bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Moroccan Barley Germplasm Preserved in the Polish Genebank as a First Step towards Selecting Forms with Increased Drought Tolerance
Authors: Boczkowska Maja , Puchta-Jasińska Marta , Bolc Paulina , Moskal Kinga , Puła Szymon , Motor Adrian , Bączek Katarzyna , Groszyk Jolanta , Podyma Wiesław
Published: November 2023

In marginal, arid, and semi-arid areas of Morocco, crops are often exposed to multiple abiotic and biotic stresses that have a major impact on yield. Farmer-maintained Moroccan landraces have been shaped by the impact of very strong selection pressures, gradually adapting to the local ecosystem and obsolete low-input agricultural practices without improvement towards high yield and quality. Considering the increasing threat of drought in Poland, it is necessary to introduce germplasm with tolerance to water deficit into barley breeding programs. The aim of this research was a DArTseq-based genetic characterization of a collection of germplasm of Moroccan origin, conserved in the Polish genebank. The results showed that all conserved landraces have a high level of heterogeneity and their gene pool is different from the material developed by Polish breeders. Based on the analysis of eco-geographical data, locations with extremely different intensities of drought stress were selected. A total of 129 SNPs unique to accessions from these locations were identified. In the neighborhood of the clusters of unique SNPs on chromosomes 5H and 6H, genes that may be associated with plant response to drought stress were identified. The results obtained may provide a roadmap for further research to support Polish barley breeding for increased drought tolerance.
Iron and Targeted Iron Therapy in Alzheimer’s Disease
Authors: Wang Jian , Fu Jiaying , Zhao Yuanxin , Liu Qingqing , Yan Xiaoyu , Su Jing
Published: November 2023

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. β-amyloid plaque (Aβ) deposition and hyperphosphorylated tau, as well as dysregulated energy metabolism in the brain, are key factors in the progression of AD. Many studies have observed abnormal iron accumulation in different regions of the AD brain, which is closely correlated with the clinical symptoms of AD; therefore, understanding the role of brain iron accumulation in the major pathological aspects of AD is critical for its treatment. This review discusses the main mechanisms and recent advances in the involvement of iron in the above pathological processes, including in iron-induced oxidative stress-dependent and non-dependent directions, summarizes the hypothesis that the iron-induced dysregulation of energy metabolism may be an initiating factor for AD, based on the available evidence, and further discusses the therapeutic perspectives of targeting iron.
Diastereoselective Synthesis of Dispiro[Imidazothiazolotriazine-Pyrrolidin-Oxindoles] and Their Isomerization Pathways in Basic Medium
Authors: Izmest′ev Alexei N. , Vinogradov Dmitry B. , Kravchenko Angelina N. , Kolotyrkina Natalya G. , Gazieva Galina A.
Published: November 2023

Highly diastereoselective methods for the synthesis of two series of regioisomeric polynuclear dispyroheterocyclic compounds with five or six chiral centers, comprising moieties of pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine of linear structure or imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine of angular structure, have been developed on the basis of a [3+2] cycloaddition of azomethine ylides to functionalized imidazothiazolotriazines. Depending on the structure of the ethylenic component, cycloaddition proceeds as an anti-exo process for linear derivatives, while cycloaddition to angular ones resulted in a syn-endo diastereomer. Novel pathways of isomerization for the synthesized anti-exo products upon treatment with sodium alkoxides have been found, which resulted in two more series of diastereomeric dispiro[imidazothiazolotriazine-pyrrolidin-oxindoles] inaccessible with the direct cycloaddition reaction. For the first series, the inversion of the configuration of one stereocenter, i.e., C-4′ atom of the pyrrolidine cycle, (epimerization) was established. For the second one, configuration of the obtained diastereomer formally corresponded to the syn-endo approach of the azomethine ylide in the case of cycloaddition to the ethylenic component.
New Derivatives of N-Hydroxybutanamide: Preparation, MMP Inhibition, Cytotoxicity, and Antitumor Activity
Authors: Balakina Anastasia , Gadomsky Svyatoslav , Kokovina Tatyana , Sashenkova Tatyana , Mishchenko Denis , Terentiev Alexei
Published: November 2023

Using a novel method of N-substituted succinimide ring opening, new N-hydroxybutanamide derivatives were synthesized. These compounds were evaluated for their ability to inhibit matrix metalloproteinases (MMPs) and their cytotoxicity. The iodoaniline derivative of N1-hydroxy-N4-phenylbutanediamide showed the inhibition of MMP-2, MMP-9, and MMP-14 with an IC50 of 1–1.5 μM. All the compounds exhibited low toxicity towards carcinoma cell lines HeLa and HepG2. The iodoaniline derivative was also slightly toxic to glioma cell lines A-172 and U-251 MG. Non-cancerous FetMSC and Vero cells were found to be the least sensitive to all the compounds. In vivo studies demonstrated that the iodoaniline derivative of N1-hydroxy-N4-phenylbutanediamide had low acute toxicity. In a mouse model of B16 melanoma, this compound showed both antitumor and antimetastatic effects, with a 61.5% inhibition of tumor growth and an 88.6% inhibition of metastasis. Our findings suggest that the iodoaniline derivative of N1-hydroxy-N4-phenylbutanediamide has potential as a lead structure for the development of new MMP inhibitors. Our new synthetic approach can be a cost-effective method for the synthesis of inhibitors of metalloenzymes with promising antitumor potential.
Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar
Authors: Mohammed Idris , Selvaraj Senthil , Ahmed Wesam S. , Al-Barazenji Tara , Hammad Ayat S , Dauleh Hajar , Saraiva Luis R. , Al-Shafai Mashael , Hussain Khalid
Published: November 2023

The leptin–melanocortin pathway is pivotal in appetite and energy homeostasis. Pathogenic variants in genes involved in this pathway lead to severe early-onset monogenic obesity (MO). The MC4R gene plays a central role in leptin–melanocortin signaling, and heterozygous variants in this gene are the most common cause of MO. A targeted gene panel consisting of 52 obesity-related genes was used to screen for variants associated with obesity. Variants were analyzed and filtered to identify potential disease-causing activity and validated using Sanger sequencing. We identified two novel heterozygous variants, c.253A>G p.Ser85Gly and c.802T>C p.Tyr268His, in the MC4R gene in two unrelated patients with morbid obesity and evaluated the functional impact of these variants. The impact of the variants on the MC4R gene was assessed using in silico prediction tools and molecular dynamics simulation. To further study the pathogenicity of the identified variants, GT1-7 cells were transfected with plasmid DNA encoding either wild-type or mutant MC4R variants. The effects of allelic variations in the MC4R gene on cAMP synthesis, MC4R protein level, and activation of PKA, ERB, and CREB signaling pathways in both stimulated and unstimulated ɑ-MSH paradigms were determined for their functional implications. In silico analysis suggested that the variants destabilized the MC4R structure and affected the overall dynamics of the MC4R protein, possibly leading to intracellular receptor retention. In vitro analysis of the functional impact of these variants showed a significant reduction in cell surface receptor expression and impaired extracellular ligand binding activity, leading to reduced cAMP production. Our analysis shows that the variants do not affect total protein expression; however, they are predicted to affect the post-translational localization of the MC4R protein to the cell surface and impair downstream signaling cascades such as PKA, ERK, and CREB signaling pathways. This finding might help our patients to benefit from the novel therapeutic advances for monogenic forms of obesity.
Single-Nuclei Multiome (ATAC + Gene Expression) Sequencing of a Primary Canine Osteosarcoma Elucidates Intra-Tumoral Heterogeneity and Characterizes the Tumor Microenvironment
Authors: Nance Rebecca L. , Wang Xu , Sandey Maninder , Matz Brad M. , Thomas AriAnna , Smith Bruce F.
Published: November 2023

Osteosarcoma (OSA) is a highly aggressive bone tumor primarily affecting pediatric or adolescent humans and large-breed dogs. Canine OSA shares striking similarities with its human counterpart, making it an invaluable translational model for uncovering the disease’s complexities and developing novel therapeutic strategies. Tumor heterogeneity, a hallmark of OSA, poses significant challenges to effective treatment due to the evolution of diverse cell populations that influence tumor growth, metastasis, and resistance to therapies. In this study, we apply single-nuclei multiome sequencing, encompassing ATAC (Assay for Transposase-Accessible Chromatin) and GEX (Gene Expression, or RNA) sequencing, to a treatment-naïve primary canine osteosarcoma. This comprehensive approach reveals the complexity of the tumor microenvironment by simultaneously capturing the transcriptomic and epigenomic profiles within the same nucleus. Furthermore, these results are analyzed in conjunction with bulk RNA sequencing and differential analysis of the same tumor and patient-matched normal bone. By delving into the intricacies of OSA at this unprecedented level of detail, we aim to unravel the underlying mechanisms driving intra-tumoral heterogeneity, opening new avenues for therapeutic interventions in both human and canine patients. This study pioneers an approach that is broadly applicable, while demonstrating significant heterogeneity in the context of a single individual’s tumor.
ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production
Authors: Kishi Shingo , Mori Shiori , Fujiwara-Tani Rina , Ogata Ruiko , Sasaki Rika , Ikemoto Ayaka , Goto Kei , Sasaki Takamitsu , Miyake Makito , Sasagawa Satoru , Kawaichi Masashi , Luo Yi , Bhawal Ujjal Kumar , Fujimoto Kiyohide , Nakagawa Hidemitsu , Kuniyasu Hiroki
Published: November 2023

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated.
Fatal Hymenoptera Venom–Triggered Anaphylaxis in Patients with Unrecognized Clonal Mast Cell Disorder—Is Mastocytosis to Blame?
Authors: Rijavec Matija , Inkret Jezerka , Bidovec-Stojković Urška , Carli Tanja , Frelih Nina , Kukec Andreja , Korošec Peter , Košnik Mitja
Published: November 2023

Hymenoptera venom–triggered anaphylaxis (HVA) affects up to 8.9% of the general population and is the most frequent cause of anaphylaxis in adults, accounting for approximately 20% of all fatal anaphylaxis cases. Quite often, a fatal reaction is a victim’s first manifestation of HVA. Mastocytosis represents one of the most important risk factors for severe HVA. We analyzed patients with documented fatal HVA for the presence of underlying clonal mast cell disorder (cMCD). Here, we report three cases of fatal HVA, with undiagnosed underlying cMCD identified by the presence of the peripheral blood and/or bone marrow KIT p.D816V missense variant postmortem. In the first case, anaphylaxis was the initial episode and was fatal. In the other two cases, both patients were treated with specific venom immunotherapy (VIT), nevertheless, one died of HVA after VIT discontinuation, and the other during VIT; both patients had cardiovascular comorbidities and were taking beta-blockers and/or ACE inhibitors. Our results point to the importance of screening all high-risk individuals for underlying cMCD using highly sensitive molecular methods for peripheral blood KIT p.D816V variant detection, including severe HVA and possibly beekeepers, for proper management and the need for lifelong VIT to prevent unnecessary deaths. Patients at the highest risk of fatal HVA, with concomitant cardiovascular and cMCD comorbidities, might not be protected from field stings even during regular VIT. Therefore, two adrenaline autoinjectors and lifelong VIT, and possibly cotreatment with omalizumab, should be considered for high-risk patients to prevent fatal HVA episodes.
An Experimental Model of Proton-Beam-Induced Radiation Dermatitis In Vivo
Authors: Anikina Viktoriia A. , Sorokina Svetlana S. , Shemyakov Alexander E. , Zamyatina Elizaveta A. , Taskaeva Iuliia S. , Teplova Polina O. , Popova Nelli R.
Published: November 2023

Radiation dermatitis (RD) is one of the most common side effects of radiation therapy. However, to date, there is a lack of both specific treatments for RD and validated experimental animal models with the use of various sources of ionizing radiation (IR) applied in clinical practice. The aim of this study was to develop and validate a model of acute RD induced using proton radiation in mice. Acute RD (Grade 2–4) was obtained with doses of 30, 40, and 50 Gy, either with or without depilation. The developed model of RD was characterized by typical histological changes in the skin after irradiation. Moreover, the depilation contributed to a skin histology alteration of the irradiated mice. The assessment of animal vital signs indicated that there was no effect of proton irradiation on the well-being or general condition of the animals. This model can be used to develop effective therapeutic agents and study the pathogenesis of radiation-induced skin toxicity, including that caused by proton irradiation.
Comparison of the Effects of Recombinant and Native Prolactin on the Proliferation and Apoptosis of Goose Granulosa Cells
Authors: Deng Donghang , Li Wen , Li Xiaopeng , Yuan Xin , Li Liang , Wang Jiwen , Han Chunchun , Hu Shenqiang
Published: November 2023

In poultry, prolactin (PRL) plays a key role in the regulation of incubation behavior, hormone secretion, and reproductive activities. However, previous in vitro studies have focused on the actions of PRL in ovarian follicles of poultry, relying on the use of exogenous or recombinant PRL, and the true role of PRL in regulating ovarian granulosa cell (GC) functions in poultry awaits a further investigation using endogenous native PRL. Therefore, in this study, we first isolated and purified recombinant goose PRL protein (rPRL) and native goose PRL protein (nPRL) using Ni-affinity chromatography and rabbit anti-rPRL antibodies-filled immunoaffinity chromatography, respectively. Then, we analyzed and compared the effects of rPRL and nPRL at different concentrations (0, 3, 30, or 300 ng/mL) on the proliferation and apoptosis of both GCs isolated from goose ovarian pre-hierarchical follicles (phGCs) and from hierarchical follicles (hGCs). Our results show that rPRL at lower concentrations increased the viability and proliferation of both phGCs and hGCs, while it exerted anti-apoptotic effects in phGCs by upregulating the expression of Bcl-2. On the other hand, nPRL increased the apoptosis of phGCs in a concentration-dependent manner by upregulating the expressions of caspase-3 and Fas and downregulating the expressions of Bcl-2 and Becn-1. In conclusion, this study not only obtained a highly pure nPRL for the first time, but also suggested a dual role of PRL in regulating the proliferation and apoptosis of goose GCs, depending on its concentration and the stage of follicle development. The data presented here can be helpful in purifying native proteins of poultry and enabling a better understanding of the roles of PRL during the ovarian follicle development in poultry.
Developing Integrated Performance Dashboards Visualisations Using Power BI as a Platform
Authors: Gonçalves Célia Talma , Gonçalves Maria José Angélico , Campante Maria Inês
Published: November 2023

The rapid advance of business technologies in recent years has made knowledge an essential and strategic asset that determines the success or failure of an organisation. Access to the right information in real time and with high selectivity can be a competitive advantage in the business environment. Business intelligence systems help corporate executives, business managers, and other operational workers make better and more informed business decisions. This study aimed to assess the impact of using business intelligence tools on the decision-making process in organisations, specifically in sales marketing. The methodology applied to realise the study’s objective was the Vercellis methodology. A set of data available on the sales marketing website SuperDataScience was used to implement a set of pressing KPIs for the business decision-making process in the area. Using these data, a complete business intelligence system solution was implemented. A data warehouse was created using the ETL (extract–transform–load) process, and the data were then explored using a set of dynamics dashboards with a view of the business metrics. The results showed the use of business intelligence systems that allow the integration and transformation of data from various sources stored in data warehouses, where it is possible to implement KPIs and carry out quick, concise, easy-to-interpret graphical analyses. This paper contributes to a better understanding of the importance of data-integrated dashboard visualisation for the decision-making process.
Correlations between Negative Symptoms and Cognitive Deficits in Individuals at First Psychotic Episode or at High Risk of Psychosis: A Systematic Review
Authors: Melillo Antonio , Caporusso Edoardo , Giordano Giulia Maria , Giuliani Luigi , Pezzella Pasquale , Perrottelli Andrea , Bucci Paola , Mucci Armida , Galderisi Silvana
Published: November 2023

The present review aims to identify correlations between negative symptoms (NS) and deficits in neurocognition and social cognition in subjects with first-episode psychosis (FEP) and at-high-risk populations (HR). A systematic search of the literature published between 1 January 2005 and 31 December 2022 was conducted on PubMed, Scopus, and PsycInfo. Out of the 4599 records identified, a total of 32 studies met our inclusion/exclusion criteria. Data on a total of 3086 FEP and 1732 HR were collected. The available evidence shows that NS correlate with executive functioning and theory of mind deficits in FEP subjects, and with deficits in the processing speed, attention and vigilance, and working memory in HR subjects. Visual learning and memory do not correlate with NS in either FEP or HR subjects. More inconsistent findings were retrieved in relation to other cognitive domains in both samples. The available evidence is limited by sample and methodological heterogeneity across studies and was rated as poor or average quality for the majority of included studies in both FEP and CHR populations. Further research based on shared definitions of first-episode psychosis and at-risk states, as well as on more recent conceptualizations of negative symptoms and cognitive impairment, is highly needed.
Obstetric and Gynecological Admissions and Hospitalizations in an Italian Tertiary-Care Hospital during COVID-19 Pandemic: A Retrospective Analysis According to Restrictive Measures
Authors: Riemma Gaetano , De Franciscis Pasquale , Tesorone Marina , Coppa Egle , Schiattarella Antonio , Billone Valentina , Lopez Alessandra , Cucinella Gaspare , Gullo Giuseppe , Carotenuto Raffaela Maria
Published: November 2023

Background: The national lockdown and the different restrictions applied in 2020 during the COVID-19 pandemic brought several changes to hospitalization procedures. The aim of this study was to evaluate the patterns in access to emergency services and hospitalization in a tertiary-care obstetric and gynecological emergency department (OG-ED) throughout the restrictions applied during 2020. Methods: A single-center retrospective comparative study on data from January to December 2020 was carried out on the following timeframes: January to February 2020 (before COVID-19 pandemic), March to June 2020 (nationwide lockdown period), July to September 2020 (removal of restrictive measures), October to December 2020 (regional lockdown) and compared to the same periods of 2019. All obstetric and gynecological patients with complete medical data admitted to the OG-ED were included. Results: Overall, 4233 accesses for 2019 and 3652 for 2020 were reported, with a decreasing trend of −13.7%. Between March and June 2020 (nationwide lockdown) and 2019, the overall number of patients attending the OG-ED decreased compared to July–September and October–December differences (Δ −23.5% vs. −3.1% and −5.9%; p = 0.001 respectively) for 2020–2019, but this reduction was not statistically significant when compared to January–February (Δ −23.5% vs. −18.5%; p = 0.356). No significant differences for obstetric patients (Δ −1.8% vs. −1.0% vs. −2.3% and +1.9% respectively; p = 0.883) were noted. Hospitalizations showed a stable trend with an increase between October–December 2019 and 2020 (Δ +4.6%; p = 0.001 vs. January–February (+2.4%) and March–June (+2.6%) 2019–2020), mainly related to regional lockdowns. Conclusions: In contrast to available national studies, in our institution, the overall rate of OG-ED admissions was slightly reduced with a similar trend of decrease even before COVID-19, with an increase in admissions for serious issues, despite expectations that the suspension of elective admissions and outpatient services would have led to an increase in non-urgent hospitalizations during the COVID-19 lockdown period.
Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease
Authors: Matama Goushi , Okamoto Masaki , Fujimoto Kiminori , Johkoh Takeshi , Tominaga Masaki , Mukae Hiroshi , Sakamoto Noriho , Komiya Kosaku , Umeki Kenji , Komatsu Masamichi , Shimizu Yasuo , Takahashi Koichiro , Tokisawa Saeko , Zaizen Yoshiaki , Matsuo Norikazu , Nouno Takashi , Kaieda Shinjiro , Ida Hiroaki , Izuhara Kenji , Hoshino Tomoaki
Published: November 2023

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD.
Morphological Comparison of Residual Ridge in Impression for Removable Partial Denture between Digital and Conventional Techniques: A Preliminary In-Vivo Study
Authors: Ishioka Yurika , Wada Junichiro , Kim Eung-Yeol , Sakamoto Kazuki , Arai Yuki , Murakami Natsuko , Yamazaki Toshiki , Takakusaki Kensuke , Hayama Hironari , Utsumi Miona , Inukai Shusuke , Wakabayashi Noriyuki
Published: November 2023

Although digital impression using an intraoral scanner (IOS) has been applied for removable partial denture (RPD) fabrication, it is still unclear how the morphology of a residual ridge recorded by digital impression would differ from that recorded by conventional impression. This in vivo study investigated the morphological difference in the recorded residual ridge between digital and conventional impressions. Vertical and horizontal displacements (VD and HD) in residual ridges recorded by digital and conventional impressions were assessed in 22 participants (15 female; mean age 78.2 years) based on the morphology of the tissue surface of in-use RPD. Additionally, the mucosal thickness of the residual ridge was recorded using an ultrasound diagnostic device. VD and HD were compared using the Wilcoxon signed-rank test, and the correlation of mucosal thickness with VD and HD was analyzed using Spearman’s ρ. The VD of digital impression was significantly greater than that of a conventional impression (p = 0.031), while no significant difference was found in HD (p = 0.322). Meanwhile, the mucosal thickness showed no significant correlation with the recorded morphology of the residual ridge, regardless of the impression techniques. It was concluded that the digital impression would result in a greater displacement in the height of the residual ridge from the morphology of in-use RPD than the conventional impression.
Evolution of the Therapeutic Management of Giant Cell Arteritis: Analysis of Real-Life Practices over Two Timeframes (2014–2017 and 2018–2020)
Authors: de Boysson Hubert , Dumont Anael , Castan Paul , Gallou Sophie , Boutemy Jonathan , Maigné Gwénola , Martin Silva Nicolas , Nguyen Alexandre , Deshayes Samuel , Aouba Achille
Published: November 2023

Objectives: To determine how therapeutic strategies for giant cell arteritis (GCA), especially glucocorticoid (GC) management, evolved between 2014 and 2020. Patients and Methods: Consecutive GCA patients followed for at least 24 months in a single tertiary center were enrolled and separated into two groups: those diagnosed from 2014 to 2017 and those diagnosed from 2018 to 2020. GC doses (mg/kg/day) were analyzed at onset, at Month 3 (M3) and, if continued, at M6, M12, M18 and M24. Physicians’ practices were also individually analyzed. Results: Among the 180 patients included, 96 (53%) were diagnosed in 2014–2017 and 84 (47%) in 2018–2020. All patients received GC at diagnosis without a difference in the initial dose between the two groups (p = 0.07). At M3, the daily dose was lower in patients treated after 2017 (p = 0.002). In patients who still received GC at M6 (p = 0.0008), M12 (p = 0.01) and M24 (p = 0.02), the daily GC dose was still lower in patients treated after 2017. The proportion of patients who definitively discontinued GC use before M18 (42% versus 21%, p = 0.003) was higher in those treated after 2017. The rates of immunosuppressant use were not different between the two time periods (31% versus 38%, p = 0.34), but tocilizumab replaced methotrexate. Significant differences were observed among practitioners regarding the GC doses at M6 (p = 0.04) and M12 (p = 0.04), the total GC duration (p = 0.02) and the ability to stop GC before M18 (p = 0.007). Conclusions: This real-life study showed a global change in GC management over time for GCA patients, with important variability among physicians’ practices.
Combined Hormonal Contraception during Breastfeeding—A Survey of Physician’s Recommendations
Authors: Segev Lior , Weitzman Gideon , Katz-Samson Goldie , Samson Abraham O. , Shrem Guy , Srebnik Naama
Published: November 2023

Until breastfeeding is established, progesterone-only pill (POP) use is preferable over combined hormonal contraception (CHC), as the latter potentially reduces milk production. Yet, POPs are often associated with breakthrough bleeding (BTB), and irregular spotting is often a reason for their cessation. Conversely, CHC is less associated with BTB but is not usually prescribed, even if breastfeeding has been established, despite its verified safety profile. Here, we surveyed physicians’ perception of CHC safety during breastfeeding through an online questionnaire (N = 112). Physicians were asked if they would prescribe CHC to a woman three months postpartum, breastfeeding fully, and suffering from BTB while using POPs. Half of the physicians responded they would, 28% would not until six months postpartum, while 14% would not during breastfeeding. Of the physicians that would prescribe CHC, 58% would without any reservation, 24% would only after discussing milk reduction with the patient, 9% would use a pill with a lower hormonal dose, and 9% would only prescribe CHC 3 months postpartum. The main risk associated with CHC during breastfeeding, as perceived by physicians, is a potential decrease in breast milk production (88%). While some physicians consider CHC unsafe during breastfeeding, most health organizations consider CHC compatible with breastfeeding 5–6 weeks after birth. Thus, there is a gap in the attitude and knowledge of physicians about the safety profile of CHC, and only half acknowledge that the risk of BTB justifies the use of CHC instead of POPs while breastfeeding three months postpartum. We highlight the importance of physician’s education, advocate CHC breastfeeding compatibility if breastfeeding has been established (i.e., 30 days postpartum), and underline the importance of discussing the option of CHC with patients in case POPs have unwanted side effects.
Imagistic Findings Using Artificial Intelligence in Vaccinated versus Unvaccinated SARS-CoV-2-Positive Patients Receiving In-Care Treatment at a Tertiary Lung Hospital
Authors: Stoichita Alexandru , Ghita Maria , Mahler Beatrice , Vlasceanu Silviu , Ghinet Andreea , Mosteanu Madalina , Cioacata Andreea , Udrea Andreea , Marcu Alina , Mitra George Daniel , Ionescu Clara Mihaela , Iliesiu Adriana
Published: November 2023

Background: In December 2019 the World Health Organization announced that the widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection had become a global pandemic. The most affected organ by the novel virus is the lung, and imaging exploration of the thorax using computer tomography (CT) scanning and X-ray has had an important impact. Materials and Methods: We assessed the prevalence of lung lesions in vaccinated versus unvaccinated SARS-CoV-2 patients using an artificial intelligence (AI) platform provided by Medicai. The software analyzes the CT scans, performing the lung and lesion segmentation using a variant of the U-net convolutional network. Results: We conducted a cohort study at a tertiary lung hospital in which we included 186 patients: 107 (57.52%) male and 59 (42.47%) females, of which 157 (84.40%) were not vaccinated for SARS-CoV-2. Over five times more unvaccinated patients than vaccinated ones are admitted to the hospital and require imaging investigations. More than twice as many unvaccinated patients have more than 75% of the lungs affected. Patients in the age group 30–39 have had the most lung lesions at almost 69% of both lungs affected. Compared to vaccinated patients with comorbidities, unvaccinated patients with comorbidities had developed increased lung lesions by 5%. Conclusion: The study revealed a higher percentage of lung lesions among unvaccinated SARS-CoV-2-positive patients admitted to The National Institute of Pulmonology “Marius Nasta” in Bucharest, Romania, underlining the importance of vaccination and also the usefulness of artificial intelligence in CT interpretation.
Serum-Creatinine-to-Cystatin C-to-Waist-Circumference Ratios as an Indicator of Severe Airflow Limitation in Older Adults
Authors: Li Jinxuan , Sun Qi , Zhang Hongguang , Li Bingjie , Zhang Chaoyu , Zhao Yixin , Lu Jianbo , Ma Xu
Published: November 2023

Background: This study aimed to investigate the association between the serum-creatinine-to-cystatin C-to-waist-circumference (CCR/WC) ratio with lung function and severe airflow limitation (SAL). Methods: The data were derived from the China Health and Retirement Longitudinal Study. Peak expiratory flow (PEF) was used as a measure of lung function parameter. Logistic and linear regression were utilized separately to evaluate the relationship between the CCR/WC ratio with PEF and SAL in baseline. Restricted cubic spline was used to explore potential non-linear associations between the CCR/WC ratio and SAL. Cox proportional-hazards models were used to assess the association between CCR/WC quartiles and the risk of new-onset SAL. Results: A total of 6105 participants were included. This study revealed a positive association between the CCR/WC ratio and lung function (PEF: β [partial coefficient]: 25.95, 95%CI: 12.72 to 39.18, p < 0.001; PEF/PEF prediction: β = 0.08, 95%CI: 0.05 to 0.12, p < 0.001) and an inverse association relationship with SAL (OR [odds ratio]: 0.64, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.003). Subgroup analysis showed a significant association between the CCR/WC ratio and SAL in males (OR: 0.58, 95% CI: 0.37 to 0.90, p = 0.017) but not in females (p = 0.059). Cox regression analysis revealed a decreased risk of SAL in the quartiles (Q2–4) compared to the first quartile of the CCR/WC ratio (hazard ratios [HRs]: 0.49 to 0.73, all p < 0.05). Conclusions: This study highlights a positive association between the CCR/WC ratio and lung function, with a potential protective effect against SAL.
Contemporary Echocardiographic Evaluation of Mitral Regurgitation and Guidance for Percutaneous Mitral Valve Repair
Authors: Marchetti Davide , Di Lenarda Francesca , Novembre Maria Laura , Paolisso Pasquale , Schillaci Matteo , Melotti Eleonora , Doldi Marco , Terzi Riccardo , Gallazzi Michele , Conte Edoardo , Volpato Valentina , Bartorelli Antonio , Andreini Daniele
Published: November 2023

Mitral valve regurgitation (MR) is a multifaceted valvular heart disease. Echocardiography plays a central role in etiology assessment, severity quantification, treatment candidacy, outcome evaluation, and patient follow-up. In this review, we describe the comprehensive echocardiographic assessment of MR, including transthoracic (TTE) and transesophageal (TEE) approaches, 2D and 3D modalities, strain imaging, stress echocardiography, and artificial intelligence (AI) applications. Transcatheter edge-to-edge mitral valve repair (TEER) has been established as a key therapy for patients with severe, symptomatic MR and high surgical risk. TEER is performed under TEE guidance. We outline a practical overview of echocardiographic guidance on TEER.
Numerical Simulation of Dynamic Degradation and Fatigue Damage of Degradable Zinc Alloy Stents
Authors: Qi Jing , Zhang Hanbing , Chen Shiliang , Du Tianming , Zhang Yanping , Qiao Aike
Published: November 2023

Current research on the fatigue properties of degradable zinc alloy stents has not yet considered the issue of the fatigue life changing with material properties during the dynamic degradation process. Therefore, in this paper, we established a fatigue damage algorithm to study the fatigue problem affected by the changing of material properties during the dynamic degradation process of the stent under the action of pulsating cyclic loading. Three models: the dynamic degradation model, the dynamic degradation model under pulsating cyclic loading, and the coupled model of fatigue damage and dynamic degradation, were developed to verify the effect of fatigue damage on stent life. The results show that fatigue damage leads to a deeper degree of inhomogeneous degradation of the stent, which affects the service life of the stent. Fatigue damage is a factor that cannot be ignored. Therefore, when studying the mechanical properties and lifetime of degradable stents, incorporating fatigue damage into the study can help more accurately assess the lifetime of the stents.
Oral Administration of Platinum Nanoparticles with SOD/CAT Cascade Catalytic Activity to Alleviate Ulcerative Colitis
Authors: Liu Hao , Zhang Yujie , Zhang Mingzhen , Yu Zhaoxiang , Zhang Mingxin
Published: November 2023

Ulcerative colitis (UC) is a refractory chronic inflammatory disease involving the colon and rectum, falling under the category of inflammatory bowel disease (IBD). The accumulation of reactive oxygen species (ROS) in local tissues has been identified as a crucial contributor to the escalation of inflammatory responses. Therefore, eliminating ROS in the inflamed colon is a promising approach to treating UC. Nanomaterials with intrinsic enzyme-like activities (nanozymes) have shown significant therapeutic potential in UC. In this study, we found that platinum nanoparticles (Pt NPs) exhibited remarkable superoxide dismutase (SOD) and catalase (CAT) cascade catalytic activities, as well as effective hydroxyl radical (•OH) scavenging ability. The in vitro experiments showed that Pt NPs could eliminate excessive ROS to protect cells against oxidative stress. In the colitis model, oral administration of Pt NPs (loaded in chitosan/alginate hydrogel) could significantly alleviate UC, including reducing the colon length, the damaged epithelium, and the infiltration of inflammatory cells. Without appreciable systemic toxicity, Pt NPs represent a novel therapeutic approach to UC and are expected to achieve long-term inflammatory remission.
New Functional Bionanocomposites by Combining Hybrid Host-Guest Systems with a Fully Biobased Poly(lactic acid)/Poly(butylene succinate-co-adipate) (PLA/PBSA) Binary Blend
Authors: Cicogna Francesca , Passaglia Elisa , Telleschi Alice , Oberhauser Werner , Coltelli Maria-Beatrice , Panariello Luca , Gigante Vito , Coiai Serena
Published: November 2023

In this study, we have developed innovative polymer nanocomposites by integrating magnesium-aluminum layered double hydroxide (LDH)-based nanocarriers modified with functional molecules into a fully biobased poly(lactic acid)/poly(butylene succinate-co-adipate) (PLA/PBSA) matrix. These LDH-based hybrid host-guest systems contain bioactive compounds like rosmarinic acid, ferulic acid, and glycyrrhetinic acid, known for their antioxidant, antimicrobial, and anti-inflammatory properties. The bioactive molecules can be gradually released from the nanocarriers over time, allowing for sustained and controlled delivery in various applications, such as active packaging or cosmetics. The morphological analysis of the polymer composites, prepared using a discontinuous mechanical mixer, revealed the presence of macroaggregates and nano-lamellae at the polymer interface. This resulted in an enhanced water vapor permeability compared to the original blend. Furthermore, the migration kinetics of active molecules from the thin films confirmed a controlled release mechanism based on their immobilization within the lamellar system. Scaling-up experiments evaluated the materials’ morphology and mechanical and thermal properties. Remarkably, stretching deformation and a higher shear rate during the mixing process enhanced the dispersion and distribution of the nanocarriers, as confirmed by the favorable mechanical properties of the materials.
An Automatic Pixel-Wise Multi-Penalty Approach to Image Restoration
Authors: Bortolotti Villiam , Landi Germana , Zama Fabiana
Published: November 2023

This work tackles the problem of image restoration, a crucial task in many fields of applied sciences, focusing on removing degradation caused by blur and noise during the acquisition process. Drawing inspiration from the multi-penalty approach based on the Uniform Penalty principle, discussed in previous work, here we develop a new image restoration model and an iterative algorithm for its effective solution. The model incorporates pixel-wise regularization terms and establishes a rule for parameter selection, aiming to restore images through the solution of a sequence of constrained optimization problems. To achieve this, we present a modified version of the Newton Projection method, adapted to multi-penalty scenarios, and prove its convergence. Numerical experiments demonstrate the efficacy of the method in eliminating noise and blur while preserving the image edges.
Next-Gen Manufacturing: Machine Learning for Surface Roughness Prediction in Ti-6Al-4V Biocompatible Alloy Machining
Authors: Kosarac Aleksandar , Tabakovic Slobodan , Mladjenovic Cvijetin , Zeljkovic Milan , Orasanin Goran
Published: November 2023

Mechanical engineering plays an important role in the design and manufacture of medical devices, implants, prostheses, and other medical equipment, where the machining of bio-compatible materials have a special place. There are a lot of different conventional and non-conventional types of machining of biocompatible materials. One of the most frequently used methods is milling. The first part of this research explores the machining parameters optimization minimizing surface roughness in milling titanium alloy Ti-6Al-4V. A full factorial design involving four factors (cutting speed, feed rate, depth of cut, and the cooling/lubricating method), each having three levels, implies the 81 experimental runs. Using the Taguchi method, the number of experimental runs was reduced from 81 to 27 through an orthogonal design. According to the analysis of variance (ANOVA), the most significant parameter for surface roughness is feed rate. The second part explores the possibilities of using different ML techniques to create a predictive model for average surface roughness using the previously created small datasets. The paper presents a comparative analysis of several commonly used techniques for handling small datasets and regression problems. The best results indicate that the widely used machine learning algorithm Random Forest excels in handling regression problems and small datasets.
Sliding Mode Control with Adaptive-Reaching-Law-Based Fault-Tolerant Control for AUV Sensors and Thrusters
Authors: Li Jiawen , Wang Yujia , Li Haiyan , Liu Xing , Chen Zhengyu
Published: November 2023

Ocean currents, mechanical collisions and electronic damage can cause faults in an autonomous underwater vehicle (AUV), including sensors and thrusters. For such problems, this paper designs a fault-tolerant controller that is independent of the results of the fault diagnosis. An adaptive reaching law is developed based on sliding mode control to shorten convergence times. For the chattering phenomenon, a weighted hyperbolic tangent function is adopted instead of the traditional sign function in sliding mode control. Simulations are carried out when thruster and sensor fail under the condition of ocean current disturbance, model uncertainty and sensor noise. Comparative simulation results show that the proposed method can accelerate the convergence speed of the state point and improve the trajectory tracking effect of the AUV. Consequently, the effectiveness of the proposed method is confirmed.
Realization and Online Optimization for Gliding and Flapping Propulsion of a Manta Ray Robot
Authors: Cao Yonghui , Cao Yingzhuo , Ma Shumin , Li Xinhao , Qu Yilin , Cao Yong
Published: November 2023

Currently, the bionic robotic fish is primarily devoted to the bionic appearance of fish and rarely involves the bionic swimming posture. However, biological studies have proved that fish have extraordinary swimming ability, so it is necessary to imitate the swimming posture of fish. This paper introduces a manta ray robot driven by three fin rays, with its pectoral fins being structurally simulated using silicone rubber. According to the manta ray’s integrated gliding and flapping propulsion characteristics, we established a central-pattern-generator-based (CPG-based) biomimetic-motion-control method to realize the manta ray robot’s integrated gliding and flapping propulsion control. We designed an evaluation method of motion–posture similarity for the manta ray robot and optimized the control parameters to enhance the resemblance to the manta ray robot. The experimental results show that the online similarity-optimization method based on particle swarm optimization enhances the resemblance to 86.93%, and its swimming stability is also improved to some extent, which verifies the effectiveness of the optimization method. This study provides a new idea for optimizing motion control of the manta ray robot and realizing environmental affinity.
Aicardi–Goutières Syndrome with Congenital Glaucoma Caused by Novel TREX1 Mutation
Authors: Świerczyńska Marta , Tronina Agnieszka , Filipek Erita
Published: November 2023

Background: Aicardi–Goutières syndrome (AGS) is a rare genetic disorder characterized by microcephaly, white matter lesions, numerous intracranial calcifications, chilblain skin lesions and high levels of interferon-α (IFN-α) in the cerebrospinal fluid (CSF). However, ocular involvement is reported significantly less frequently. Case presentation: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops. Conclusions: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.