bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoy receptors as biomarkers for exploring aetiology and designing new therapies
Authors: Zoccali Carmine , Tripepi Giovanni , Stel Vianda , Fu Edouard L , Mallamaci Francesca , Dekker Friedo , Jager Kitty J
Published: July 2024

Soluble decoy receptors (DR) are circulating proteins that act as molecular traps for ligands that modulate various signalling pathways. These proteins can be exploited as biomarkers and, in some cases, as drugs in various disease contexts. Inflammation is a key area where DRs have shown significant potential. By binding to pro-inflammatory cytokines, inflammatory DRs, such as soluble tumour necrosis factor receptors (sTNFRs), can inhibit downstream inflammatory signalling. This modulation of the inflammatory response holds promise for therapeutic interventions in various inflammatory conditions, including cardiovascular and chronic kidney diseases. Soluble DRs for advanced glycation end products (sRAGE) bind to advanced glycation end products (AGEs), reducing their detrimental effects on vascular function and atherosclerosis. High circulating sRAGE levels are associated with a lower risk for CV events, highlighting the potential of these soluble receptors for assessing the role of AGEs in CV diseases and managing the attendant risk. DRs may serve as biomarkers and therapeutic agents to advance our understanding of disease mechanisms and improve patients' outcomes. Their ability to modulate signalling pathways in a controlled manner opens up new opportunities for therapeutic interventions in various diseases, ranging from inflammation to cardiovascular and renal disorders.
Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study
Authors: Byrne Christina , Kjærgaard Jesper , Møller Jacob E , Biering-Sørensen Tor , Borregaard Britt , Schmidt Henrik , Hassager Christian
Published: July 2024

Aims

To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension.

Methods and results

A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P < 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67).

Conclusion

Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target.
Ticagrelor 60 vs. 90 mg in elderly ACS patients undergoing PCI: a randomized, crossover trial
Authors: Piccolo Raffaele , Simonetti Fiorenzo , Avvedimento Marisa , Cutillo Maria , Canonico Mario Enrico , Conti Valeria , Gargiulo Giuseppe , Paolillo Roberta , Dal Piaz Fabrizio , Filippelli Amelia , Charlier Bruno , Spinelli Alessandra , Cristiano Stefano , Cirillo Plinio , Di Serafino Luigi , Franzone Anna , Esposito Giovanni
Published: July 2024

Aims

Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI).

Methods and results

PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: −4; 95% confidence interval: −16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg.

Conclusion

Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI.
Low-pressure versus standard-pressure pneumoperitoneum in minimally invasive colorectal surgery: a systematic review, meta-analysis, and meta-regression analysis
Authors: Dourado Justin , Rogers Peter , Horesh Nir , Emile Sameh Hany , Aeschbacher Pauline , Wexner Steven D
Published: July 2024

Background

We aimed to assess the efficacy and safety of low-pressure pneumoperitoneum (LPP) in minimally invasive colorectal surgery.

Methods

A PRISMA-compliant systematic review/meta-analysis was conducted, searching PubMed, Scopus, Google Scholar, and clinicaltrials.gov for randomized-controlled trials assessing outcomes of LPP vs standard-pressure pneumoperitoneum (SPP) in colorectal surgery. Efficacy outcomes [pain score in post-anesthesia care unit (PACU), pain score postoperative day 1 (POD1), operative time, and hospital stay] and safety outcomes (blood loss and postoperative complications) were analyzed. Risk of bias2 tool assessed bias risk. The certainty of evidence was graded using GRADE.

Results

Four studies included 537 patients (male 59.8%). LPP was undertaken in 280 (52.1%) patients and associated with lower pain scores in PACU [weighted mean difference: −1.06, 95% confidence interval (CI): −1.65 to −0.47, P = 0.004, I2 = 0%] and POD1 (weighted mean difference: −0.49, 95% CI: −0.91 to −0.07, P = 0.024, I2 = 0%). Meta-regression showed that age [standard error (SE): 0.036, P < 0.001], male sex (SE: 0.006, P < 0.001), and operative time (SE: 0.002, P = 0.027) were significantly associated with increased complications with LPP. In addition, 5.9%–14.5% of surgeons using LLP requested pressure increases to equal the SPP group. The grade of evidence was high for pain score in PACU and on POD1 postoperative complications and major complications, and blood loss, moderate for operative time, low for intraoperative complications, and very low for length of stay.

Conclusions

LPP was associated with lower pain scores in PACU and on POD1 with similar operative times, length of stay, and safety profile compared with SPP in colorectal surgery. Although LPP was not associated with increased complications, older patients, males, patients undergoing laparoscopic surgery, and those with longer operative times may be at risk of increased complications.
Building, Maintaining, and (re-)Deploying Genetic Toolkits during Convergent Evolution
Authors: Oakley Todd H
Published: July 2024

Synopsis

A surprising insight from the advent of genomic sequencing was that many genes are deeply conserved during evolution. With a particular focus on genes that interact with light in animals, I explore the metaphor of genetic toolkits, which can be operationalized as lists of genes involved in a trait of interest. A fascinating observation is that genes of a toolkit are often used again and again during convergent evolution, sometimes across vast phylogenetic distances. Such a pattern in the evolution of toolkits requires three different stages: (i) origin, (ii) maintenance, and (iii) redeployment of the genes. The functional origins of toolkit genes might often be rooted in interactions with external environments. The origins of light interacting genes in particular may be tied to ancient responses to photo-oxidative stress, inspiring questions about the extent to which the evolution of other toolkits was also impacted by stress. Maintenance of genetic toolkits over long evolutionary timescales requires gene multifunctionality to prevent gene loss when a trait of interest is absent. Finally, the deployment of toolkit genes in convergently evolved traits like eyes sometimes involves the repeated use of similar, ancient genes yet other times involves different genes, specific to each convergent origin. How often a particular gene family is used time and again for the same function may depend on how many possible biological solutions are available. When few solutions exist and the genes are maintained, evolution may be constrained to use the same genes over and over. However, when many different solutions are possible, convergent evolution often takes multiple different paths. Therefore, a focus on genetic toolkits highlights the combination of legacy-plus-innovation that drives the evolution of biological diversity.
Charting the Impact of Maternal Antibodies and Repeat Exposures on Sapovirus Immunity in Early Childhood From a Nicaraguan Birth Cohort
Authors: Bucardo Filemón , Mallory Michael L , González Fredman , Reyes Yaoska , Vielot Nadja A , Yount Boyd L , Sims Amy C , Nguyen Cameron , Cross Kaitlyn , Toval-Ruíz Christian , Gutiérrez Lester , Vinjé Jan , Baric Ralph S , Lindesmith Lisa C , Becker-Dreps Sylvia
Published: July 2024

Background

Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity.

Methods

We measured sapovirus-specific IgG in serum collected between 2017 and 2020 of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n = 112 dyads), using virus-like particles representing 3 sapovirus genotypes (GI.1, GI.2, GV.1).

Results

Of the 112 children, 16 (14.3%) experienced at least 1 sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined by antigenic cartography: newborns share their mothers’ broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections.

Conclusions

By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.
Introducing the UK Antimicrobial Registry (UKAR) study: providing real world data on new antimicrobials to support antimicrobial stewardship and tackle antimicrobial resistance
Authors: Sneddon Jacqueline , Macfarlane Gary J , Jones Gareth T , Moir Laura , Parr Rebecca , Jenkins David , Guise Tracey , Sandoe Jonathan A T , Seaton R Andrew ,   UKAR Steering Committee, Brown Nicholas , Longshaw Christopher , Garraghan Fran
Published: July 2024

The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials.
Comparative analysis of three plasmids from Plesiomonas shigelloides strain MS-17-188 and their role in antimicrobial resistance
Authors: Abdelhamed Hossam , Mannan Shahnewaj Bin , Riman Munshi Mustafiz , Tekedar Hasan C , Lawrence Mark L
Published: July 2024

Background

Plesiomonas shigelloides strain MS-17-188 was isolated from a deceased catfish from East Mississippi and showed resistance to florfenicol, tetracyclines and a sulphonamide. WGS of strain MS-17-188 revealed three plasmids (pPSMS-171881, pPSMS-171882 and pPSMS-171883).

Objectives

To accurately determine the impact of three plasmids found in P. shigelloides strain MS-17-188 on the dissemination of antibiotic resistance genes and to provide insights into the molecular structure of these plasmids.

Methods

The genetic features of these plasmids in terms of genes associated with antimicrobial resistance (AMR), virulence, transfer, maintenance and replication were identified using bioinformatic tools. Additionally, we investigated the in vitro mobilization and stability of plasmid-mediated resistance. The Comprehensive Antibiotic Resistance Database and Virulence Factors Database were used to detect the AMR genes and virulence genes of P. shigelloides plasmids. Moreover, plasmid mobility was evaluated by a filter-mating assay using strain MS-17-188 as a donor and azide-resistant Escherichia coli J53 as a recipient strain. A stability experiment was conducted to explore the persistence of plasmid-mediated antibiotic resistance in strain MS-17-188 in the absence and presence of selection.

Results

pPSMS-171881 harboured multidrug efflux complex (adeF) and two genes responsible for arsenic resistance (arsB and arsC). pPSMS-171882 had a region of 7085 bp encoding type IV secretion system proteins. pPSMS-171883 carried the tetracycline resistance genes tet(A) and tet(R), and a phenicol resistance gene (floR), which were flanked by two transposable elements and mobilization proteins, suggesting that there is a conjugative mechanism by which this plasmid can be mobilized. Results from the stability experiment indicated that pPSMS-171883 is lost over time in the absence of selective pressure. Moreover, pPSMS-171883 is more stable in P. shigelloides at growth temperatures of 30°C and 37°C compared with 40°C and 43°C. After intraperitoneal injection in catfish, P. shigelloides strain MS-17-188 resulted in no mortalities.

Conclusions

This is the first study to report plasmid-mediated AMR in Plesiomonas isolated from cultured fish, which needs continued monitoring. This study will provide an understanding of the genetic mechanisms of AMR and virulence of P. shigelloides.
Utilization of Texture Analysis in Differentiating Benign and Malignant Breast Masses: Comparison of Grayscale Ultrasound, Shear Wave Elastography, and Radiomic Features
Authors: Mannina Daniel , Kulkarni Ameya , van der Pol Christian B , Al Mazroui Reem , Abdullah Peri , Joshi Sayali , Alabousi Abdullah
Published: July 2024

Objective

This study aims to determine which qualitative and quantitative US features are independently associated with malignancy, including those derived from grayscale imaging morphology, shear wave elastography (SWE), and texture analysis.

Methods

This single-center retrospective study was approved by the institutional research ethics board. Consecutive breast US studies performed between January and December 2020 were included. Images were acquired using a Canon Aplio i800 US unit (Canon Medical Systems, Inc., CA) and i18LX5 wideband linear matrix transducer. Grayscale US features, SWE mean, and median elasticity were obtained. Single representative grayscale images were analyzed using dedicated software (LIFEx, version 6.30). First-order and gray-level co-occurrence matrix second-order texture features were extracted. Multivariate logistic regression was performed to assess for predictors of malignancy (STATA v16.1).

Results

One hundred forty-seven cases with complete SWE data were selected for analysis (mean age 54.3, range 21-92). The following variables were found to be independently associated with malignancy: age (P <.001), family history (P = .013), irregular mass shape (P = .024), and stiffness on SWE (mean SWE ≥40 kPa; P <.001). Remaining variables (including texture features) were not found to be independently associated with malignancy (P >.05).

Conclusion

US texture analysis features were not associated with malignancy independent of other qualitative and quantitative US characteristics currently utilized in clinical practice. This suggests texture analysis may not be warranted when differentiating benign and malignant breast masses on US. In contrast, irregular mass shape on grayscale imaging and increased stiffness on SWE were found to be independent predictors of malignancy.
Regulating embryo models in the UK
Authors: Jackson Emily
Published: July 2024

One of this century’s most dramatic scientific developments is the reprogramming of stem cells in order to create self-organizing embryo-like entities, known as stem cell based embryo models (SCBEMs). The science is moving very quickly, but if, as increasingly appears to be the case, scientists are capable of creating entities that are effectively indistinguishable from sperm and egg derived embryos, important legal questions arise. In countries like the UK, where a strict regulatory regime applies to research on embryos, should this be extended to SCBEM research, or would a different regulatory response be appropriate? Drawing on the 1984 Warnock Report, the Human Fertilisation and Embryology Act 1990 and the latest guidelines from the International Society for Stem Cell Research, this article considers principles for the regulation of the creation and use of SCBEMs.
Laundry-on-Air: Cultural Intimacy and the Transnational Circulation of Popular Culture
Authors: Abramson Yehonatan , Press-Barnathan Galia
Published: July 2024

TV shows and movies, as dominant forms of modern popular culture, often trigger domestic discussions, especially when dealing with sensitive and thorny issues in society. But what happens when these domestically-created cultural productions are globally circulated and consumed? In recent years, especially following the streaming revolution, there have been increasing numbers of national TV shows and films that are internationally distributed and broadcast. Focusing on the Israeli case, this article examines discursive responses to conflict-related TV shows and films that were created in Israel and are broadcast to an international audience. Situating these responses within International Relations constructivism and Social Psychology literature, we argue that the Israeli harsh and emotional response is a result of three dimensions related to these productions: (1) they deal with culturally intimate issues; (2) they expose Israeli vulnerabilities to outsiders; and (3) they are created by Israeli citizens, expected to align with group norms. In addition to bringing to the surface domestic identity debates, these internationally consumed cultural productions add another layer of ontological anxiety—the uncomfortable feeling associated with “airing the dirty laundry in public.”
Spin-related excited-state phenomena in photochemistry
Authors: Zhang Chuang , Ye Chen , Yao Jiannian , Wu Li-Zhu
Published: July 2024

The spin of electrons plays a vital role in chemical reactions and processes, and the excited state generated by the absorption of photons shows abundant spin-related phenomena. However, the importance of electron spin in photochemistry studies has been rarely mentioned or summarized. In this review, we briefly introduce the concept of spin photochemistry based on the spin multiplicity of the excited state, which leads to the observation of various spin-related photophysical properties and photochemical reactivities. Then, we focus on the recent advances in terms of light-induced magnetic properties, excited-state magneto-optical effects and spin-dependent photochemical reactions. The review aims to provide a comprehensive overview to utilize the spin multiplicity of the excited state in manipulating the above photophysical and photochemical processes. Finally, we discuss the existing challenges in the emerging field of spin photochemistry and future opportunities such as smart magnetic materials, optical information technology and spin-enhanced photocatalysis.
A Retrospective Longitudinal Study of Refugees With Eosinophilia at an Academic Center in the United States From 2015 to 2020
Authors: Ding Ann , Osorio Marcela , Teferi Maranatha , Gallo Marin Benjamin , Cruz-Sánchez Margarita , Lorenz Matthew , Michelow Ian C
Published: July 2024

Background

Refugees to the United States frequently have parasitic infections. If untreated, parasites can cause severe complications. The purpose of this study was to investigate the incidence, management, and outcomes of eosinophilia as a biomarker for parasites.

Methods

We conducted a retrospective longitudinal chart review of consecutive refugees attending 3 refugee clinics in Rhode Island that manage the health care of all pediatric and adult refugees.

Results

Among 812 refugees who met inclusion criteria, 147 (18.1%) had eosinophilia upon arrival and almost half had ≥1 symptom. The rates and severity of eosinophilia in those with predeparture presumptive treatment records who did (112/115, 97.4%) or did not (488/498, 98.0%) receive predeparture antiparasitic treatment were similar. All refugees with eosinophilia had ≥1 parasitic test in the United States. The most common attributable parasites were Schistosoma and Strongyloides stercoralis. Overall, parasites were detected in 63 (42.9%) of 147 refugees with eosinophilia by either stool testing, serology, or blood smear, but testing was inconsistent and likely underestimated true incidence. Only some of the identified parasites typically cause eosinophilia. Forty-five (30.6%) refugees with eosinophilia received antiparasitics in the United States. Of 81 (55.1%) individuals who had repeat blood tests, eosinophilia had resolved in 52 (64.2%). Five individuals (3.4%) had alternative diagnoses, including eczema, myelofibrosis, and drug allergy.

Conclusions

Our findings support Centers for Disease Control and Prevention recommendations to screen for eosinophilia in newly arrived refugees. Follow-up after 3–6 months is critical to confirm resolution of residual eosinophilia, which frequently occurs after effective predeparture treatment or if eosinophilia persists, to diagnose active parasitic infections.
Glutamatergic signaling from melanin-concentrating hormone-producing neurons: A requirement for memory regulation, but not for metabolism control
Authors: Pham Xuan Thang , Abe Yoshifumi , Mukai Yasutaka , Ono Daisuke , Tanaka Kenji F , Ohmura Yu , Wake Hiroaki , Yamanaka Akihiro
Published: July 2024

Melanin-concentrating hormone-producing neurons (MCH neurons), found mainly in the lateral hypothalamus and surrounding areas, play essential roles in various brain functions, including sleep and wakefulness, reward, metabolism, learning, and memory. These neurons coexpress several neurotransmitters and act as glutamatergic neurons. The contribution of glutamate from MCH neurons to memory- and metabolism-related functions has not been fully investigated. In a mouse model, we conditionally knocked out Slc17a6 gene, which encodes for vesicular glutamate transporter 2 (vGlut2), in the MCH neurons exclusively by using two different methods: the Cre recombinase/loxP system and in vivo genome editing using CRISPR/Cas9. Then, we evaluated several aspects of memory and measured metabolic rates using indirect calorimetry. We found that mice with MCH neuron-exclusive vGlut2 ablation had higher discrimination ratios between novel and familiar stimuli for novel object recognition, object location, and three-chamber tests. In contrast, there was no significant change in body weight, food intake, oxygen consumption, respiratory quotient, or locomotor activity. These findings suggest that glutamatergic signaling from MCH neurons is required to regulate memory, but its role in regulating metabolic rate is negligible.
Behavioural Responses to Wealth Taxation: Evidence from Colombia
Authors: Londoño-Vélez Juliana , Ávila-Mahecha Javier
Published: July 2024

We study behavioural responses to personal wealth taxes in Colombia. We utilise tax microdata from 1993 to 2016 linked with the leaked Panama Papers to investigate offshoring to the country’s key tax havens. We leverage variation from discrete jumps in tax liability and four major reforms to the wealth tax system, including changes in tax rates and duration, using bunching and difference-in-difference techniques. We find compelling evidence that taxpayers instantly reduce the wealth they declare in response to a wealth tax. Moreover, these effects can persist for years even after the wealth tax is no longer in place, providing the first evidence of a hysteresis effect for a temporary tax policy. The response is driven by misreporting items that authorities cannot cross-verify, such as overstating debt and understating non-third-party-reported business assets. Additionally, the wealthiest taxpayers respond to wealth tax increases by hiding assets in hard-to-track entities in tax havens.
Recipe for fatigue: sleep, work patterns, and well-being of galley workers on surface ships of the US Navy
Authors: Shattuck Nita Lewis , Matsangas Panagiotis
Published: July 2024

Study Objectives

The purpose of the study was to compare the fatigue levels, work/rest patterns, health-related behaviors, and well-being of galley workers with other sailors on US Navy ships while underway.

Methods

Analysis was based on a retrospective comparison of data from 3 fit-for-duty groups of sailors: 67 galley workers, 192 non-watchstanders, and 466 watchstanders. Participants completed questionnaires (Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI], Pittsburgh Sleep Quality Index [PSQI], and Profile of Mood States [POMS]) and activity logs, and wore actigraphs.

Results

Galley workers slept MD = 6.57 (IQR = 1.42) h/d and worked MD = 12.8 (IQR = 2.42) h/d. Approximately 84% of the galley workers were classified as poor sleepers, ~57% reported having excessive daytime sleepiness (EDS), and ~38% reported elevated insomnia symptoms. Compared to non-watchstanders, galley workers had worse scores on POMS (total mood disturbance, tension-anxiety, depression, anger-hostility, fatigue, and confusion-bewilderment), ESS, ISI, and PSQI. Compared to non-watchstanders, galley workers had a higher risk for symptoms of EDS (75%), symptoms of clinically relevant insomnia (126%), and for being classified as poor sleepers (27%). Galley workers slept less and worked on average 2 h/d more than non-watchstanders. Compared to watchstanders, galley workers had worse ESS, ISI, and anger-hostility scores. More watchstanders napped compared to galley workers.

Conclusions

Although they are considered day workers, the sleep patterns, fatigue levels, and mood of galley workers are comparable to, or worse than, watchstanders or other non-watchstanders. To ameliorate the effects of long work hours on sailor well-being, ship leadership should consider adopting strategies to improve galley workers’ well-being.
MISEV2023 provides an updated and key reference for researchers studying the basic biology and applications of extracellular vesicles
Authors: Upadhya Dinesh , Shetty Ashok K
Published: July 2024

The recently published “Minimal information for studies of extracellular vesicles - 2023 (MISEV2023)” in the Journal of Extracellular Vesicles has provided practical solutions to the numerous challenges extracellular vesicles (EVs) researchers face. These guidelines are imperative for novice and experienced researchers and promote unity within the EV community. It is strongly recommended that laboratories working with EVs make MISEV2023 an essential handbook and that researchers actively promote these guidelines during laboratory meetings, journal clubs, seminars, workshops, and conferences. A collective effort from EV researchers is crucial to steer the progress of EV science in a positive direction.
Virulence Determinants Are Unevenly Distributed Within Streptomyces Species and Strains Causing Potato Common Scab in the Province of Quebec, Canada
Authors: Biessy Adrien , Cadieux Mélanie , Ciotola Marie , St-Onge Renée , Blom Jochen , Filion Martin
Published: July 2024

Potato common scab is an important bacterial disease afflicting potatoes around the world. Better knowledge of the local Streptomyces spp. populations causing this disease is key to developing durable control strategies. In this study, we isolated 230 Streptomyces strains from scab-infected potato tubers harvested from commercial potato fields located across the province of Quebec, Canada. The genetic diversity of this collection was first studied using repetitive element-based PCR fingerprinting, and the genomes of 36 representative strains were sequenced using PacBio’s sequencing technology. This enabled us to identify the strains to the species level, to study the distribution of previously characterized virulence-associated genes and clusters, and to explore the repertoires of putative plant cell wall-degrading enzymes. In parallel, the virulence of the 36 strains was evaluated using a potato tuber slice assay. The diversity was higher than previously reported, as 11 phytopathogenic species were found across the province. Among them, S. scabiei and S. acidiscabies were the most abundant as well as the most virulent. Strains belonging to these two species harbored numerous virulence determinants, including the thaxtomin biosynthetic gene cluster. By contrast, most weakly virulent strains lacked this cluster but harbored at least one known virulence determinant. The results obtained suggest that a higher number of virulence-associated genes and clusters in the genome of phytopathogenic Streptomyces spp. are associated with greater virulence. This study contributes to increasing the publicly available genomic resources of scab-causing Streptomyces spp. and expands our knowledge on the diversity and virulence of this important bacterial pathogen.
Evaluation of a Novel Online Webinar for Health Care Practitioner Education on the Health Effects of Smoking Cannabis in the Airway
Authors: Hu Amanda , Deane Emily Catherine , Gill Simran , Lynn Brenna
Published: July 2024

Introduction:

The rapid legalization of cannabis has led to a knowledge gap among health care practitioners (HCPs). This study aimed to evaluate a novel online webinar for HCP education on the health effects of smoking cannabis.

Methods:

An educational activity was developed by a multidisciplinary panel of experts. The webinar was recorded for on-demand viewing. A 10-item knowledge test was created by the multidisciplinary panel with content validity and was administered pre- and posteducational activity.

Results:

Six hundred seven HCPs participated. Pre- to posttest scores increased from 56.9% ± 23.9% to 63.5% ± 24.7% (P < .0001). The live group had a significantly higher improvement in scores (10.5% [7.1-13.8% 95% CI] (P < .0001)) than the on-demand group. In multivariable regression model, the following factors were associated with a greater improvement in scores: older age (P = .0074), physician occupation (P = .026), live mode of learning interacted with lower pretest score (P < .0001), and live mode of learning interacted with female gender (P = .001). Approximately three-quarters of participants rated the webinar as above average (44.8%) or outstanding (29.8%).

Discussion:

This novel online educational activity increased knowledge and awareness of the health effects of smoking cannabis in the airway among HCPs and engaged learners virtually during the COVID-19 pandemic.
Antenatal Noninvasive Fetal Electrocardiography: A Literature Review
Authors: Pegorie Claire , Liu Becky , Thilaganathan Basky , Bhide Amar
Published: July 2024

Fetal heart rate (FHR) monitoring is one of the central parts of obstetric care. Ultrasound-based technologies such as cardiotocography (CTG) remain the most common method for FHR monitoring. The CTG’s limitations, including subjective interpretation, high interobserver variability, and the need for skilled professionals, led to the development of computerized CTG (cCTG). While cCTG demonstrated advantages, its superiority over visual interpretation remains inconclusive. This has prompted the exploration of alternatives like noninvasive fetal electrocardiography (NIFECG). This review explores the landscape of antenatal FHR monitoring and the need for remote FHR monitoring in a patient-centered care model. Additionally, FHR monitoring needs to evolve from the traditional approach to incorporate artificial intelligence and machine learning. The review underscores the importance of aligning fetal monitoring with modern healthcare, leveraging artificial intelligence algorithms for accurate assessments, and enhancing patient engagement. The physiology of FHR variability (FHRV) is explained emphasizing its significance in assessing fetal well-being. Other measures of FHRV and their relevance are described. It delves into the promising realm of NIFECG, detailing its history and recent technological advancements. The potential advantages of NIFECG are objective FHR assessment, beat-to-beat variability, patient comfort, remote prolonged use, and less signal loss with increased maternal body mass index. Despite its promise, challenges such as signal loss must be addressed. The clinical application of NIFECG, its correlation with cCTG measures, and ongoing technological advancements are discussed. In conclusion, this review explores the evolution of antenatal FHR monitoring, emphasizing the potential of NIFECG in providing reliable, home-based monitoring solutions. Future research directions are outlined, urging longitudinal studies and evidence generation to establish NIFECG’s role in enhancing fetal well-being assessments during pregnancy.
The Omega Mastopexy Technique for the Correction of Breast Ptosis after Breast Implant Explantation
Authors: Bletsis Patrick P. , Lommen Etienne J.M.C.P. , van der Lei Berend
Published: July 2024

Background:

The past few years have seen a 50% increase in breast implant explantations. Patients with ptotic breasts may desire mastopexy, although conventional techniques are often invasive. We describe our experience with the omega mastopexy technique after breast implant explantation and capsulectomy.

Methods:

In the past 2 years, 10 patients with breast Regnault classification ptosis grade I–III underwent the omega mastopexy technique following breast implant explantation and capsulectomy. A detailed description of our operating technique is provided.

Results:

This series includes a total of 10 patients. The median age was 48.5 (IQR 42.8–52.5), median body mass index 26 (23.8–28.3) and median implant volume 355 (IQR 325–375). Excellent and stable aesthetic results were achieved without recurring ptosis. One patient, an active smoker, underwent reexcision after 1 year due to hypertrophic scars. No complications have been reported until this date at 2 years follow-up.

Conclusions:

The omega mastopexy technique offers an excellent alternative to classic lifting techniques for ptotic breasts after breast implant explantation. Patients with increased risk of wound healing impairment are especially likely to benefit.
Liver stiffness progression in biopsy-proven metabolic dysfunction–associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study
Authors: Huang Daniel Q. , Wilson Laura A. , Behling Cynthia , Amangurbanova Maral , Kleiner David E. , Kowdley Kris V. , Dasarathy Srinivasan , Terrault Norah A. , Diehl Anna Mae , Chalasani Naga , Neuschwander-Tetri Brent A. , Sanyal Arun J. , Tonascia James , Loomba Rohit ,   for the NASH Clinical Research Network
Published: July 2024

Background and Aims:

There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction–associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study.

Approach and Results:

This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction–associated steatotic liver disease who had VCTEs at least 1 year apart. LSM progression and regression were defined by a ≥20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n = 680) versus no T2DM (n = 551) at baseline. The mean (±SD) age and body mass index were 51.8 (±12.0) years and 34.0 (±6.5) kg/m2, respectively. The median (IQR) time between the first and last VCTE measurements was 4.1 (2.5–6.5) years. Participants with T2DM had higher LSM progression at 4 years (12% vs. 10%), 6 years (23% vs. 16%), and 8 years (50% vs. 39%),p= 0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR: 1.35, 95% CI: 1.01–1.81,p= 0.04). T2DM was not associated with LSM regression (p= 0.71). Mean HbA1c was significantly associated with LSM progression (p= 0.003) and regression (p= 0.02).

Conclusions:

Using serial VCTE data from a multicenter study of participants with biopsy-proven metabolic dysfunction–associated steatotic liver disease, we demonstrate that T2DM and HbA1c are associated with LSM progression.
Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone
Authors: Patidar Kavish R. , Tu Wanzhu , Cotter Thomas G. , Simonetto Douglas A. , Asgharpour Amon , Jan Muhammad Y. , Tang Qing , Yu Yunpeng , Li Yang , Taiwo Moyinoluwa , Thevkar Nagesh Prashanth , Dasarathy Srinivasan , Kamath Patrick S. , McClain Craig J. , Chalasani Naga , Szabo Gyongyi , Bataller Ramon , Mitchell Mack , Mehal Wajahat Z. , Nagy Laura E. , Shah Vijay H. , Gawrieh Samer , Sanyal Arun J. ,   for The AlcHepNet Investigators
Published: July 2024

Background and Aims:

In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and Results:

Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, with death treated as a competing event. Risk factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, HE, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than in PRED (45% [n=33] versus 22% [n=16],p=0.001). AKI phenotypes were similar between the 2 treatment arms (p=0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n=21 [63.6%] vs. n=8 [50.0%],p=0.035). At baseline, urine-neutrophil-gelatinase–associated lipocalin levels were similar between participants who developed AKI in both treatment arms (p=0.319). However, day 7 and 14 urine-neutrophil-gelatinase–associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI (p=0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35,p=0.005).

Conclusions:

AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z–treated participants with AKI had higher urine-neutrophil-gelatinase–associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.
Epigenetic heterogeneity hotspots in human liver disease progression
Authors: Hlady Ryan A. , Zhao Xia , El Khoury Louis Y. , Wagner Ryan T. , Luna Aesis , Pham Kien , Pyrosopoulos Nikolaos T. , Jain Dhanpat , Wang Liguo , Liu Chen , Robertson Keith D.
Published: July 2024

Background and Aims:

Disruption of the epigenome is a hallmark of human disease, including liver cirrhosis and HCC. While genetic heterogeneity is an established effector of pathologic phenotypes, epigenetic heterogeneity is less well understood. Environmental exposures alter the liver-specific DNA methylation landscape and influence the onset of liver cancer. Given that currently available treatments are unable to target frequently mutated genes in HCC, there is an unmet need for novel therapeutics to prevent or reverse liver damage leading to hepatic tumorigenesis, which the epigenome may provide.

Approach and Results:

We performed genome-wide profiling of DNA methylation, copy number, and gene expression from multiple liver regions from 31 patients with liver disease to examine their crosstalk and define the individual and combinatorial contributions of these processes to liver disease progression. We identified epigenetic heterogeneity hotspots that are conserved across patients. Elevated epigenetic heterogeneity is associated with increased gene expression heterogeneity. Cirrhotic regions comprise 2 distinct cohorts—one exclusively epigenetic, and the other where epigenetic and copy number variations collaborate. Epigenetic heterogeneity hotspots are enriched for genes central to liver function (eg, HNF1A) and known tumor suppressors (eg, RASSF1A). These hotspots encompass genes including ACSL1, ACSL5, MAT1A, and ELFN1, which have phenotypic effects in functional screens, supporting their relevance to hepatocarcinogenesis. Moreover, epigenetic heterogeneity hotspots are linked to clinical measures of outcome.

Conclusions:

Substantial epigenetic heterogeneity arises early in liver disease development, targeting key pathways in the progression and initiation of both cirrhosis and HCC. Integration of epigenetic and transcriptional heterogeneity unveils putative epigenetic regulators of hepatocarcinogenesis.
Discriminant prediction equation using an optical biometer for identifying postmyopic laser vision correction eyes
Authors: Nishida Tomoya , Kojima Takashi , Isogai Naoki , Yoshida Yoko , Nakamura Tomoaki
Published: July 2024

Purpose:

To create an equation for identifying postmyopic laser vision correction (M-LVC) eyes by using corneal shape parameters in a swept-source optical coherence tomography (SS-OCT) biometer and verify its accuracy.

Setting:

Nagoya Eye Clinic, Nagoya, Japan.

Design:

Retrospective evaluation of a screening approach.

Methods:

Control participants were selected retrospectively from patients who visited the clinic for cataract surgery or refractive surgery. M-LVC patients were selected retrospectively from patients who visited the clinic for cataract surgery or M-LVC postoperative checkups. The control and post–M-LVC patients with keratometric values between 39 diopters (D) and 43 D were included in the final analysis. Patients were randomly assigned to equation-creation and validation groups in a 2:1 ratio. To discriminate post–M-LVC patients from control participants, multiple logistic regression analysis was performed with the corneal shape parameters from the optical biometer as independent variables.

Results:

The M-LVC and control groups consisted of 90 eyes from 90 patients and 97 eyes from 97 patients, respectively. The average keratometry (Ave-K) values did not differ significantly between the control and M-LVC groups (P = .187). The multiple logistic analysis identified the asymmetry component (regression coefficient, 5.357; odds ratio, 212.158) and corneal eccentricity index (regression coefficient, −5.088; odds ratio, 0.006) as explanatory variables. The area under the receiver operating characteristic curve in the predictive equation-creation group was 0.946. The sensitivity and specificity in the validation group were 93.3% and 87.5%, respectively.

Conclusions:

The M-LVC discriminant prediction equation with the topography-equipped SS-OCT biometer was effective in detecting post–M-LVC eyes with high accuracy.