bluuebunny/crossref_metadata_2025 huggingface dataset:
English in Specialized Communication and its Impact on Spanish Medical Lexicon
Authors: Porras-Garzón Jorge M
Published: February 2024

The use of English-written publications (articles, books, book chapters, etc.) in university Medicine classes, in Spanish-speaking settings, results in a direct influence on lexical units in written text and oral discourse, particularly, with respect to prototypical terminological units. The extent of said influence has not been evaluated until now in the Colombian Spanish-speaking university context, which is, like in most countries in the world, a context that responds to the dynamics of the Internationalisation of Higher Education. As we will see in the following empirical study and its results, the use of English-written materials in university Medicine courses in Colombia has an impact on the presence of Terminological Anglicisms in both written texts and oral discourse in Spanish. And this, not surprisingly, does not promote the creation of new native Spanish vocabulary, on the contrary, it is detrimental to the specialized communicative suitability of the local language.
N-Desmethylmajusculamide B, a lipopeptide isolated from the Okinawan cyanobacterium Okeania hirsuta
Authors: Zhang Bo-Tao , Nishino Haruka , Kawabe Ryoya , Kamio Michiya , Watanabe Ryuichi , Uchida Hajime , Satake Masayuki , Nagai Hiroshi
Published: February 2024

A new lipopeptide, N-desmethylmajusculamide B (1), was isolated from the Okinawan cyanobacterium Okeania hirsuta along with 2 known compounds majusculamide A (2) and majusculamide B (3). The planar structure of (1) was elucidated by a detailed analysis of mass spectrometry and nuclear magnetic resonance spectra. The absolute configurations of the amino acid residues were determined using Marfey's analysis. The configuration of C-16 in the α-methyl-β-keto-decanoyl moiety was determined unambiguously to be S by conducting a semisynthesis of N-desmethylmajusculamide B from 3. The cytotoxicity against mouse L1210 leukemia cells was evaluated for majusculamides (1-3).
Can females differentially allocate resources to offspring sired by different males?
Authors: Levell Samantha T , Bedgood Samuel A , Travis Joseph , Reznick David N
Published: February 2024

The viviparity-driven conflict hypothesis postulates that the evolution of matrotrophy (postfertilization maternal provisioning) will result in a shift from a pre- to postcopulatory mate choice and thus accelerate the evolution of postcopulatory reproductive isolation. Here, we perform artificial insemination experiments on Heterandria formosa, a matrotrophic poeciliid fish, to probe for evidence of postcopulatory female choice. We established laboratory populations from Wacissa River (WR) and Lake Jackson (LJ). The WR females normally produce larger offspring than the LJ females. We artificially inseminated females with sperm from each population or from both populations simultaneously. When LJ females were inseminated with sperm from WR and LJ males, they allocated fewer resources to WR-sired offspring than when they were inseminated with WR sperm alone. The LJ females carrying developing offspring sired by males from different populations were thus able to discriminate against non-resident males when allocating resources to developing young. The WR females, which normally produce larger offspring than LJ females, did not discriminate among males from different localities. These findings provide insights into the ability of females from one population to exercise a form of postcopulatory mate selection.
Gathering round Big Tech: How the market for acquisitions concentrates the digital sector
Authors: Ioramashvili Carolin , Feldman Maryann , Guy Frederick , Iammarino Simona
Published: February 2024

Small businesses within the digital sector are spread across the USA. However, a significant number of promising small businesses concentrate in major technology hubs, either initially or through relocation. This phenomenon can be attributed to the influential role played by localized markets for financing and acquisition, which is, in turn, driven by the dominant market positions held by major digital platforms. Our research demonstrates a clear pattern of localized acquisition markets, particularly in sectors frequently targeted by the seven largest American digital giants—Amazon, Alphabet (Google), Apple, Microsoft, Meta (Facebook), Oracle, and Adobe, collectively known as ‘Big Tech’. This localization trend has become more pronounced between 2000 and 2020. Our analysis indicates that the gravitational pull of these acquisition markets poses challenges to local initiatives aimed at fostering digital businesses. These efforts would be more successful if measures were taken to limit the market influence of digital platforms.
Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study
Authors: Zeng Guyu , Zhu Pei , Yuan Deshan , Wang Peizhi , Li Tianyu , Li Qinxue , Xu Jingjing , Tang Xiaofang , Song Ying , Chen Yan , Zhang Ce , Jia Sida , Liu Ru , Jiang Lin , Song Lei , Gao Runlin , Yang Yuejin , Zhao Xueyan , Yuan Jinqing
Published: February 2024

Background and hypothesis

Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI).

Methods

From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60–90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)].

Results

Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without.

Conclusion

The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.
The role of human extracellular matrix proteins in defining Staphylococcus aureus biofilm infections
Authors: Bhattacharya Mohini , Horswill Alexander R
Published: February 2024

Twenty to forty one percent of the world’s population is either transiently or permanently colonized by the Gram-positive bacterium, Staphylococcus aureus. In 2017, the CDC designated methicillin-resistant S. aureus (MRSA) as a serious threat, reporting ∼300 000 cases of MRSA-associated hospitalizations annually, resulting in over 19 000 deaths, surpassing that of HIV in the USA. S. aureus is a proficient biofilm-forming organism that rapidly acquires resistance to antibiotics, most commonly methicillin (MRSA). This review focuses on a large group of (>30) S. aureus adhesins, either surface-associated or secreted that are designed to specifically bind to 15 or more of the proteins that form key components of the human extracellular matrix (hECM). Importantly, this includes hECM proteins that are pivotal to the homeostasis of almost every tissue environment [collagen (skin), proteoglycans (lung), hemoglobin (blood), elastin, laminin, fibrinogen, fibronectin, and fibrin (multiple organs)]. These adhesins offer S. aureus the potential to establish an infection in every sterile tissue niche. These infections often endure repeated immune onslaught, developing into chronic, biofilm-associated conditions that are tolerant to ∼1000 times the clinically prescribed dose of antibiotics. Depending on the infection and the immune response, this allows S. aureus to seamlessly transition from colonizer to pathogen by subtly manipulating the host against itself while providing the time and stealth that it requires to establish and persist as a biofilm. This is a comprehensive discussion of the interaction between S. aureus biofilms and the hECM. We provide particular focus on the role of these interactions in pathogenesis and, consequently, the clinical implications for the prevention and treatment of S. aureus biofilm infections.
Spatial Population Structuring and Genetic Analysis of Exotic Grevillea robusta in Northwestern India
Authors: Dabral Aman , Meena Rajendra K , Shankhwar Rajeev , Kant Rama , Pandey Shailesh , Ginwal Harish S , Bhandari Maneesh S
Published: February 2024

The introduction of exotics is common in forestry, and majorly important species, like eucalypts, poplar, and Casuarina sp., occupy vast areas in the Indian subcontinent. Importantly, with the latest cost-effective sequencing techniques, genetic diversity research through molecular marker approaches on major exotics provides novel information for genetic improvement in economic traits with climatic adaptation. The study was carried out on Grevillea robusta to assess genetic relatedness and diversity among 228 genotypes belonging to five northwestern states in India. These genotypes were assayed using twelve simple sequence repeat (SSR) markers. A population structure analysis using structure software identified four major gene pool subgroups with clear-cut differences from each other. Principal coordinate analysis also supports the clustering patterns of the unweighted pair group method with arithmetic mean analysis. In the case of genetic diversity assessment, a total of seventy-three alleles were detected from twelve SSRs, with an average of 6.08 ± 0.71 per locus. Polymorphism information content ranged from 0.17 to 0.67 with a mean of 0.44 ± 0.045, indicating high levels of polymorphism across the genotypes. All the evaluated SSRs demonstrated moderate genetic diversity (observed heterozygosity = 0.31 ± 0.03; expected heterozygosity = 0.32 ± 0.03; and genetic differentiation = 0.295) among the sampled genotypes. These findings indicate significant genetic variability in the germplasm to warrant selection and have potential for a long-term tree improvement program of G. robusta in India.

Study Implications: The study on population genetics of Grevillea robusta in exotic environments assessed probable gene pools, provenances, and genetic diversity in geographical distribution range of the species in the Indian scenario. The basic population genetic measures revealed the high diversity areas and probable seed zones of G. robusta in its exotic range. Importantly, the study will be helpful in the selection of candidate plus trees of G. robusta to further strengthen the genotype × environment interaction study for future breeding programs. Further, studying the genetic makeup for moderately diverse species offers valuable insights into evolutionary history, population dynamics, and ecological interactions, which may lead to conservation efforts and guidance for the management of trees such as G. robusta in their native and introduced regions.
Estimation of Additive and Dominance Effects in an Acacia crassicarpa Multi-Environment Progeny Trial Using Genomic Pedigree Reconstruction
Authors: Martins Gustavo S , Yuliarto Muhammad , Ching Yong Wong , Melia Tisha , Maretha Maggie V , Sharma Mukesh , Lakey Nathan , Ordway Jared , Acosta Juan José , Hodge Gary
Published: February 2024

Acacia crassicarpa is an important tree species in Southeast Asia, where hundreds of thousands of hectares of planted forests are supported by advancements in silviculture and genetic improvement. Although possible, controlled pollination is impractical for advancing breeding populations, requiring an unreasonable effort to produce more than a few crosses per year. For this reason, breeding populations often are bred by open pollination. This study used large-scale pedigree reconstruction in multi-environment trials to assess full-sib families to model the genetics of the quantitative traits survival, straightness, height, diameter at breast height, tree volume, mean annual increment (MAI), and basic density. The traits were predominantly controlled by additive effects, with heritabilities between 0.09 for survival and 0.45 for basic density. The genetic correlation across sites was high for all traits, showing the low impact of genotype-by-environment interaction. The trait-trait correlation showed that straightness was independent of any other traits, survival was only correlated with MAI, and growth traits were highly correlated among themselves. Basic density was positively correlated with growth traits and MAI.

Study Implications: Parentage analysis using an informative single nucleotide polymorphism panel was used to reconstruct pedigree and allow a full-sib family model to estimate additive and dominance effects and genetic correlations across sites and among important traits in an open-pollinated population. The genetic control of all traits assessed in this study was mainly additive. In this scenario, the recommended breeding strategy is forward selection of outstanding progeny for advanced generation breeding and backward selection of outstanding parents to produce seed for deployment via family forestry. Full-sib families can be identified by pedigree reconstruction at a seedling stage, followed by tissue culture multiplication, rooted cutting propagation, and plantation establishment.
PACMAN: PAC-style bounds accounting for the Mismatch between Accuracy and Negative log-loss
Authors: Vera Matias , Rey Vega Leonardo , Piantanida Pablo
Published: February 2024

The ultimate performance of machine learning algorithms for classification tasks is usually measured in terms of the empirical error probability (or accuracy) using a testing dataset, although these algorithms are optimized through the minimization of a typically different—more convenient—loss function using a training set. For classification tasks, this loss function is often the negative log-loss that yields the well-known cross-entropy risk that is typically better behaved (in terms of numerical behavior) than the 0-1 loss. Conventional studies on the generalization error do not usually take into account the underlying mismatch between losses at training and testing phases. In this work, we introduce a theoretical analysis based on a pointwise probably approximately correct (PAC) approach over the generalization gap considering the mismatch of testing on the accuracy metric and training on the negative log-loss, referred to as PACMAN. Building on the fact that the resulting mismatch can be written as a likelihood ratio, concentration inequalities can be used to obtain insights into the generalization gap in terms of PAC bounds, which depend on some meaningful information-theoretic quantities. An analysis of the obtained bounds and a comparison with available results in the literature is also provided.
The accuracy and characteristics of gastric cancer treatment information in the national data of the hospital-based cancer registry
Authors: Fujishita Manami , Sakakibara Naoki , Higashi Takahiro , Watanabe Tomone , Kumamaru Hiraku , Miyata Hiroaki
Published: February 2024

Objective

The hospital-based cancer registry is used extensively for research to support cancer control activities by providing an overview of how cancer treatments are provided nationwide. This study aimed to shed light on the quality and characteristics of treatment data in the hospital-based cancer registry using the linked dataset on gastric cancer.

Methods

Using the nationally linked data of the hospital-based cancer registry and the health services utilization data, the treatment data in the hospital-based cancer registry for patients who were newly diagnosed with gastric cancer in 2016 and 2017 and received the first course of treatment at their own institutions were examined. The agreement rates between registry data and utilization data were analyzed by stage, treatment, age, period from the date of diagnosis to the date of treatment and hospital type.

Results

The sensitivity of open surgery, laparoscopic surgery and endoscopic treatment tended to decrease in advanced stages, whereas the sensitivity of chemotherapy and radiation therapy increased. Specificity was high for all treatments and stages, at ˃90%. Sensitivity by age was slightly different for chemotherapy and radiation therapy, but specificities did not differ.

For all treatments, the longer the time from diagnosis to treatment implementation, the higher the coverage rate.

Conclusions

The hospital-based cancer registry recorded the treatment performed appropriately. It is necessary to interpret the data from the hospital-based cancer registry whilst keeping in mind that, chemotherapy and radiation therapy are registered less frequently than surgical treatments administered.
Herbicides Have Variable Effects on Understory Plant and Insect Communities in Southern United States Working Forests
Authors: Briggs Emma L , Greene Daniel U , Clabo David C , Gandhi Kamal J K
Published: February 2024

Working pine (Pinus spp.) forests in the southern United States rely on herbicides to remove competing vegetation and improve productivity. We conducted a review of the effects of herbicides on understory plants in southern working forests. We also discuss the impacts of herbicides on insect taxa associated with understory vegetation and its litter layer, including Coleoptera (carabid beetles), Hemiptera (true bugs), Hymenoptera (bees/ants), Lepidoptera (moths/butterflies), and Orthoptera (grasshoppers). Herbicides have few reported long-term impacts on understory herbaceous cover and species richness/diversity when applied according to labeled uses and application rates. However, the method of chemical treatment (e.g., broadcast spray or banded application) may influence understory plant structure and composition. Responses of insects to herbicides were species- and taxa-specific and highly variable given their forage/habitat requirements and life histories. Long-term research is needed to evaluate the effects of herbicides on vegetation-associated insects to provide a comprehensive profile of herbicide nontarget impacts.

Study Implications: Land managers rely on herbicides to remove competing vegetation and increase working forest productivity. Given the objective of sustainable forest management to conserve biodiversity, it is important to understand how biological communities respond to chemical applications in intensively managed forest ecosystems. Our review indicated that herbicides have few reported long-term impacts on understory plant communities when applied appropriately. Despite their taxonomic diversity, invertebrates were rarely included in assessments of forest herbicides. Further research is needed to assess the potential nontarget impacts of herbicide applications on forest insect communities.
Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce
Authors: Willis Zachary I , Oliveira Carlos R , Abzug Mark J , Anosike Brenda I , Ardura Monica I , Bio Laura L , Boguniewicz Juri , Chiotos Kathleen , Downes Kevin , Grapentine Steven P , Hersh Adam L , Heston Sarah M , Hijano Diego R , Huskins W Charles , James Scott H , Jones Sarah , Lockowitz Christine R , Lloyd Elizabeth C , MacBrayne Christine , Maron Gabriela M , Hayes McDonough Molly , Miller Christine M , Morton Theodore H , Olivero Rosemary M , Orscheln Rachel C , Schwenk Hayden T , Singh Prachi , Soma Vijaya L , Sue Paul K , Vora Surabhi B , Nakamura Mari M , Wolf Joshua
Published: February 2024

Background

Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy.

Methods

A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus.

Results

There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.
Discovery of a nova super-remnant cavity surrounding RS Ophiuchi
Authors: Healy-Kalesh M W , Darnley M J , Harvey É J , Newsam A M
Published: February 2024

The prototypical nova super-remnant (NSR) was uncovered around the most rapidly recurring nova (RN), M31N 2008-12a. Simulations of the growth of NSRs revealed that these large structures should exist around all novae, whether classical or recurrent. NSRs consist of large shell-like structures surrounding excavated cavities. Predictions, informed by these simulations, led to the discovery of an extended cavity coincident with the Galactic RN, RS Ophiuchi (RS Oph), in far-infrared archival IRAS images. We propose that this cavity is associated with RS Oph and is therefore evidence of another NSR to be uncovered.
Machine intelligence in metamaterials design: a review
Authors: Cerniauskas Gabrielis , Sadia Haleema , Alam Parvez
Published: February 2024

Machine intelligence continues to rise in popularity as an aid to the design and discovery of novel metamaterials. The properties of metamaterials are essentially controllable via their architectures and until recently, the design process has relied on a combination of trial-and-error and physics-based methods for optimization. These processes can be time-consuming and challenging, especially if the design space for metamaterial optimization is explored thoroughly. Artificial intelligence (AI) and machine learning (ML) can be used to overcome challenges like these as pre-processed massive metamaterial datasets can be used to very accurately train appropriate models. The models can be broad, describing properties, structure, and function at numerous levels of hierarchy, using relevant inputted knowledge. Here, we present a comprehensive review of the literature where state-of-the-art machine intelligence is used for the design, discovery and development of metamaterials. In this review, individual approaches are categorized based on methodology and application. We further present machine intelligence trends over a wide range of metamaterial design problems including: acoustics, photonics, plasmonics, mechanics, and more. Finally, we identify and discuss recent research directions and highlight current gaps in knowledge.
Service-learning outreach to attract high school students to degrees and careers in agricultural sciences
Authors: Blanton Emily A , Anderson Ryan G , Drewery Merritt L
Published: February 2024

Given projected deficits and a lack of diversity, there is a critical need to recruit and develop the next generation of the agricultural workforce. The objectives of our study were to evaluate if AgCamp, a one day workshop focused on agriculture delivered through a college student-led service-learning platform: (1) increased high school students’ knowledge of agriculture, (2) changed their interests in pursuing degrees and careers in agriculture, and (3) increased their comfort and confidence in communicating with others in agriculture. We hosted high school students at AgCamp and provided them with instruction in animal science, horticulture, and agricultural mechanics. Pre- and post-test survey instruments were developed and distributed at the beginning and end of AgCamp. Data were analyzed with SPSS 26.0 using paired sample t-tests. As a result of attending this outreach initiative, high school students (n = 26) reported having more knowledge of horticulture (P < 0.01) and agricultural mechanics (P < 0.01), but not animal science (P = 0.12), likely due to greater incoming knowledge of this sub-discipline, as reflected on the pre-test value. High school participants were also more interested in pursuing a college degree (P = 0.04) and career (P < 0.01) in agriculture and became more confident approaching other high school students (P < 0.01), college students (P < 0.01), and college faculty (P = 0.01) involved in agriculture. Ultimately, participating in AgCamp stimulated high school students’ knowledge and interest in pursuing agricultural degrees and careers, indicating there is value in offering youth outreach as short-term programming to attract students to agriculture.
Randomized trial of an integrated care intervention among Latino adults: Sustained effects on diabetes management
Authors: Rosas Carlos E , Talavera Gregory A , Roesch Scott C , Mendez-Rodriguez Heidy , Muñoz Fatima , Castañeda Sheila F , Mendoza Paulina M , Gallo Linda C
Published: February 2024

We examined the 12-month maintenance effects of a previously successful integrated model of diabetes care at improving glycemic management and psychological well-being among Latino adults with type 2 diabetes (T2D). A randomized controlled trial (2015–19) compared an integrated care intervention (ICI) with usual care among 456 adults with T2D. The ICI included integrated medical and behavioral care and health education over 6 months. Assessments were completed at baseline, 3, 6, 9, and 12 months. Most participants were female (63.7%) with a mean age of 55.7 years. In multilevel models, significant Group × Time (quadratic) interaction effects were found for HbA1c [Bint = 0.10, 95% confidence interval (CI) 0.02, 0.17, P < .01] and anxiety symptoms (Bint = 0.20, 95% CI 0.05, 0.35, P < .009), but not depression symptoms (Bint = 0.15, 95% CI −0.01, 0.31, P < .07). Analyses of instantaneous rate of change in the ICI group showed significant decreases at 3 and 6 months for both HbAc1 (B = −0.31 at 3 months; B = −0.12 at 6 months) and anxiety symptoms (B = −0.92 at 3 months; B = −0.46 at 6 months), and no significant instantaneous changes at 9 or 12 months, suggesting that initial improvements were largely maintained. The usual care group showed a small decrease in anxiety symptoms at 6 months (B = −0.17), but no other significant changes at any time-point for anxiety or HbA1c (all Ps > .05). This culturally tailored integrated care model shows potential in producing and sustaining positive effects on clinical and psychological outcomes above standard care.
Revised one-bag IV fluid protocol for pediatric DKA: a feasible approach and retrospective comparative study
Authors: Doğan Durmuş , Gökalp Hatice D C , Eren Erdal , Sağlam Halil , Tarım Ömer
Published: February 2024

Background

This study compared the effectiveness of the traditional and revised one-bag protocols for pediatric diabetic ketoacidosis (DKA) management.

Methods

This single-center retrospective cohort study included children diagnosed with DKA upon admission between 2012 and 2019. Our institution reevaluated and streamlined the traditional one-bag protocol (revised one-bag protocol). The revised one-bag protocol rehydrated all pediatric DKA patients with dextrose (5 g/100 ml) containing 0.45% NaCl at a rate of 3500 ml/m2 per 24 h after the first 1 h bolus of normal saline, regardless of age or degree of dehydration. This study examined acidosis recovery times and the frequency of healthcare provider interventions to maintain stable blood glucose levels.

Results

The revised one-bag protocol demonstrated a significantly shorter time to acidosis recovery than the traditional protocol (12.67 and 18.20 h, respectively; p < 0.001). The revised protocol group required fewer interventions for blood glucose control, with an average of 0.25 dextrose concentration change orders per patient, compared to 1.42 in the traditional protocol group (p < 0.001). Insulin rate adjustments were fewer in the revised protocol group, averaging 0.52 changes per patient, vs. 2.32 changes in the traditional protocol group (p < 0.001).

Conclusion

The revised one-bag protocol for pediatric DKA is both practical and effective. This modified DKA management achieved acidosis recovery more quickly and reduced blood glucose fluctuations compared with the traditional one-bag protocol. Future studies, including randomized controlled trials, should assess the safety and effectiveness of the revised protocol in a broad range of pediatric patients with DKA.
Effects of Satellite-Linked Telemetry Tags on Humpback Whales in the Gulf of Maine: Photographic Assessment of Tag Sites
Authors: Gulland Frances M.D. , Robbins Jooke , Zerbini Alexandre N. , Andrews-Goff Virginia , Bérubé Martine , Clapham Phillip J. , Double Michael , Gales Nicholas , Kennedy Amy S. , Landry Scott , Mattila David K. , Sandilands Doug , Tackaberry Jennifer E. , Uhart Marcela , Vanstreels Ralph E. T.
Published: February 2024

Hundreds of large whales have been tracked using consolidated (Type-C) satellite tags, yet there have been few studies on their impacts on whale health. In 2011, we initiated the first study designed to evaluate the effects of these tags in a baleen whale. Between 2011 and 2018, we tagged 79 North Atlantic humpback whales in the Gulf of Maine. We initially deployed commonly-used tags with an articulation between the anchor and transmitter (n=35, 2011-2012). However, evidence of breakage prompted the development and use of more robust, integrated tags (n=45). Tagged individuals were photographed immediately prior to, during and up to 11 years after tagging. They were re-encountered on an average of 41.3 days (SD=44.3), yielding 2,971 photographed sightings through 2022. An objective scoring system was developed to characterise tag site tissue responses based on photographs and to identify risk factors for prolonged healing. The initial tissue response to tagging was minimal, followed by skin loss around the tag, sometimes a degree of swelling, occasional extrusion of blubber, changes in skin colour, local depression formation, tag loss and skin healing over the tag site, sometimes with a depression remaining. At last sighting, most non-integrated and integrated tag sites exhibited small shallow skin depressions (58.8% and 66.7%, respectively). Some exhibited deeper depressions with differing adjacent skin coloration (26.5% and 15.6%, respectively) or barely detectable marks (11.8% and 15.6%, respectively). Mild swellings occasionally persisted at the tag site, but this was uncommon for both tag designs (2.9% and 2.2%, respectively). More severe tissue responses were associated with non-integrated tags and placements lower on the body. This study highlights the importance of using robust tag designs to minimise negative effects from Type-C tags. Furthermore, because tag placement was shown to affect outcome, precision equipment, experienced taggers and vessel operators are critical for optimal deployments.
Ligand-induced conformational changes in the β1-Adrenergic Receptor Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry
Authors: Toporowska Joanna , Kapoor Parth , Musgaard Maria , Gherbi Karolina , Sengmany Kathy , Qu Feng , Soave Mark , Yen Hsin-Yung , Hansen Kjetil , Jazayeri Ali , Hopper Jonathan T.S. , Politis Argyris
Published: February 2024

G-Protein Coupled Receptors (GPCRs) constitute the largest family of signalling proteins responsible for translating extracellular stimuli into intracellular functions. When dysregulated, GPCRs drive numerous diseases and are the most targeted proteins in drug discovery. GPCR structural dynamics and activity can be modulated by a wide range of drugs, including full/partial agonists and antagonists. While crucial for developing novel therapeutics targeting GPCRs, the structural dynamics of the receptors associated with their activity upon drug interactions are not yet fully understood. Here, we employ Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS), to characterise the structural dynamics of turkey β1-adrenergic receptor (tβ1AR) in complex with nine ligands, including agonists, partial agonists and antagonists. We show that dynamic signatures across the GPCR structure can be grouped by compound modality. Surprisingly, we discovered repeated destabilisation of the intracellular loop 1 (ICL1) upon full agonist binding and stabilisation upon antagonist binding, suggesting that increased dynamics in this region are an essential component for G-protein recruitment. Multiple sequence alignments and molecular dynamics simulations indicate that L72 in ICL1 plays important structural role. Differential HDX-MS experiment of tβ1AR and tβ1AR L72A construct in complex with miniGs, in response to various ligands, suggests involvement of ICL1 in stabilising the GDP bound state by influencing the stability of HG helix of miniGs. Overall, our results provide a platform for determining drug modality and highlight how HDX-MS can be used to dissect receptor ligand interaction properties and GPCR mechanism.

Significance statement

Recent advances in hydrogen-deuterium exchange mass spectrometry have allowed probing conformational signatures of challenging membrane protein assemblies. We studied the structural dynamics of a class A GPCR, namely tβ1AR, in response to diverse ligands including agonists, antagonists and partial agonists. We demonstrate that the functional effect of compounds can be discerned by simply profiling the dynamics induced across the receptor, without the need for downstream interaction partners. We showed that ICL1 undergoes a significant change in dynamics between activated and inhibited states consistent with a role in downstream signaling pathways in class A GPCRs.
Upregulation of the Proto-Oncogene Src Kinase in Alzheimer’s Disease: From Molecular Interactions to Therapeutic Potential
Authors: Mastroeni Diego , Chan Chun Kit , Morshed Nader , Diouf David , de Ávila Camila , Suazo Crystal , Nolz Jennifer , Lopatin Ulia , Wang Qi , Serrano Geidy , Beach Thomas , Dunkley Travis , Jensen Kendall , Van Den Hove Daniel , White Forest M. , Chiu Po-Lin , Singharoy Abhishek , Reiman Eric M. , Readhead Benjamin P.
Published: February 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, resulting in an irreversible deterioration of multiple brain regions associated with cognitive dysfunction. Phosphorylation of the microtubule-associated protein, Tau, is known to occur decades before symptomatic AD. The Src family of tyrosine kinases are known to phosphorylate select tyrosine sites on Tau and promote microtubule disassembly and subsequent neurofibrillary tangle (NFT) formation. Our data show that the proto-oncogene, non-receptor tyrosine kinase Src colocalizes with a range of late (PHF1) to early (MC1) AD-associated phosphorylated Tau epitopes. The strongest co-occurrence is seen with MC1 (probability of MC1 given Src =100%), an early AD-specific conformational dependent epitope. Single-cell RNA sequencing data of 101 subjects show thatSrcis upregulated in both AD inhibitory and excitatory neurons. The most significantly affected, by orders of magnitude, were excitatory neurons which are the most prone to pathological Tau accumulation. We measured Src phosphorylation by mass spectrometry across a cohort of 48 patient neocortical tissues and found that Src has increased phosphorylation on Ser75, Tyr187, and Tyr440 in AD, showing that Src kinase undergoes distinct phosphorylation alterations in AD. Through Brownian dynamics simulations of Src and Tau, we show that as Tau undergoes the transition into disease-associated paired helical filaments, there is a notable seven-fold increase in Src contact with Tau. These results collectively emphasize Src kinase’s central role in Tau phosphorylation and its close association with Tau epitopes, presenting a promising target for potential therapeutic intervention.
The dietary ellagitannin metabolite urolithin A is produced by a molybdenum-dependent dehydroxylase encoded by prevalent human gutEnteroclosterspp
Authors: Pidgeon Reilly , Mitchell Sacha , Shamash Michael , Suleiman Layan , Dridi Lharbi , Maurice Corinne F. , Castagner Bastien
Published: February 2024

Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota that can affect host health by stimulating mitophagy. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing dietary precursor (uroC) are unknown. Here, we use a combination of untargeted bacterial transcriptomics, proteomics, and comparative genomics to uncover an inducible uroC dehydroxylase (ucd) operon inEnteroclosterspp. We show thatEnteroclosterspp. are sensitive to iron chelation by uroC, and dehydroxylation to uroA rescues growth by disrupting the iron-binding catechol. Importantly, only microbiota samples actively transcribingucdcould produce uroA, establishingucd-containingEnteroclosterspp. as keystone urolithin metabolizers. Overall, this work identifiesEnteroclosterspp. and theucdoperon as main contributors to uroA production and establishes a multi-omics framework to further our mechanistic understanding of polyphenol metabolism by the human gut microbiota.
Characterization ofNeisseria gonorrhoeaecolonization of macrophages under distinct polarization states and nutrients environment
Authors: Juárez Rodríguez María Dolores , Marquette Madison , Youngblood Reneau , Dhungel Nilu , Escobar Ascención Torres , Ivanov Stanimir , Dragoi Ana-Maria
Published: February 2024

Neisseria gonorrhoeae (Ng)is a uniquely adapted human pathogen and the etiological agent of gonorrhea, a sexually transmitted disease.Nghas developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses.Ngsuccessfully colonizes and establishes topologically distinct colonies in human macrophages and avoids phagocytic killing. During colonization,Ngmanipulates the actin cytoskeleton to invade and create an intracellular niche supportive of bacterial replication. The cellular reservoir(s) supporting bacterial replication and persistence in gonorrhea infections are poorly defined. The manner in which gonococci colonize macrophages points to this innate immune phagocyte as a strong candidate for a cellular niche during natural infection. Here we investigate whether nutrients availability and immunological polarization alter macrophage colonization byNg. Differentiation of macrophages in pro-inflammatory (M1-like) and tolerogenic (M2-like) phenotypes prior to infection reveals thatNgcan invade macrophages in all activation states, albeit with lower efficiency in M1-like macrophages. These results suggest that during natural infection, bacteria could invade and grow within macrophages regardless of the nutrients availability and the macrophage immune activation status.
Fourfold increase in photocurrent generation ofSynechocystissp. PCC 6803 by exopolysaccharide deprivation
Authors: Wey Laura T. , Wroe Evan , Sadilek Viktor , Shang Linying , Chen Xiaolong , Zhang Jenny Z. , Howe Christopher J.
Published: February 2024

Photosynthetic microorganisms, including algae and cyanobacteria, export electrons in a light-stimulated phenomenon called ‘exoelectrogenesis’. However, the route(s) by which electrons reach an external electrode from the cell remain(s) unclear. For the model cyanobacteriumSynechocystissp. PCC 6803, it has been established that electron transfer does not depend on direct extracellular electron transfer by type IV pili. However, the role of the exopolysaccharide matrix in which cells are embedded has not been investigated. We show that aSynechocystismutant with substantially reduced exopolysaccharide production has a four-fold greater photocurrent than wild-type cells. This increase is due in part to increased adhesion of exopolysaccharide-deficient cells to electrodes. Stirred system experiments reveal that a substantial portion of the photocurrent depends on an endogenous diffusible electron mediator, supporting indirect extracellular electron transfer as the bioelectrochemical mechanism of exoelectrogenesis. These findings will be important in harnessing exoelectrogenesis for sustainable electricity generation in biophotovoltaic devices.
Dynamics of White Matter Architecture in Lexical Production among Middle-Aged Adults
Authors: Guichet Clément , Roger Élise , Attyé Arnaud , Achard Sophie , Mermillod Martial , Baciu Monica
Published: February 2024

This study aimed to elucidate the white matter changes associated with lexical production (LP) difficulties that typically emerge in middle age, resulting in increased naming latencies. To delay the onset of LP decline, middle-aged adults may rely on domain-general (DG) and language-specific (LS) compensatory mechanisms as proposed by the LARA model (Lexical Access and Retrieval in Aging). However, our knowledge of the white matter changes supporting these mechanisms remains incomplete. Based on a sample of 155 middle-aged adults from the CAMCAN cohort, we combined dimensionality reduction techniques with multivariate statistical methods to jointly examine the relationships between diffusion-weighted imaging and LP-related neuropsychological data. Our findings (i) show that midlife constitutes a pivotal period marked by a discontinuity in brain structure within distributed networks within dorsal, ventral, and anterior cortico-subcortical pathways, and (ii) reveal that this discontinuity signals a neurocognitive transition around age 53-54, marking the onset of LP decline. Indeed, our results propose that middle-aged adults may initially adopt a “semantic strategy” to compensate for initial LP challenges. Still, this strategy may be compromised when late middle-aged adults (age 55-60) lose the ability to exert cognitive control over semantic representations (i.e., reduced semantic control).

In summary, our study advances our comprehension of brain structure changes that underpin the neurocognitive profile of LP in middle age. Specifically, we underscore the importance of considering the interplay between DG and LS processes when studying the trajectory of LP performance in healthy aging. Furthermore, these findings offer valuable insights into identifying predictive biomarkers related to the compensatory dynamics observed in midlife, which can help understand language-related neurodegenerative pathologies.

Highlights

Midlife constitutes a pivotal period characterized by a discontinuity in brain structure.

Early middle-aged adults (age 45-55) adopt a “semantic strategy” to facilitate semantic access and sustain lexical production (LP) performances.

Late middle-aged adults (age 55-60) gradually lose the ability to exert cognitive control over semantic representations, marking the onset of LP decline.
Defense systems and horizontal gene transfer in bacteria
Authors: Kogay Roman , Wolf Yuri I. , Koonin Eugene V.
Published: February 2024

Horizontal gene transfer (HGT) is a fundamental process in the evolution of prokaryotes, making major contributions to diversification and adaptation. Typically, HGT is facilitated by mobile genetic elements (MGEs), such as conjugative plasmids and phages that generally impose fitness costs on their hosts. However, a substantial fraction of bacterial genes is involved in defense mechanisms that limit the propagation of MGEs, raising the possibility that they can actively restrict HGT. Here we examine whether defense systems curb HGT by exploring the connections between HGT rate and the presence of 73 defense systems in 12 bacterial species. We found that only 6 defense systems, 3 of which are different CRISPR-Cas subtypes, are associated with the reduced gene gain rate on the scale of species evolution. The hosts of such defense systems tend to have a smaller pangenome size and harbor fewer phage-related genes compared to genomes lacking these systems, suggesting that these defense mechanisms inhibit HGT by limiting the integration of prophages. We hypothesize that restriction of HGT by defense systems is species-specific and depends on various ecological and genetic factors, including the burden of MGEs and fitness effect of HGT in bacterial populations.
Productivity development enablers in the infrastructure sector: capability maturity model integration approach
Authors: Laitinen Kaisu , Luhtala Mika , Örmä Maiju , Vaismaa Kalle
Published: February 2024

Purpose

Insufficient productivity development in the global and Finnish infrastructure sectors indicates that there are challenges in genuinely achieving the goals of resource efficiency and digitalization. This study adapts the approach of capability maturity model integration (CMMI) for examining the capabilities for productivity development that reveal the enablers of improving productivity in the infrastructure sector.

Design/methodology/approach

Civil engineering in Finland was selected as the study area, and a qualitative research approach was adopted. A novel maturity model was constructed deductively through a three-step analytical process. Previous research literature was adapted to form a framework with maturity levels and key process areas (KPAs). KPA attributes and their maturity criteria were formed through a thematic analysis of interview data from 12 semi-structured group interviews. Finally, validation and refinement of the model were performed with an expert panel.

Findings

This paper provides a novel maturity model for examining and enhancing the infrastructure sector’s maturity in productivity development. The model brings into discussion the current business logics, relevance of lifecycle-thinking, binding targets and outcomes of limited activities in the surrounding infrastructure system.

Originality/value

This paper provides a new approach for pursuing productivity development in the infrastructure sector by constructing a maturity model that adapts the concepts of CMMI and change management. The model and findings benefit all actors in the sector and provide an understanding of the required elements and means to achieve a more sustainable built environment and effective operations.