bluuebunny/crossref_metadata_2025 huggingface dataset:
Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review
Authors: Li Ruolin , Shokri Fereshteh , Rincon Alejandro , Rivadeneira Fernando , Medina-Gomez Carolina , Ahmadizar Fariba
Published: August 2023

Background: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. Methods: A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Results: Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., Bifidobacterium) and decrease harmful taxa (e.g., Bacteroides and Intestinibacter). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., Enterococcus faecium (i.e., E. faecium)) in T2D patients with poor compared to optimal glycemic control. Conclusions: This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment.
Combined Single Gene Testing and Genome Sequencing as an Effective Diagnostic Approach for Anophthalmia and Microphthalmia Patients
Authors: Basharat Rabia , Rodenburg Kim , Rodríguez-Hidalgo María , Jarral Afeefa , Ullah Ehsan , Corominas Jordi , Gilissen Christian , Zehra Syeda Tatheer , Hameed Usman , Ansar Muhammad , de Bruijn Suzanne E.
Published: August 2023

Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more than half of A/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with A/M from Pakistani cohort and an unknown molecular basis. Single gene testing of FOXE3 was performed, followed by genome sequencing for unsolved probands in order to establish a genetic diagnosis for these families. All seven families were provided with a genetic diagnosis. The identified variants were all homozygous, classified as (likely) pathogenic and present in an A/M-associated gene. Targeted FOXE3 sequencing revealed two previously reported pathogenic FOXE3 variants in four families. In the remaining families, genome sequencing revealed a known pathogenic PXDN variant, a novel 13bp deletion in VSX2, and one novel deep intronic splice variant in PXDN. An in vitro splice assay was performed for the PXDN splice variant which revealed a severe splicing defect. Our study confirmed the utility of genome sequencing as a diagnostic tool for A/M-affected individuals. Furthermore, the identification of a novel deep intronic pathogenic variant in PXDN highlights the role of non-coding variants in A/M-disorders and the value of genome sequencing for the identification of this type of variants.
Special Issue: New Advances in Bioinformatics and Biomedical Engineering Using Machine Learning Techniques, IWBBIO-2022
Authors: Valenzuela Olga , Ortuño Francisco , Benso Alfredo , Schwartz Jean-Marc , de Brevern Alexandre G. , Rojas Ignacio
Published: August 2023

Bioinformatics is revolutionizing Biomedicine in the way we treat and diagnose pathologies related to biological manifestations resulting from variations or mutations of our DNA [...]
Fanaticism and E. M. Cioran’s “Lyrical Leprosy”
Authors: Airaksinen Timo
Published: August 2023

People harass people to defend and promote their fundamental beliefs, political ideologies, religious dogmas, and the Truth. They create these with marvelous lucidity and unnerving verve, spreading, guarding, and enforcing their convictions. Fanatical ideologies penetrate and pollute our life world like “lyrical leprosy”. We need a coping strategy. Conformists may want to go along and join the perpetrators, whomever they happen to be. Activists fight ideological pollution, a risky strategy. Indifference and apathy do not pollute others and are less dangerous than rebelling. Following E. M. Cioran, I discuss three defensive strategies: those of a skeptic, an idler, and an aesthete. I reject trivializing the third strategy; instead, I discuss an ironist’s options. A recommendable route to indifference is to read the Truth metaphorically and ironize it. This voids its contents, and the result is adiaphora. We can also start with irony and metaphorize it. Such linguistic–aesthetic methods thwart the viperous dogmas that otherwise harass us from the cradle to the grave. The Truth is a treacherous construct. How to avoid it? How to deflect ideologically motivated terror?
Communication and Violence in the Poetics of Terayama Shūji: From the Poetic to the Theatric
Authors: Okada Shunsuke , Beckman Jason M.
Published: August 2023

This article will focus on the theory of poetics Terayama Shūji develops in Postwar Poetry: The Absence of Ulysses (Sengoshi: yurishīzu no fuzai, 1965) and Language as Violence (Bōryoku toshite no gengo, 1970). Postwar Poetry, his first theoretical writings on prose poetry, can be said to be a book about the poetic communication and “discommunication”—a wasei-eigo coinage of Tsurumi Shunsuke’s that Terayama frequently invokes—that occurs in mass communication, stemming from the conflict with print (katsuji). In this book, Terayama develops not autonomous “monologue”, but a theory of the taiwa/dialogue of poetry. However, Language as Violence contains not only the taiwa (dialogue) of his early poetics but the problem of bōryoku (violence) in his later theatrical works and theory of theater, which becomes an important theme in his body of work. Comparing with Georges Sorel’s Réflexions sur la violence that he cited, I would like to examine the description of the book’s titualar violence. As I shed light on Terayama’s poetics and view of language, I will attempt to establish a connection with his plays and theory of theater.
Interviews with HIV Experts for Development of a Mobile Health Application in HIV Care—A Qualitative Study
Authors: Schaaf Jannik , Weber Timm , von Wagner Michael , Stephan Christoph , Carney Jonathan , Köhler Susanne Maria , Voigt Alexander , Noll Richard , Storf Holger , Müller Angelina
Published: August 2023

The Communication and Tracing App HIV (COMTRAC-HIV) project aims to develop a mobile health application for integrated care of HIV patients due to the low availability of those apps in Germany. This study addressed organizational conditions and necessary app functionalities, especially for the care of late diagnosed individuals (late presenters) and those using pre-exposure prophylaxis. We followed a human-centered design approach and interviewed HIV experts in Germany to describe the context of use of the app. The interviews were paraphrased and analyzed with a qualitative content analysis. To define the context of use, user group profiles were defined and tasks derived, which will represent the functionalities of the app. A total of eight experts were included in the study. The results show that the app should include a symptom diary for entering symptoms, side effects, and their intensity. It offers chat/video call functionality for communication with an HIV expert, appointment organization, and sharing findings. The app should also provide medication overview and reminders for medications and appointments. This qualitative study is a first step towards the development of an app for HIV individuals in Germany. Further research includes involving patients in the initial app design and test design usability.
Involving a Dedicated Epidural-Caring Nurse in Labor Ward Practice Improves Maternal Satisfaction towards Childbirth: A Retrospective Study
Authors: Su Yun-Han , Su Hsiu-Wei , Chang Szu-Ling , Tsai Yu-Lian , Juan Po-Kai , Tsai Jen-Fu , Lai Hui-Chin
Published: August 2023

The quality of healthcare is crucially linked to patient satisfaction, particularly in the provision of neuraxial analgesia for labor pain. Neuraxial analgesia for labor pain control should ideally be readily available when requested. However, in real-world practice, anesthesiologists may not always respond immediately to maternal demands, which can compromise the quality of care. To address this issue, this study aimed to evaluate the effectiveness of involving a dedicated nurse in epidural care to improve maternal satisfaction. This study was conducted in a single tertiary center. Medical records of women with singleton pregnancies above 36 gestational weeks who received neuraxial analgesia for labor pain control were reviewed (N = 354). Among them, 104 women (29%) received care from a dedicated nurse. The results showed that involving a dedicated nurse led to higher maternal satisfaction scores before (4.7 ± 0.5 versus 4.5 ± 0.6, p = 0.001), during (4.7 ± 0.6 versus 4.5 ± 0.6, p = 0.002), and at 24 h postpartum (4.7 ± 0.5 versus 4.5 ± 0.5, p = 0.001), without any adverse impact on maternal, neonatal, or epidural-related complications. These findings suggest that allocating a dedicated nurse to epidural care can effectively enhance maternal satisfaction and potentially improve overall care quality.
Comparison of the Effects of Self-Administered Moxibustion versus Acupressure on Blood Pressure, Stress, Sleep Quality, and Quality of Life in Hypertensive Patients: A Randomized Parallel Trial
Authors: Jung Jongsin , Kim Jaehee
Published: August 2023

This study aimed to evaluate the effects of an 8-week self-administered moxibustion program on blood pressure, stress, sleep quality, and quality of life in hypertensive patients. We compared its effects with those of self-acupressure to assess the feasibility of using moxibustion as a self-management method for hypertension. Forty-six subjects were recruited and randomly assigned to a moxibustion group and an acupressure group. The moxibustion group applied moxa sticks to seven acupoints by themselves five times a week for 8 weeks, while the acupressure group placed acupressure patches on the same acupoints by themselves. Systolic and diastolic blood pressures were measured. Stress was assessed with plasma epinephrine, plasma norepinephrine, and the Perceived Stress Scale (PSS). Sleep quality and quality of life were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF), respectively. Systolic and diastolic blood pressures decreased in the moxibustion and acupressure groups to a similar extent after the 8-week intervention. Plasma epinephrine and norepinephrine levels and PSQI variables were not changed in both groups. PSS decreased only in the moxibustion group. Quality of life related to physical health and environmental health, as assessed by the WHOQOL-BREF, significantly improved to a similar degree in both groups. Both self-administered moxibustion and acupressure therapies were effective in reducing blood pressure in hypertensive patients.
Exogenous Activation of the Ethylene Signaling Pathway Enhances the Freezing Tolerance of Young Tea Shoots by Regulating the Plant’s Antioxidant System
Authors: Chen Yao , Tang Junwei , Ren Hengze , Li Yuteng , Li Congcong , Wang Haoqian , Wang Lu , Yang Yajun , Wang Xinchao , Hao Xinyuan
Published: August 2023

Tea plants (Camellia sinensis (L.) O. Kuntze) frequently suffer severe damage as a result of freezing temperatures in early spring, which severely affect tea quality and tea production in China. Emerging evidence has demonstrated that the ethylene signaling pathway plays an important role in tea plants’ freezing responses. However, how ethylene modulates the response to freezing in sprouting tea shoots is not clear. This study verified that the measurement of relative electrolyte leakage in young shoots after 1 h at −5 °C is a rapid way to evaluate their freezing tolerance in the laboratory. Further exploration of the mechanism involved in increasing tea-shoot freezing tolerance by monitoring changes in the transcription of ethylene-related genes and cold signaling-related genes, and the physiological and biochemical changes after the application of ethephon (2-chloroethylphosphonic acid, an ethylene release reagent), revealed that exogenous ethephon significantly increased the freezing tolerance of tea shoots within 3 days of treatment, while concomitantly altering the expression of the ethylene signaling pathway-related genes (i.e., CsETR1, CsETR2, and CsEBF1). Moreover, antioxidant enzyme activities, including superoxide dismutase, catalase, and peroxidase, were uniformly upregulated, which might constitute a major physiological change induced by ethylene signaling and may be responsible for the observed increase in freezing resistance. Nevertheless, soluble sugars and starch, trehalose metabolism, and cold signaling-related genes did not appear relevant to the freezing tolerance increase following ethephon application. This study demonstrated that the freezing tolerance of sprouting tea shoots can be rapidly increased by the exogenous activation of the ethylene signaling pathway and upregulation of the plant’s antioxidant system.
Meanings and Experiences of Prisoners and Family Members Affected by the COVID-19 Pandemic in a Brazilian Prison Unit: A Grounded Theory Analysis
Authors: Baccon Wanessa Cristina , Salci Maria Aparecida , Carreira Lígia , Gallo Adriana Martins , Marques Francielle Renata Danielli Martins , Paiano Marcelle , Baldissera Vanessa Denardi Antoniassi , Laranjeira Carlos
Published: August 2023

Worldwide, the COVID-19 pandemic represented a health emergency for prisons. This study sought to understand the meanings and experiences through the narratives of prisoners and family members affected by the COVID-19 pandemic in the context of a maximum-security state penitentiary complex in southern Brazil. For this purpose, a qualitative study was developed based on the methodological framework of constructivist grounded theory. Data were collected between February and August 2022 through individual in-depth interviews and field notes. The sample consisted of 41 participants: 28 male prisoners, and 13 family members. Guided by the Charmaz method of grounded theory analysis, the study afforded the core category “Feeling trapped in prison during the COVID-19 pandemic” with three interrelated phases: “Triggering”, “Escalating”, and “Readjustment”. The “Triggering” phase refers to COVID-19-related elements or events that triggered certain reactions, processes, or changes in prison. During the “Escalating” phase, participants became overwhelmed by the suffering caused by incarceration and the pandemic crisis. The “Readjustment” phase involved adapting, reorienting, or reformulating previous approaches or strategies for dealing with a specific situation. Prisons faced complex challenges during the pandemic and were forced to prioritize protecting public health. However, the measures adopted must be carefully evaluated, ensuring their needs and that they are based on scientific evidence. The punitive approach can undermine inmate trust in prison authorities, making it difficult to report symptoms and adhere to preventive measures.
Investigating Metropolitan Hierarchies through a Spatially Explicit (Local) Approach
Authors: Salvia Rosanna , Quaranta Giovanni , Rontos Kostas , Cudlin Pavel , Salvati Luca
Published: August 2023

Assuming a non-neutral impact of space, an explicit assessment of metropolitan hierarchies based on local regression models produces a refined description of population settlement patterns and processes over time. We used Geographically Weighted Regressions (GWR) to provide an enriched interpretation of the density gradient in Greece, estimating a spatially explicit rank–size relationship inspired by Zipf’s law. The empirical results of the GWR models quantified the adherence of real data (municipal population density as a predictor of metropolitan hierarchy) to the operational assumptions of the rank–size relationship. Local deviations from its prediction were explained considering the peculiarity of the metropolitan cycle (1961–2011) in the country. Although preliminary and exploratory, these findings decomposed representative population dynamics in two stages of the cycle (namely urbanization, 1961–1991, and suburbanization, 1991–2011). Being in line with earlier studies, this timing allowed a geographical interpretation of the evolution of a particularly complex metropolitan system with intense (urban) primacy and a weak level of rural development over a sufficiently long time interval. Introducing a spatially explicit estimation of the rank–size relationship at detailed territorial resolutions provided an original contribution to regional science, covering broad geographical scales.
Exploring Equity in a Hierarchical Medical Treatment System: A Focus on Determinants of Spatial Accessibility
Authors: Du Xishihui , Liu Maohua , Luo Siqi
Published: August 2023

It is essential to understand the spatial equity of healthcare services to achieve the Sustainable Development Goals. Spatial and non-spatial factors affect access to healthcare, resulting in inequality in the hierarchical medical treatment system. Thus, to provide a comprehensive equity evaluation, it is indispensable to investigate the extent to which spatial accessibility to healthcare services varies due to various factors. This study attempted to analyze the determinants of healthcare accessibility under multi-trip modes and integrate them into Theil index, as a demand index to evaluate spatial equity in the system. The results reveal an inadequate and inequitable distribution of healthcare resources. While access to primary hospitals is limited (47.37% of residential locations cannot access them on foot), 96.58% of residential locations can access general and tertiary hospitals via public transport or driving. Furthermore, inequitable access to the three-tiered medical system was evaluated on a more granular scale, with primary hospitals being closest to achieving equity (inequitable for only 48.83% of residential locations), followed by general and tertiary hospitals (82.01% and 89.20%, respectively). The unequal residential locations brought on by an abundance of medical resources are far from those with a shortage of resources (66.86% > 5.34%). It is thus suggested that services be expanded or resources be transferred to move toward a more equitable system. Our findings provide policymakers with insights into how to increase accessibility to public health.
The Role of Bifidobacterium bifidum novaBBF7, Bifidobacterium longum novaBLG2 and Lactobacillus paracasei TJB8 to Improve Mechanisms Linked to Neuronal Cells Protection against Oxidative Condition in a Gut-Brain Axis Model
Authors: Ferrari Sara , Galla Rebecca , Mulè Simone , Rosso Giorgia , Brovero Arianna , Macchi Valentina , Ruga Sara , Uberti Francesca
Published: August 2023

Despite the identification of several innovative targets for avoiding cognitive decline, there has yet to be a widely accepted approach that deals with minimising the deterioration of cognitive function. In this light, recent studies suggest that regulating the gut-brain axis with probiotics is a potential therapeutic strategy to support brain health. For this reason, in vitro models were used to examine the efficacy of different probiotic combinations to enhance intestinal homeostasis and positively affect the brain. Therefore, the new formulation has been evaluated for its capacity to modify intestinal barrier functions in a 3D in vitro model without any adverse effects and directly impact the mechanisms underlying cognitive function in a gut-brain axis model. According to our findings, B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL and L. paracasei TJB8 10 mg/mL may successfully modify the intestinal barrier and improve SCFA production. Successively, the probiotics studied caused no harm at the neuronal level, as demonstrated by iNOS, mitochondrial potential, and cell viability tests, confirming their safety features and enhancing antioxidant mechanisms and antineuroinflammation activity. Additionally, the damage caused by oxidative stress was also healed, and critical pathways that result in cognitive impairment were changed by synergetic action, supporting the hypothesis that brain ageing and neurodegeneration are slowed down. All these findings demonstrate the ability of probiotics to affect cognitive processes and their ability to sustain the mechanisms underlying cognitive function by acting on intestinal function.
Galectin-4 Is Involved in the Structural Changes of Glycosphingolipid Glycans in Poorly Differentiated Gastric Cancer Cells with High Metastatic Potential
Authors: Hachisu Kazuko , Tsuchida Akiko , Takada Yoshio , Mizuno Mamoru , Ideo Hiroko
Published: August 2023

Gastric cancer with peritoneal dissemination is difficult to treat surgically, and frequently recurs and metastasizes. Currently, there is no effective treatment for this disease, and there is an urgent need to elucidate the molecular mechanisms underlying peritoneal dissemination and metastasis. Our previous study demonstrated that galectin-4 participates in the peritoneal dissemination of poorly differentiated gastric cancer cells. In this study, the glycan profiles of cell surface proteins and glycosphingolipids (GSLs) of the original (wild), galectin-4 knockout (KO), and rescue cells were investigated to understand the precise mechanisms involved in the galectin-4-mediated regulation of associated molecules, especially with respect to glycosylation. Glycan analysis of the NUGC4 wild type and galectin-4 KO clones with and without peritoneal metastasis revealed a marked structural change in the glycans of neutral GSLs, but not in N-glycan. Furthermore, mass spectrometry (MS) combined with glycosidase digestion revealed that this structural change was due to the presence of the lacto-type (β1-3Galactosyl) glycan of GSL, in addition to the neolacto-type (β1-4Galactosyl) glycan of GSL. Our results demonstrate that galectin-4 is an important regulator of glycosylation in cancer cells and galectin-4 expression affects the glycan profile of GSLs in malignant cancer cells with a high potential for peritoneal dissemination.
Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis
Authors: Kikyo Nobuaki
Published: August 2023

Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA.
The Bladder Tumor Microenvironment Components That Modulate the Tumor and Impact Therapy
Authors: Patwardhan Mugdha Vijay , Mahendran Ratha
Published: August 2023

The tumor microenvironment (TME) is complex and involves many different cell types that seemingly work together in helping cancer cells evade immune monitoring and survive therapy. The advent of single-cell sequencing has greatly increased our knowledge of the cell types present in the tumor microenvironment and their role in the developing cancer. This, coupled with clinical data showing that cancer development and the response to therapy may be influenced by drugs that indirectly influence the tumor environment, highlights the need to better understand how the cells present in the TME work together. This review looks at the different cell types (cancer cells, cancer stem cells, endothelial cells, pericytes, adipose cells, cancer-associated fibroblasts, and neuronal cells) in the bladder tumor microenvironment. Their impact on immune activation and on shaping the microenvironment are discussed as well as the effects of hypertensive drugs and anesthetics on bladder cancer.
Synthesis, Properties, and Biomedical Application of Dicationic Gemini Surfactants with Dodecane Spacer and Carbamate Fragments
Authors: Vasileva Leysan , Gaynanova Gulnara , Valeeva Farida , Romanova Elvira , Pavlov Rais , Kuznetsov Denis , Belyaev Grigory , Zueva Irina , Lyubina Anna , Voloshina Alexandra , Petrov Konstantin , Zakharova Lucia
Published: August 2023

A synthesis procedure and aggregation properties of a new homologous series of dicationic gemini surfactants with a dodecane spacer and two carbamate fragments (N,N′-dialkyl-N,N′-bis(2-(ethylcarbamoyloxy)ethyl)-N,N′-dimethyldodecan-1,6-diammonium dibromide, n-12-n(Et), where n = 10, 12, 14) were comprehensively described. The critical micelle concentrations of gemini surfactants were obtained using tensiometry, conductometry, spectrophotometry, and fluorimetry. The thermodynamic parameters of adsorption and micellization, i.e., maximum surface excess (Гmax), the surface area per surfactant molecule (Amin), degree of counterion binding (β), and Gibbs free energy of micellization (∆Gmic), were calculated. Functional activity of the surfactants, including the solubilizing capacity toward Orange OT and indomethacin, incorporation into the lipid bilayer, minimum inhibitory concentration, and minimum bactericidal and fungicidal concentrations, was determined. Synthesized gemini surfactants were further used for the modification of liposomes dual-loaded with α-tocopherol and donepezil hydrochloride for intranasal treatment of Alzheimer’s disease. The obtained liposomes have high stability (more than 5 months), a significant positive charge (approximately + 40 mV), and a high degree of encapsulation efficiency toward rhodamine B, α-tocopherol, and donepezil hydrochloride. Korsmeyer-Peppas, Higuchi, and first-order kinetic models were used to process the in vitro release curves of donepezil hydrochloride. Intranasal administration of liposomes loaded with α-tocopherol and donepezil hydrochloride for 21 days prevented memory impairment and decreased the number of Aβ plaques by 37.6%, 40.5%, and 72.6% in the entorhinal cortex, DG, and CA1 areas of the hippocampus of the brain of transgenic mice with Alzheimer’s disease model (APP/PS1) compared with untreated animals.
Electrification of Transport Service Applied to Massawa–Asmara
Authors: Colombo Cristian Giovanni , Saldarini Alessandro , Longo Michela , Yaici Wahiba , Borghetti Fabio , Brenna Morris
Published: August 2023

Considering the proposed strict new constraints of public authorities, decarbonization has become a key trend in recent years. Although several countries have started the process of decarbonization through the introduction of electric vehicles in their public services, for many countries, especially developing countries, transportation is still a hard sector to decarbonize. The presence of obsolete and polluting vehicles discourages citizens from using public transport and thus incentivizes the use of private vehicles, which create traffic congestion and increase emissions. Based on these considerations, this paper aimed to implement a simulation for a public service in Eritrea, evaluating whether it is possible to take a long trip using an electric minibus. A case study is implemented highlighting the barriers of electrifying transportation in this area, producing results on fuel consumption and service reliability. In the case study, four scenarios are presented to estimate the service. The scenarios evaluate the possibility to perform from three to five recharges. Fewer charges mean longer charging time, leading to a 2 h charging phase in Scenario 1, while recharging more than twice along the route will lead to shorter 30 min charges, as in Scenario 3. The case study also highlights the relevance of the slope in electric vehicle performance, as reported for the case of Asmara–Massawa travel (Econs= 6.688 kWh). Finally, an environmentally sustainable solution, such as a 92 kWh/day photovoltaic plant, is proposed to power the service.
PEPPSI-Type Pd(II)—NHC Complexes on the Base of p-tert-Butylthiacalix[4]arene: Synthesis and Catalytic Activities
Authors: Gafiatullin Bulat , Akchurina Aigul , Fedoseeva Angelina , Sultanova Elza , Islamov Daut , Usachev Konstantin , Burilov Vladimir , Solovieva Svetlana , Antipin Igor
Published: August 2023

The creation of effective catalytic systems for cross-coupling reactions, reduction, etc., capable of working in water-organic or pure aqueous media is in great demand. The article presents the synthesis of NHC-palladium complexes of the PEPPSI type based on monoimidazolium derivatives of thiacalix[4]arene. The structure of the imidazolium precursors, obtained in 81–88% yields and the complexes themselves, obtained in 40–50% yields, is established using modern methods, including X-ray structural analysis and high-resolution mass spectrometry. It is shown that the obtained complex with bulk substituents near the palladium atom is not inferior to the well-known PEPPSI-type Organ’s catalyst in the catalysis of Suzuki-Miyaura coupling and is four times superior to the latter in the p-nitrophenol reduction reaction. Given the presence of free phenolic hydroxyl groups in the macrocycle, the obtained complexes are of interest for further post-modification or for immobilization on a carrier.
Assessment Methods for Marginal and Internal Fit of Partial Crown Restorations: A Systematic Review
Authors: Di Fiore Adolfo , Zuccon Andrea , Carraro Filippo , Basilicata Michele , Bollero Patrizio , Bruno Giovanni , Stellini Edoardo
Published: August 2023

Background: Different methods are used for the analysis of marginal and internal fit of partial crowns, but not all of them are applicable for in vivo studies. The aim of this review is to search the available methods, described in the current literature, to assess marginal and internal fit in partial crowns. Methods: an electronic search was performed on Pubmed and Web of Science databases to find studies published from 1 January 2017 up to 2 March 2023, following PRISMA guidelines and Cochrane handbook for systematic reviews. The search strategy applied was: “(marginal) AND (fit OR gap OR adaptation OR discrepancy) AND (inlay OR onlay OR partial crown)”. In vitro studies which evaluated marginal and internal fit on CAD CAM or 3D printed partial crowns were included in this review. Quality of the studies was assessed by using Quality Assessment Tool For In Vitro Studies (QUIN tool). Results: 22 studies were included. Among conventional methods, direct view with microscope, indirect view on resin replicas, and silicone replica technique (SRT) were used. Considering new digital methods, micro-CT, SRT 3D and triple scan technique (TST) were applied. Conclusions: Among 2D methods, direct view technique is the most used marginal fit analysis. For a more comprehensive evaluation, a 3D digital analysis is suggested. SRT and indirect view are the only 2D methods available for in vivo analysis. A protocol for the application of TST for assessment in vivo is now available, but no studies are reported in literature yet.
Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches
Authors: Baumeier Christian , Harms Dominik , Aleshcheva Ganna , Gross Ulrich , Escher Felicitas , Schultheiss Heinz-Peter
Published: August 2023

The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches.
Correlations between Dental Implant Infectious Pathologies and Maxillary Sinusitis: A Review Article
Authors: Iușan Simina Angela Lăcrimioara , Costache Carmen , Lucaciu Ondine Patricia , Petrescu Bianca-Nausica , Mirică Ioana Codruța , Toc Dan-Alexandru , Albu Silviu
Published: August 2023

(1) Background: The demands of patients for aesthetic and functional rehabilitation of edentulous areas led to the use of dental implants as therapeutic means on an increasingly large scale. This aspect determined the appearance of some infectious pathologies with a peri-implant starting point that can be complicated by various sinus diseases. The purpose of this review article is to synthesize the existing information in the specialized literature regarding the existing correlations between peri-implant and maxillary sinusitis. (2) Methods: The articles published in five databases were researched using different combinations of search terms. We selected 12 articles from the 250 found, by applying the inclusion and exclusion criteria and removing duplicates. (3) Results: We analyzed the included studies and we found that all of them reported a positive correlation between maxillary sinusitis and peri-implant infectious diseases. There are also reported other pathologies with a peri-implant infectious disease as a starting point such as abscesses, oro-antral communications, or foreign body reactions due to implant or bone graft materials migration. (4) Conclusions: This scoping review highlighted the existence of correlations between peri-implant and sinus pathology and the importance of preventing peri-implant diseases of an infectious nature to avoid the occurrence of these complications.
Prescribed Versus Taken Polypharmacy and Drug–Drug Interactions in Older Cardiovascular Patients during the COVID-19 Pandemic: Observational Cross-Sectional Analytical Study
Authors: Anfinogenova Nina D. , Novikova Oksana M. , Trubacheva Irina A. , Efimova Elena V. , Chesalov Nazary P. , Ussov Wladimir Y. , Maksimova Aleksandra S. , Shelkovnikova Tatiana A. , Ryumshina Nadezhda I. , Stepanov Vadim A. , Popov Sergey V. , Repin Alexey N.
Published: August 2023

The study aimed to assess clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019–2022). Medscape Drug Interaction Checker was used to identify pairwise drug–drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, the total number of DDIs was significantly higher among the prescribed medications (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among the prescribed and taken medications, respectively (p < 0.05). Median numbers of DDIs between the prescribed vs. taken medications were Me = 2, IQR 0–7 vs. Me = 3, IQR 0–7 per record, respectively. Prevalence of polypharmacy was significantly higher among the prescribed medications compared with that among the taken drugs (p < 0.05). Women were taking significantly more drugs and had higher prevalence of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, implement patient engagement in reporting adverse drug reactions, and provide genetic profiling of patients to avoid potentially serious DDIs.
PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement
Authors: Isla Dolores , Sánchez Alfredo , Casal Joaquín , Cobo Manuel , Majem Margarita , Reguart Noemi , Zugazagoitia Jon , Bernabé Reyes
Published: August 2023

Introduction: There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups. Methods: Nominal group and Delphi techniques were used. Eight Spanish experts in lung cancer (the scientific committee of the project) analyzed the use of immunotherapy monotherapy as first-line treatment in patients with NSCLC and high PD-L1 expression. The expert scientific committee formulated several statements based on a scientific review and their own clinical experience. Subsequently, 17 additional Spanish lung cancer experts were selected to appraise the committee’s statements through two Delphi rounds. They completed a Delphi round via an online platform and voted according to a scale from 1 (strongly disagree) to 10 (strongly agree). The statements were approved if ≥70% of experts voted 7 or more. Results: A total of 20 statements were proposed covering the following areas: (1) general characteristics of pivotal clinical trials; (2) overall main outcomes of pivotal clinical trials; and (3) subgroup analysis. All statements reached consensus in the first round. Conclusions: AT, CEMI, and PEMBRO as monotherapy can be considered the standard of care in patients with advanced NSCLC and high PD-L1 expression (≥50%). Moreover, some differences noted among the drugs analyzed in this document might facilitate treatment decision-making, especially in clinically relevant patient subgroups, when using PD-1/PD-L1 inhibitors. The high level of agreement reached among experts supports the proposed statements.
Association between Lipid Levels, Anti-SARS-CoV-2 Spike Antibodies and COVID-19 Mortality: A Prospective Cohort Study
Authors: Mink Sylvia , Saely Christoph H. , Frick Matthias , Leiherer Andreas , Drexel Heinz , Fraunberger Peter
Published: August 2023

Background: Recent studies suggest that both lipid levels and anti-severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) antibody levels are associated with outcome in coronavirus disease 2019 (COVID-19). While both parameters have separately been implicated in the neutralization and clearance of pathogens during severe infections, it is currently unclear whether the interplay of these parameters affects outcome in COVID-19. We therefore aimed to determine whether there was a relationship between lipoproteins, anti-SARS-CoV-2 antibodies, and COVID-19 mortality. Methods: In this prospective, multicenter cohort study, we recruited 1152 hospitalized patients with COVID-19 from five hospitals. Total cholesterol (TC), LDL-C, HDL-C, triglycerides, and anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The investigated endpoint was in-hospital mortality. Results: LDL-C, HDL-C, and TC were significantly lower in non-survivors than in survivors (mg/dL, 95%CI; 56.1, 50.4–61.8 vs. 72.6, 70.2–75.0, p < 0.001; 34.2, 31.7–36.8 vs. 38.1, 37.2–39.1, p = 0.025; 139.3, 130.9–147.7 vs. 157.4, 54.1–160.6, p = 0.002). Mortality risk increased progressively with lower levels of LDL-C, HDL-C, and TC (aOR 1.73, 1.30–2.31, p < 0.001; 1.44, 1.10–1.88, p = 0.008; 1.49, 1.14–1.94, p < 0.001). Mortality rates varied between 2.1% for high levels of both LDL-C and anti-SARS-CoV-2 antibodies and 16.3% for low levels of LDL-C and anti-SARS-CoV-2 antibodies (aOR 9.14, 95%CI 3.17–26.34, p < 0.001). Accordingly, for total cholesterol and anti-SARS-CoV-2 antibodies, mortality rates varied between 2.1% and 15.0% (aOR 8.01, 95%CI 2.77–23.18, p < 0.001). Conclusion: The combination of serum lipid levels and anti-SARS-CoV-2 antibodies is strongly associated with in-hospital mortality of patients with COVID-19. Patients with low levels of LDL-C and total cholesterol combined with low levels of anti-SARS-CoV-2 antibodies exhibited the highest mortality rates.
Research Progress on Nanomaterials for Tissue Engineering in Oral Diseases
Authors: Jiang Tong , Su Wen , Li Yan , Jiang Mingyuan , Zhang Yonghong , Xian Cory J. , Zhai Yuankun
Published: August 2023

Due to their superior antibacterial properties, biocompatibility and high conductivity, nanomaterials have shown a broad prospect in the biomedical field and have been widely used in the prevention and treatment of oral diseases. Also due to their small particle sizes and biodegradability, nanomaterials can provide solutions for tissue engineering, especially for oral tissue rehabilitation and regeneration. At present, research on nanomaterials in the field of dentistry focuses on the biological effects of various types of nanomaterials on different oral diseases and tissue engineering applications. In the current review, we have summarized the biological effects of nanoparticles on oral diseases, their potential action mechanisms and influencing factors. We have focused on the opportunities and challenges to various nanomaterial therapy strategies, with specific emphasis on overcoming the challenges through the development of biocompatible and smart nanomaterials. This review will provide references for potential clinical applications of novel nanomaterials in the field of oral medicine for the prevention, diagnosis and treatment of oral diseases.
Synthesis and Characterization of Dental Nanocomposite Resins Reinforced with Dual Organomodified Silica/Clay Nanofiller Systems
Authors: Saridou Maria , Nikolaidis Alexandros K. , Koulaouzidou Elisabeth A. , Achilias Dimitris S.
Published: August 2023

Quaternary ammonium (QA) compounds have been widely studied as potential disinfectants in dental restorative materials. The present work investigates whether the gradual displacement of nanosilica by QA-clay nanoparticles may have an impact on the physicochemical and mechanical properties of dental nanocomposite resins. For this purpose, Bis-GMA/TEGDMA-based composite resins were initially synthesized by incorporating 3-(trimethoxysilyl)propyl methacrylate (γ-MPS)-modified nanosilica/QA-clay nanoparticles at 60/0, 55/5, 50/10, 40/20, and 30/30 wt% filler loadings. Their structural characterization was performed by means of scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). The degree of double bond conversion (DC) over time and the polymerization shrinkage were determined with Fourier transform infrared spectroscopy (FTIR) and a linear variable displacement transducer (LVDT), respectively. Mechanical properties as well as water sorption and solubility parameters were also evaluated after storage of nanocomposites in water for 7 days at 37 °C. Spectral data revealed intercalated clay configurations along with areas characterized by silica-clay clusters for clay loadings up to 30 wt%. Furthermore, the insertion of 10 wt% QA-clay enhanced the auto-acceleration effect also sustaining the ultimate (DC), reduced the setting contraction and solubility, and, finally, yielded flexural modulus and strength very close to those of the control nanocomposite resin. The acquired results could herald the advanced design of dental restorative materials appropriate for contemporary clinical applications.
Trends in the Epidemiology of Pneumocystis Pneumonia in Immunocompromised Patients without HIV Infection
Authors: Xue Ting , Kong Xiaomei , Ma Liang
Published: August 2023

The increasing morbidity and mortality of life-threatening Pneumocystis pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.