bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the damping characteristics of a hybrid piezo-shunt nanocomposite using a two-step homogenization approach
Authors: Sedighi S B , Sarfaraz R , Safarpour P
Published: October 2023

Composite materials containing piezoelectric particles have attracted remarkable attention because of their distinctive electromechanical conversion characteristics. These supreme properties lead to their applications in various fields, such as vibration damping of structures. The damping parameter of dynamic systems is crucial, especially when they undergo resonance phenomena. Multi-phase polymer matrix composites consisting of piezoelectric particles are innovative material systems that have been recently introduced to convert the mechanical vibrations into electrical energy, and subsequently dissipate into heat through an internal electrical circuit. The present study aims to analytically investigate the viscoelastic characteristics of a shunted three-phase composite composed of a polymer matrix, electrically conductive nanoparticles and piezoelectric particles. The effective viscoelastic characteristics of a shunted composite are calculated using one- and two-step homogenization procedures and by considering the viscoelastic characteristics of constituent materials. The influence of several key parameters, namely, the non-dimensional frequency, the volume fraction of electrically conductive nanoparticles and piezoelectric particles, and the shape of the inclusions, on viscoelastic characteristics, such as phase angles, the storage modulus and loss modulus, are examined. The viscoelastic characteristics are considerably affected by these parameters, and the perceived behavior is justified by the governing equations. The assessment of results confirms that the damping characteristics can be improved by careful selection of a volume fraction of constituent materials and control of the excitation frequency of the smart composite, while avoiding additional costs and likely inconveniences in the fabrication process.
Under the Hood: The Scientific Leadership, Clinical Operations, Statistical and Data Management, and Laboratory Centers of the Antibacterial Resistance Leadership Group
Authors: Cross Heather R , Greenwood-Quaintance Kerryl E , Souli Maria , Komarow Lauren , Geres Holly S , Hamasaki Toshimitsu , Chambers Henry F , Fowler Vance G , Evans Scott R , Patel Robin ,   for the Antibacterial Resistance Leadership Group
Published: October 2023

Developing and implementing the scientific agenda of the Antibacterial Resistance Leadership Group (ARLG) by soliciting input and proposals, transforming concepts into clinical trials, conducting those trials, and translating trial data analyses into actionable information for infectious disease clinical practice is the collective role of the Scientific Leadership Center, Clinical Operations Center, Statistical and Data Management Center, and Laboratory Center of the ARLG. These activities include shepherding concept proposal applications through peer review; identifying, qualifying, training, and overseeing clinical trials sites; recommending, developing, performing, and evaluating laboratory assays in support of clinical trials; and designing and performing data collection and statistical analyses. This article describes key components involved in realizing the ARLG scientific agenda through the activities of the ARLG centers.
The Next Generation: Mentoring and Diversity in the Antibacterial Resistance Leadership Group
Authors: Harris Anthony D , Souli Maria , Pettigrew Melinda M ,   for the Antibacterial Resistance Leadership Group
Published: October 2023

The Antibacterial Resistance Leadership Group (ARLG) Mentoring Program was established to develop and prepare the next generation of clinician-scientists for a career in antibacterial resistance research. The ARLG Diversity, Equity, and Inclusion Working Group partners with the Mentoring Committee to help ensure diversity and excellence in the clinician-scientist workforce of the future. To advance the field of antibacterial research while fostering inclusion and diversity, the Mentoring Program has developed a number of fellowships, awards, and programs, which are described in detail in this article.
Priorities and Progress in Gram-negative Bacterial Infection Research by the Antibacterial Resistance Leadership Group
Authors: Satlin Michael J , van Duin David , Tamma Pranita D , Lodise Thomas P , Van Tyne Daria , Rodvold Keith A , Rouphael Nadine , Evans Scott R , Fowler Vance G , Hamasaki Toshimitsu , Patel Robin , Komarow Lauren , Baum Keri , Souli Maria , Schwager Nyssa , Bonomo Robert A , Doi Yohei ,   for the Antibacterial Resistance Leadership Group, Wang Minggui , Wenzler Eric , Schooley Robert , Evans Beth , Hopkins Deborah , Cathcart Felecia , Mocka Elizabeth , Schuler Carl , Sund Zoe , Zaharoff Smitha , Wickward Cathy , Estes Leslie , Mau Donald , Booth Grant , Abbenante Erin , Bhojani Minal , Zahir Hirra , Ge Lizhao , Giri Abhigya , Dai Weixiao , Diao Guoqing , Fidler Tamara , Shao Wanying , Li Yixuan , Zeng Lijuan , Zhang Shanshan , Greenwood-Quaintance Kerryl , Malan Suzannah Schmidt , Parmar Krupa Mukesh , Cunningham Scott , Ghazaryan Varduhi , Raterman Erica , Samuel Tamika , Lee Marina , Nayak Seema
Published: October 2023

Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients. The ARLG has conducted pharmacokinetic studies to inform the optimal dosing of antibiotics that are important in the treatment of drug-resistant gram-negative bacteria, including oral fosfomycin, intravenous minocycline, and a combination of intravenous ceftazidime-avibactam and aztreonam. In addition, randomized clinical trials have assessed the safety and efficacy of step-down oral fosfomycin for complicated urinary tract infections and single-dose intravenous phage therapy for adult patients with cystic fibrosis who are chronically colonized with P. aeruginosa in their respiratory tract. Thus, the focus of investigation in the ARLG has evolved from improving understanding of drug-resistant gram-negative bacterial infections to positively affecting clinical care for affected patients through a combination of interventional pharmacokinetic and clinical studies, a focus that will be maintained moving forward.
Prophylactic epicardial pacemaker implantation in tricuspid valve replacement
Authors: Bazire Baptiste , Para Marylou , Raffoul Richard , Nataf Patrick , Cachier Agnès , Extramiana Fabrice , Iung Bernard , Algalarrondo Vincent
Published: October 2023

OBJECTIVES

Patients undergoing surgical tricuspid valve replacement (TVR) are at high risk of atrioventricular conduction disorders. Because implanting a lead through the tricuspid bioprosthesis is discouraged, the patients who undergo TVR in our centre are usually given a prophylactic epicardial pacemaker. Our aim was to assess the benefits and risks of this strategy.

METHODS

Among the patients who underwent TVR with prophylactic epicardial pacemaker implantation, clinical evaluations and pacemaker reports were analysed retrospectively after surgery. The need for cardiac pacing were assessed by characterizing the atrioventricular conduction, while the risks were evaluated by listing and adjudicating post-operative events.

RESULTS

A total of 80 patients were analysed (mean age was 57 ± 16 years old, 30% males). TVR was isolated in 28 (35%) patients, but most often associated with another valve surgery. In the postoperative period, heart rhythm was analysed in 59/80 patients during a median follow-up of 35 months. Cardiac pacing was needed in 46% patients: 14% had complete pacing dependency, 17% had high degree AV block, while 15% had a high ventricular pacing rate (>80%). No pre- or per-operative variables could predict cardiac pacing requirement. Post-operatively, a spontaneous heart rate >70 bpm (P = 0.02) and the presence of narrow QRS (P = 0.03) were significantly associated with a lower risk of cardiac pacing requirement. Complications related to epicardial pacemaker were documented in 2 (2.5%) patients.

CONCLUSIONS

After TVR, cardiac pacing was needed in 46% of patients for post-operative atrioventricular conduction disorders. This high incidence associated with an acceptable safety profile supports a prophylactic epicardial pacing strategy for the patients undergoing TVR.
Two distinct non-ribosomal peptide synthetase-independent siderophore synthetase gene clusters identified in Armillaria and other species in the Physalacriaceae
Authors: Narh Mensah Deborah L , Wingfield Brenda D , Coetzee Martin P A
Published: October 2023

Siderophores are important for ferric iron solubilization, sequestration, transportation, and storage, especially under iron-limiting conditions such as aerobic conditions at high pH. Siderophores are mainly produced by non-ribosomal peptide synthetase-dependent siderophore pathway, non-ribosomal peptide synthetase-independent siderophore synthetase pathway, or the hybrid non-ribosomal peptide synthetases/non-ribosomal peptide synthetases-independent siderophore pathway. Outcompeting or inhibition of plant pathogens, alteration of host defense mechanisms, and alteration of plant-fungal interactions have been associated with fungal siderophores. To understand these mechanisms in fungi, studies have been conducted on siderophore biosynthesis by ascomycetes with limited focus on the basidiomycetes. Armillaria includes several species that are pathogens of woody plants and trees important to agriculture, horticulture, and forestry. The aim of this study was to investigate the presence of non-ribosomal peptide synthetases-independent siderophore synthetase gene cluster(s) in genomes of Armillaria species using a comparative genomics approach. Iron-dependent growth and siderophore biosynthesis in strains of selected Armillaria spp. were also evaluated in vitro. Two distinct non-ribosomal peptide synthetases-independent siderophore synthetase gene clusters were identified in all the genomes. All non-ribosomal peptide synthetases-independent siderophore synthetase genes identified putatively encode Type A′ non-ribosomal peptide synthetases-independent siderophore synthetases, most of which have IucA_IucC and FhuF-like transporter domains at their N- and C-terminals, respectively. The effect of iron on culture growth varied among the strains studied. Bioassays using the CAS assay on selected Armillaria spp. revealed in vitro siderophore biosynthesis by all strains irrespective of added FeCl3 concentration. This study highlights some of the tools that Armillaria species allocate to iron homeostasis. The information generated from this study may in future aid in developing molecular based methods to control these phytopathogens.
Near-infrared photoimmunotherapy and anti-cancer immunity
Authors: Nakajima Kohei , Ogawa Mikako
Published: October 2023

The activation of the anti-cancer immune system is an important strategy to control cancer. A new form of cancer phototherapy, near-infrared photoimmunotherapy (NIR-PIT), was approved for clinical use in 2020 and uses IRDye® 700DX (IR700)-conjugated antibodies and NIR light. After irradiation with NIR light, the antibody–IR700 conjugate forms water-insoluble aggregations on the plasma membrane of target cells. This aggregation causes lethal damage to the plasma membrane, and effectively leads to immunogenic cell death (ICD). Subsequently, ICD activates anti-cancer immune cells such as dendritic cells and cytotoxic T cells. Combination therapy with immune-checkpoint blockade has synergistically improved the anti-cancer effects of NIR-PIT. Additionally, NIR-PIT can eliminate immunosuppressive immune cells in light-irradiated tumors by using specific antibodies against regulatory T cells and myeloid-derived suppressor cells. In addition to cancer-cell-targeted NIR-PIT, such immune-cell-targeted NIR-PIT has shown promising results by activating the anti-cancer immune system. Furthermore, NIR-PIT can be used to manipulate the tumor microenvironment by eliminating only targeted cells in the tumor, and thus it also can be used to gain insight into immunity in basic research.
In vitro synergy of the combination of sulbactam-durlobactam and cefepime at clinically relevant concentrations against A. baumannii, P. aeruginosa and Enterobacterales
Authors: Fouad Aliaa , Nicolau David P , Gill Christian M
Published: October 2023

Background

Sulbactam-durlobactam is a potent combination active against Acinetobacter baumannii; however, it lacks activity against other nosocomial pathogens. Cefepime is a common first-line therapy for hospital/ventilator-associated pneumonia caused by Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacterales. With increasing resistance to cefepime, and the significant proportion of polymicrobial nosocomial infections, effective therapy for infections caused by Acinetobacter baumannii, P. aeruginosa and Enterobacterales is needed. This study investigated the in vitro synergy of sulbactam-durlobactam plus cefepime against relevant pathogens.

Methods

Static time–kills assays were performed in duplicate against 14 cefepime-resistant isolates (A. baumannii, n = 4; P. aeruginosa, n = 4; Escherichia coli, n = 3; Klebsiella pneumoniae, n = 3). One WT K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients.

Results

Sulbactam-durlobactam alone showed significant activity against A. baumannii consistent with the MIC values. Sulbactam-durlobactam plus cefepime showed synergy against one A. baumannii isolate with an elevated MIC to sulbactam-durlobactam (32 mg/L). Against all P. aeruginosa isolates, synergy was observed with sulbactam-durlobactam plus cefepime. For the Enterobacterales, one E. coli isolate demonstrated synergy while the others were indifferent due to significant kill from sulbactam-durlobactam alone. The combination of sulbactam-durlobactam plus cefepime showed synergy against one of the K. pneumoniae and additive effects against the other two K. pneumoniae tested. No antagonism was observed in any isolates including the WT strain.

Conclusions

Synergy and no antagonism was observed with a combination of sulbactam-durlobactam and cefepime; further in vivo pharmacokinetic/pharmacodynamics data and clinical correlation are necessary to support our findings.
Predictive factors and oncological outcomes of pathological T3a upstaging in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy
Authors: Ishiyama Ryo , Omae Kenji , Kondo Tsunenori , Iizuka Junpei , Yoshida Kazuhiko , Fukuda Hironori , Tachibana Hidekazu , Ishihara Hiroki , Kobayashi Hirohito , Takagi Toshio
Published: October 2023

Objectives

To investigate predictive factors and oncological outcomes of pathological T3a upstaging in renal cell carcinoma patients who were initially diagnosed as clinical T1 and treated with partial nephrectomy.

Methods and materials

The clinical records and survival data of 1617 patients, who had undergone partial nephrectomy for clinical T1 renal cell carcinoma at Tokyo Women’s Medical University, Tokyo, Japan between January 2011 and December 2020, were analyzed retrospectively.

Results

Of 1617 clinical T1 renal cell carcinoma patients who underwent partial nephrectomy, 28 (1.73%) had pathological T3a upstaging. In the multivariable analysis for pathological T3a upstaging using logistic regression models, male sex and clinical T1b were significant factors associated with pathological T3a upstaging (male sex: odds ratio = 5.07, 95% confidence interval: 1.18–21.8, clinical T1b: odds ratio = 8.36, 95% confidence interval: 3.56–19.6). The Kaplan–Meier method of the recurrence-free survival showed shorter recurrence-free survival in patients with pathological T3a upstaging than in those with pathological T1 (P < 0.0001). In the multivariable analysis using Cox proportional hazards regression models, pathological T3a upstaging was no longer significantly associated with recurrence-free survival after adjustment for other pathological factors (hazard ratio = 1.59, 95% confidence interval: 0.58–4.36). In a sensitivity analysis that analyzed its components individually instead of whole pathological T3a, neither perinephric fat invasion, sinus fat invasion, nor renal vein invasion was associated with recurrence-free survival.

Conclusions

Male sex and clinical T1b were significant predictors for pathological T3a upstaging after partial nephrectomy in clinical T1 renal cell carcinoma patients. Although patients with pathological T3a upstaging had worse recurrence-free survival compared with those without upstaging, multivariable analyses revealed that pathological T3a upstaging was not an independent predictor for poor recurrence-free survival.
Metaphilosophical myopia and the ideal of expansive pluralism
Authors: Kidd Ian James
Published: October 2023

This paper argues for the diversification of university-level philosophy curricula. I defend the ideal of expansionist pluralism and connect it to metaphilosophical myopia—problematically limited or constrained visions of the range of forms taken by philosophy. Expansively pluralist curricula work to challenge metaphilosophical myopia and one of its costs, namely, a specific kind of hermeneutical injustice, perpetrated against the communities and traditions shaped by the occluded forms of philosophy.
Pyrroline-5-carboxylate metabolism protein complex detected in Arabidopsis thaliana leaf mitochondria
Authors: Zheng Yao , Cabassa-Hourton Cécile , Eubel Holger , Chevreux Guillaume , Lignieres Laurent , Crilat Emilie , Braun Hans-Peter , Lebreton Sandrine , Savouré Arnould
Published: October 2023

Proline dehydrogenase (ProDH) and pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDH) catalyse the oxidation of proline into glutamate via the intermediates P5C and glutamate-semialdehyde (GSA), which spontaneously interconvert. P5C and GSA are also intermediates in the production of glutamate from ornithine and α-ketoglutarate catalysed by ornithine δ-aminotransferase (OAT). ProDH and P5CDH form a fused bifunctional PutA enzyme in Gram-negative bacteria and are associated in a bifunctional substrate-channelling complex in Thermus thermophilus; however, the physical proximity of ProDH and P5CDH in eukaryotes has not been described. Here, we report evidence of physical proximity and interactions between Arabidopsis ProDH, P5CDH, and OAT in the mitochondria of plants during dark-induced leaf senescence when all three enzymes are expressed. Pairwise interactions and localization of the three enzymes were investigated using bimolecular fluorescence complementation with confocal microscopy in tobacco and sub-mitochondrial fractionation in Arabidopsis. Evidence for a complex composed of ProDH, P5CDH, and OAT was revealed by co-migration of the proteins in native conditions upon gel electrophoresis. Co-immunoprecipitation coupled with mass spectrometry analysis confirmed the presence of the P5C metabolism complex in Arabidopsis. Pull-down assays further demonstrated a direct interaction between ProDH1 and P5CDH. P5C metabolism complexes might channel P5C among the constituent enzymes and directly provide electrons to the respiratory electron chain via ProDH.
Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans
Authors: Guilbaud Axel , Ghanegolmohammadi Farzan , Wang Yijun , Leng Jiapeng , Kreymerman Alexander , Gamboa Varela Jacqueline , Garbern Jessica , Elwell Hannah , Cao Fang , Ricci-Blair Elisabeth M , Liang Cui , Balamkundu Seetharamsing , Vidoudez Charles , DeMott Michael S , Bedi Kenneth , Margulies Kenneth B , Bennett David A , Palmer Abraham A , Barkley-Levenson Amanda , Lee Richard T , Dedon Peter C
Published: October 2023

DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC–MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1–26-month-old rats and 111 in human heart and brain by ‘stepped MRM’ LC–MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.
Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities
Authors: Müller-Dott Sophia , Tsirvouli Eirini , Vazquez Miguel , Ramirez Flores Ricardo O , Badia-i-Mompel Pau , Fallegger Robin , Türei Dénes , Lægreid Astrid , Saez-Rodriguez Julio
Published: October 2023

Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, and their target genes, the so called TF regulons, can be coupled with computational algorithms to estimate the activity of TFs. However, to interpret these findings accurately, regulons of high reliability and coverage are needed. In this study, we present and evaluate a collection of regulons created using the CollecTRI meta-resource containing signed TF–gene interactions for 1186 TFs. In this context, we introduce a workflow to integrate information from multiple resources and assign the sign of regulation to TF–gene interactions that could be applied to other comprehensive knowledge bases. We find that the signed CollecTRI-derived regulons outperform other public collections of regulatory interactions in accurately inferring changes in TF activities in perturbation experiments. Furthermore, we showcase the value of the regulons by examining TF activity profiles in three different cancer types and exploring TF activities at the level of single-cells. Overall, the CollecTRI-derived TF regulons enable the accurate and comprehensive estimation of TF activities and thereby help to interpret transcriptomics data.
TCOD: an integrated resource for tropical crops
Authors: Kang Hailong , Huang Tianhao , Duan Guangya , Meng Yuyan , Chen Xiaoning , He Shuang , Xia Zhiqiang , Zhou Xincheng , Chao Jinquan , Tang Bixia , Wang Zhonghuang , Zhu Junwei , Du Zhenglin , Sun Yanlin , Zhang Sisi , Xiao Jingfa , Tian Weimin , Wang Wenquan , Zhao Wenming
Published: October 2023

Tropical crops are vital for tropical agriculture, with resource scarcity, functional diversity and extensive market demand, providing considerable economic benefits for the world's tropical agriculture-producing countries. The rapid development of sequencing technology has promoted a milestone in tropical crop research, resulting in the generation of massive amount of data, which urgently needs an effective platform for data integration and sharing. However, the existing databases cannot fully satisfy researchers’ requirements due to the relatively limited integration level and untimely update. Here, we present the Tropical Crop Omics Database (TCOD, https://ngdc.cncb.ac.cn/tcod), a comprehensive multi-omics data platform for tropical crops. TCOD integrates diverse omics data from 15 species, encompassing 34 chromosome-level de novo assemblies, 1 255 004 genes with functional annotations, 282 436 992 unique variants from 2048 WGS samples, 88 transcriptomic profiles from 1997 RNA-Seq samples and 13 381 germplasm items. Additionally, TCOD not only employs genes as a bridge to interconnect multi-omics data, enabling cross-species comparisons based on homology relationships, but also offers user-friendly online tools for efficient data mining and visualization. In short, TCOD integrates multi-species, multi-omics data and online tools, which will facilitate the research on genomic selective breeding and trait biology of tropical crops.
BioKA: a curated and integrated biomarker knowledgebase for animals
Authors: Wang Yibo , Lin Yihao , Wu Sicheng , Sun Jiani , Meng Yuyan , Jin Enhui , Kong Demian , Duan Guangya , Bei Shaoqi , Fan Zhuojing , Wu Gangao , Hao Lili , Song Shuhui , Tang Bixia , Zhao Wenming
Published: October 2023

Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals’ biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein–protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA–miRNA–mRNA associations, lncRNA–miRNA associations and protein–protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.
No adults allowed: Adolescents and Medical Decision Making
Authors: Nemetz Elisheva T A , Huang Ryan S , Das Sunit
Published: October 2023

The majority of the literature focused on whether consent should be extended to the adolescent population arises from themes adapted from American tort law. In contrast to the USA, Ontario does not delineate an age of consent for medical treatment and relying on American guidelines to guide practice in Ontario is problematic. While the literature is saturated with discussions for and against seeking adolescent consent, there are currently no bioethical guidelines on adolescent consent in the province of Ontario. This paper explores adolescent refusal of care and adolescent request for care in opposition to parental wishes. The paper seeks to answer the following questions: What is the difference between an adolescent and an adult in medical decision-making? What are the barriers to seeking adolescent consent? And, can the neurobiological argument be an accurate guide for obtaining adolescent consent?
Silicate Microfiber Scaffolds Support the Formation and Expansion of the Cortical Neuronal Layer of Cerebral Organoids With a Sheet-Like Configuration
Authors: Terada Eisaku , Bamba Yohei , Takagaki Masatoshi , Kawabata Shuhei , Tachi Tetsuro , Nakamura Hajime , Nishida Takeo , Kishima Haruhiko
Published: October 2023

Cerebral organoids (COs) are derived from human-induced pluripotent stem cells in vitro and mimic the features of the human fetal brain. The development of COs is largely dependent on “self-organization” mechanisms, in which differentiating cells committed to cortical cells autonomously organize into the cerebral cortex-like tissue. However, extrinsic manipulation of their morphology, including size and thickness, remains challenging. In this study, we discovered that silicate microfiber scaffolds could support the formation of cortical neuronal layers and successfully generated cortical neuronal layers, which are 9 times thicker than conventional COs, in 70 days. These cortical neurons in the silicate microfiber layer were differentiated in a fetal brain-like lamination pattern. While these cellular characteristics such as cortical neurons and neural stem/progenitor cells were like those of conventional COs, the cortical neuronal layers were greatly thickened in sheet-like configuration. Moreover, the cortical neurons in the scaffolds showed spontaneous electrical activity. We concluded that silicate microfiber scaffolds support the formation of the cortical neuronal layers of COs without disturbing self-organization-driven corticogenesis. The extrinsic manipulation of the formation of the cortical neuronal layers of COs may be useful for the research of developmental mechanisms or pathogenesis of the human cerebral cortex, particularly for the development of regenerative therapy and bioengineering.
Is Over-parameterization a Problem for Profile Mixture Models?
Authors: Baños Hector , Susko Edward , Roger Andrew J
Published: October 2023

Biochemical constraints on the admissible amino acids at specific sites in proteins lead to heterogeneity of the amino acid substitution process over sites in alignments. It is well known that phylogenetic models of protein sequence evolution that do not account for site heterogeneity are prone to long-branch attraction (LBA) artifacts. Profile mixture models were developed to model heterogeneity of preferred amino acids at sites via a finite distribution of site classes each with a distinct set of equilibrium amino acid frequencies. However, it is unknown whether the large number of parameters in such models associated with the many amino acid frequency vectors can adversely affect tree topology estimates because of over-parameterization. Here, we demonstrate theoretically that for long sequences, over-parameterization does not create problems for estimation with profile mixture models. Under mild conditions, tree, amino acid frequencies, and other model parameters converge to true values as sequence length increases, even when there are large numbers of components in the frequency profile distributions. Because large sample theory does not necessarily imply good behavior for shorter alignments we explore the performance of these models with short alignments simulated with tree topologies that are prone to LBA artifacts. We find that over-parameterization is not a problem for complex profile mixture models even when there are many amino acid frequency vectors. In fact, simple models with few site classes behave poorly. Interestingly, we also found that misspecification of the amino acid frequency vectors does not lead to increased LBA artifacts as long as the estimated cumulative distribution function of the amino acid frequencies at sites adequately approximates the true one. In contrast, misspecification of the amino acid exchangeability rates can severely negatively affect parameter estimation. Finally, we explore the effects of including in the profile mixture model an additional “F-class” representing the overall frequencies of amino acids in the data set. Surprisingly, the F-class does not help parameter estimation significantly and can decrease the probability of correct tree estimation, depending on the scenario, even though it tends to improve likelihood scores.
Evolutionary origins of the lampriform pelagic radiation
Authors: Brownstein Chase Doran , Near Thomas J
Published: October 2023

Ray-finned fishes, which compose nearly half of living vertebrate diversity, provide an excellent system for studying the evolution of novel body forms. Lampriformes is a species-poor lineage of acanthomorph ray-finned fishes that has evolved two very different and highly specialized body plans suited to life in pelagic oceanic habitats: the deep, round-bodied bathysomes and the ribbon-like taeniosomes. Here, we present a new phylogenetic hypothesis and divergence time estimates for lampriform fishes based on an updated morphological dataset and DNA sequences from nuclear genes for all but one of the living lampriform families and 55% of recognized extant genera. Our analyses resolve two major clades in Lampriformes: the Bathysomi and the Taeniosomi. A time calibrated phylogeny shows that the origin of living lampriforms coincides with the aftermath of the Cretaceous–Palaeogene extinction and that anatomically modern pelagic morphotypes evolved 10 Myr after the start of the Palaeogene.
Pathotype Characterization of Plasmodiophora brassicae by European Clubroot Differential and Williams Sets in China
Authors: Zeng Lingyi , Zhang Yi , Wu Yupo , Zhang Xiong , Zhao Chuanji , Ren Li , Huang Junyan , Cheng Xiaohui , Liu Shengyi , Liu Lijiang
Published: October 2023

Clubroot disease caused by the soil-borne Plasmodiophora brassicae is devastating to Brassicaceae crops and spreading rapidly in China in recent years, resulting in great yield losses annually. Virulence of P. brassicae populations specializes and is in dynamic change in the fields. Information on the pathotypes and their distributions is crucial to control the clubroot disease. Presently, the pathotypes of P. brassicae prevalent in China, however, are not well determined. In this study, we used 16 Brassica hosts, including the European Clubroot Differential (ECD) and Williams sets, to designate the pathotypes of 33 P. brassicae populations from 13 provinces. The 33 P. brassicae populations could be divided into 26 pathotypes by the ECD set or seven pathotypes by the Williams set, revealing ECD16/15/31 and ECD16/31/31 or P4 and P2 as the predominant pathotypes. We found that the Brassica rapa differentials ECD01 to ECD04 showed stable and high levels of resistance to most pathotypes of P. brassicae in China, thereby providing valuable resources for clubroot-resistance breeding of Brassicaceae crops. The ECD set exhibited much higher discernibility and further divided the isolates that belonged to the P4 pathotype into 10 ECD pathotypes. Isolates of ECD16/23/31 and ECD16/15/31 were strongly virulent on Huashuang 5R, the first and widely used clubroot-resistant cultivar of oilseed rape in China. As we learn, 26 pathotypes are the most diverse populations of P. brassicae characterized until now in China. Our study provides new insights into virulence specialization of P. brassicae and their geographical distributions, contributing to exploitation of clubroot-resistant resources and the field layout of the present resistant Brassica crops in China.
The gut microbiome in the fight against obesity: The potential of dietary factors
Authors: Ahmad Jamil , Khan Imran , Zengin Gokhan , Mahomoodally Mohamad Fawzi
Published: October 2023

Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.
Utilization of Healthcare Resources by Vascular Anomaly Patients: An Assessment of Healthcare Burden by Lesion Complexity
Authors: Truong Albert Y. , Iaconetti Emma , Clapp Averill , Brackett Shannon , Fallon Erica M. , Garzon Maria C. , Tulin-Silver Sheryl , Wu June K.
Published: October 2023

Background:

Vascular anomalies (VAs) are heterogeneous lesions. Symptoms vary widely by lesion type and complexity. VA patients often require life-long interdisciplinary care; however, there is a paucity of data on the healthcare utilization of VA patients, and their burden on the healthcare system remains largely unquantified. We hypothesize that healthcare utilization by complex lymphatic malformation (LM) and venous malformation (VM) patients will be significantly higher compared with simple LM and VM patients.

Methods:

A retrospective, longitudinal study was performed of LM/VM patients seen through multidisciplinary VA clinics between January 1, 2019 and December 31, 2020. Data were collected from each patient’s first presentation through December 31, 2021 and included number of office visits, imaging studies, specialists involved, procedures, hospitalization data, and approximate costs, normalized to per year utilization. Patients were divided into “simple” and “complex” LMs/VMs. Involvement of the airway, more than one anatomic area, and/or complex lymphatic anomalies were defined as “complex.”

Results:

In total, 28 simple and 29 complex LM patients and 51 simple and 18 complex VM patients were identified. Complex LM and VM patients had significantly higher numbers of imaging studies, specialists involved, procedures and hospitalizations, and costs incurred. Complex LM patients also had significantly higher per year office visits.

Conclusions:

VA care is chronic and costly, especially for complex LM/VM patients. LM/VM complexity was a predictor for increased inpatient and outpatient healthcare utilization and higher costs. Better awareness of the healthcare utilization trends of LM/VM patients will allow for improved counseling for these patients regarding prognosis and expectations.
Macrophage immunometabolism in diabetes-associated atherosclerosis
Authors: Gindri dos Santos Bernardo , Goedeke Leigh
Published: October 2023

Macrophages play fundamental roles in atherosclerotic plaque formation, growth, and regression. These cells are extremely plastic and perform different immune functions depending on the stimuli they receive. Initial in vitro studies have identified specific metabolic pathways that are crucial for the proper function of pro-inflammatory and pro-resolving macrophages. However, the plaque microenvironment, especially in the context of insulin resistance and type 2 diabetes, constantly challenges macrophages with several simultaneous inflammatory and metabolic stimuli, which may explain why atherosclerosis is accelerated in diabetic patients. In this mini review, we discuss how macrophage mitochondrial function and metabolism of carbohydrates, lipids, and amino acids may be affected by this complex plaque microenvironment and how risk factors associated with type 2 diabetes alter the metabolic rewiring of macrophages and disease progression. We also briefly discuss current challenges in assessing macrophage metabolism and identify future tools and possible strategies to alter macrophage metabolism to improve treatment options for diabetes-associated atherosclerosis.
Efficacy and safety of Xiang-Sha-Liu-Jun-Zi (XSLJZ) for treatment of Semaglutide-induced gastrointestinal side effects: Study protocol for a multicentre, randomized, open-label trial
Authors: Liu Meixi , Qiu Xianliang , Fu Shunlian , Tian Yuting , Li Wen , Li Qing , Chen Qiu
Published: October 2023

Background:

Semaglutide is a newly approved glucagon-like peptide 1 receptor agonist(GLP-1 RA), significantly reducing HbA1c and body weight. However, it is associated with an increased incidence of gastrointestinal adverse events. Xiang-Sha-Liu-jun-Zi (XSLJZ), is a classic traditional Chinese medicine (TCM) formula with the effects of modulating gastrointestinal disturbance.

This study aims to evaluate the clinical efficacy and safety of the XSLJZ for treatment of Semaglutide-induced gastrointestinal side effects.

Methods:

This is a multicentre, randomized, open-label trial. The trial included a run-in period within 2 weeks, a 4-week treatment period, and another 4 weeks after the end of the experimental phase. Patients who have Gastrointestinal Adverse Reactions during the run-in period will be randomly divided (1:1) into 2 groups. The primary outcome measures were changes in scores on the Gastrointestinal System Rating Scale(GSRS), the duration of individual gastrointestinal adverse events. The secondary outcomes were TCM syndrome score, changes in glycaemic excursions, homeostatic model assessment 2-B (HOMA2-B)and homeostatic model assessment 2-insulin resistance(HOMA2-IR), glucagon, C-peptide, plasma lipids, Anthropometric parameters: body weight, body mass index, waist-hip circumference, waist-hip ratio.

Discussion:

The results of this trial will provide initial evidence for the use of XSLJZ as an alternative and complementary intervention to manage Semaglutide-induced gastrointestinal side effects.
Exploring the rationale for prescribing ankle–foot orthoses and supramalleolar orthoses in children with cerebral palsy: A narrative synthesis of rationale statements
Authors: Dailey Asumi H. , Landers Jessica , Anderson Sarah , Dillon Michael P.
Published: October 2023

Background:

To help improve outcomes for children with cerebral palsy (CP), ankle–foot orthoses (AFOs) and supramalleolar orthoses (SMOs) are prescribed. However, it is not clear why one intervention is prescribed over the other.

Objectives:

To explore the rationale for prescribing AFOs and SMOs in children with CP and its link to the choice of outcome measure used.

Study design:

Narrative review.

Methods:

Six databases were searched (eg, Medline) and data extracted from articles that met the inclusion criteria. Data describing the participant demographics, type of orthosis, and outcome measures used were summarized to provide context for the different rationale for orthotic prescription that were thematically analyzed.

Discussion:

Forty-seven articles were included. Participants were aged 9 ± 2 years, 59% were male, 79% had diplegia, and 38% were classified as Gross Motor Function Classification System level I. All studies included a rationale for prescribing AFOs that, in most cases, reflected the outcome measures used. These rationale statements were synthesized into 5 specific themes (e.g., reduced energy expenditure and metabolic costs). By comparison, 5 of these studies described the rationale for providing SMOs, and of those that did, most of the rationale statements were nonspecific.

Conclusions:

A large and contemporary body of literature describes the rationale for prescribing AFOs for children with CP. There are opportunities for future research that clearly articulates the rationale for prescribing SMOs for children living with CP and to focus the rational for orthotic intervention on the real-world challenges that are most important to children living with CP, such as the ability to participate among peers.
Initial Staging and Response Evaluation With 18F-FDG PET/CT in a Rare Case of Nested Variant Urothelial Urethral Cancer
Authors: Barashki Somaye , Aghaee Atena , Sahebkari Azade , Norouzbeigi Nasim , Sadeghi Ramin
Published: October 2023

Primary urothelial urethral cancer is a relatively infrequent but serious form of cancer in the urinary tract, and nested variant is extremely rare. Until now, no studies have been published regarding 18F-FDG PET/CT in patients with primary urothelial urethral cancer. In this study, we discussed the role of 18F-FDG PET/CT in the initial staging, treatment response evaluation, and recurrence assessment of a 53-year-old woman with nested variant urothelial urethral cancer, which could lead to timely diagnosis and evaluation of the extent of involvement, thus achieving the best treatment plan for this group of patients.
Radioligand Therapy With 177Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer
Authors: Demirkol Mehmet Onur , Esen Barış , Seymen Hülya , Şen Melis , Uçar Burcu , Kurtuldu Sevgilay , Mandel Nil Molinas , Bavbek Sevil , Falay Okan , Tilki Derya , Esen Tarık
Published: October 2023

Introduction

This study aimed to investigate the oncological outcomes and toxicity profile of 177Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and Methods

A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1–7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria.

Results

In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%–99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC.

Conclusions

177Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.