soodyall Himla , Pakendorf Brigitte , Bostoen Koen , Schlebusch Carina M.
Published: April 2023

With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ∼4000 years ago in western Africa. We have genotyped 1,740 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals. Our results show that Bantu speakers received significant gene-flow from local groups in regions they expanded into. We show for the first time that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the DRC as possible crossroads of interaction. Using spatially explicit methods and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial founder migration model. Finally, we discuss the utility of our dataset as an exhaustive modern-day African comparative dataset for ancient DNA studies. These new findings and data will be important to a wide range of disciplines from science and humanities as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.

One-sentence summary

A comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.
Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region
Authors: Tang Zhichao , Hegde Shalakha , Hao Siyuan , Selvaraju Manikandan , Qiu Jianming , Wang Jingxin
Published: April 2023

One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new type of coumarin derivatives, such asC30andC34, which bind to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical probe was directed to crosslink with the 2’-OH groups of ribose at the ligand binding site. This crosslinked RNA could then create read-through mutations during reverse transcription (i.e., primer extension) at single-nucleotide resolution to uncover the acylation locations. cgSHAPE-seq unambiguously determined that a bulged G in SL5 was the primary binding site ofC30in the SARS-CoV-2 5’ UTR, which was validated through mutagenesis and in vitro binding experiments.C30was further used as a warhead in RNA-degrading chimeras to reduce viral RNA expression levels. We demonstrated that replacing the acylating moiety in the cgSHAPE probe with ribonuclease L recruiter (RLR) moieties yielded RNA degraders active in the in vitro RNase L degradation assay and SARS-CoV-2 5’ UTR expressing cells. We further explored another RLR conjugation site on the E ring ofC30/C34and discovered improved RNA degradation activities in vitro and in cells. The optimized RNA-degrading chimeraC64inhibited live virus replication in lung epithelial carcinoma cells.
Phenotypic and genotypic detection of the virulence factors and their association with antibiotic resistance inEnterococcusspecies
Authors: Momotaz Tahani , Afroz Fatima , Chowdhury Sharmin , islam Nahidul , Sarwar Mohammad Tanvir , Khan Rehana Razzak , Sattar Abu Naser Ibne
Published: April 2023

Abstract-Along with the emergence of drug resistantEnterococcalinfection, role of various virulence factors inEnterococciis an emerging concept. A number of virulence factors like biofilm formation, hemolysin production, gelatin hydrolysis have important role in the pathogenesis ofEnterococciand also associated with antibiotic resistance. The aim of our study was to detect the virulence factors and their encoding genes (asa, gelE, esp, ebpR, hylgene for biofilm;cylAgene for hemolysis;gelEgene for gelatin hydrolysis) and also observe their association with antimicrobial resistanceEnterococci. A total of 87Enterococciwere collected from different clinical samples. Virulence factors were detected phenotypically and antibiotic sensivity were done by Kirby Bauer disc diffusion method. Virulence genes were detected by conventional multiplex PCR and only theebpRgene was detected by single conventional PCR. Majority of the isolatedEnterococciwereE. faecalis(75%) followed byE. faecium(23%) and (2%)E. raffinosuswere also detected. About 52.3% ofE. faecalisand 35% ofE. faeciumisolates were biofilm producers. Significant association was found between biofilm formation andasa, esp, ebpRgenes both inE. faecalisand inE. faecium.Hemolysis was observed phenotypically in 30.8% isolates ofE. faecalisand 20% isolates ofE. faecium. Significant association was observed betweencylAgene and hemolysin production inE. faecalis. Antibiotic resistance were higher in biofilm and hemolysin producing isolates of both species. Resistance to some antibiotics including ampicillin, ciprofloxacin, gentamicin were significantly higher among biofilm and hemolysin producer inE. faecalis.
Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors
Authors: He Yixuan , Qian David C. , Diao James A. , Cho Michael H. , Silverman Edwin K. , Gusev Alexander , Manrai Arjun K. , Martin Alicia R. , Patel Chirag J.
Published: April 2023

Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We hypothesize that considering other socioeconomic and environmental factors can better predict and stratify the risk of COPD in both non-smokers and smokers. We performed longitudinal analysis of COPD in the UK Biobank to develop the Socioeconomic and Environmental Risk Score (SERS) which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. We tested the ability of SERS to predict and stratify the risk of COPD in current, previous, and never smokers of European and non-European ancestries in comparison to a composite genome-wide polygenic risk score (PGS). We tested associations using Cox regression models and assessed the predictive performance of models using Harrell’s C index. SERS (C index = 0.770, 95% CI 0.756 to 0.784) was more predictive of COPD than smoking status (C index = 0.738, 95% CI 0.724 to 0.752), pack-years (C index = 0.742, 95% CI 0.727 to 0.756). Compared to the remaining population, individuals in the highest decile of the SERS had hazard ratios (HR) = 7.24 (95% CI 6.51 to 8.05, P < 0.0001) for incident COPD. Never smokers in the highest decile of exposure risk were more likely to develop COPD than previous and current smokers in the lowest decile with HR=4.95 (95% CI 1.56 to 15.69, P=6.65×10−3) and 2.92 (95%CI 1.51 to 5.61, P=1.38×10−3), respectively. In general, the prediction accuracy of SERS was lower in the non-European populations compared to the European evaluation set. In addition to genetic factors, socioeconomic and environmental factors beyond smoking can predict and stratify COPD risk for both non- and smoking individuals. Smoking status is often considered in screening; other non-smoking environmental and non-genetic variables should be evaluated prospectively for their clinical utility.
Radio-frequency ablation versus hepatic surgery for the treatment of hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Dani Avichal , Gandhi Khushi Vishal , Desai Dev
Published: April 2023

Background

Hepatocellular carcinoma (HCC) is the most common malignant tumor composed of cells resembling hepatocytes. It is the fourth most common cause of cancer□related death on earth. Treatment involves radio frequency ablation (RFA)or hepatic resection (HR). This is a review & evaluation of evidence comparing either methods by using meta-analysis technique.

Materials and methods

We conducted a database search of the PUBMED, GOOGLE SCHOLAR, Cochrane, EMBASE etc. in which total of 36 observational studies and 3 RCTs following PRISMA guidelines till September 2020 and matching inclusion and exclusion criteria were collected. These studies include total 16,700 patients out of which 8565 were treated with RFA & 8135 with surgery. The following search strings were used: “ RFA vs HR”, “hepatocellular carcinoma treatment “. The primary end point was overall survival rate in 3&5 years respectively, including hospital stay duration & local recurrence. RevMan 5.3 was used for appropriate statistical tests. Fixed and Random Effect Model Tests was used and p<0.05 was considered statistically significant.

Results

Meta-analysis showed that RFA was associated with significant decrease in the length of hospital stay for RCTs (SMD = -2.171, CI = -2.381 to - 1.962, p=<0.001) and non-RCTs (SMD = -1.048, CI = 1.492 to -0.937, p=<0.001) respectively. However, it was also associated with significant increase incidence of recurrence (RR = 1.749, 95% CI = 1.444 to 2.119, p=<0.001) and significantly poorer 3-year (RR = 0.850, 95% CI = 0.772 to 0.935, p=0.001); (RR = 0.941, 95%CI = 0.927 to 0.956, p=<0.001) survival chances for RCTs and non-RCTs respectively. 5-year survivability was (RR=0.856, 95% CI = 0.835 to 0.878, p=0.001).

Conclusion

Although RFA was associated with decreased duration of hospital stay, it was associated with increased chances of recurrence compared to hepatic resection. 3-year survival rate was also poorer.
p53 translational-isoform Δ40p53 regulates cell cycle by modulating the miR-4671-5p/SGSH axis
Authors: Pal Apala , Ghosh Pritam Kumar , Ghosh Sahana , Tripathi Sachin Kumar , Guha Sohini , Coca Pragnya , Patra Subrata , Prathima K.M. , Khan Debjit , Das Manjula , Maitra Arindam , Das Saumitra
Published: April 2023

Parsing functions of tumour suppressor geneTP53is inherently complicated owing to multiple p53 isoforms it encodes. Δ40p53, the only translational isoform, alters p53 target gene expression both positively and negatively, thereby modulating p53 functional activity. Independent of p53, Δ40p53 regulates miR-186-5p–YY1 axis to decrease cell proliferation. To uncover more such miRNAs that are differentially regulated by Δ40p53 and p53, in this study, we performed small RNA sequencing. Overexpression of Δ40p53, but not full-length (FL) p53, substantially downregulated expression of miR-4671-5p. However, upon overexpression of different ratios of Δ40p53 and FLp53, changes in miR-4671-5p levels implied that it is a FLp53 modifiable target. In anin-silicoapproach, we identified N- sulfoglucosamine sulfohydrolase (SGSH) as a candidate miR-4671-5p target. The expression levels of SGSH show potential prognostic significance for survival that trends oppositely to miR-4671-5p levels associated with the same cancer types, which supports a direct physiological relevance of their interaction. Furthermore, decreasedSGSHmRNA and protein levels were observed with siΔ40p53 as well as upon overexpression of miR-4671-5p, confirming the molecular interplay. Notably, overexpression of miR-4671-5p led to intra-S- phase cell cycle arrest. Therefore, the Δ40p53-miR-4671-5p-SGSH axis emerges as a novel regulatory pathway influencing cell cycle progression. We also expanded our study to a cohort of colorectal cancer patient samples. Results indicate that the expression level of Δ40p53 can stratify miR-4671-5p andSGSHmRNA levels, validating their inverse correlation observed in the cellular scenario. Collectively, these findings significantly enhance our understanding of the functions of Δ40p53 mediated by miRNAs, contributing to the maintenance of metabolic and cellular homeostasis independent of full-length p53.
Microeukaryotic predators shape the wastewater microbiome
Authors: Heck Nils , Freudenthal Jule , Dumack Kenneth
Published: April 2023

The physicochemical parameters that shape the prokaryotic community composition in wastewater have been extensively studied. In contrast, it is poorly understood whether and how biotic interactions affect the prokaryotic community composition in wastewater. We used metatranscriptomics data from a bioreactor sampled weekly over 14 months to investigate the wastewater microbiome, including often neglected microeukaryotes. Our analysis revealed that while prokaryotes are unaffected by seasonal changes in water temperature, they are impacted by a seasonal, temperature-induced change in the microeukaryotic community. Our findings suggest that selective predation pressure exerted by microeukaryotes is a significant factor shaping the prokaryotic community in wastewater. This study underscores the importance of investigating the entire wastewater microbiome to develop a comprehensive understanding of wastewater treatment.