bluuebunny/crossref_metadata_2025 huggingface dataset:
Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke
Authors: Zheng Haoran , Haroon Khan , Liu Mengdi , Hu Xiaowen , Xu Qun , Tang Yaohui , Wang Yongting , Yang Guo-Yuan , Zhang Zhijun
Published: January 2024

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12.
Circ-MBOAT2 Regulates Angiogenesis via the miR-495/NOTCH1 Axis and Associates with Myocardial Perfusion in Patients with Coronary Chronic Total Occlusion
Authors: Gao Wei , Li Chenguang , Yuan Jie , Zhang Youming , Liu Guobing , Zhang Jianhui , Shi Hongcheng , Liu Haibo , Ge Junbo
Published: January 2024

Revascularization of coronary chronic total occlusion (CTO) still remains controversial. The factors that impact collateral circulation and myocardial perfusion are of interest. Circular RNA (circRNA) has been shown to regulate the process of angiogenesis. However, the effects of circ-membrane-bound O-acyltransferase domain containing 2 (circ-MBOAT2) on angiogenesis in patients with CTO were unclear. In this study, we evaluated circulating circRNAs and miRNAs in patients with CTO and stable coronary artery disease using high-throughput sequencing. Another cohort of patients were selected to verify the expressions of circ-MBOAT2 and miR-495. The role and mechanism of circ-MBOAT2 in the process of angiogenesis were explored through in vitro and vivo studies. Finally, we came back to a clinical perspective and investigated whether circ-MBOAT2 and miR-495 were associated with the improvement of myocardial perfusion evaluated by single-photon emission computed tomography (SPECT). We found that the expression of circ-MBOAT2 was significantly up-regulated while miR-495 was significantly down-regulated in patients with CTO. The expression of circ-MBOAT2 was negatively correlated with miR-495 in patients with CTO. In an in vitro study, we found that circ-MBOAT2 promoted tube formation and cell migration via the miR-495/NOTCH1 axis in endothelial cells. In an in vivo study, we showed that the inhibition of miR-495 caused the increase in collateral formation in mice after hindlimb ischemia. In a human study, we showed the expressions of circ-MBOAT2 and miR-495 were associated with myocardial perfusion improvement after revascularization of CTO. In conclusion, circ-MBOAT2 regulates angiogenesis via the miR-495/NOTCH1 axis and associates with myocardial perfusion in patients with CTO. Our findings suggest that circ-MBOAT2 and miR-495 may be potential therapeutic targets and prognostic factors for patients with CTO.
Heart Failure with Preserved Ejection Fraction: The Pathophysiological Mechanisms behind the Clinical Phenotypes and the Therapeutic Approach
Authors: Stoicescu Laurențiu , Crişan Dana , Morgovan Claudiu , Avram Lucreţia , Ghibu Steliana
Published: January 2024

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field.
Genome-Wide Identification and Characterization of MYB Gene Family and Analysis of Its Sex-Biased Expression Pattern in Spinacia oleracea L.
Authors: Zhang Zhilong , Liu Zhiyuan , Wu Hao , Xu Zhaosheng , Zhang Helong , Qian Wei , Gao Wujun , She Hongbing
Published: January 2024

The members of the myeloblastosis (MYB) family of transcription factors (TFs) participate in a variety of biological regulatory processes in plants, such as circadian rhythm, metabolism, and flower development. However, the characterization of MYB genes across the genomes of spinach Spinacia oleracea L. has not been reported. Here, we identified 140 MYB genes in spinach and described their characteristics using bioinformatics approaches. Among the MYB genes, 54 were 1R-MYB, 80 were 2R-MYB, 5 were 3R-MYB, and 1 was 4R-MYB. Almost all MYB genes were located in the 0–30 Mb region of autosomes; however, the 20 MYB genes were enriched at both ends of the sex chromosome (chromosome 4). Based on phylogeny, conserved motifs, and the structure of genes, 2R-MYB exhibited higher conservation relative to 1R-MYB genes. Tandem duplication and collinearity of spinach MYB genes drive their evolution, enabling the functional diversification of spinach genes. Subcellular localization prediction indicated that spinach MYB genes were mainly located in the nucleus. Cis-acting element analysis confirmed that MYB genes were involved in various processes of spinach growth and development, such as circadian rhythm, cell differentiation, and reproduction through hormone synthesis. Furthermore, through the transcriptome data analysis of male and female flower organs at five different periods, ten candidate genes showed biased expression in spinach males, suggesting that these genes might be related to the development of spinach anthers. Collectively, this study provides useful information for further investigating the function of MYB TFs and novel insights into the regulation of sex determination in spinach.
Does Precision-Based Medicine Hold the Promise of a New Approach to Predicting and Treating Spontaneous Preterm Birth?
Authors: Khan Hiba , Singh Natasha , Yovera Leyva Luis , Malawana Johann , Shah Nishel M.
Published: January 2024

Background: Preterm birth (PTB) is a leading cause of childhood disability, and it has become a key public health priority recognized by the World Health Organization and the United Nations. Objectives: This review will: (1) summarize current practice in the diagnosis and management of PTB, (2) outline developments in precision-based medicine for diagnostics to improve the care provided to pregnant women at risk of PTB, and (3) discuss the implications of current research in personalized medicine and the potential of future advances to influence the clinical care of women at risk of PTB. Methodology: This is a narrative literature review. Relevant journal articles were identified following searches of computerized databases. Key Results: Current and emerging technologies for the utility of personalized medicine in the context of PTB have the potential for applications in: (1) direct diagnostics to identify and target infection as one of the main known causes of PTB, (2) identifying novel maternal and fetal biomarkers, (3) the use of artificial intelligence and computational modeling, and (4) combining methods to enhance diagnosis and treatment. Conclusions: In this paper, we show how current research has moved in the direction of the targeted use of biomarkers in the context of PTB, with many novel approaches.
Clinical Implementation of MicroRNAs in Cancer Immunology
Authors: Schwarzenbach Heidi
Published: January 2024

MicroRNAs (miRNAs), or small non-coding RNAs, modulate the expression of mRNAs and, consequently, a variety of signal transduction pathways. Due to their dysregulation in cancer, they exert oncogenic pressure and have an impact on the immune system with their protective functions. These immunosuppressive characteristics of miRNAs in cancer promote cancer progression and metastasis, causing the dysregulation of immune cells and the immune escape of tumor cells. In contrast, there are also tumor suppressor miRNAs that are able to activate the immune system. Therefore, studies on the altered expression of miRNAs that consider both the oncogenic and tumor-suppressive aspects of miRNAs have become an important research field for advancing immunotherapeutic interventions using miRNAs or their inhibitors as therapeutics. In the current review, their potential in the immunomodulation of immune cells and their use as immune stimulatory molecules to elicit specific cytotoxic responses against the tumor are discussed.
Higher Education Students’ Task Motivation in the Generative Artificial Intelligence Context: The Case of ChatGPT
Authors: Hmoud Mohammad , Swaity Hadeel , Hamad Nardin , Karram Omar , Daher Wajeeh
Published: January 2024

Artificial intelligence has been attracting the attention of educational researchers recently, especially ChatGPT as a generative artificial intelligence tool. The context of generative artificial intelligence could impact different aspects of students’ learning, such as the motivational aspect. The present research intended to investigate the characteristics of students’ task motivation in the artificial intelligence context, specifically in the ChatGPT context. The researchers interviewed 15 students about their experiences with ChatGPT to collect data. The researchers used inductive and deductive content analysis to investigate students’ motivation when learning with ChatGPT. To arrive at the categories and sub-categories of students’ motivation, the researchers used the MAXQDA 2022. Five main categories emerged: task enjoyment, reported effort, result assessment, perceived relevance, and interaction. Each category comprised at least two sub-categories, and each sub-category was further organized into codes. The results indicated more positive characteristics of motivation than negative ones. The previous results could be due to the conversational or social aspect of the chatbot, enabling relationships with humans and enabling the maintenance of good quality conversations with them. We conclude that a generative AI could be utilized in educational settings to promote students’ motivation to learn and thus raise their learning achievement.
Culicoides-Specific Fitness Increase of Vesicular Stomatitis Virus in Insect-to-Insect Infections
Authors: Rozo-Lopez Paula , Drolet Barbara S.
Published: January 2024

Vesicular stomatitis virus (VSV) is an arthropod-borne virus affecting livestock. In the United States, sporadic outbreaks result in significant economic losses. During epizootics, Culicoides biting midges are biological vectors and key to the geographic expansion of outbreaks. Additionally, Culicoides may play a role in VSV overwintering because females and males are capable of highly efficient venereal transmission, despite their relatively low virus titers. We hypothesized that VSV propagated within a midge has increased fitness for subsequent midge infections. To evaluate the potential host-specific fitness increase, we propagated three viral isolates of VSV in porcine skin fibroblasts and Culicoides cell lines. We then evaluated the viral infection dynamics of the different cell-source groups in Culicoides sonorensis. Our results indicate that both mammalian- and insect-derived VSV replicate well in midges inoculated via intrathoracic injection, thereby bypassing the midgut barriers. However, when the virus was required to infect and escape the midgut barrier to disseminate after oral acquisition, the insect-derived viruses had significantly higher titers, infection, and dissemination rates than mammalian-derived viruses. Our research suggests that VSV replication in Culicoides cells increases viral fitness, facilitating midge-to-midge transmission and subsequent replication, and further highlights the significance of Culicoides midges in VSV maintenance and transmission dynamics.
Macroecology of Dung Beetles in Italy
Authors: Fattorini Simone , Vitozzi Alessia , Di Biase Letizia , Bergamaschi Davide
Published: January 2024

The Italian fauna includes about 170 species/subspecies of dung beetles, being one of the richest in Europe. We used data on dung beetle distribution in the Italian regions to investigate some macroecological patterns. Specifically, we tested if species richness decreased southward (peninsula effect) or northward (latitudinal gradient). We also considered the effects of area (i.e., the species–area relationship), topographic complexity, and climate in explaining dung beetle richness. Finally, we used multivariate techniques to identify biotic relationships between regions. We found no support for the peninsula effect, whereas scarabaeines followed a latitudinal gradient, thus supporting a possible role of southern areas as Pleistocene refuges for this group of mainly thermophilic beetles. By contrast, aphodiines were more associated with cold and humid climates and do not show a distinct latitudinal pattern. In general, species richness was influenced by area, with the Sardinian fauna being however strongly impoverished because of its isolation. Faunal patterns for mainland regions reflect the influence of current ecological settings and historical factors (Pleistocene glaciations) in determining species distributions.
Central American and Caribbean Consensus Document for the Optimal Management of Oral Anticoagulation in Patients with Non-Valvular Atrial Fibrillation Endorsed by the Central American and Caribbean Society of Arterial Hypertension and Cardiovascular Prevention
Authors: Wyss Fernando , Barrios Vivencio , Méndez Máxima , Ramos Samuel , Gonzalez Ángel , Ortiz Héctor , Díaz Marco Rodas , Castillo Gabriela , Quesada Daniel , Franco Carlos Enrique , Ventura Jaime , López Emilio Peralta , Somoza Francisco , Montealegre Ariel Arguello , Meneses Daniel , Pichel Daniel , Valdez Osiris
Published: January 2024

Atrial fibrillation (AF) is the most common arrhythmia in adults. Prevention of the ischaemic risk with oral anticoagulants (OACs) is widely recommended, and current clinical guidelines recommend direct oral anticoagulants (DOACs) as preference therapy for stroke prevention. However, there are currently no clinical practice guidelines or recommendation documents on the optimal management of OACs in patients with AF that specifically address and adapt to the Central American and Caribbean context. The aim of this Delphi-like study is to respond to doubts that may arise in the management of OACs in patients with non-valvular AF in this geographical area. A consensus project was performed on the basis of a systematic review of the literature, a recommended ADOLOPMENT-like approach, and the application of a two-round Delphi survey. In the first round, 31 recommendations were evaluated and 30 reached consensus, of which, 10 unanimously agreed. The study assessed expert opinions in a wide variety of contextualized recommendations for the optimal management of DOACs in patients with non-valvular atrial fibrillation (NVAF). There is a broad consensus on the clinical practice guideline (CPG) statements used related to anticoagulation indication, patient follow-up, anticoagulation therapy complications, COVID-19 management and prevention, and cardiac interventions.
Lower Urinary Tract Inflammation and Infection: Key Microbiological and Immunological Aspects
Authors: Dickson Kayle , Zhou Juan , Lehmann Christian
Published: January 2024

The urinary system, primarily responsible for the filtration of blood and waste, is affected by several infectious and inflammatory conditions. Focusing on the lower tract, this review outlines the physiological and immune landscape of the urethra and bladder, addressing key immunological and microbiological aspects of important infectious/inflammatory conditions. The conditions addressed include urethritis, interstitial cystitis/bladder pain syndrome, urinary tract infections, and urosepsis. Key aspects of each condition are addressed, including epidemiology, pathophysiology, and clinical considerations. Finally, therapeutic options are outlined, highlighting gaps in the knowledge and novel therapeutic approaches.
Racial Disparities in Infliximab Efficacy for Ulcerative Colitis: Evidence Synthesis and Effect Modification Assessment
Authors: Bonovas Stefanos , Tsantes Andreas G. , Sokou Rozeta , Tsantes Argirios E. , Nikolopoulos Georgios K. , Piovani Daniele
Published: January 2024

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods to generate race-specific efficacy estimates. Then, we tested the effect modification by race by comparing the race-specific estimates derived from independent evidence syntheses. We computed ratios of relative risks (RRRs) and performed tests of statistical interaction. We analyzed data from five randomized, placebo-controlled trials evaluating IFX as induction and maintenance therapy for adults with moderate-to-severe UC (875 participants; 45% Asians). We found no substantial evidence of racial differences concerning the efficacy of IFX in inducing clinical response (RRR = 0.89, 95% CI: 0.66–1.20; p = 0.44), clinical remission (RRR = 0.58, 95% CI: 0.24–1.44; p = 0.24), and mucosal healing (RRR = 0.99, 95% CI: 0.69–1.41; p = 0.95), or maintaining clinical remission (RRR = 0.81, 95% CI: 0.46–1.42; p = 0.45) and mucosal healing (RRR = 0.84, 95% CI: 0.48–1.46; p = 0.53), between Asian and Caucasian populations. Future clinical studies should expand the participation of racial minorities to comprehensively assess potential racial differences in the effectiveness of advanced therapies, including IFX, in the context of treating UC.
Patient Involvement in the Rehabilitation Process Is Associated with Improvement in Function and Goal Attainment: Results from an Explorative Longitudinal Study
Authors: Sagen Joachim Støren , Kjeken Ingvild , Habberstad Andreas , Linge Anita Dyb , Simonsen Ann Elisabeth , Lyken Anne Dorte , Irgens Eirik Lind , Framstad Heidi , Lyby Peter Solvoll , Klokkerud Mari , Dagfinrud Hanne , Moe Rikke Helene
Published: January 2024

The objective was to explore the associations between patient involvement in the rehabilitation process and improvements in function and goal attainment in the first year after rehabilitation. The longitudinal multicenter study RehabNytte provided data from participants who had been referred to rehabilitation (n = 2113). Quality indicator (QI) pass rates (% yes) were used to assess patient involvement in the rehabilitation process. The Patient-Specific Functional Scale (PSFS) (10 = best possible) was used to assess function. The outcome QI on goal achievement (response options of yes/no) was used to assess goal attainment. Logistic regression and paired sample t-tests were used to examine associations and mean changes in function from rehabilitation admission up to 3, 6, and 12 months. Most participants (95%) were involved in goal-setting, which was positively associated with younger age (OR 0.97, 95% CI 0.95–0.99) and female sex (OR 1.87, 95% CI 1.15–3.02). Function improved over the follow-up period, with greater improvements in the active goal-setting group. Being involved in goal planning almost tripled the odds of goal attainment (OR 2.78, 95% CI 1.60–4.83) and involvement in the rehabilitation plan almost doubled it (OR 1.99, 95% CI 1.41–2.81). Most participants were involved in rehabilitation goal-setting/planning and being involved was associated with beneficial functional outcomes and greater goal attainment.
The Utility of Intravenous Methylprednisolone as an Adjunct Treatment for Drug-Resistant Amiodarone-Induced Thyrotoxicosis
Authors: Lewandowski Krzysztof Cezary , Kawalec Joanna , Kusiński Michał , Dąbrowska Katarzyna , Matusiak Aleksandra Ewa , Dudek Iga , Lewiński Andrzej
Published: January 2024

Background: Amiodarone-induced thyrotoxicosis (AIT) may pose treatment challenges. We present a series of patients in which we achieved the normalisation of free T3 (FT3) using intravenous methylprednisolone (ivMP) in AIT refractory to thiamazole and oral prednisone. Namely, in three males (aged 56, 50 and 64, all with a history of AF and/or a low ejection fraction), an addition of ivMP resulted in the normalisation of FT3, which allowed successful thyroidectomy. In another case of a 65-year-old man, we initially succeeded in the normalisation of FT3 using ivMP from FT4 > 7.77 ng/dL (0.93–1.7) to 2.41 ng/dL and in that of FT3 from 14.95 pg/mL (2–4.4) to 2.05 pg/mL), but four weeks after stopping ivMP, despite the continuation of thiamazole and prednisone, there was rebound thyrotoxicosis: FT4 > 7.77 ng/dL and FT3—5.46 pg/mL. Intravenous MP was restated leading to a decline in FT4 to 2.51 ng/dL and in FT3 to 1.92 pg/mL, thus allowing a successful thyroidectomy. Finally, in a 78-year-old man with AF, goitre, and AIT resistant to thiamazole, prednisone and lithium carbonate, we obtained a reduction in FT4 to 1.51 ng/dL and in FT3 to 3.17 pg/mL after seven pulses of ivMP. Oral prednisone was gradually reduced and successfully stopped about six months later. He remained on low-dose thiamazole (5 mg od). Conclusions: Pulse ivMP in addition to oral steroids may be a useful adjunct therapy either for the preparation of a thyroidectomy or as a treatment modality in drug-resistant AIT. Though a total cure is possible, there is a danger of a rebound worsening of thyrotoxicosis after premature discontinuation of ivMP.
Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes
Authors: Potiris Anastasios , Perros Paraskevas , Drakaki Eirini , Mavrogianni Despoina , Machairiotis Nikolaos , Sfakianakis Antonios , Karampitsakos Theodoros , Vrachnis Dionysios , Antonakopoulos Nikolaos , Panagopoulos Periklis , Drakakis Peter , Stavros Sofoklis
Published: January 2024

Background: Infertility affects about 80 million individuals worldwide and 10–15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. Methods: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. Results: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. Conclusions: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children.
A Comprehensive Clinical Review of Maxillary Sinus Floor Elevation in Patients with Well-Defined Faintly Radiopaque Lesions in the Antrum
Authors: Nosaka Yasuhiro , Nosaka Hitomi , Munakata Motohiro , Sanda Minoru
Published: January 2024

Well-defined, faintly radiopaque lesions are occasionally observed in the antrum of the maxillary sinus in asymptomatic patients during maxillary sinus floor elevation. These lesions are treated as antral pseudocysts (AP) based on the clinical diagnosis in some cases, and maxillary sinus floor elevation is performed without enucleating these lesions. However, further surgery is required after implant placement if the lesion is a mucocele, odontogenic cyst, or tumour. This comprehensive clinical review aimed to identify an appropriate approach for maxillary sinus floor elevation in patients with well-defined, faintly radiopaque lesions in the antrum based on our clinical experience.
Influence of Seasonality and Public-Health Interventions on the COVID-19 Pandemic in Northern Europe
Authors: Quinn Gerry A. , Connolly Michael , Fenton Norman E. , Hatfill Steven J. , Hynds Paul , ÓhAiseadha Coilín , Sikora Karol , Soon Willie , Connolly Ronan
Published: January 2024

Background: Most government efforts to control the COVID-19 pandemic revolved around non-pharmaceutical interventions (NPIs) and vaccination. However, many respiratory diseases show distinctive seasonal trends. In this manuscript, we examined the contribution of these three factors to the progression of the COVID-19 pandemic. Methods: Pearson correlation coefficients and time-lagged analysis were used to examine the relationship between NPIs, vaccinations and seasonality (using the average incidence of endemic human beta-coronaviruses in Sweden over a 10-year period as a proxy) and the progression of the COVID-19 pandemic as tracked by deaths; cases; hospitalisations; intensive care unit occupancy and testing positivity rates in six Northern European countries (population 99.12 million) using a population-based, observational, ecological study method. Findings: The waves of the pandemic correlated well with the seasonality of human beta-coronaviruses (HCoV-OC43 and HCoV-HKU1). In contrast, we could not find clear or consistent evidence that the stringency of NPIs or vaccination reduced the progression of the pandemic. However, these results are correlations and not causations. Implications: We hypothesise that the apparent influence of NPIs and vaccines might instead be an effect of coronavirus seasonality. We suggest that policymakers consider these results when assessing policy options for future pandemics. Limitations: The study is limited to six temperate Northern European countries with spatial and temporal variations in metrics used to track the progression of the COVID-19 pandemic. Caution should be exercised when extrapolating these findings.
Clinical Efficacy of 5-Fluorouracil and Bleomycin in Dermatology
Authors: Kim Suyeon , Woo Yu Ri , Cho Sang Hyun , Lee Jeong Deuk , Kim Hei Sung
Published: January 2024

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin treatment is effective in hypertrophic scars and warts, but intralesional 5-FU may also be considered since it is cheaper and less painful. Moreover, intralesional 5-FU and bleomycin injection is a viable option for premalignant lesions (i.e., actinic keratosis) and inoperable skin cancers. Both bleomycin and 5-FU have been applied as treatment adjuncts for vitiligo, with 5-FU showing a slightly better outcome. Both agents have a good safety profile, and no serious side effects have been reported following their use in the field of dermatology.
CMR Mapping: The 4th-Era Revolution in Cardiac Imaging
Authors: Carrabba Nazario , Amico Mattia Alexis , Guaricci Andrea Igoren , Carella Maria Cristina , Maestrini Viviana , Monosilio Sara , Pedrotti Patrizia , Ricci Fabrizio , Monti Lorenzo , Figliozzi Stefano , Torlasco Camilla , Barison Andrea , Baggiano Andrea , Scatteia Alessandra , Pontone Gianluca , Dellegrottaglie Santo
Published: January 2024

Cardiac magnetic resonance (CMR) imaging has witnessed substantial progress with the advent of parametric mapping techniques, most notably T1 and T2 mapping. These advanced techniques provide valuable insights into a wide range of cardiac conditions, including ischemic heart disease, cardiomyopathies, inflammatory cardiomyopathies, heart valve disease, and athlete’s heart. Mapping could be the first sign of myocardial injury and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. The ability of parametric mapping to offer a quantitative assessment of myocardial tissue properties addresses the limitations of conventional CMR methods, which often rely on qualitative or semiquantitative data. However, challenges persist, especially in terms of standardization and reference value establishment, hindering the wider clinical adoption of parametric mapping. Future developments should prioritize the standardization of techniques to enhance their clinical applicability, ultimately optimizing patient care pathways and outcomes. In this review, we endeavor to provide insights into the potential contributions of CMR mapping techniques in enhancing the diagnostic processes across a range of cardiac conditions.
Valve-in-Valve Transcatheter Aortic Valve Replacement: From Pre-Procedural Planning to Procedural Scenarios and Possible Complications
Authors: Di Muro Francesca , Cirillo Chiara , Esposito Luca , Silverio Angelo , Ferruzzi Germano , D’Elia Debora , Formisano Ciro , Romei Stefano , Vassallo Maria , Di Maio Marco , Attisano Tiziana , Meucci Francesco , Vecchione Carmine , Bellino Michele , Galasso Gennaro
Published: January 2024

Over the last decades, bioprosthetic heart valves (BHV) have been increasingly implanted instead of mechanical valves in patients undergoing surgical aortic valve replacement (SAVR). Structural valve deterioration (SVD) is a common issue at follow-up and can justify the need for a reintervention. In the evolving landscape of interventional cardiology, valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has emerged as a remarkable innovation to address the complex challenges of patients previously treated with SAVR and has rapidly gained prominence as a feasible technique especially in patients at high surgical risk. On the other hand, the expanding indications for TAVR in progressively younger patients with severe aortic stenosis pose the crucial question on the long-term durability of transcatheter heart valves (THVs), as patients might outlive the bioprosthetic valve. In this review, we provide an overview on the role of ViV TAVR for failed surgical and transcatheter BHVs, with a specific focus on current clinical evidence, pre-procedural planning, procedural techniques, and possible complications. The combination of integrated Heart Team discussion with interventional growth curve makes it possible to achieve best ViV TAVR results and avoid complications or put oneself ahead of time from them.
Drug-Related Problems and Sick Day Management Considerations for Medications that Contribute to the Risk of Acute Kidney Injury
Authors: Truong Mimi , Tesfaye Wubshet , Sud Kamal , Van Connie , Seth Shrey , Croker Nerida , Castelino Ronald Lynel
Published: January 2024

Background: Medication use during acute illness increases the risk of experiencing drug related problems (DRPs), including acute kidney injuries. It is recommended that potentially nephrotoxic medications are withheld during acute illness, including sulfonylureas, angiotensin converting enzyme inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatories and sodium glucose co-transporter 2 inhibitors (SADMANS). It is unknown if Australian pharmacists currently provide sick day medication management advice regarding SADMANS medications. Hence, we aimed to identify current DRPs and the recommendations made during residential medication management reviews (RMMRs), especially with SADMANS medications. Methods: A retrospective review of 408 RMMRs was conducted. DRPs and pharmacist recommendations were classified according to a modified DOCUMENT system. General practitioners’ (GP) recommendations were also categorised. Results: Over 97% of residents experienced at least one DRP. Common problems for non-SADMANS medications were “toxicity or adverse drug reaction”, “drug selection” and “over/underdosing” and those for SADMANS medications included “toxicity or adverse drug reaction”, “monitoring” and “drug selection”. GPs agreed with pharmacist recommendations approximately 40% of the time. No pharmacists provided sick day medication management advice for SADMANS medications. Conclusion: DRPs remain highly prevalent in aged care facilities. Medication reviews effectively identify and resolve DRPs approximately 40% of the time, but do not currently minimise the risk associated with using SADMANS medications during sick days, which is a potential area of improvement.
Chronic Kidney Disease in the Older Adult Patient with Diabetes
Authors: Ravender Raja , Roumelioti Maria-Eleni , Schmidt Darren W. , Unruh Mark L. , Argyropoulos Christos
Published: January 2024

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and older adult individuals. DM may accelerate the aging process, and the age-related declines in the estimated glomerular filtration rate (eGFR) can pose a challenge to diagnosing diabetic kidney disease (DKD) using standard diagnostic criteria especially with the absence of severe albuminuria among older adults. In the presence of CKD and DM, older adult patients may need multidisciplinary care due to susceptibility to various health issues, e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to older adults. We review the evidence that the benefits from these newer therapies apply equally to older and younger patients with CKD and diabetes type 2 and propose a comprehensive management. This framework will address nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), sodium glucose co-transporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and glucagon like peptide 1 receptor agonists (GLP1-RAs).
Prognostic Value of Combined Neutrophil-to-Lymphocyte Ratio and Imaging Tumor Capsule in Solitary Hepatocellular Carcinoma Patients after Narrow-Margin Hepatectomy
Authors: Chen Desheng , Mao Pengjuan , Sun Chen , Fan Xuhui , Zhu Qi , Chen Zeping , He Zeping , Lou Yichao , Sun Hongcheng
Published: January 2024

Background: The study aimed to investigate the clinical value and prognostic patterns of the neutrophil-to-lymphocyte ratio (NLR) and imaging tumor capsule (ITC) in solitary hepatocellular carcinoma (HCC) patients undergoing narrow-margin hepatectomy. Methods: Data for solitary HCC patients treated with narrow-margin surgery were extracted from Shanghai General Hospital. Clinical features of recurrence-free survival (RFS), overall survival (OS), and early recurrence were investigated by Cox/logistic regression. The significant variables were subsequently incorporated into the nomogram pattern. Survival analysis stratified by NLR and ITC was also performed. Results: The study included a cohort of 222 patients, with median RFS and OS of 24.083 and 32.283 months, respectively. Both an NLR ≥ 2.80 and incomplete ITC had a significant impact on prognosis. NLR and ITC independently affected RFS and OS, whereas alpha-fetoprotein (AFP) and ITC were identified as independent factors for early relapse. The RFS and OS nomogram, generated based on the Cox model, demonstrated good performance in validation. The combination of NLR and ITC showed greater predictive accuracy for 5-year RFS and OS. Subgroups with an NLR ≥ 2.80 and incomplete ITC had the worst prognosis. Conclusions: Both NLR and ITC significantly affected RFS, OS, and early recurrence among solitary HCC patients who underwent narrow-margin hepatectomy. The combination of NLR and ITC has the potential to guide rational clinical treatment and determine the prognosis.
Quantification of hs-Troponin Levels and Global Longitudinal Strain among Critical COVID-19 Patients with Myocardial Involvement
Authors: Alsagaff Mochamad Yusuf , Wardhani Louisa Fadjri Kusuma , Nugraha Ricardo Adrian , Putra Tony Santoso , Khrisna Bagus Putra Dharma , Al-Farabi Makhyan Jibril , Gunadi Ruth Irena , Azmi Yusuf , Budianto Christian Pramudita , Fagi Rosi Amrilla , Luthfah Nadya , Subagjo Agus , Oktaviono Yudi Her , Lefi Achmad , Dharmadjati Budi Baktijasa , Alkaff Firas Farisi , Pikir Budi Susetyo
Published: January 2024

Background. Myocardial involvement among critically ill patients with coronavirus disease 2019 (COVID-19) often has worse outcomes. An imbalance in the oxygen supply causes the excessive release of pro-inflammatory cytokines, which results in increased ventilation requirements and the risk of death in COVID-19 patients. Purpose. We evaluated the association between the hs-troponin I levels and global longitudinal strain (GLS) as evidence of myocardial involvement among critical COVID-19 patients. Methods. We conducted a prospective cohort study from 1 February to 31 July 2021 at RSUD Dr. Soetomo, Surabaya, as a COVID-19 referral center. Of the 65 critical COVID-19 patients included, 41 (63.1%) were men, with a median age (interquartile range) of 51.0 years (20.0–75.0). Subjects were recruited based on WHO criteria for severe COVID-19, and myocardial involvement in the form of myocarditis was assessed using CDC criteria. Subjects were examined using echocardiography to measure the GLS, and blood samples were taken to measure the hs-troponin. Subjects were then followed for their need for mechanical ventilation and in-hospital mortality. Results. Severe COVID-19 patients with cardiac injury were associated with an increased need for intubation (78.5%) and an increased incidence of myocarditis (50.8%). There was a relationship between the use of intubation and the risk of death in patients (66.7% vs. 33.3%, p-value < 0.001). Decreased GLS and increased hs-troponin were associated with increased myocarditis (p values < 0.001 and 0.004, respectively). Decreased GLS was associated with a higher need for mechanical ventilation (12.17 + 4.79 vs. 15.65 + 4.90, p-value = 0.02) and higher mortality (11.36 + 4.64 vs. 14.74 + 4.82; p-value = 0.005). Elevated hs-troponin was associated with a higher need for mechanical ventilation (25.33% vs. 3.56%, p-value = 0.002) and higher mortality (34.57% vs. 5.76%, p-value = 0.002). Conclusions. Critically ill COVID-19 patients with myocardial involvement and elevated cardiac troponin levels are associated with a higher need for mechanical ventilation and higher mortality.
The Effects of Neuromonitoring and Cerebrolysin Administration on Outcomes in Patients with Traumatic Brain Injury—An Interventional Pilot Study
Authors: Jarosz Konrad , Kojder Klaudyna , Skonieczna-Żydecka Karolina , Andrzejewska Agata , Sołek-Pastuszka Joanna , Jurczak Anna
Published: January 2024

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality. Methods: A cohort of 56 patients was included in this non-randomised, real-time, pre–post-interventional study. The patients were assessed with the Glasgow Coma Scale (GCS) and divided into two groups: severe (GCS < 8) and non-severe (GCS > 8). After the radiological examination (CT scan), the patients were qualified for an immediate neurosurgical procedure if needed. The patients were admitted to the intensive care unit, where a standardised protocol for TBI treatment was implemented. Additional neuromonitoring was applied. Results: There were 56 patients (19 females; 33.9%), of which 41 were considered severe cases; the patients were allocated to the Cerebrolysin (n = 25) or control groups (n = 31). In a generalised linear model (GLM) approach, the use of Cerebrolysin was associated with a decrease in the probability of death in non-severe patients (by 0.333 (standard error (SE) = 0.157, p = 0.034)) but not in severe patients (estimate (Est.) = −0.115, SE = 0.127, p = 0.364). Patients who received Cerebrolysin and who were neuromonitored had favourable outcomes and better survival rates. Conclusions: A multimodal treatment approach with monitoring and Cerebrolysin may have a beneficial effect on patients with less severe TBIs; however, the present study has multiple limitations, and further research is needed.
Design and Assessment of Hybrid MTJ/CMOS Circuits for In-Memory-Computation
Authors: Barla Prashanth , Shivarama Hemalatha , Deepa Ganesan , Ujjwal Ujjwal
Published: January 2024

Hybrid magnetic tunnel junction/complementary metal oxide semiconductor (MTJ/CMOS) circuits based on in-memory-computation (IMC) architecture is considered as the next-generation candidate for the digital integrated circuits. However, the energy consumption during the MTJ write process is a matter of concern in these hybrid circuits. In this regard, we have developed a novel write circuit for the contemporary three-terminal perpendicular-MTJs that works on the voltage-gated spin orbit torque (VG+SOT) switching mechanism to store the information in hybrid circuits for IMC architecture. Investigation of the novel write circuit reveals a remarkable reduction in the total energy consumption (and energy delay product) of 92.59% (95.81) and 92.28% (42.03%) than the conventional spin transfer torque (STT) and spin-Hall effect assisted STT (SHE+STT) write circuits, respectively. Further, we have developed all the hybrid logic gates followed by nonvolatile full adders (NV-FAs) using VG+SOT, STT, and SHE+STT MTJs. Simulation results show that with the VG+SOT NOR-OR, NAND-AND, XNOR-XOR, and NV-FA circuits, the reduction in the total power dissipation is 5.35% (4.27%), 5.62% (3.2%), 3.51% (2.02%), and 4.46% (2.93%) compared to STT (SHE+STT) MTJs respectively.
The Metallotolerance and Biosorption of As(V) and Cr(VI) by Black Fungi
Authors: Medina-Armijo Cristy , Isola Daniela , Illa Josep , Puerta Anna , Viñas Marc , Prenafeta-Boldú Francesc X.
Published: January 2024

A collection of 34 melanized fungi isolated previously from anthropogenic contaminated sites were assessed for their tolerance to toxic concentrations of As(V) and Cr(VI) anions. Three strains of the species Cyphellophora olivacea, Rhinocladiella similis, and Exophiala mesophila (Chaetothyriales) were identified as hyper-metallotolerant, with estimated IC50 values that ranged from 11.2 to 16.9 g L−1 for As(V) and from 2.0 to 3.4 g L−1 for Cr(VI). E. mesophila and R. similis were selected for subsequent assays on their biosorption capacity and kinetics under different pH values (4.0 and 6.5) and types of biomass (active and dead cells and melanin extracts). The fungal biosorption of As(V) was relatively ineffective, but significant removal of Cr(VI) was observed from liquid cultures. The Langmuir model with second-order kinetics showed maximum sorption capacities of 39.81 mg Cr6+ g−1 for R. similis and 95.26 mg Cr6+ g−1 for E. mesophila on a dry matter basis, respectively, while the kinetic constant for these two fungi was 1.32 × 10−6 and 1.39 × 10−7 g (mg Cr6+ min)−1. Similar experiments with melanin extracts of E. mesophila showed maximum sorption capacities of 544.84 mg Cr6+ g−1 and a kinetic constant of 1.67 × 10−6 g (mg Cr6+ min)−1. These results were compared to bibliographic data, suggesting that metallotolerance in black fungi might be the result of an outer cell-wall barrier to reduce the diffusion of toxic metals into the cytoplasm, as well as the inner cell wall biosorption of leaked metals by melanin.