bluuebunny/crossref_metadata_2025 huggingface dataset:
Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission
Authors: Carpagnano Giovanna Elisiana , Portacci Andrea , Nolasco Santi , Detoraki Aikaterini , Vatrella Alessandro , Calabrese Cecilia , Pelaia Corrado , Montagnolo Francesca , Scioscia Giulia , Valenti Giuseppe , D’Amato Maria , Caiaffa Maria Filomena , Triggiani Massimo , Scichilone Nicola , Crimi Claudia
Published: January 2024

Introduction

Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria.

Methods

We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission.

Results

30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement.

Discussion

anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.
CD8+ Trms against malaria liver-stage: prospects and challenges
Authors: Zhu Chengyu , Jiao Shiming , Xu Wenyue
Published: January 2024

Attenuated sporozoites provide a valuable model for exploring protective immunity against the malarial liver stage, guiding the design of highly efficient vaccines to prevent malaria infection. Liver tissue-resident CD8+ T cells (CD8+ Trm cells) are considered the host front-line defense against malaria and are crucial to developing prime-trap/target strategies for pre-erythrocytic stage vaccine immunization. However, the spatiotemporal regulatory mechanism of the generation of liver CD8+ Trm cells and their responses to sporozoite challenge, as well as the protective antigens they recognize remain largely unknown. Here, we discuss the knowledge gap regarding liver CD8+ Trm cell formation and the potential strategies to identify predominant protective antigens expressed in the exoerythrocytic stage, which is essential for high-efficacy malaria subunit pre-erythrocytic vaccine designation.
Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis
Authors: Gruden Eva , Kienzl Melanie , Ristic Dusica , Kindler Oliver , Kaspret David Markus , Schmid Sophie Theresa , Kargl Julia , Sturm Eva , Doyle Alfred D. , Wright Benjamin L. , Baumann-Durchschein Franziska , Konrad Julia , Blesl Andreas , Schlager Hansjörg , Schicho Rudolf
Published: January 2024

Introduction

Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing.

Methods

In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus.

Results

Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE.

Discussion

Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models.
Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals
Authors: Leung Jacqueline M. , Wu Michelle J. , Kheradpour Pouya , Chen Chen , Drake Katherine A. , Tong Gary , Ridaura Vanessa K. , Zisser Howard C. , Conrad William A. , Hudson Natalia , Allen Jared , Welberry Christopher , Parsy-Kowalska Celine , Macdonald Isabel , Tapson Victor F. , Moy James N. , deFilippi Christopher R. , Rosas Ivan O. , Basit Mujeeb , Krishnan Jerry A. , Parthasarathy Sairam , Prabhakar Bellur S. , Salvatore Mirella , Kim Charles C.
Published: January 2024

Background

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.

Methods

We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.

Results

During the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.

Conclusions

We found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC.
Assessment of preparedness and proficiency in basic and advanced life support among nursing professionals: a cross-sectional study
Authors: Izquierdo-Condoy Juan S. , Arias Rodríguez Fabián D. , Duque-Sánchez Erick , Alegría N. Nicolás , Rojas Cadena Marlon , Naranjo-Lara Patricio , Mendoza Alexander Puglla , Jima-Sanmartín Jackson , Casanova Dayana Andrade , García Balbina , Giraldo Natalia Castaño
Published: January 2024

Background

Cardiac diseases are among the leading causes of death worldwide, including sudden cardiac arrest in particular. Nursing professionals are often the first to encounter these scenarios in various settings. Adequate preparation and competent knowledge among nurses significantly impact survival rates positively.

Aim

To describe the state of knowledge about Basic and Advanced Life Support guidelines among Ecuadorian nursing professionals.

Methodology

A nationwide, descriptive, cross-sectional study was conducted from February to April 2023 among Ecuadorian nursing professionals. Participants were invited through official social media groups such as WhatsApp and Facebook. The study utilized a self-administered online questionnaire to evaluate theoretical knowledge of Basic Life Support (BLS) and Advanced Life Support (ALS). Knowledge scores were assigned based on the number of correct answers on the tests. T-tests and one-way ANOVA were used to examine relationships between knowledge scores and demographic and academic training variables.

Results

A total of 217 nursing professionals participated in the study. The majority of the participants were female (77.4%) and held a university degree (79.9%). Among them, only 44.7% claimed to have obtained a BLS training certificate at least once, and 19.4% had ALS certification. The overall BLS knowledge score (4.8/10 ± 1.8 points) was higher than the ALS score (4.3/10 ± 1.8 points). Participants who had obtained BLS certification and those who used evidence-based summaries as a source of extracurricular training achieved higher BLS and ALS knowledge scores.

Conclusion

Ecuadorian nursing professionals in this study exhibited a significant deficiency in theoretical knowledge of BLS and ALS. Formal training and preparation positively impact life support knowledge. Support and inclusion of Ecuadorian nurses in training and academic preparation programs beginning at the undergraduate level are essential for promoting life support knowledge and improving outcomes.
Antimicrobial activity of nature-inspired molecules against multidrug-resistant bacteria
Authors: Hamad Mohamad , Al-Marzooq Farah , Srinivasulu Vunnam , Sulaiman Ashna , Menon Varsha , Ramadan Wafaa S. , El-Awady Raafat , Al-Tel Taleb H.
Published: January 2024

Multidrug-resistant bacterial infections present a serious challenge to global health. In addition to the spread of antibiotic resistance, some bacteria can form persister cells which are tolerant to most antibiotics and can lead to treatment failure or relapse. In the present work, we report the discovery of a new class of small molecules with potent antimicrobial activity against Gram-positive bacteria and moderate activity against Gram-negative drug-resistant bacterial pathogens. The lead compound SIMR 2404 had a minimal inhibitory concentration (MIC) of 2 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate Staphylococcus aureus (VISA). The MIC values against Gram-negative bacteria such as Escherichia coli and Actinobacteria baumannii were between 8–32 μg/mL. Time-kill experiments show that compound SIMR 2404 can rapidly kill tested bacteria. Compound SIMR 2404 was also found to rapidly kill MRSA persisters which display high levels of tolerance to conventional antibiotics. In antibiotic evolution experiments, MRSA quickly developed resistance to ciprofloxacin but failed to develop resistance to compound SIMR 2404 even after 24 serial passages. Compound SIMR 2404 was not toxic to normal human fibroblast at a concentration of 4 μg/mL which is twice the MIC concentration against MRSA. However, at a concentration of 8 μg/mL or higher, it showed cytotoxic activity indicating that it is not ideal as a candidate against Gram-negative bacteria. The acceptable toxicity profile and rapid antibacterial activity against MRSA highlight the potential of these molecules for further studies as anti-MRSA agents.
Genome analysis of “Candidatus Aschnera chinzeii,” the bacterial endosymbiont of the blood-sucking bat fly Penicillidia jenynsii (Insecta: Diptera: Nycteribiidae)
Authors: Koga Ryuichi , Moriyama Minoru , Nozaki Tomonari , Fukatsu Takema
Published: January 2024

Insect–microbe endosymbiotic associations are omnipresent in nature, wherein the symbiotic microbes often play pivotal biological roles for their host insects. In particular, insects utilizing nutritionally imbalanced food sources are dependent on specific microbial symbionts to compensate for the nutritional deficiency via provisioning of B vitamins in blood-feeding insects, such as tsetse flies, lice, and bedbugs. Bat flies of the family Nycteribiidae (Diptera) are blood-sucking ectoparasites of bats and shown to be associated with co-speciating bacterial endosymbiont “Candidatus Aschnera chinzeii,” although functional aspects of the microbial symbiosis have been totally unknown. In this study, we report the first complete genome sequence of Aschnera from the bristled bat fly Penicillidia jenynsii. The Aschnera genome consisted of a 748,020 bp circular chromosome and a 18,747 bp circular plasmid. The chromosome encoded 603 protein coding genes (including 3 pseudogenes), 33 transfer RNAs, and 1 copy of 16S/23S/5S ribosomal RNA operon. The plasmid contained 10 protein coding genes, whose biological function was elusive. The genome size, 0.77 Mbp, was drastically reduced in comparison with 4–6 Mbp genomes of free-living γ-proteobacteria. Accordingly, the Aschnera genome was devoid of many important functional genes, such as synthetic pathway genes for purines, pyrimidines, and essential amino acids. On the other hand, the Aschnera genome retained complete or near-complete synthetic pathway genes for biotin (vitamin B7), tetrahydrofolate (vitamin B9), riboflavin (vitamin B2), and pyridoxal 5'-phosphate (vitamin B6), suggesting that Aschnera provides these vitamins and cofactors that are deficient in the blood meal of the host bat fly. Similar retention patterns of the synthetic pathway genes for vitamins and cofactors were also observed in the endosymbiont genomes of other blood-sucking insects, such as Riesia of human lice, Arsenophonus of louse flies, and Wigglesworthia of tsetse flies, which may be either due to convergent evolution in the blood-sucking host insects or reflecting the genomic architecture of Arsenophonus-allied bacteria.
Cost-effective strategies to knock down genes of interest in the retinas of adult zebrafish
Authors: Shihabeddin Eyad , Santhanam Abirami , Aronowitz Alexandra L. , O’Brien John
Published: January 2024

High throughput sequencing has generated an enormous amount of information about the genes expressed in various cell types and tissues throughout the body, and about how gene expression changes over time and in diseased conditions. This knowledge has made targeted gene knockdowns an important tool in screening and identifying the roles of genes that are differentially expressed among specific cells of interest. While many approaches are available and optimized in mammalian models, there are still several limitations in the zebrafish model. In this article, we describe two approaches to target specific genes in the retina for knockdown: cell-penetrating, translation-blocking Vivo-Morpholino oligonucleotides and commercially available lipid nanoparticle reagents to deliver siRNA. We targeted expression of the PCNA gene in the retina of a P23H rhodopsin transgenic zebrafish model, in which rapidly proliferating progenitor cells replace degenerated rod photoreceptors. Retinas collected 48 h after intravitreal injections in adult zebrafish reveal that both Vivo-Morpholinos and lipid encapsulated siRNAs were able to successfully knock down expression of PCNA. However, only retinas injected with Vivo-Morpholinos showed a significant decrease in the formation of P23H rhodopsin-expressing rods, a downstream effect of PCNA inhibition. Surprisingly, Vivo-Morpholinos were able to exit the injected eye and enter the contralateral non-injected eye to inhibit PCNA expression. In this article we describe the techniques, concentrations, and considerations we found necessary to successfully target and inhibit genes through Vivo-Morpholinos and lipid encapsulated siRNAs.
Convergent validity and responsiveness of The Standing and Walking Assessment Tool (SWAT) among individuals with non-traumatic spinal cord injury
Authors: Alavinia Mohammad , Farahani Farnoosh , Musselman Kristin , Plourde Kristina , Omidvar Maryam , Verrier Molly C. , Aliabadi Saina , Craven B. Catharine
Published: January 2024

Aim

This study aimed to (1) describe the use of the Standing and Walking Assessment Tool (SWAT) among individuals with non-traumatic spinal cord injury or disease (NT-SCI/D); (2) evaluate the convergent validity of SWAT for use among inpatients with NT-SCI/D; (3) describe SWAT responsiveness; and (4) explore the relationship between hours of walking therapy and SWAT change.

Methods

A quality improvement project was conducted at the University Health Network between 2019 and 2022. Participants’ demographics and impairments data, rehabilitation length of stay, and FIM scores were obtained from the National Rehabilitation Reporting System. The walking measure data were collected by therapists as part of routine practice. Hours of part- or whole-gait practice were abstracted from medical records. To determine convergent validity, Spearman’s correlation coefficients were calculated between SWAT stages (admission and discharge) and the walking measures. The change in SWAT levels was calculated to determine responsiveness. Spearman’s correlation coefficient was calculated between SWAT change and hours of walking therapy.

Results

Among adult NT-SCI/D participants with potential walking capacity (SWAT≥1B), the majority were classified as American Spinal Injury Association (ASIA) Impairment Scale D (AIS D) at admission. The SWAT category of 1C (N = 100, 18%) was the most frequent at admission. The most frequent SWAT stage at discharge was 3C among participants with NT-SCI/D, with positive conversions in SWAT stages from admission to discharge (N = 276, 33%). The mean change in SWAT score was 3 for participants with T-SCI and NT-SCI/D. Moderate correlations between SWAT stages and walking measures were observed. The correlation of hours of gait therapy with the SWAT change (admission to discharge) was 0.44 (p < 0001).

Conclusion

The SWAT has sufficient convergent validity and responsiveness for describing standing and walking recovery and communicating/monitoring rehabilitation progress among patients with NT-SCI/D.
A neural network underlying cognitive strategies related to eating, weight and body image concerns
Authors: Marques Cristiana C. , Sayal Alexandre , Crisóstomo Joana , Duarte João V. , Castilho Paula , Goss Kenneth , Pereira Ana T. , Castelo-Branco Miguel
Published: January 2024

Concerns about food intake, weight and body shape can trigger negatively loaded emotions, which may prompt the use of cognitive strategies to regulate these emotional states. A novel fMRI task was developed to assess the neurobehavioral correlates of cognitive strategies related to eating, weight and body image concerns, such as self-criticism, avoidance, rumination, and self-reassurance. Fourteen healthy females were presented audio sentences referring to these conditions and instructed to repeat these internally while engaging their thoughts with the content of food or body images. Participants were asked to report the elicited emotion and rate their performance. All cognitive strategies recruited a network including the inferior and superior frontal gyri, orbitofrontal and anterior cingulate cortex, insula, and dorsal striatum. These brain regions are involved in emotional, reward and inhibitory control processing. Representational similarity analysis revealed distinct patterns of neural responses for each cognitive strategy. Additionally, self-report measures showed that self-criticism was positively associated with superior frontal gyrus (SFG) activation. Self-compassion scores were negatively correlated with activations in the insula and right putamen, while self-reassurance scores were negatively associated with activity in the orbitofrontal cortex. These findings identify a neural network underlying cognitive strategies related to eating, weight and body image concerns, where neurobehavioral correlation patterns depend on the cognitive strategy.
Intracranial electrophysiology of spectrally degraded speech in the human cortex
Authors: Nourski Kirill V. , Steinschneider Mitchell , Rhone Ariane E. , Berger Joel I. , Dappen Emily R. , Kawasaki Hiroto , Howard III Matthew A.
Published: January 2024

Introduction

Cochlear implants (CIs) are the treatment of choice for severe to profound hearing loss. Variability in CI outcomes remains despite advances in technology and is attributed in part to differences in cortical processing. Studying these differences in CI users is technically challenging. Spectrally degraded stimuli presented to normal-hearing individuals approximate input to the central auditory system in CI users. This study used intracranial electroencephalography (iEEG) to investigate cortical processing of spectrally degraded speech.

Methods

Participants were adult neurosurgical epilepsy patients. Stimuli were utterances /aba/ and /ada/, spectrally degraded using a noise vocoder (1–4 bands) or presented without vocoding. The stimuli were presented in a two-alternative forced choice task. Cortical activity was recorded using depth and subdural iEEG electrodes. Electrode coverage included auditory core in posteromedial Heschl’s gyrus (HGPM), superior temporal gyrus (STG), ventral and dorsal auditory-related areas, and prefrontal and sensorimotor cortex. Analysis focused on high gamma (70–150 Hz) power augmentation and alpha (8–14 Hz) suppression.

Results

Chance task performance occurred with 1–2 spectral bands and was near-ceiling for clear stimuli. Performance was variable with 3–4 bands, permitting identification of good and poor performers. There was no relationship between task performance and participants demographic, audiometric, neuropsychological, or clinical profiles. Several response patterns were identified based on magnitude and differences between stimulus conditions. HGPM responded strongly to all stimuli. A preference for clear speech emerged within non-core auditory cortex. Good performers typically had strong responses to all stimuli along the dorsal stream, including posterior STG, supramarginal, and precentral gyrus; a minority of sites in STG and supramarginal gyrus had a preference for vocoded stimuli. In poor performers, responses were typically restricted to clear speech. Alpha suppression was more pronounced in good performers. In contrast, poor performers exhibited a greater involvement of posterior middle temporal gyrus when listening to clear speech.

Discussion

Responses to noise-vocoded speech provide insights into potential factors underlying CI outcome variability. The results emphasize differences in the balance of neural processing along the dorsal and ventral stream between good and poor performers, identify specific cortical regions that may have diagnostic and prognostic utility, and suggest potential targets for neuromodulation-based CI rehabilitation strategies.
The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study
Authors: Chao Linda L. , Sullivan Kimberly , Krengel Maxine H. , Killiany Ronald J. , Steele Lea , Klimas Nancy G. , Koo Bang-Bong
Published: January 2024

Introduction

Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding.

Methods

We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs).

Results

We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes.

Discussion

Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration’s recent approval of and the VA’s decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains.
Investigating the thermal and irradiation stability of chemical vapor deposited erbium oxide tritium barrier coatings for Li breeder blanket applications
Authors: Gardner Hazel M. , Zilahi Gyula , Wade-Zhu James
Published: January 2024

Two-micron thick erbium oxide tritium barrier coatings have been prepared by aerosol injection chemical vapor deposition and subsequently irradiated with 33 MeV Au 6+ ions at fluences up to 2.1 × 1016 Au/m2 at 550°C. Scanning electron microscopy, X-ray diffraction and transmission electron microscopy were used to investigate the coating surface morphologies, phase structures and cross-sectional microstructures as a function of irradiation and thermal treatment. XRD data was also used to extract information about the evolution of lattice strain in the coating. Some of the cubic erbia transformed to the monoclinic phase in the sample that was ion irradiated at temperature, and this was accompanied by a change from columnar to a more equiaxed grain structure. All coatings were found to experience out-of-plane tensile strain, thought to originate from thermal stresses created during coating manufacture. Thermal treatment reduced microstrains present in the as-deposited sample, whilst the cubic-to-monoclinic phase transformation reduced strain in the cubic phase but increased strain in the monoclinic phase.
Phase equilibria of advanced technology uranium silicide-based nuclear fuel
Authors: Ulrich Tashiema L. , Besmann Theodore M.
Published: January 2024

The phases in uranium-silicide binary system were evaluated in regards to their stabilities, phase boundaries, crystal structures, and phase transitions. The results from this study were used in combination with a well assessed literature to optimize the U-Si phase diagram using the CALPHAD method. A thermodynamic database was developed, which could be used to guide nuclear fuel fabrication, could be incorporated into other nuclear fuel thermodynamic databases, or could be used to generate data required by fuel performance codes to model fuel behavior in normal or off-normal reactor operations. The U3Si2 and U3Si5 phases were modeled using the Compound Energy Formalism model with 3 sublattices to account for the variation in composition. The crystal structure used for the USi phase was the tetragonal with an I4/mmm space. Above 450°C, the U3Si5 phase was modeled. The composition of the USi2 phase was adjusted to USi1.84. The calculated invariant reactions and the enthalpy of formation for the stoichiometric phases were in agreement with experimental data.
Beverage consumption in patients with metabolic syndrome and its association with non-alcoholic fatty liver disease: a cross-sectional study
Authors: Kositamongkol Chayanis , Ngaohirunpat Sorawis , Samchusri Supawit , Chaisathaphol Thanet , Srivanichakorn Weerachai , Washirasaksiri Chaiwat , Auesomwang Chonticha , Sitasuwan Tullaya , Tinmanee Rungsima , Sayabovorn Naruemit , Charatcharoenwitthaya Phunchai , Phisalprapa Pochamana
Published: January 2024

Introduction

Previous research has examined the association between coffee and tea consumption and non-alcoholic fatty liver disease (NAFLD). Preclinical studies have indicated the potential hepatoprotective properties of cocoa/chocolate. However, clinical research on the consumption of cocoa/chocolate and soft drinks and their relation to NAFLD, particularly among individuals with metabolic syndrome, is limited. This study primarily aimed to assess the association between beverage consumption and NAFLD in these patients.

Methods

This cross-sectional study enrolled adult patients with metabolic syndrome visited the Medicine Outpatient Department at Siriraj Hospital, Thailand, from November 2011 to January 2013. The exclusion criteria were secondary causes of hepatic steatosis, such as excessive alcohol use, viral hepatitis, or drug-induced hepatitis. Participants completed a 23-item self-administered questionnaire covering their beverage consumption habits, including type, frequency, volume, duration, and additives in drinks, namely, coffee, tea, cocoa/chocolate, and soft drinks. To ensure accurate responses, these questionnaires were supplemented by face-to-face interviews. Ultrasonography was employed early in the methodology to diagnose NAFLD. Univariable analyses were used to compare the beverage consumption behaviors of participants with and without NAFLD. Multivariable logistic regression was used to adjust for potential confounders, including total beverage energy intake, age, anthropometric data, laboratory results, and comorbidities.

Results

This study included 505 patients with metabolic syndrome. Of these, 341 (67.5%, 95%CI: 63.2–71.6%) were diagnosed with NAFLD. The consumption rates of coffee, cocoa/chocolate, and soft drinks were similar between the two groups. However, tea consumption was significantly more common in patients with NAFLD (68.3% vs. 51.8%, p < 0.001). The groups had no significant differences in caffeine intake or total energy intake from beverages. Notably, daily intake of three or more cups of coffee was correlated with a reduced prevalence of NAFLD, with an adjusted odds ratio of 0.35 (95%CI: 0.14–0.89).

Conclusion

This study revealed that patients with metabolic syndrome, irrespective of NAFLD status, exhibited similar patterns of beverage consumption. While no definitive associations were identified between the intake of coffee, tea, cocoa/chocolate, or soft drinks and NAFLD, a notable exception was observed. A higher consumption of coffee (≥3 cups daily) was associated with a lower prevalence of NAFLD.
Serum levels of trimethylamine N-oxide and kynurenine novel biomarkers are associated with adult metabolic syndrome and its components: a case-control study from the TEC cohort
Authors: Mirzababaei Atieh , Mahmoodi Maryam , Keshtkar Abbasali , Ashraf Haleh , Abaj Faezeh , Soveid Neda , Hajmir Mahya Mehri , Radmehr Mina , Khalili Pardis , Mirzaei Khadijeh
Published: January 2024

Background

Epidemiologic research suggests that gut microbiota alteration (dysbiosis) may play a role in the pathogenesis of metabolic syndrome (MetS). Dysbiosis can influence Trimethylamine N-oxide (TMAO) a gut microbiota-derived metabolite, as well as kynurenine pathways (KP), which are known as a new marker for an early predictor of chronic diseases. Hence, the current study aimed to investigate the association between KYN and TMAO with MetS and its components.

Methods

This case-control study was conducted on 250 adults aged 18 years or over of Tehran University of Medical Sciences (TUMS) Employee’s Cohort study (TEC) in the baseline phase. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ) and dietary intakes of nitrite and nitrate were estimated using FFQ with 144 items. MetS was defined according to the NCEP ATP criteria. Serum profiles TMAO and KYN were measured by standard protocol.

Result

The mean level of TMAO and KYN in subjects with MetS was 51.49 pg/mL and 417.56 nmol/l. High levels of TMAO (≥30.39 pg/mL) with MetS were directly correlated, after adjusting for confounding factors, the odds of MetS in individuals 2.37 times increased (OR: 2.37, 95% CI: 1.31–4.28, P-value = 0.004), also, high levels of KYN (≥297.18 nmol/L) increased odds of Mets+ 1.48 times, which is statistically significant (OR: 1.48, 95% CI: 0.83–2.63, P-value = 0.04). High levels of TMAO compared with the reference group increased the odds of hypertriglyceridemia and low HDL in crude and adjusted models (P < 0.05). Additionally, there was a statistically significant high level of KYN increased odds of abdominal obesity (P < 0.05).

Conclusion

Our study revealed a positive association between serum TMAO and KYN levels and MetS and some of its components. For underlying mechanisms and possible clinical implications of the differences. Prospective studies in healthy individuals are necessary.
Current insights into genome-based personalized nutrition technology: a patent review
Authors: Park Soo-Hyun , Choi Hyo-Kyoung , Park Jae Ho , Hwang Jin-Taek
Published: January 2024

Unlike general nutritional ranges that meet the nutritional needs essential for maintaining the life of an entire population, personalized nutrition is characterised by maintaining health through providing customized nutrition according to individuals’ lifestyles or genetic characteristics. The development of technology and services for personalized nutrition is increasing, owing to the acquisition of knowledge about the differences in nutritional requirements according to the diversity of individuals and an increase in health interest. Regarding genetics, technology is being developed to distinguish the various characteristics of individuals and provide customized nutrition. Therefore, to understand the current state of personalized nutrition technology, understanding genomics is necessary to acquire information on nutrition research based on genomics. We reviewed patents related to personalized nutrition-targeting genomics and examined their mechanisms of action. Using the patent database, we searched 694 patents on nutritional genomics and extracted 561 highly relevant valid data points. Furthermore, an in-depth review was conducted by selecting core patents related to genome-based personalized nutrition technology. A marked increase was observed in personalized nutrition technologies using methods such as genetic scoring and disease-specific dietary recommendations.
Outcomes of transforaminal epidural injection of amniotic membrane/umbilical cord particulate for lumbar radiculopathy: a case series
Authors: Miedema Mark , Anderson Angela
Published: January 2024

Background

Radiculopathy can be a debilitating condition. Amniotic membrane/umbilical cord (AM/UC) particulate is a relatively new injectable treatment modality. Herein we report the outcomes of epidural injection of AM/UC particulate in managing lumbar radiculopathy.

Methods

Consecutive patients with lumbar radiculopathy who received epidural injection of AM/UC particulate for lumbar radiculopathy were included. Primary outcome was change in pain as measured by the 11-point numerical rating scale. Safety was assessed by AM/UC- and procedure-related complications. Paired t-tests were used to determine statistical significance.

Results

A total of 12 patients with a mean age of 56.7 ± 21.0 years were included in the analysis. The patients were previously treated with physical therapy (91.7%), chiropractic corrective measures (16.7%), epidural steroid injection (83.3%), and radiofrequency ablation (8.3%). Two patients (16.7%) were taking opioids for chronic pain syndrome. After AM/UC injection, the average pain score decreased from 6.6 ± 1.5 to 5.2 ± 1.9 at 1–3 months, 2.0 ± 1.4 at 6 months, and 2.9 ± 1.4 at last mean follow-up of 21.3 ± 11.1 months (p < 0.001). No patients required subsequent treatment or surgery. There were also no complications.

Conclusion

This case series supports the preliminary safety and shows potential benefit of epidural AM/UC particulate injection in this cohort of patients with lumbar radiculopathy pain.
Case Report: Neurally adjusted ventilatory assist as an effective rescue treatment for pulmonary interstitial emphysema in extremely low birth weight infants
Authors: Chen Chien-Ming , Chung Mei-Yung , Kang Hong-Ya , Ou-Yang Mei-Chen , Wang Teh-Ming , Hsu Chung-Ting
Published: January 2024

Pulmonary interstitial emphysema (PIE) is a complication observed in extremely low birth weight (ELBW) infants on mechanical ventilation. Despite various proposed therapeutic interventions, the success rates have shown inconsistency. Neurally adjusted ventilatory assist (NAVA) stands out as a novel respiratory support mode, offering lower pressure and tidal volume in comparison to conventional ventilation methods. In this case report, we present five ELBW infants with refractory PIE who were transitioned to NAVA ventilation. Following the switch to NAVA, all cases of PIE gradually resolved. In contrast to traditional modes, NAVA provided respiratory support with significantly lower fraction of inspired oxygen, reduced peak inspiratory pressure, diminished mean airway pressure, and decreased tidal volume within 7 days of NAVA utilization (p = 0.042, 0.043, 0.043, and 0.042, respectively). Consequently, we propose that NAVA could serve as a valuable rescue treatment for ELBW infants with PIE.
Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals
Authors: Stojković Maja , Todorović Zoran , Protić Dragana , Stevanovic Strahinja , Medić Dragana , Charvet Claude L. , Courtot Elise , Marjanović Djordje S. , Nedeljković Trailović Jelena , Trailović Saša M.
Published: January 2024

The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic ACh receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh, but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre- and post-synaptic action at the neuromuscular junction.
J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine
Authors: Kuo A. , Imam M. Z. , Li R. , Lin L. , Raboczyj A. , Bohmer A. E. , Nicholson J. R. , Corradini L. , Smith M. T.
Published: January 2024

There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST4) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70 mg/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8–12-weeks (morphine-sensitive phase; Phase 1) and 16–18-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30 mg/kg), gabapentin (100 mg/kg i.p.), subcutaneous morphine (1 mg/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156 at 30 mg/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5 h compared with 1 h for gabapentin and morphine. The durations of action for all three compounds were greater than 3 h. The corresponding mean (±SEM) extent and duration of anti-allodynia (ΔPWT AUC) for gabapentin did not differ significantly from that for J-2156 (30 mg/kg) or morphine. However, in Phase 2, the ΔPWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (±SEM) ΔPWT AUC for J-2156 (30 mg/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (±SEM) ΔPWT AUCs did not differ significantly (p > 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST4 receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.
β2-Adrenoceptors activation regulates muscle trophic-related genes following acute resistance exercise in mice
Authors: Abdalla-Silva Ronaldo L. , Zanetti Gustavo O. , Lautherbach Natalia , Schavinski Aline Zanatta , Heck Lilian C. , Gonçalves Dawit A. P. , Kettelhut Isis C. , Navegantes Luiz C. C. , Silveira Wilian A.
Published: January 2024

Resistance exercise (RE) training and pharmacological stimulation of β2-Adrenoceptors (β2-ARs) alone can promote muscle hypertrophy and prevent muscle atrophy. Although the activation of the sympathetic nervous system (SNS) is a well-established response during RE, the physiological contribution of the endogenous catecholamines and β2-ARs to the RE-induced changes on skeletal muscle protein metabolism remains unclear. This study investigated the effects of the β2-ARs blockade on the acute molecular responses induced by a single bout of RE in rodent skeletal muscles. Male C57BL6/J mice were subjected to a single bout of progressive RE (until exhaustion) on a vertical ladder under β2-AR blockade with ICI 118,551 (ICI; 10 mg kg-1, i. p.), or vehicle (sterile saline; 0.9%, i. p.), and the gene expression was analyzed in gastrocnemius (GAS) muscles by qPCR. We demonstrated that a single bout of RE acutely increased the circulating levels of stress-associated hormones norepinephrine (NE) and corticosterone (CORT), as well as the muscle phosphorylation levels of AMPK, p38 MAPK and CREB, immediately after the session. The acute increase in the phosphorylation levels of CREB was followed by the upregulation of CREB-target genes Sik1, Ppargc1a and Nr4a3 (a central regulator of the acute RE response), 3 h after the RE session. Conversely, β2-AR blockade reduced significantly the Sik1 and Nr4a3 mRNA levels in muscles of exercised mice. Furthermore, a single bout of RE stimulated the mRNA levels of the atrophic genes Map1lc3b and Gabarapl1 (autophagy-related genes) and Mstn (a well-known negative regulator of muscle growth). Unexpectedly, the gene expression of Igf-1 or Il-6 were not affected by RE, while the atrophic genes Murf1/Trim63 and Atrogin-1/Mafbx32 (ubiquitin-ligases) were increased only in muscles of exercised mice under β2-AR blockade. Interestingly, performing a single bout of RE under β2-AR blockade increased the mRNA levels of Mstn in muscles of exercised mice. These data suggest that β2-ARs stimulation during acute RE stimulates the hypertrophic gene Nr4a3 and prevents the overexpression of atrophic genes such as Mstn, Murf1/Trim63, and Atrogin-1/Mafbx32 in the first hours of postexercise recovery, indicating that he SNS may be physiologically important to muscle adaptations in response to resistance training.
Genome-wide association studies for a comprehensive understanding of the genetic architecture of culm strength and yield traits in rice
Authors: Badri Jyothi , Padmashree Revadi , Anilkumar Chandrappa , Mamidi Akshay , Isetty Subhakara Rao , Swamy AVSR , Sundaram Raman Menakshi
Published: January 2024

Lodging resistance in rice is a complex trait determined by culm morphological and culm physical strength traits, and these traits are a major determinant of yield. We made a detailed analysis of various component traits with the aim of deriving optimized parameters for measuring culm strength. Genotyping by sequencing (GBS)-based genome-wide association study (GWAS) was employed among 181 genotypes for dissecting the genetic control of culm strength traits. The VanRaden kinship algorithm using 6,822 filtered single-nucleotide polymorphisms (SNPs) revealed the presence of two sub-groups within the association panel with kinship values concentrated at<0.5 level, indicating greater diversity among the genotypes. A wide range of phenotypic variation and high heritability for culm strength and yield traits were observed over two seasons, as reflected in best linear unbiased prediction (BLUP) estimates. The multi-locus model for GWAS resulted in the identification of 15 highly significant associations (p< 0.0001) for culm strength traits. Two novel major effect marker–trait associations (MTAs) for section modulus and bending stress were identified on chromosomes 2 and 12 with a phenotypic variance of 21.87% and 10.14%, respectively. Other MTAs were also noted in the vicinity of previously reported putative candidate genes for lodging resistance, providing an opportunity for further research on the biochemical basis of culm strength. The quantitative trait locus (QTL) hotspot identified on chromosome 12 with the synergistic association for culm strength trait (section modulus, bending stress, and internode breaking weight) and grain number can be considered a novel genomic region that can serve a dual purpose of enhancing culm strength and grain yield. Elite donors in the indica background with beneficial alleles of the identified major QTLs could be a valuable resource with greater significance in practical plant breeding programs focusing on improving lodging resistance in rice.