bluuebunny/crossref_metadata_2025 huggingface dataset:
The Letters of Shahrbarāz and Middle Persian Historiography on the Last Great War of Late Antiquity
Authors: Hämeen-Anttila Jaakko
Published: September 2023

The article analyses stories about letters sent by Kisrā Abarwīz to his general Shahrbarāz during the last Great War of Late Antiquity. The analysis sheds light on Middle Persian historiography and the transmission of historical information in the Late Sasanian and Early Islamic periods, information we need in order to understand the history of the period. Based on the study of this episode, supported by wider evidence, the article suggests that Middle Persian historiography was prone to literary embellishment, that it was solipsistic, almost exclusively interested in matters Persian, and that for its Persian sections Arabic historiography inherited this attitude from Middle Persian sources. The article also points to previously unused, or underused, sources that can throw more light on the relations between Middle Persian, Christian, and Islamic historiography.
A Tyrant’s Legacy in Medieval Syria: Al-Ḥajjāj b. Yūsuf on Trial in Ibn ʿAsākir’s History of Damascus
Authors: Klasova Pamela
Published: September 2023

This article presents a case study on the use of early Islamic memory in medieval Syria. It offers a close reading of a biography of al-Ḥajjāj b. Yūsuf al-Thaqafī (d. 714), the infamous tyrant of Islam, from the monumental biographical dictionary by Ibn ʿAsākir (d. 1176) Tārīkh madīnat Dimashq ( History of Damascus). I argue that Ibn ʿAsākir carefully structured the biography to lend support to his own theological Ashʿarite positions on the legitimacy of an unjust ruler and the status of a sinner in Islam. This study also highlights the multi-layered meanings of the individual reports in the biography.
EVALUATION OF SEISMIC PERFORMANCE OF HOSPITAL BUILDING USING PUSHOVER ANALYSIS BASED ON ATC-40
Authors: Zebua Dermawan , Putra As Andika Sah , Wibowo Leonardus Setia Budi , Alfiani Sania
Published: September 2023

Hospitals are crucial healthcare facilities that play a significant role in improving the health level of people in Aceh. The Cut Nyak Dien Meulaboh Aceh Regional Referral Hospital is located in an area with a high earthquake intensity, making earthquake-resistant building aspects indispensable. The hospital was designed in 2016, but changes were made to its structural elements during construction. The aim of this study was to establish the performance level criteria for the hospital building structures that underwent design changes in practice. The research revealed that the structure could exhibit nonlinear behaviour, as shown by the distribution of plastic hinges that started with the yielding of the beam, followed by yielding of the column. This aligns with the planning concept of strong weak beam earthquake-resistant column (SCWB). The pushover analysis results demonstrated that the performance point displacement in the x-direction was 0.052 m with a base shear of 20090.204 KN and the displacement in the y-direction was 0.058 m with a base shear of 19832.572 KN. With a maximum story drift value based on ATC-40 during an earthquake in the x and y directions of D > 0.01, the structure falls under the category of Immediate Occupancy.
Prospective study of metalloproteinase 9 expression in a cohort of South American patients with and without ST elevation coronary artery disease.
Authors: Estevez Maria , Dulcey Luis , Theran Juan , Gomez Jaime , Gutierrez Emily , Caltagirone Raimondo , Blanco Edgar , Ciliberti Maria , Martinez Juan , Mayorca Juan , Hernandez Carlos , Cala Maria , Vargas Jorge , Lizcano Angie , Amaya Maria , Quintero Aldahir , Acevedo Diego , Castillo Silvia , Camargo Valentina , Cespedes Nikoll , Chaves Melissa , Contreras Kerlyn , Cordoba Yaritza , Cortes Mariana , Cortes Mariana , Castillo Juan , Moreno Nicolas
Published: September 2023

Introduction: MMP type 9 (MMP-9) plays an important role in the degradation of the extracellular matrix, destabilizing atherosclerotic plaques. Materials and methods: A prospective open study was carried out in a South American hospital. All patients gave their voluntary informed consent to participate and process the results of the survey. The scientific work was approved by the local ethics committee of the Educational Institution of Higher Education. Results: During the recruitment of the index group, we examined 297 people. Our study included 121 people, exclusively men, who underwent angioplasty after STEMI of the anteroseptal and posterior wall of the left ventricle. In the group of patients we examined, MMP-9 content was correlated with BMI, WC, and WC/WCa. Conclusions: The results found here force us to consider new variables as prognostic determinants in coronary heart disease.
Carmen González Gómez (2023). «El análisis del discurso político»
Authors: Chavero Macarro Javier
Published: September 2023

Carmen González Gómez (2023). «El análisis del discurso político», Madrid, Arco Libros (col. Cuadernos de Lengua Española, n.º 154), 2023, 96 pp., ISBN 978-84-7133-888-4
Asthma routinization, family asthma management, caregiver depressive symptoms, and medication adherence in Head Start preschool children
Authors: Lu Monica A. , Ruvalcaba Elizabeth , McQuaid Elizabeth L. , Rand Cynthia S. , Riekert Kristin A. , Eakin Michelle N.
Published: September 2023

Introduction

Medication adherence is suboptimal in childhood asthma. Children rely on caregivers to manage medication administration. It is important to detect families who are at risk for poor adherence or to identify potential areas that can assist families with better adherence to asthma medications in order to improve asthma outcomes. We investigated the association between asthma routines, family asthma management knowledge and skills, and caregiver depressive symptoms with daily controller medication adherence among Head Start preschool children in Baltimore City.

Methods

Our study included 256 low-income urban preschool children who were prescribed a daily controller medication. Asthma routinization (by the Asthma Routines Questionnaire), family asthma management [by the Family Asthma Management System Scale (FAMSS)], and caregiver depressive symptoms (by the Center for Epidemiological Studies – Depression) were assessed at baseline. The medication possession ratio (MPR) to measure adherence to daily controller medications was calculated at baseline and 12 months from pharmacy fill records. Multiple regression models evaluated the relationship between asthma routinization, the FAMSS, the CES-D, and MPR.

Results

Results indicated that only 7% of families had an MPR above 80% at baseline, and 24% of caregivers had clinically significant depressive symptoms. Higher asthma medication routines were associated with higher MPR at baseline (b = 0.05, p = 0.03). Higher family asthma management was associated with higher MPR at both baseline (b = 0.04, p < 0.01) and 12 months (b = 0.05, p < 0.01).

Discussion

Our findings highlight the importance of family asthma management and maintaining medication routines over time to improve asthma controller medication adherence.
Reasonable design of thick electrodes in lithium-ion batteries
Authors: Sim Yoon Bo , Park Bo Keun , Kim Ki Jae
Published: September 2023

To achieve a high energy density for Li-ion batteries (LIBs) in a limited space, thick electrodes play an important role by minimizing passive component at the unit cell level and allowing higher active material loading within the same volume. Currently, the capacity of active materials is close to the theoretical capacity; therefore, thick electrodes provide the clearest solution for the development of high-energy-density batteries. However, further research is needed to resolve the electrochemical and mechanical instabilities inside the electrode owing to its increased thickness. This review summarizes the various methods and recent research aimed at fabricating electrodes with low-torsion and uniform pore structure for fast ion transport, based on an in-depth consideration of the challenges encountered in thick electrodes. In addition, future developments and research directions necessary to apply these methods to the industry are presented. This review will be a valuable milestone for manufacturing robust thick electrodes with high performance and for realizing ultrahigh-capacity/density batteries in the future.
Chitosan as a biomaterial for the prevention and treatment of dental caries: antibacterial effect, biomimetic mineralization, and drug delivery
Authors: Qu Shanlin , Ma Xiaolin , Yu Shuo , Wang Rui
Published: September 2023

Dental caries is a chronic, progressive disease caused by plaque, influenced by multiple factors and can damage the hard tissues of the teeth. In severe cases, it can also lead to the onset and development of other oral diseases, seriously affecting patients’ quality of life. The creation of effective biomaterials for the prevention and treatment of dental caries has become one of the relentless goals of many researchers, with a focus on inhibiting the production of cariogenic plaque and retaining beneficial bacteria, guiding and promoting the reconstruction of dental hard tissues, and delaying the progression of existing caries. Chitosan is a natural cationic polymer extracted from the shells of crustaceans and shellfish. Since its discovery, chitosan has shown to have various biological functions such as antibacterial, biomimetic mineralization, drug delivery, etc., making it one of the most promising biopolymers for new caries prevention and materials of prostheses. Therefore, this article provides an overview of the anti-caries applications of chitosan, which mainly covers the basic research on the application of chitosan in caries prevention and treatment since 2010, with a focus on categorizing and summarizing the following characteristics of chitosan as a caries prevention material, including its antibacterial effect, biomimetic mineralization effect and delivery ability of caries prevention drugs and vaccines. It also explores the limitations of current research on chitosan as a caries prevention biomaterial and the difficulties that need to be focused on and overcome in the future to provide theoretical reference for the clinical implementation of chitosan as a caries prevention biomaterial.
Parameters, practices, and preferences for regulatory review of emerging biotechnology products in food and agriculture
Authors: Kuzma Jennifer , Grieger Khara , Cimadori Ilaria , Cummings Christopher L. , Loschin Nick , Wei Wei
Published: September 2023

This paper evaluates the U.S. regulatory review of three emerging biotechnology products according to parameters, practices, and endpoints of assessments that are important to stakeholders and publics. First, we present a summary of the literature on variables that are important to non-expert publics in governing biotech products, including ethical, social, policy process, and risk and benefit parameters. Second, we draw from our USDA-funded project results that surveyed stakeholders with subject matter expertise about their attitudes towards important risk, benefit, sustainability, and societal impact parameters for assessing novel agrifood technologies, including biotech. Third, we evaluate the regulatory assessments of three food and agricultural biotechnology case studies that have been reviewed under U.S. regulatory agencies and laws of the Coordinated Framework for the Regulation of Biotechnology, including gene-edited soybeans, beef cattle, and mustard greens. Evaluation of the regulatory review process was based on parameters identified in steps 1 and 2 which were deemed important to both publics and stakeholders. Based on this review, we then propose several policy options for U.S. federal agencies to strengthen their oversight processes to better align with a broader range of parameters to support sustainable agrifood products that rely on novel technologies. These policy options include 1) those that would not require new institutions or legal foundations (such as conducting Environmental Impact Statements and/or requiring a minimal level of safety data), 2) those that would require a novel institutional or cross-institutional framework (such as developing a publicly-available website and/or performing holistic sustainability assessments), and 3) those that would require the agencies to have additional legal authorities (such as requiring agencies to review biotech products according to a minimal set of health, environmental, and socio-economic parameters). Overall, the results of this analysis will be important for guiding policy practice and formulation in the regulatory assessment of emerging biotechnology products that challenge existing legal and institutional frameworks.
Optimized nucleus isolation protocol from frozen mouse tissues for single nucleus RNA sequencing application
Authors: Minati Marie-Albane , Fages Angeline , Dauguet Nicolas , Zhu Jingjing , Jacquemin Patrick
Published: September 2023

The single cell RNA sequencing technique has been particularly used during the last years, allowing major discoveries. However, the widespread application of this analysis has showed limitations. Indeed, the direct study of fresh tissues is not always feasible, notably in the case of genetically engineered mouse embryo or sensitive tissues whose integrity is affected by classical digestion methods. To overcome these limitations, single nucleus RNA sequencing offers the possibility to work with frozen samples. Thus, single nucleus RNA sequencing can be performed after genotyping-based selection on samples stocked in tissue bank and is applicable to retrospective studies. Therefore, this technique opens the field to a wide range of applications requiring adapted protocols for nucleus isolation according to the tissue considered. Here we developed a protocol of nucleus isolation from frozen murine placenta and pancreas. These two complex tissues were submitted to a combination of enzymatic and manual dissociation before undergoing different steps of washing and centrifugation. The entire protocol was performed with products usually present in a research lab. Before starting the sequencing process, nuclei were sorted by flow cytometry. The results obtained validate the efficiency of this protocol which is easy to set up and does not require the use of commercial kits. This specificity makes it adaptable to different organs and species. The association of this protocol with single nucleus RNA sequencing allows the study of complex samples that resist classical lysis methods due to the presence of fibrotic or fatty tissue, such as fibrotic kidney, tumors, embryonic tissues or fatty pancreas.
Copper radionuclides for theranostic applications: towards standardisation of their nuclear data. A mini-review
Authors: Hussain Mazhar , Qaim Syed M. , Spahn Ingo , Aslam M. Naveed , Neumaier Bernd
Published: September 2023

Copper has several clinically relevant radioisotopes and versatile coordination chemistry, allowing attachment of its radionuclides to biological molecules. This characteristic makes it suitable for applications in molecular imaging or radionuclide targeted therapy. Of particular interest in nuclear medicine today is the theranostic approach. This brief review considers five radionuclides of copper. These are Cu-60, Cu-61, Cu-62, Cu-64, and Cu-67. The first four are positron emitters for imaging, and the last one Cu-67 is a β–-emitting radionuclide suitable for targeted therapy. The emphasis here is on theory-aided evaluation of available experimental data with a view to establishing standardised cross-section database for production of the relevant radionuclide in high purity. Evaluated cross section data of the positron emitters have been already extensively reported; so here they are only briefly reviewed. More attention is given to the data of the 68Zn(p,2p)67Cu intermediate energy reaction which is rather commonly used for production of 67Cu.
Comparative study on the international coal trade network before and after COVID-19 outbreak
Authors: Zhao Jingying , Huang Hui
Published: September 2023

COVID-19 that broke out at the end of 2019 made countries to implement strict blockade measures to curb the spread of the virus. These measures have seriously disrupted the coal import and export trade, causing a significant impact on the coal trade network. This study aims to investigate the disparities between coal trade networks before and after COVID-19 outbreak. First, using complex network theory, we constructed global coal trade networks for the years 2019 and 2020. Subsequently, utilizing a cascading failure model, we developed a coal supply risk propagation framework. Through an analysis of network topology and theoretical supply risk propagation, we explored the similarities and differences of the coal trade networks during these 2 years. In terms of network topology structure, our findings reveal a decrease in trade tightness in the coal trade network of 2020 compared to 2019. Moreover, the Netherlands no longer retains its significance as an important trade hub country in 2020. Looking at the theoretical perspective of supply risk transmission, we observed that in 2020, COVID-19 resulted in a higher number of countries experiencing crisis outbreaks compared to 2019. However, it is noteworthy that the core countries within the coal trade network have remained consistent, and their roles as either net importers or net exporters have not changed. This indicates that the position of coal core countries is very stable. Therefore, no matter what happens, the country should pay timely attention to the dynamics of core countries. Interestingly, in 2020, the risk associated with coal supply did not conform to the spatial patterns typically seen in trade. For instance, the Russian Federation, identified as a country facing a crisis outbreak, transmits supply risks to geographically distant regions in West Asia, including countries like Ghana and Western Sahara.
The biophysical effects of potential changes in irrigated crops on diurnal land surface temperature in Northeast China
Authors: Li Xintao , Hai Quansheng , Xia Ke , Vandansambuu Battsengel , Bao Yuhai
Published: September 2023

Irrigated crops have experienced a significant global expansion. The biophysical response of climate change to irrigated crop expansion in different regions, particularly in terms of monitoring the influence mechanism of nighttime land surface temperature (LST) change, however, remains insufficiently explored. Taking the three northeastern provinces of China as our study area, we apply window analysis, partial correlation analysis, and geographical detector to quantitatively characterize the spatial and temporal distribution pattern of daytime and nighttime LST (diurnal LST) and biophysical parameters, and the main driving mechanism of diurnal LST change. The results showed that irrigated crop expansion led to asymmetric changes in daytime (−2.11 ± 0.2°C, 97.4%) and nighttime (0.64 ± 0.2°C, 79.9%) LST. ΔLSTDT had a negative correlation with ΔLE (63%), but a positive correlation with ΔSSR and ΔH (91% and 77%). This revealed that the cooling effect caused by the superposition of the output latent heat flux and the absorbed solar shortwave radiation was greater than its heating effect. ΔLSTNT and ΔLE had a positive connection across 69% of the region. ΔLSTNT demonstrated a negative correlation with ΔSSR and ΔH in 82% and 75% of the regions, respectively. At this time, the superposition of latent heat flux and heating potential term produces a greater heating effect. The explanatory power of the single factor (the mean of q<0.50) of biophysical parameters for diurnal LST variation was significantly smaller than that of the interaction factor (the mean of q>0.50, p<0.01). This study shows more detailed dynamic information of diurnal LST and biophysical parameters from 8day scale. The findings highlighted the critical role of asymmetric changes in the diurnal surface thermal environment caused by irrigated crop expansion in the global climate from a land surface hydrothermal energy balance perspective.
Using ethanol and other lures to monitor invasive ambrosia beetles in endemic populations: case study from the Czech Republic
Authors: Fiala Tomáš , Pyszko Petr , Holuša Jaroslav
Published: September 2023

Bark and ambrosia beetles pose significant threats to the stability of forest stands worldwide, making their control crucial. Among these pests, Gnathotrichus materiarius, a polyphagous invasive ambrosia beetle living on conifers, has successfully established itself in Europe. Early identification of these pests plays a fundamental role in designing effective pest control strategies. The work aimed to assess the efficacy of different lures in Ecotrap® for capturing of invasive ambrosia bark beetles. The lures tested included Wood Stainers Lure (containing the potential pheromone sulcatol for capturing Gnathotrichus materiarius adults), α-pinene, ethanol UHR, and Cembräwit. The objective was to determine the most suitable lure for use in traps. In four locations in western Bohemia, a total of 7,410 individuals from 46 species of ambrosia and bark beetleswere captured. The abundance of invasive ambrosia beetles (Gnathotrichus materiarius, Cyclorhipidion bodoanum, Xyleborinus attenuatus, and Xylosandrus germanus) primarily depended on the day of the season and secondarily on the lure used. Although their population density was low, more beetles were caught using ethanol as the lure. Notably, these invasive ambrosia beetles accounted for less than 3 % of the total number of ambrosia and bark beetles detected (187 individuals). Ethanol was found to be a universal lure for attracting ambrosia beetles, with the majority of Scolytinae species being captured in traps baited with ethanol.
Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor
Authors: Wang Qianwen , Mu Yunchuan , Ji Shunxian , Liu Yang , Lou Yanbo , Wei Shumei , Dong Xin , Zhang Bo
Published: September 2023

Background

Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy.

Case presentation

We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated β-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC.

Conclusion

chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.
Combined regulation of pro-inflammatory cytokines production by STAT3 and STAT5 in a model of B. pertussis infection of alveolar macrophages
Authors: Khiter Fethi , Kherrouche Zoulika , Dubois Violaine , Slupek Stéphanie , Petit Emmanuelle , Debrie Anne-Sophie , Cauchi Stéphane , Barois Nicolas , Rouanet Carine , Mielcarek Nathalie
Published: September 2023

Bordetella pertussis is a highly contagious respiratory pathogen responsible for whooping-cough or pertussis. Despite high vaccination coverage worldwide, this gram-negative bacterium continues to spread among the population. B. pertussis is transmitted by aerosol droplets from an infected individual to a new host and will colonize its upper respiratory tract. Alveolar macrophages (AMs) are effector cells of the innate immune system that phagocytose B. pertussis and secrete both pro-inflammatory and antimicrobial mediators in the lungs. However, understanding their role in B. pertussis pathogenesis at the molecular level is hampered by the limited number of primary AMs that can be collected in vivo. In order to decipher the regulation of innate response induced by B. pertussis infection, we used for the first time self-renewing, non-transformed cells, called Max Planck Institute (MPI) cells, which are phenotypically and functionally very close to pulmonary AMs. Using optimized infection conditions, we characterized the entry and the clearance of B. pertussis within MPI macrophages. We showed that under these conditions, MPI cells exhibit a pro-inflammatory phenotype with the production of TNF, IL-1β, IL-6 and MIP-2α, similarly to primary AMs purified from broncho-alveolar fluids of mice. In addition, we explored the yet uncharacterized role of the signal transduction activator of transcription (STAT) proteins family in the innate immune response to B. pertussis infection and showed for the first time the parallel regulation of pro-inflammatory cytokines by STAT3 and STAT5 in MPI macrophages infected by B. pertussis. Altogether, this work highlights the interest of using MPI cells for experiments optimization and preliminary data acquisition to understand B. pertussis interaction with AMs, and thus significantly reduce the number of animals to be sacrificed.
Response of microbial communities in the phyllosphere ecosystem of tobacco exposed to the broad-spectrum copper hydroxide
Authors: Feng Ruichao , Wang Hancheng , Liu Tingting , Wang Feng , Cai Liuti , Chen Xingjiang , Zhang Songbai
Published: September 2023

Copper hydroxide is a broad-spectrum copper fungicide, which is often used to control crop fungal and bacterial diseases. In addition to controlling targeted pathogens, copper hydroxide may also affect other non-targeted microorganisms in the phyllosphere ecosystem. At four time points (before spraying, and 5, 10 and 15 days after fungicide application), the response of diseased and healthy tobacco phyllosphere microorganisms to copper hydroxide stress was studied by using Illumina high-throughput sequencing technology, and Biolog tools. The results showed that the microbiome communities of the healthy group were more affected than the disease group, and the fungal community was more sensitive than the bacterial community. The most common genera in the disease group were Alternaria, Boeremia, Cladosporium, Pantoea, Ralstonia, Pseudomonas, and Sphingomonas; while in the healthy group, these were Alternaria, Cladosporium, Symmetrospora, Ralstonia, and Pantoea. After spraying, the alpha diversity of the fungal community decreased at 5 days for both healthy and diseased groups, and then showed an increasing trend, with a significant increase at 15 days for the healthy group. The alpha diversity of bacterial community in healthy and diseased groups increased at 15 days, and the healthy group had a significant difference. The relative abundance of Alternaria and Cladosporium decreased while that of Boeremia, Stagonosporopsis, Symmetrospora, Epicoccum and Phoma increased in the fungal communities of healthy and diseased leaves. The relative abundance of Pantoea decreased first and then increased, while that of Ralstonia, Pseudomonas and Sphingomonas increased first and then decreased in the bacterial communities of healthy and diseased leaves. While copper hydroxide reduced the relative abundance of pathogenic fungi Alternaria and Cladosporium, it also resulted in the decrease of beneficial bacteria such as Actinomycetes and Pantoea, and the increase of potential pathogens such as Boeremia and Stagonosporopsis. After treatment with copper hydroxide, the metabolic capacity of the diseased group improved, while that of the healthy group was significantly suppressed, with a gradual recovery of metabolic activity as the application time extended. The results revealed changes in microbial community composition and metabolic function of healthy and diseased tobacco under copper hydroxide stress, providing a theoretical basis for future studies on microecological protection of phyllosphere.
Biosynthetic gene profiling and genomic potential of the novel photosynthetic marine bacterium Roseibaca domitiana
Authors: Gattoni Giuliano , Di Costanzo Fabiana , de la Haba Rafael R. , Fernández Ana B. , Guerrero-Flores Shaday , Selem-Mojica Nelly , Ventosa Antonio , Corral Paulina
Published: September 2023

Shifting the bioprospecting targets toward underexplored bacterial groups combined with genome mining studies contributes to avoiding the rediscovery of known compounds by revealing novel, promising biosynthetic gene clusters (BGCs). With the aim of determining the biosynthetic potential of a novel marine bacterium, strain V10T, isolated from the Domitian littoral in Italy, a comparative phylogenomic mining study was performed across related photosynthetic bacterial groups from an evolutionary perspective. Studies on polyphasic and taxogenomics showed that this bacterium constitutes a new species, designated Roseibaca domitiana sp. nov. To date, this genus has only one other validly described species, which was isolated from a hypersaline Antarctic lake. The genomic evolutionary study linked to BGC diversity revealed that there is a close relationship between the phylogenetic distance of the members of the photosynthetic genera Roseibaca, Roseinatronobacter, and Rhodobaca and their BGC profiles, whose conservation pattern allows discriminating between these genera. On the contrary, the rest of the species related to Roseibaca domitiana exhibited an individual species pattern unrelated to genome size or source of isolation. This study showed that photosynthetic strains possess a streamlined content of BGCs, of which 94.34% of the clusters with biotechnological interest (NRPS, PKS, RRE, and RiPP) are completely new. Among these stand out T1PKS, exclusive of R. domitiana V10T, and RRE, highly conserved only in R. domitiana V10T and R. ekhonensis, both categories of BGCs involved in the synthesis of plant growth-promoting compounds and antitumoral compounds, respectively. In all cases, with very low homology with already patented molecules. Our findings reveal the high biosynthetic potential of infrequently cultured bacterial groups, suggesting the need to redirect attention to microbial minorities as a novel and vast source of bioactive compounds still to be exploited.
Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica
Authors: Xiang Xueyan , Vilar Gomez Arturo A. , Blomberg Simone P. , Yuan Huifang , Degnan Bernard M. , Degnan Sandie M.
Published: September 2023

Interkingdom signalling within a holobiont allows host and symbionts to communicate and to regulate each other’s physiological and developmental states. Here we show that a suite of signalling molecules that function as neurotransmitters and neuromodulators in most animals with nervous systems, specifically dopamine and trace amines, are produced exclusively by the bacterial symbionts of the demosponge Amphimedon queenslandica. Although sponges do not possess a nervous system, A. queenslandica expresses rhodopsin class G-protein-coupled receptors that are structurally similar to dopamine and trace amine receptors. When sponge larvae, which express these receptors, are exposed to agonists and antagonists of bilaterian dopamine and trace amine receptors, we observe marked changes in larval phototactic swimming behaviour, consistent with the sponge being competent to recognise and respond to symbiont-derived trace amine signals. These results indicate that monoamines synthesised by bacterial symbionts may be able to influence the physiology of the host sponge.
Case report: A novel CACNA1S mutation associated with hypokalemic periodic paralysis
Authors: Nuzhnyi Evgenii P. , Arestova Alina S. , Rossokhin Alexey V. , Protopopova Anna O. , Abramycheva Nataliya Yu , Suponeva Natalia A. , Illarioshkin Sergey N.
Published: September 2023

Background

Hypokalemic periodic paralysis (HypoKPP) is a rare neuromuscular genetic disorder causing recurrent episodes of flaccid paralysis. Most cases are associated with CACNA1S mutation, causing defect of calcium channel and subsequent impairment of muscle functions. Due to defined management approaches early diagnosis is crucial for promptly treatment and prevention new attacks.

Materials and methods

We report a case of HypoKPP associated with previously unreported mutation in CACNA1S gene (p.R900M). Molecular modeling of CaV1.1 was applied to evaluate its pathogenicity.

Results

As a patient referred between attacks neurological status, laboratory and neurophysiological examination were unremarkable. Molecular modeling predicted that the p.R900M mutation affects the process of calcium channels activation.

Conclusion

Novel CACNA1S mutation, associated with HypoKPP was identified. Monte-Carlo energy minimization of the CaV1.1 model supported the association of this mutation with this disease.
Alpha/beta-gamma decoupling in methylphenidate medicated ADHD patients
Authors: Zammit Nowell , Muscat Richard
Published: September 2023

There is much interest to understand how different neural rhythms function, interact and are regulated. Here, we focus on WM delay gamma to investigate its coupling with alpha/beta rhythms and its neuromodulation by methylphenidate. We address this through the use of human EEG conducted in healthy and ADHD subjects which revealed ADHD-specific electrophysiological deficits and MPH-induced normalization of gamma amplitude and its coupling with alpha/beta rhythms. Decreased alpha/beta-gamma coupling is known to facilitate memory representations via disinhibition of gamma ensembles coding the maintained stimuli. Here, we present EEG evidence which suggests that these dynamics are sensitive to catecholaminergic neuromodulation. MPH decreased alpha/beta-gamma coupling and this was related to the increase in delay-relevant gamma activity evoked by the same drug. These results add further to the neuromodulatory findings that reflect an electrophysiological dimension to the well-known link between WM delay and catecholaminergic transmission.
Study of prevalence and risk factors of chemotherapy-induced mucositis in gastrointestinal cancer using machine learning models
Authors: Huang Lin , Ye Xianhui , Wu Fengqing , Wang Xiuyun , Qiu Meng
Published: September 2023

Objective

Chemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population.

Methods

To achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed.

Results

The study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026).

Conclusion

In conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies.
miR-186-ANXA9 signaling inhibits tumorigenesis in breast cancer
Authors: Wang Zhongrui , Zhou Xiqian , Deng Xiaochong , Ye Danrong , Liu Diya , Zhou Baian , Zheng Wenfang , Wang Xuehui , Wang Yuying , Borkhuu Oyungerel , Fang Lin
Published: September 2023

Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA in cells mostly functioning to silence the target mRNAs. In the current study, a miRNA screening analysis identified miR-186-5p to be downregulated in human breast cancer tumors. Functional studies in vitro demonstrated that overexpression of miR-186-5p inhibited cellular proliferation and induced cell apoptosis in multiple breast cancer cell lines including MDA-MB-231, MCF-7, and BT549 cells. Transplantation of the miR-186-5p-overexpressing MDA-MB-231 cells into nude mice significantly inhibited mammary tumor growth in vivo. Sequence blast analysis predicted annexin A9 (ANXA9) as a target gene of miR-186-5p, which was validated by luciferase reporter assay, QRT-PCR analysis, and western blot. Additional gene expression analysis of clinical tumor samples indicated a negative correlation between miR-186-5p and ANXA9 in human breast cancer. Knockdown of ANXA9 mimicked the phenotype of miR-186-5p overexpression. Reintroduction of ANXA9 back rescued the miR-186-5p-induced cell apoptosis. In addition, miR-186-5p decreased the expression of Bcl-2 and increased the expression of p53, suggesting a mechanism regulating miR-186-5p-induced cellular apoptosis. In summary, our study is the first to demonstrate miR-186-5p-ANXA9 signaling in suppressing human breast cancer. It provided a potential therapeutic target in breast cancer.
Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Chen Connie , Layman Rachel M. , Rugo Hope S.
Published: September 2023

Background

Elderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data are needed to inform clinical management of elderly patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer (mBC). This subanalysis of the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness of palbociclib plus an aromatase inhibitor (AI) versus an AI alone among patients with HR+/HER2− mBC aged ≥ 75 years treated in routine clinical practice in the United States.

Methods

This retrospective observational cohort study used electronic health records from the Flatiron Health Analytic Database. Palbociclib treatment patterns, overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Three methods were used for comparative analyses: (1) an unadjusted analysis, (2) stabilized inverse probability treatment weighting (sIPTW; primary analysis), and (3) propensity score matching (PSM; sensitivity analysis).

Results

A total of 961 patients aged ≥ 75 years with HR+/HER2− mBC were identified who started palbociclib plus an AI (n = 313) or an AI alone (n = 648) as first-line (1L) therapy between February 2015 and March 2020 (data cut-off: September 30, 2020). Among patients in the palbociclib plus an AI group with a documented palbociclib starting dose (n = 306), approximately 75% started palbociclib at 125 mg/day, and approximately 40% experienced dose adjustment. After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51–0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59–0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55–0.87]; P = 0.0014). These significant improvements in OS, rwPFS, and TTC remained consistent in the unadjusted analysis and after PSM.

Conclusion

This real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2− mBC aged ≥ 75 years. These findings support palbociclib plus an AI as a standard-of-care 1L treatment for elderly patients with HR+/HER2− mBC.
An online home-based exercise program improves autonomic dysfunction in breast cancer survivors
Authors: Lavín-Pérez Ana Myriam , Collado-Mateo Daniel , Hinojo González Carmen , Batista Marco , Mayo Xián , Ruisánchez Villar Cristina , Jiménez Alfonso
Published: September 2023

Introduction: Exercise interventions for breast cancer survivors have proved their potential to improve clinical, physical, and psychosocial outcomes. However, limited studies have explored exercise effects on autonomic dysfunction and the measurement of exercise tolerance and progression through daily heart rate variability (HRV).

Purpose: To analyze the effects of a 16-wk exercise intervention on the autonomic modulation of breast cancer survivors, as well as to examine the evolution of daily measured HRV and its interaction with exercise sessions in this population.

Methods: A total of 29 patients who had undergone chemotherapy and radiotherapy were randomly assigned to the exercise group or to the control group. The exercise intervention was delivered remotely through online meetings and consisted of supervised training resistance and cardiovascular exercise 3 times per week. During the intervention all patients measured their HRV daily obtaining the napierian logarithm of the root mean square of successive differences between normal heartbeats (lnrMSSD) and the napierian logarithm of the standard deviation of the interbeat interval of normal sinus beats (lnSDNN) values at four moments: day 0 (the morning of the training sessions), 24, 48, and 72 h after exercise.

Results: The results revealed a significant interaction between group and months during the intervention period for lnrMSSD and lnSDNN (p < 0.001). Additionally, there were significant differences in lnSDNN recovery time between months (p < 0.05), while differences in lnrMSSD become apparent only 24 h after exercise (p = 0.019). The control group experienced a significant decrease in both variables monthly (p < 0.05) while exercise group experienced a significant increment (p < 0.05).

Conclusion: HRV is daily affected by exercise training sessions in cancer patients. Although results strongly support the role of exercise as a post-chemotherapy and radiotherapy rehabilitation strategy for breast cancer survivors to improve autonomic imbalance, further research is necessary to validate these initial findings.
Respiratory muscle training induces additional stress and training load in well-trained triathletes—randomized controlled trial
Authors: Kowalski Tomasz , Kasiak Przemysław Seweryn , Rebis Kinga , Klusiewicz Andrzej , Granda Dominika , Wiecha Szczepan
Published: September 2023

Background: Respiratory muscle training (RMT) has been investigated in the context of improved athletic performance and pulmonary function. However, psychophysiological costs of RMT remain understudied. Voluntary isocapnic hyperpnoea (VIH) and inspiratory pressure threshold loading (IPTL) are widely applied RMT methods. The main purposes of this study were to assess whether RMT induces additional load on well-trained triathletes and determine differences in RMT-induced load between sexes and applied methods.

Materials and Methods: 16 well-trained triathletes (n = 16, 56% males) underwent 6 weeks of VIH or IPTL program with progressive overload. Blood markers, subjective measures, cardiac indices, near-infrared spectroscopy indices, inspiratory muscle fatigue, and RMT-induced training load were monitored pre-, in and post-sessions. We used multiple ANOVA to investigate effects of sex, training method, and time on measured parameters.

Results: There were significant interactions for acid-base balance (p = 0.04 for sex, p < 0.001 for method), partial carbon dioxide pressure (p = 0.03 for sex, p < 0.001 for method), bicarbonate (p = 0.01 for method), lactate (p < 0.001 for method), RMT-induced training load (p = 0.001 for method for single session, p = 0.03 for method per week), average heart rate (p = 0.03 for sex), maximum heart rate (p = 0.02 for sex), intercostales muscle oxygenation (p = 0.007 for testing week), and intercostales muscle oxygenation recovery (p = 0.003 for testing week and p = 0.007 for method).

Conclusion: We found that RMT induced additional load in well-trained triathletes. Elicited changes in monitored variables depend on sex and training method. VIH significantly increased subjective training load measures. IPTL was associated with disbalance in blood gasometry, increase in lactate, and reports of headaches and dizziness. Both methods should be applied with consideration in high-performance settings.
Willingness to be vaccinated against COVID-19: the role of risk perception, trust in institutions, and affects
Authors: Fleury-Bahi Ghozlane , Sapin Arnaud , Navarro Oscar , Boudoukha Abdel Halim , Galharret Jean-Michel , Bret Amélie , Congard Anne
Published: September 2023

Introduction

Vaccination is one of the most effective ways to stop the COVID-19 pandemic and prevent severe disease. This study aims to ascertain the determinants of COVID-19 vaccination acceptance in the French population before the vaccine was introduced (France’s second lockdown) and during the roll-out of the vaccination campaign (France’s third lockdown). We focus on the following as determinants of willingness to be vaccinated: risk perception, affects related to the risk, and trust in political and health institutions.

Method

The study was conducted among two convenient samples including 591 and 474 participants. The results show that the timing of the crisis was important. While the intention to be vaccinated was relatively low before the vaccines were introduced, it became significantly higher when the vaccination campaign was deployed.

Results

The results show that risk perception and trust in health institutions are the most relevant predictors of intention to be vaccinated.

Discussion

Results are discussed in terms of the effectiveness of communication campaigns.