bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteolysis targeting chimera extracellular vesicles for therapeutic development treating triple negative breast cancer
Authors: Erwin Nina , De Umasankar , Xiao Yufeng , Wang Lei , Maharjan Chandra , Pan Xiaoshu , Awasthee Nikee , Zheng Guangrong , Liao Daiqing , Zhang Weizhou , He Mei 
Published: August 2024

AbstractProteolysis targeting chimeras (PROTACs) are an emerging targeted cancer therapy approach, but wide-spread clinical use of PROTAC is limited due to poor cell targeting and penetration, and instability in vivo. To overcome such issues and enhance the in vivo efficacy of PROTAC drugs, microfluidic droplet-based electroporation (µDES) was developed as a novel extracellular vesicle (EVs) transfection system, which enables the high-efficient PROTAC loading and effective delivery in vivo. Our previously developed YX968 PROTAC drug had shown the selectively degradation of HDAC3 and 8, which effectively suppresses the growth of breast tumor cell lines, including MDA-MB-231 triple negative breast cancer (TNBC) line, via dual degradation without provoking a global histone hyperacetylation. In this study, we demonstrated that µDES-based PROTAC loading in EVs significantly enhanced therapeutic function of PROTAC drug in vivo in the TNBC breast tumor mouse model. NSG mice with pre-established MDA-MB-231 tumors and treated with intraperitoneal injection of EVs for tumor inhibition study, which showed significantly higher HDAC 3 and 8 degradation efficiency and tumor inhibition than PROTAC only group. The liver, spleen, kidney, lung, heart, and brain were collected for safety testing, which exhibited improved toxicity. The EV delivery of PROTAC drug enhances drug stability and bioavailability in vivo, transportability, and drug targeting ability, which fills an important gap in current development of PROTAC therapeutic functionality in vivo and clinical translation. This novel EV-based drug transfection and delivery strategy could be applicable to various therapeutics for enhancing in vivo delivery, efficacy, and safety.
N-Acetylglucosamine Facilitates Coordinated Myoblast Flow, Forming the Foundation for Efficient Myogenesis
Authors: Satoh Masahiko S. , Rancourt Ann , St-Pierre Guillaume , Bouchard Elizabeth , Fillion Maude , Hagiwara Kana , Nakajima Kazuki , Sato Sachiko 
Published: August 2024

AbstractSkeletal muscle comprises 30-40% of a mammal’s body mass, maintaining its integrity through efficient muscle fiber regeneration, which involves myoblast differentiation into myotubes. Previously, we reported that N-acetylglucosamine (GlcNAc) promotes myogenesis in C2C12 cells, although the underlying mechanisms were unclear. UDP-GlcNAc, the activated form of GlcNAc, is critical for the biosynthesis of highly branched (N-acetyllactosamine-rich) N-linked oligosaccharides, which are recognized by galectin-3 (Gal-3), facilitating dynamic cell-cell and cell-matrix interactions. In this study, we used primary myoblasts from wild-type and Gal-3 null (Gal-3KO) mice, observing myotube formation through long-term live-cell imaging and single-cell tracking. We found that GlcNAc enhances myoblast fusion in a dose-dependent manner, and the addition of Gal-3 with GlcNAc leads to the formation of larger myotubes. Gal-3KO myoblasts exhibited a reduced capacity for myotube formation, a deficiency that was rectified by supplementing with GlcNAc and Gal-3. Our results highlight the critical role of Gal-3 interaction with oligosaccharides whose synthesis was promoted by GlcNAc in facilitating myotube formation. Single-cell tracking revealed that GlcNAc and Gal-3 increase myoblast motility, creating a faster-coordinated cell flow—a directed movement of myoblasts, along which myotubes form through cell fusion. Interestingly, myoblasts contributing to myotube formation were pre-positioned along the eventual shape of the myotubes before the establishment of the coordinated flow. These myoblasts moved along the flow, paused, and even moved against the flow, suggesting that both flow and initial positioning play roles in aligning myoblasts into the shape of a myotube. Overall, our findings demonstrate that GlcNAc, in conjunction with Gal-3, enhances myotube formation by fostering an environment conducive to myoblast positioning, establishing coordinated flow, and facilitating fusion. This suggests potential therapeutic applications of GlcNAc in muscle repair and muscle disorders.
Vasculature segmentation in 3D hierarchical phase-contrast tomography images of human kidneys
Authors: Jain Yashvardhan , Walsh Claire L. , Yagis Ekin , Aslani Shahab , Nandanwar Sonal , Zhou Yang , Ha Juhyung , Gustilo Katherine S. , Brunet Joseph , Rahmani Shahrokh , Tafforeau Paul , Bellier Alexandre , Weber Griffin M. , Lee Peter D. , Börner Katy 
Published: August 2024

AbstractEfficient algorithms are needed to segment vasculature in new three-dimensional (3D) medical imaging datasets at scale for a wide range of research and clinical applications. Manual segmentation of vessels in images is time-consuming and expensive. Computational approaches are more scalable but have limitations in accuracy. We organized a global machine learning competition, engaging 1,401 participants, to help develop new deep learning methods for 3D blood vessel segmentation. This paper presents a detailed analysis of the top-performing solutions using manually curated 3D Hierarchical Phase-Contrast Tomography datasets of the human kidney, focusing on the segmentation accuracy and morphological analysis, thereby establishing a benchmark for future studies in blood vessel segmentation within phase-contrast tomography imaging.
Body dissatisfaction widens the racial disparities of Benzophenone-3, a chemical biomarker of personal care and consumer product usage
Authors: Nguyen Vy Kim , Zimmerman Samuel , Colacino Justin , Jolliet Olivier , Patel Chirag J 
Published: August 2024

AbstractBackgroundBody dissatisfaction can drive individuals to use personal care products, exposing themselves to Benzophenone-3 (BP3). Yet, no study has examined the link between body dissatisfaction and elevated chemical exposures.ObjectivesOur study examines how body dissatisfaction impacts the racial differences in BP3 exposures.MethodsUsing NHANES 2003-2016 data for 3,072 women, we ascertained body dissatisfaction with a questionnaire on weight perception. We ran two generalized linear models with log10-transformed urinary concentrations of BP3 as the outcome variable and the following main predictors: one with race/ethnicity and another combining race/ethnicity and body dissatisfaction. We also conducted stratified analyses by race/ethnicity. We adjusted for poverty income ratio, BMI, urinary creatinine, and sunscreen usage.ResultsBP3 levels in Mexican American, Other Hispanic, Other Race, non-Hispanic White, and non-Hispanic Asian women were on average 59%, 56%, 33%, 16%, and 9% higher, respectively, compared to non-Hispanic Black women. Racial differences in BP3 levels are accentuated with body dissatisfaction. For example, Other Hispanic women perceiving themselves as overweight had 69% higher BP3 levels than non-Hispanic Black women (p-value = 0.01), while those perceiving themselves as at the right weight had 32% higher levels (p-value = 0.31). Moreover, minority women perceiving themselves as overweight tended to have higher BP3 levels than those who do not. For example, BP3 levels in Other Hispanic women perceiving themselves as overweight are significantly higher compared to those who do not (73%, p-value = 0.03). In contrast, such differences in the non-Hispanic White women are minimal (-0.5%, p-value = 0.98).DiscussionMinority women with body dissatisfaction show elevated BP3 exposure independent of sunscreen usage, implying that their elevated exposures may stem from using other personal care and consumer products. Further research is needed to determine if increases of exposure to potential toxicants occur among minority women with body dissatisfaction.Highlights⍰First integration of measures of body dissatisfaction with national chemical biomonitoring data⍰Analyzed data from a diverse US nationally representative sample of 3,072 women⍰Minority women with body dissatisfaction show higher BP3 levels independent of sunscreen use and BMI⍰Minimal differences in BP3 levels by body dissatisfaction in non-Hispanic White women⍰Developed a visualization tool to show how racial disparities widen due to body dissatisfaction
Quantifying the health impact of crop breeding: Revisiting the Disability-Adjusted Life Years Approach
Authors: Lenaerts Bert 
Published: August 2024

AbstractCrop breeding, through methods like biofortification, plays a crucial role in increasing agricultural yields, contributing to a stable and healthy food supply by boosting the micronutrient content of staples, which is pivotal for combating chronic and hidden hunger, especially in rural areas. This shift towards improved nutrition can be sustainably integrated into regular diets, marking a significant stride in public health. The burden of hunger and its consequences on health are increasingly quantified using the Disability-Adjusted Life Years (DALYs) approach, which merges years of life lost and years lived with disability, offering a comprehensive view of health impacts and aiding in resource allocation despite its complexity and subjective nature. A practical formula for quantifying the health impact of biofortification was introduced by Stein et al. (2005) and Zimmermann and Qaim (2004). This entails calculating the efficacy or relative reduction in hunger burden based on the current and post-intervention nutrient intake against the recommended dietary allowances. As data on consumption and recommended intake levels are variable and not readily available, this paper proposes relying on relative estimates to bridge the data gaps and uncertainties, thus streamlining the quantification of crop breeding’s impact on diets and overall health.
Cross-site predictions of readmission after psychiatric hospitalization with mood or psychotic disorders
Authors: Ren Boyu , Yoon WonJin , Thomas Spencer , Savova Guergana , Miller Timothy , Hall Mei-Hua 
Published: August 2024

AbstractPatients with mood or psychotic disorders have high rates of unplanned readmission, and predicting readmission likelihood may guide discharge decisions. In this retrospective, multi-site study, we assess the predictive power of various structured variables from electronic health records for all-cause readmission in each site separately and evaluate the generalizability of the in-site prediction models across sites. We find that the set of relevant predictors vary significantly across. For example, length of stay is strongly predictive of readmission at only three out of the four sites. We also find a general lack of cross-site generalizability of the in-site prediction models, with in-site predictions having an average F1 score of 0.666, compared to an average F1 score of 0.551 for cross-site predictions. The generalizability cannot be improved even after adjusting for differences in the distributions of predictors. These results indicate that, with this set of predictors, fitting individual models at each site is necessary to achieve reasonable prediction accuracy. Additionally, they suggest that more sophisticated predictors variables or predictive algorithms are needed to develop generalizable models capable of extracting robust insights into the root causes of early psychiatric readmissions.
An evaluation of the adequacy of Indian national and state Essential Medicines Lists (EMLs) for palliative care medical needs - a comparative analysis
Authors: Agrawal Disha , Shrinivas Divya , Sharma Parth , Rajagopal M R , Ghoshal Arun , Zadey Siddhesh 
Published: August 2024

AbstractObjectivesEssential Medicines Lists (EMLs) guide the public sector procurement and supply of medications to impact access to adequate and appropriate palliative care drugs. This study evaluates the adequacy of India’s national and sub-national EMLs that can directly impact palliative care for 5.4 million patients.MethodsIn this qualitative document review, we compared Indian national, and state EMLs acquired from official government websites with the International Association for Hospice & Palliative Care (IAHPC) EML recommendations. We analysed data on the indication and formulation of drugs under the different categories of formulations present (all, some, and no), and drugs absent. Literature review and inputs from palliative care experts provided alternatives of absent medications to assess the adequacy of lists in managing the symptoms listed by IAPHC.ResultsWe analysed 3 national and 25 state lists for 33 recommended drugs. The Central Government Health Services list had the maximum availability of all formulations of drugs (16 [48%]) nationally. Among states and union territories, the Delhi EML was the closest to IAHPC with 17 (52%) drugs with all formulations present. Nagaland had the most incomplete EML with only 3 (9%) drugs with all formulations present. No EML had all the recommended formulations of morphine. In one national and sixteen state EMLs, oral morphine was absent.ConclusionWhile Indian EMLs lack drugs for palliative care when compared with the IAHPC EML, symptom management is adequate. There is a need for countries with limited resources to modify the IAPHC list for their settings.What is already known on this topicEssential Medicines Lists (EMLs) are instrumental in guiding public sector procurement of drugs. The implementation of EMLs is known to improve drug availability and prescription practices. The rising burden of people requiring end-of-life care globally necessitates the availability of appropriate drugs for the medical management of symptoms, which can be achieved through their inclusion in local EMLs.What this study addsThe national and sub-national EMLs of India do not fully adhere to the International Association for Hospice and Palliative Care (IAHPC) recommendations. However, they contain adequate drugs for the management of the listed symptoms. Additionally, the inclusion of various formulations of morphine remains a challenge to be addressed.How this study might affect research, practice or policyThis study highlights the need to develop a fit-for-purpose EML for palliative care, taking into account the geographical variations in palliative care needs, and resource constraints in healthcare delivery at the state and country level.
Generation of Risk Score for Serious Non-Steroidal Anti-Inflammatory Drug (NSAID) Induced Cardiovascular Events (NAÏVE) among Active-Duty Service Members and Veterans
Authors: Atkinson Timothy J , Petway Justin , Forbes Whitney , Thorfinnson Hannah , Costantino Major Ryan C , Gressler Laura E 
Published: August 2024

AbstractImportanceCardiovascular disease (CVD) is a major global health concern, responsible for a significant proportion of deaths annually. Despite the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) in managing various conditions, their association with cardiovascular events poses a challenge, and existing guidelines lack a reliable risk prediction tool. This study addresses the critical need for an evidence-based instrument to assess the likelihood of NSAID-induced cardiovascular events, that provides clinicians with valuable decision support to improve safety in their use for pain management, especially in patients vulnerable to cardiovascular events.ObjectiveTo develop a practical risk scoring tool, NSAID Induced Cardiovascular Events (NAÏVE), for estimating the risk of serious cardiovascular events associated with NSAID use.DesignRetrospective nested case-control studySettingThe study leveraged data from the DAVINCI database, integrating electronic health records, administrative data, and clinical data from both the Veterans Health Administration (VHA) and the Department of Defense (DoD).ParticipantsThe study cohort consisted of individuals with at least one NSAID pharmacy claim, with cases defined as those experiencing non-fatal myocardial infarction, non-fatal stroke, or new heart failure.InterventionsDevelopment of the NAÏVE risk scoring tool involved a comprehensive analysis of demographic, clinical, and prescription-related variables, including NSAID exposure, comorbidities, and medication history.Main Outcomes/MeasuresThe primary outcome was the first occurrence of a cardiovascular event.ResultsThe study cohort comprised 231,967 cases and 2,319,670 controls, identified from individuals with at least one NSAID pharmacy claim between October 1, 2016, and September 30, 2020. The risk index, NAÏVE, demonstrated strong discriminatory ability and calibration, with a C-statistic of 0.88. Variables such as age, NSAID exposure, comorbidities, and medication history were associated with increased odds of NSAID-induced cardiovascular events.Conclusions/RelevanceNAÏVE is the first evidence-based risk scoring tool providing clinicians with valuable decision support for assessing the potential risk of serious cardiovascular events associated with NSAID use. It fills a crucial gap in clinical practice, allowing for transparent discussions with patients and shared decision-making regarding NSAID prescriptions. Further validation and prospective testing are warranted for broader applicability.
Chloroplastic ROS bursts initiate salicylic acid biosynthesis in plant immunity
Authors: Roussin-Léveillée Charles , St-Amand Méliane , Desbiens-Fortin Philippe , Perreault Rosaëlle , Pelletier Antoine , Gauthier Sabrina , Gaudreault-Lafleur Faye , Laforest-Lapointe Isabelle , Moffett Peter 
Published: August 2024

AbstractChloroplasts are essential centers of signal integration and transduction in plants. They are involved in the biosynthesis of primary and specialized metabolites, including salicylic acid (SA), a key defense phytohormone synthesized via the conserved chorismate biosynthetic pathway. However, the identity of the signal(s) that ultimately triggers SA induction in chloroplasts upon perception of a biotic threat has remained elusive. Here, we provide evidence of a functional link between chloroplast-derived reactive oxygen species (cROS) and SA production. We observe that inhibiting ROS bursts generated from photosystem II during plant immune activation completely abrogates the induction of SA synthesis in response to immunity-inducing signals, without affecting SA-independent immune responses. Indeed, time course analyses show that the induction of SA marker genes parallels that of cROS production during an immune response. Consistent with this, preventing cROS induction is sufficient to nullify the immune protection normally conferred by activating immunity prior to an infection. Analyses of transcriptomes and photosynthetic efficiency show that two conserved effectors from the phytopathogenPseudomonas syringae, HopM1 and AvrE1, redundantly disrupt photosynthesis and cROS bursts. These effects reduce SA accumulation and are mediated via the impact of HopM1 and AvrE1 in inducting host abscisic acid signaling. Our results suggest that a change in chloroplastic redox homeostasis induced by biotic stressors acts as an initiator of plant immunity through the production of SA, and that this response is targeted by conserved pathogen effector proteins.
Fetal liver neutrophils are responsible for the postnatal neutrophil surge
Authors: Ishiwata Ryo , Morimoto Yuji 
Published: August 2024

AbstractMammalian neonates experience an abrupt surge of blood neutrophil count within the first day of life. The postnatal neutrophil surge is regarded as a defensive reaction against infection; however, the mechanisms underlying this surge remain unclear.The present study demonstrates that the postnatal neutrophil surge arises from the liver neutrophil pool. In rat neonates, the neutrophil surge was evident at 6 hours after birth. The proportion and immaturity of bone marrow neutrophils remained unaltered at 6 hours but increased only after the surge had peaked. In the rat fetal and neonatal livers, we observed prenatal neutrophil accumulation and acute loss of the neutrophils coinciding with the postnatal neutrophil surge. InLys-EGFPmice, an acute loss of liver neutrophils was observed within 12 hours of birth. This loss was characterized by a decrease in mature neutrophils and by perivascular neutrophil localization in the livers. Additionally, mouse fetuses exhibited an accumulation of the liver neutrophil pool during the late gestational period (e15-18), which was attributable to neutrophil-biased myeloid differentiation mediated by granulocyte-colony stimulating factor (G-CSF). The liver neutrophils exhibited characteristic transcriptomic alterations within three hours of birth, exemplified by an increase in theNos2 (iNOS) gene. The administration of a non-selective NOS inhibitor or an iNOS-selective inhibitor resulted in the inhibition of the postnatal neutrophil surge in rat neonates, accompanied by the retention of liver neutrophils.These findings shed light on the previously unidentified source of the postnatal neutrophil surge and the stimulus initiating it.Significance statementInfections in newborns, particularly those occurring within the first 72 hours of life, are leading cause of mortality and morbidity. Neutrophil, a type of leukocytes, acutely increases within 24 hours after birth in the newborns’ blood. This neutrophil surge is regarded as an innate defensive system against infection; however, the mechanisms of the surge have remained unknown. Here, we examined rats and mice and found that the neutrophils accumulated in the fetal livers during the late pregnancy and were released into blood after birth. We also found a specific factor causing the release of the liver neutrophils. These findings might explain why preterm or low-birth weight newborns often lack the postnatal neutrophil surge and are thus more susceptible to infections.
Bradyrhizobium hardenbergiaesp. nov., isolated fromHardenbergia violaceain Australia, represents a novel basal lineage of theB. elkaniisupergroup
Authors: Lafay Bénédicte , Coquery Elina , Oger Philippe M. 
Published: August 2024

ABSTRACTBradyrhizobia are widespread across the Australian continent, where they are essential to Australian ecosystems by helping legumes to compensate nutrient deficiencies and low fertility of Australian soils. Among theBradyrhizobiumgenospecies identified during a survey of Australian native rhizobia communities in 1994-1995, genospecies L appeared to be only distantly related to anyBradyrhizobiumlineages known at the time. We take advantage of the recent sequencing of the genome of strain BDV5419, the original strain corresponding toBradyrhizobiumgenospecies L, to re-assess this lineage taxonomic status. We characterized further strain BDV5419 based on morpho-physiological traits and determined its phylogenetic relationships with the type strains of the 88 currently knownBradyrhizobiumspecies based on sequence comparisons of SSU rRNA genes and complete genomes. The digital DNA–DNA hybridization relatedness with any type strain was less than 33% and both SSU rRNA gene and genome phylogenies confirmed that this strain does not belong to any formerly described species within theBradyrhizobiumgenus. Whereas its position within the lineage encompassing theB. elkaniiandB. jicamaesupergroups is unresolved in the SSU rDNA phylogeny, strain BDV5419 appears to be one of most basal lineages of theB. elkaniisupergroup in the genome comparison. All data thus support the description of the novel speciesBradyrhizobium hardenbergiaesp. nov. which type strain is BDV5419T(= CFBP 9111T= LMG 32897T), isolated from a nodule ofHardenbergia violaceaein Black Mountain Nature Reserve, in Canberra, ACT, Australia.