bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Coffee on Lipopolysaccharide-Induced Immortalized Human Oral Keratinocytes
Authors: Song Jianan , Kim Byunggook , Kim Oksu , Yang Ying , Liu Danyang , Fu Wenqi , Ma Guowu , Kim Young , Kim Okjoon
Published: July 2022

Periodontitis is a common inflammatory disease that is strongly influenced by dietary habits. Coffee is one of the most common dietary components; however, current research on the relationship between coffee consumption and periodontitis, as well as its underlying mechanisms, is limited. Based on a previous report, caffeine (CA) and chlorogenic acid (CGA) were formulated into artificial coffee (AC) for this experiment. Cell viability, prostaglandin E2 release, Western blotting, cellular reactive oxygen species (ROS) production, and NF-E2-related factor 2 (Nrf2) translocation analyses were performed to explore the effects of AC on lipopolysaccharide (LPS)-induced immortalized human oral keratinocytes (IHOKs) and elucidate their underlying mechanisms. AC pretreatment attenuated LPS-induced inflammatory mediator release, ROS production, and nuclear factor kappa B translocation in IHOKs. CA and CGA promoted AMP-activated protein kinase phosphorylation and down-regulated the nuclear factor-κB pathways to exert anti-inflammatory effects. Additionally, CGA promoted Nrf2 translocation and heme oxygenase-1 expression and showed anti-oxidative effects. Furthermore, AC, CA, and CGA components showed synergistic effects. Thus, we predict that coffee consumption may be beneficial for alleviating periodontitis. Moreover, the main coffee components CA and CGA seem to play a synergistic role in periodontitis.
Genetic and Phenotypic Factors Affecting Glycemic Response to Metformin Therapy in Patients with Type 2 Diabetes Mellitus
Authors: Nasykhova Yulia , Barbitoff Yury , Tonyan Ziravard , Danilova Maria , Nevzorov Ivan , Komandresova Tatiana , Mikhailova Anastasiia , Vasilieva Tatiana , Glavnova Olga , Yarmolinskaya Maria , Sluchanko Evgenia , Glotov Andrey
Published: July 2022

Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist–hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment.
From Nobody to Somebody: Romantic Epistemology in Jane Austen’s Persuasion
Authors: Bystydzieńska Grażyna
Published: July 2022

The aim of this article is to substantiate the thesis that together with the development of the plot of Persuasion, the cognitive power of the principal heroine expands, and she becomes a highly sensitive reader of human minds. This thesis is supported by references to the new ‘Romantic’ psychology, emphasizing the close links between the innate aspects of the mind and the body. Psychological insight demonstrates the fragmentation of Anne Elliot’s mind, the role of the unconscious, and the division between the interior and the exterior. There is also analysis of the significance of Anne’s frequent change of transitory lodgings, along with interpretation of the narrative strategy, especially free indirect speech and mediated speech (the function of eavesdropping) and the important role of body language.
Analysis on Burnout, Job Conditions, Alexithymia, and Other Psychological Symptoms in a Sample of Italian Anesthesiologists and Intensivists, Assessed Just before the COVID-19 Pandemic: An AAROI-EMAC Study
Authors: Vittori Alessandro , Marinangeli Franco , Bignami Elena Giovanna , Simonini Alessandro , Vergallo Alessandro , Fiore Gilberto , Petrucci Emiliano , Cascella Marco , Pedone Roberto
Published: July 2022

Background. It was previously reported that health care professionals working in the fields of anesthesiology and emergency are at higher risk of burnout. However, the correlations between burnout, alexithymia, and other psychological symptoms are poorly investigated. Furthermore, there is a lack of evidence on which risk factors, specific to the work of anesthetists and intensivists, can increase the risk of burnout, and which are useful for developing remedial health policies. Methods. This cross-sectional study was conducted in 2020 on a sample of 300 professionals recruited from AAROI-EMAC subscribers in Italy. Data collection instruments were a questionnaire on demographic, education, job characteristics and well-being, the Maslach Burnout Inventory Tool, the Toronto Alexithymia Scale, the Symptom Checklist-90-R, and the Rosenberg Self-Esteem Scale administered during refresher courses in anesthesiology. Correlations between burnout and physical and psychological symptoms were searched. Results. With respect to burnout, 29% of individuals scored at high risk on emotional exhaustion, followed by 36% at moderate–high risk. Depersonalization high and moderate–high risk were scored by 18.7% and 34.3% of individuals, respectively. Burnout personal accomplishment was scored by 34.7% of respondents. The highest mean scores of burnout dimensions were related to dissatisfaction with one’s career, conflicting relationships with surgeons, and, finally, difficulty in explaining one’s work to patients. Conclusions. Burnout rates in Italian anesthesiologists and intensivists have been worrying since before the COVID-19 pandemic. Anesthesiologists with higher levels of alexithymia are more at risk for burnout. It is therefore necessary to take urgent health policy measures.
Using the Concept of Health Literacy to Understand How People Living with Motor Neurone Disease and Carers Engage in Healthcare: A Longitudinal Qualitative Study
Authors: Paynter Camille , Mathers Susan , Gregory Heidi , Vogel Adam P. , Cruice Madeline
Published: July 2022

The growing body of information-seeking and decision-making literature in motor neurone disease (MND) has not yet explored the impact of health literacy. Health literacy relates to the skills people have to access, understand, and use health information and is influenced by motivation to engage with healthcare. We aimed to better understand how people affected by MND engage in healthcare by examining longitudinal interview data using the construct of health literacy. Semi-structured interviews were conducted with 19 persons living with MND and 15 carers recruited from a specialist MND clinic using maximum variation sampling. Transcripts were deductively coded using a framework of health literacy behaviours. The analysis used a matrix-based approach for thematic analysis of longitudinal data. People living with MND and carers sought nuanced information dependent on their priorities and attitudes. Information uptake was influenced by perceived relevancy and changed over time. Time allowed opportunity to reflect on and understand the significance of information provided. The findings indicate that persons living with MND and carers benefit when information and consultations are adapted to meet their communication needs. The results highlight the potential benefits of gaining an early understanding of and accommodating the communication needs, personal preferences, and emotional readiness for information for persons living with MND and their carers.
Public Awareness of Chronic Kidney Disease in Jazan Province, Saudi Arabia—A Cross-Sectional Survey
Authors: Assiry Ali , Alshahrani Saeed , Banji David , Banji Otilia J. F. , Syed Nabeel Kashan , Alqahtani Saad S.
Published: July 2022

Chronic Kidney Disease (CKD) is a significant public health concern worldwide and many people continue to ignore their early warning symptoms. The present study assessed the level of knowledge about CKD the awareness of the risk factors and the awareness of the complications associated with CKD, among the general population of Jazan Province, Saudi Arabia. 440 residents of Jazan Province participated in an online cross-sectional survey during a seven-month period from November (2020) to July (2021). Data was collected using a validated 73-item self-report survey. More than half of the respondents were males (n = 286; 65%) with an age ranging from 18 to 59 years, and a mean age of 32.66 years (SD ± 10.83). A very low percentage of the sample (27.3%; 7.5%, 9.3%) demonstrated good knowledge, a high level of awareness of the risk factors, and a high level of awareness of the complications associated with CKD, respectively. Participants’ knowledge was significantly associated with being a student or being employed (Government/private employee) (χ2 = 29.90; p < 0.001), having completed graduate studies (χ2 = 63.86; p < 0.001), residing in urban areas (χ2 = 138.62; p < 0.001), belonging to the age group (18–39 years), and having no co-morbidities (χ2 = 24.55; p < 0.001). Positive and significant correlations were also noted between the knowledge score and the awareness of risk factor score (r = 0.42; p < 0.01), as well as the awareness of complications score (r = 0.25; p < 0.01). These findings warrant an urgent need for extensive CKD educational initiatives concentrating on improving the general knowledge and awareness of the public towards CKD.
Health Needs Assessment: Chronic Kidney Disease Secondary to Type 2 Diabetes Mellitus in a Population without Social Security, Mexico 2016–2032
Authors: Martínez-Valverde Silvia , Zepeda-Tello Rodrigo , Castro-Ríos Angélica , Toledano-Toledano Filiberto , Reyes-Morales Hortensia , Rodríguez-Matías Adrián , Durán-Arenas Juan
Published: July 2022

Health needs assessment is a relevant tracer of planning process of healthcare programs. The objective is to assess the health needs of chronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2 DM) in a population without social security in Mexico. The study design was a statistical simulation model based on data at the national level of Mexico. A stochastic Markov model was used to simulate the progression from diabetes to CKD. The time horizon was 16 years. The results indicate that in 2022, kidney damage progression and affectation in the diabetic patient cohort will be 34.15% based on the time since T2 DM diagnosis. At the end of the 16-year period, assuming that the model of care remains unchanged, early renal involvement will affect slightly more than twice as many patients (118%) and cases with macroalbuminuria will triple (228%). The need for renal replacement therapy will more than double (169%). Meanwhile, deaths associated with cardiovascular risk will more than triple (284%). We concluded that the clinical manifestations of patients with CKD secondary to T2 DM without social security constitute a double challenge. The first refers to the fact that the greatest health need is early care of CKD, and the second is the urgent need to address cardiovascular risk in order to reduce deaths in the population at risk.
Mining Type-β Co-Location Patterns on Closeness Centrality in Spatial Data Sets
Authors: Zou Muquan , Wang Lizhen , Wu Pingping , Tran Vanha
Published: July 2022

A co-location pattern is a set of spatial features whose instances are frequently correlated to each other in space. Its mining models always consist of two essential steps. One step is to generate neighbor relationships between spatial instances, and another step is to check the prevalence of candidate patterns on the clique, star or Delaunay triangulation relationships. At least three major issues are addressed in this paper. First, since different spatial regions, different distribution densities, it is difficult to set appropriate parameters to generate ideal neighbor relationships. Second, the clique relationship and the others are so strongly rigid that the users’ personal interests are suppressed; some interesting patterns are neglected without increasing redundancy. Third, the different strength of correlations among instances are neglected in prevalence calculation. It causes correlations among features to be undifferentiated. Accordingly, the main work of this paper includes: (1) The neighbor relationship generation can be improved on the idea that the distances between an instance and any of its neighbors are not remarkably different. (2) The type-β co-location pattern is defined and checked based on a co-occurrence where the closeness centrality of each instance is not less than a given threshold β. (3) Since the closeness centrality carries strength of correlations among instances, the strength of the correlations between a feature and the other ones in a type-β co-location pattern can be evaluated with prevalence calculation. Finally, experiments on synthetic and real-world spatial data sets are used to assess the effectiveness and efficiency of our works. The results show that fewer spatial neighbor relationships are generated, and more interesting patterns can be discovered by flexibly adjusting β according to the user’s preferences.
Mouthpart Ecomorphology and Predatory Behaviour in Selected Rove Beetles of the “Staphylinine Group” (Coleoptera: Staphylinidae: Staphylininae, Paederinae)
Authors: Stocker Benedict , Barthold Sonja , Betz Oliver
Published: July 2022

The representatives of the megadiverse rove beetle subfamilies Paederinae and Staphylininae (Coleoptera: Staphylinidae) are considered generalist predators, although their exact prey-capture behaviour and performance and possible links to mouthpart morphology have rarely been described. Here, we examine these relationships for selected species by SEM analyses of mouthparts and front legs and highspeed videography of prey-capture behaviour. We describe the observed behaviours and structural properties and quantify relationships between prey type, mouthpart morphology, and predatory performance based on morphometric measurements of both the shape and lever properties of the mandible. We show that the Staphylininae considered have morphological and behavioural properties generally associated with generalist predation and that the Paederinae considered display characteristics that are highly specialized on elusive prey such as Collembola. We found correlations between mandible shape and leverage, and body size and prey type. We report distinct prey-capture behaviours: the beetles use front legs and/or mandibles to attack prey, drag prey, or cage it between their legs. These strategies differ among species and situations. Overall, this exploratory study provides insights into the morphology and types of prey capture that must have played a major role in the evolution of these beetles.
A Telehealth Intervention for Nutritional Counseling in Amyotrophic Lateral Sclerosis Patients
Authors: De Marchi Fabiola , Serioli Marcella , Collo Alessandro , Belotti Evelyn Gisell , Alloatti Francesca , Biroli Giampaolo , Bolioli Andrea , Cantello Roberto , Riso Sergio , Mazzini Letizia
Published: July 2022

Nutritional status is one of the most relevant prognostic factors in Amyotrophic Lateral Sclerosis (ALS), and close monitoring can help avoid severe weight loss over the disease course. We describe the impact of a Chatbot webapp on improving the communications between physicians, patients, and/or caregivers for dietary monitoring. We developed a chatbot that provides patients with a tool to register their meals through an intuitive and carefully designed conversational interface. Patients recorded their dietary intake twice weekly and received an adequate nutritional recommendation monthly. We monitored their functional and nutritional parameters. The data were compared with a control group followed up by standard counseling. We enrolled 26 patients. Regarding feasibility, 96% of participants completed the three-month follow-up, and 77% ended the six months. Regarding the change in weight in the Chatbot group, we observed a weight stabilization (F = 1.874, p-value: 0.310 for changes) over the telehealth compared to the control group (F = 1.710, p-value: 0.024 for changes). A telehealth approach for nutritional support is feasible and reproducible in an ALS setting: frequent monitoring turned out to help prevent further weight loss, allowing an early nutritional strategy adjustment.
Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis
Authors: Massacesi Luca , Mariottini Alice , Nicoletti Ferdinando
Published: July 2022

Evidence of the effectiveness of B-cell-depleting monoclonal antibodies (mAbs) in multiple sclerosis (MS) prompted a partial revisitation of the pathogenetic paradigm of the disease, which was, so far, considered a T-cell-mediated autoimmune disorder. Mechanisms underlying the efficacy of B-cell-depleting mAbs in MS are still unknown. However, they likely involve the impairment of pleiotropic B-cell functions different from antibody secretion, such as their role as antigen-presenting cells during both the primary immune response in the periphery and the secondary response within the central nervous system (CNS). A potential impact of B-cell-depleting mAbs on inflammation compartmentalised within the CNS was also suggested, but little is known about the mechanism underlying this latter phenomenon as no definite evidence was provided so far on the ability of mAbs to cross the blood–brain barrier and reliable biomarkers of compartmentalised inflammation are lacking. The present paper briefly summarises the immunopathogenesis of MS with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B-cell-depleting mAbs are also discussed.
Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation
Authors: Otsuka Ryusei , Miyagi-Shiohira Chika , Kuwae Kazuho , Nishime Kai , Tamaki Yoshihito , Yonaha Tasuku , Sakai-Yonaha Mayuko , Yamasaki Ikuo , Shinzato Misaki , Saitoh Issei , Watanabe Masami , Noguchi Hirofumi
Published: July 2022

For pancreatic islet transplantation, pancreas procurement, preservation, and islet isolation destroy cellular and non-cellular components and activate components such as resident neutrophils, which play an important role in the impairment of islet survival. It has been reported that inhibitors of neutrophil elastase (NE), such as sivelestat and α1-antitrypsin, could contribute to improvement of islet isolation and transplantation. In this study, we investigated whether pancreatic preservation with alvelestat, a novel NE inhibitor, improves porcine islet yield and function. Porcine pancreata were preserved with or without 5 μM alvelestat for 18 h, and islet isolation was performed. The islet yields before and after purification were significantly higher in the alvelestat (+) group than in the alvelestat (−) group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 55% and 5% of diabetic mice in the alvelestat (+) and alvelestat (−) groups, respectively. These results suggest that pancreas preservation with alvelestat improves islet yield and graft function and could thus serve as a novel clinical strategy for improving the outcome of islet transplantation.
Amaryllidaceae, Lycopodiaceae Alkaloids and Coumarins—A Comparative Assessment of Safety and Pharmacological Activity
Authors: Herbet Mariola , Widelski Jarosław , Piątkowska-Chmiel Iwona , Pawłowski Kamil , Dymek Aleksandra , Mroczek Tomasz
Published: July 2022

The study aimed to evaluate the safety and pharmacological activity Amaryllidaceae, Lycopodiaceae alkaloids and coumarins obtained from Narcissus triandrus L., Lycopodium clavatum L., Lycopodium annotinum L., Huperzia selago L. and Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. In the in vivo studies. The influence of the tested compounds on the central nervous system of rats was assessed in behavioral tests (locomotor activity, Y-maze, passive avoidance). In order to investigate the mechanisms of action, biochemical determinations were performed (AChE activity, BChE activity, IL-1β, IL-6 concentration). In order to assess safety, the concentrations of AST, ALT, GGT and urea and creatinine were determined. The results of the conducted studies indicate a high safety profile of the tested compounds. Behavioral tests showed that they significantly improved rodent memory in a passive avoidance test. The results of biochemical studies showed that by reducing the activity of AChE and BChE and lowering the concentration of IL-1β and IL-6, the coumarin-rich Angelica dahurica extract shows the most promising potential for future therapeutic AD strategies.
Mutations Associated to Antibiotic-Resistant Helicobacter pylori: It Is Time to Validate Sequencing Observations
Authors: Pichon Maxime , Luzarraga Victor , Burucoa Christophe
Published: July 2022

H. pylori, a Gram-negative microaerophilic microorganism, is the only bacterial pathogen classified as a Class I carcinogen [...]
When Nothing Turns Itself Inside out and Becomes Something: Coating Poly(Lactic-Co-Glycolic Acid) Spheres with Hydroxyapatite Nanoparticles vs. the Other Way Around
Authors: Uskoković Vuk , Wu Victoria M.
Published: July 2022

To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The goal of this study was to assess the biological and pharmacokinetic effects of inverting this classical core/shell structure by coating poly(lactic-co-glycolic acid) (PLGA) spheres with HAp nanoparticles. The HAp shell did not hinder the release of vancomycin; rather, it increased the release rate to a minor degree, compared to that from undecorated PLGA spheres. The decoration of PLGA spheres with HAp induced lesser mineral deposition and lesser upregulation of osteogenic markers compared to those induced by the composite particles where HAp nanoparticles were embedded inside the PLGA spheres. This was explained by homeostatic mechanisms governing the cell metabolism, which ensure than the sensation of a product of this metabolism in the cell interior or exterior is met with the reduction in the metabolic activity. The antagonistic relationship between proliferation and bone production was demonstrated by the higher proliferation rate of cells challenged with HAp-coated PLGA spheres than of those treated with PLGA-coated HAp. It is concluded that the overwhelmingly positive response of tissues to HAp-coated biomaterials for bone replacement is unlikely to be due to the direct induction of new bone growth in osteoblasts adhering to the HAp coating. Rather, these positive effects are consequential to more elementary aspects of cell attachment, mechanotransduction, and growth at the site of contact between the HAp-coated material and the tissue.
The Benefits and Costs of Netlist Randomization Based Side-Channel Countermeasures: An In-Depth Evaluation
Authors: Asghar Ali , Becher Andreas , Ziener Daniel
Published: July 2022

Exchanging FPGA-based implementations of cryptographic algorithms during run-time using netlist randomized versions has been introduced recently as a unique countermeasure against side channel attacks. Using partial reconfiguration, it is possible to shuffle between structurally different but functionally similar versions of a cryptographic implementation. The resulting varying power profile enhances the resistance against power-based side channel attacks. While side channel leakage is reduced, costs in terms of additional resources and/or lowered throughput are often increased due to the overheads of the required online partial reconfiguration. In this work, we provide an in-depth evaluation of the leakage-area-throughput trade-off.
Laboratory Experiments on Ice Melting: A Need for Understanding Dynamics at the Ice-Water Interface
Authors: McCutchan Aubrey , Johnson Blair
Published: July 2022

The ice-ocean interface is a dynamic zone characterized by the transfer of heat, salinity, and energy. Complex thermodynamics and fluid dynamics drive fascinating physics as ice is formed and lost under variable conditions. Observations and data from polar regions have shed light on the contributions that oceanic currents, meltwater plumes, subglacial hydrology, and other features of the ice-ocean boundary region can make on melting and transport. However, the complicated interaction of mechanisms related to ice loss remain difficult to discern, necessitating laboratory experiments to explore fundamental features of melting dynamics via controlled testing with rigorous measurement techniques. Here, we put forward a review of literature on laboratory experiments that explore ice loss in response to free and forced convective flows, considering melting based on laminar or turbulent flow conditions, ice geometries representing a range of idealized scenarios to those modeling glaciers found in nature, and features such as salinity and stratification. We present successful measurement techniques and highlight findings useful to understanding polar ice dynamics, and we aim to identify future directions and needs for experimental research to complement ongoing field investigations and numerical simulations to ultimately improve predictions of ice loss in our current and evolving climate.
Proof of Concept of the Contribution of the Interaction between Trait-like and State-like Effects in Identifying Individual-Specific Mechanisms of Action in Biological Psychiatry
Authors: Zilcha-Mano Sigal , Solomonov Nili , Posner Jonathan E. , Roose Steven P. , Rutherford Bret R.
Published: July 2022

Background: Identifying individual-specific mechanisms of action may facilitate progress toward precision medicine. Most studies seeking to identify mechanisms of action collapse together two distinct components: pre-treatment trait-like characteristics differentiating between individuals and state-like characteristics changing within each individual over the course of treatment. We suggest a conceptual framework highlighting the importance of studying interactions between trait-like and state-like components in the development of moderated mediation models that can guide personalized targeted interventions. Methods: To facilitate implementation of this framework, two empirical demonstrations are presented from a recent clinical trial and neuroimaging study. The first examines limbic reactivity during an emotional face task; the second concerns striatal activation in a monetary reward task. Results: In both tasks, considering the interaction between trait-like and state-like components predicted treatment outcome more robustly than did the trait-like or state-like components examined individually. Conclusions: These findings suggest that the extent to which state-like modulation of neural activations can serve as a potential treatment target depends on the pre-treatment, trait-like levels of activation in these regions. Thus, the interaction between trait-like and state-like components can serve as a promising path to the development of personalized interventions within a precision medicine framework in which mechanisms of action are individual-specific.
The Use and Utility of Machine Learning in Achieving Precision Medicine in Systemic Sclerosis: A Narrative Review
Authors: Bonomi Francesco , Peretti Silvia , Lepri Gemma , Venerito Vincenzo , Russo Edda , Bruni Cosimo , Iannone Florenzo , Tangaro Sabina , Amedei Amedeo , Guiducci Serena , Matucci Cerinic Marco , Bellando Randone Silvia
Published: July 2022

Background: Systemic sclerosis (SSc) is a rare connective tissue disease that can affect different organs and has extremely heterogenous presentations. This complexity makes it difficult to perform an early diagnosis and a subsequent subclassification of the disease. This hinders a personalized approach in clinical practice. In this context, machine learning (ML), a branch of artificial intelligence (AI), is able to recognize relationships in data and predict outcomes. Methods: Here, we performed a narrative review concerning the application of ML in SSc to define the state of art and evaluate its role in a precision medicine context. Results: Currently, ML has been used to stratify SSc patients and identify those at high risk of severe complications. Additionally, ML may be useful in the early detection of organ involvement. Furthermore, ML might have a role in target therapy approach and in predicting drug response. Conclusion: Available evidence about the utility of ML in SSc is sparse but promising. Future improvements in this field could result in a big step toward precision medicine. Further research is needed to define ML application in clinical practice.
Quantification of Idua Enzymatic Activity Combined with Observation of Phenotypic Change in Zebrafish Embryos Provide a Preliminary Assessment of Mutated idua Correlated with Mucopolysaccharidosis Type I
Authors: Lin Cheng-Yung , Lin Hsiang-Yu , Chuang Chih-Kuang , Zhang Po-Hsiang , Tu Yuan-Rong , Lin Shuan-Pei , Tsai Huai-Jen
Published: July 2022

Mucopolysaccharidosis type I (MPS I) is an inherited autosomal recessive disease resulting from mutation of the α-l-Iduronidase (IDUA) gene. New unknown mutated nucleotides of idua have increasingly been discovered in newborn screening, and remain to be elucidated. In this study, we found that the z-Idua enzymatic activity of zebrafish idua-knockdown embryos was reduced, resulting in the accumulation of undegradable metabolite of heparin sulfate, as well as increased mortality and defective phenotypes similar to some symptoms of human MPS I. After microinjecting mutated z-idua-L346R, -T364M, -E398-deleted, and -E540-frameshifted mRNAs, corresponding to mutated human IDUA associated with MPS I, into zebrafish embryos, no increase in z-Idua enzymatic activity, except of z-idua-E540-frameshift-injected embryos, was noted compared with endogenous z-Idua of untreated embryos. Defective phenotypes were observed in the z-idua-L346R-injected embryos, suggesting that failed enzymatic activity of mutated z-Idua-L346R might have a dominant negative effect on endogenous z-Idua function. However, defective phenotypes were not observed in the z-idua-E540-frameshifted-mRNA-injected embryos, which provided partial enzymatic activity. Based on these results, we suggest that the z-Idua enzyme activity assay combined with phenotypic observation of mutated-idua-injected zebrafish embryos could serve as an alternative platform for a preliminary assessment of mutated idua not yet characterized for their role in MPS I.
Personalized Approaches for the Prevention and Treatment of Breast Cancer
Authors: Nabi Hermann
Published: July 2022

Breast cancer (BC) remains a major public health issue worldwide [...]
Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress
Authors: Auti Amogh , Alessio Nicola , Ballini Andrea , Dioguardi Mario , Cantore Stefania , Scacco Salvatore , Vitiello Antonio , Quagliuolo Lucio , Rinaldi Barbara , Santacroce Luigi , Di Domenico Marina , Boccellino Mariarosaria
Published: July 2022

Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood–brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 µM group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.
Impact of Sex on Mortality in Patients Undergoing Surgical Aortic Valve Replacement
Authors: Kang Hyun-Uk , Nam Jae-Sik , Kim Dongho , Kim Kyungmi , Chin Ji-Hyun , Choi In-Cheol
Published: July 2022

Aortic stenosis (AS) is the second most common valvular heart disease in the United States. Although the prevalence of AS does not significantly differ between the sexes, there is some controversy on whether sex differences affect the long-term mortality of patients with severe AS undergoing surgical aortic valve replacement (SAVR). Therefore, we retrospectively analyzed the medical records of 917 patients (female, n = 424 [46.2%]) with severe AS who had undergone isolated SAVR at a tertiary care center between January 2005 and December 2018. During a median follow-up of 5.2 years, 74 (15.0%) male patients and 41 (9.7%) female patients died. The Kaplan–Meier analysis revealed that the 10-year mortality rate was significantly higher in male than female patients (24.7% vs. 17.9%, log-rank p = 0.005). In the sequential Cox proportional hazard regression model for assessing long-term mortality up to 10 years post-surgery, the adjusted hazard ratio of male sex for mortality was 1.93 (95% confidence interval, 1.28–2.91; p = 0.002). The association between male sex and postoperative long-term mortality was not significantly diminished by any demographic or clinical factor in subgroup analyses. In conclusion, female sex was significantly associated with better long-term survival in patients with severe AS undergoing SAVR.
Functional Independence of Taiwanese Children with Osteogenesis Imperfecta
Authors: Syu Yu-Min , Lee Chung-Lin , Chuang Chih-Kuang , Chiu Huei-Ching , Chang Ya-Hui , Lin Hsiang-Yu , Lin Shuan-Pei
Published: July 2022

Osteogenesis imperfecta (OI) is a group of rare genetic disorders that affect bone formation. Patients with OI present mainly with increased bone fragility and bone deformities. Twenty-seven Taiwanese children between 2 and 21 years of age with OI and their parents were recruited at MacKay Memorial Hospital from January 2013 to December 2019. We used the Functional Independence Measure for Children (WeeFIM) questionnaire to assess the functional independence of the children and describe any functional limitations or additional burden of daily care. Out of a potential score of 126, the mean total WeeFIM score was 113.7. There was a statistically significant difference between the scores of type I, type III and type IV OI (121.88 [SD 7.01] vs. 80.8 [SD 26.25] vs. 119.17 [SD 10.89]; p < 0.001). There were no statistically significant differences between the scores in different age groups, the male and female participants, and patients with pathogenic variants in COL1A1 and COL1A2. The mean scores for the self-care, mobility, and cognition domains were 48.78 (maximum 56, mean quotient 91.14%), 30.44 (maximum 35, mean quotient 87.12%), and 34.44 (maximum 35, mean quotient 99.05%), respectively. The best performance was in the cognition domain (mean quotient 99.05%), and the worst was in the mobility domain (mean quotient 87.12%). There were no statistically significant correlations between WeeFIM scores and age, or age when symptoms began. The total WeeFIM score and 13 subscores for the self-care and mobility domains were all positively correlated with body height (p < 0.01). The correlation was lowest for bowel and walking/wheelchair tasks, and the highest for bathing and dressing-upper tasks. For tasks in bathing, over 40% of the patients needed help. For tasks in the cognition domain, most patients required no help. For the Taiwanese children with OI, some support and supervision were required for self-care and mobility tasks, and the functional independence in these two domains was correlated with body height and disease types. The WeeFIM questionnaire may be a useful tool to assess the functional strengths and weaknesses of children with OI.
Assessing the Effectiveness of Administrative District Realignments Based on a Geographically and Temporally Weighted Regression Model
Authors: Zhu Zhenghui , Lu Yao , Wang Li , Liu Wanbo , Wang Lingen
Published: July 2022

The long-term effects of administrative division adjustments on economic development in Dalian City, China, is presently unclear. Therefore, we employed a geographically and temporally weighted regression model to construct an index assessment system using the annual number of newly registered enterprises as the dependent variable. We empirically studied the effects of administrative division adjustments of townships in Dalian City from 2010 to 2020. The results showed that: (i) adjustments in townships administrative divisions negatively affected regional enterprise concentrations and economic development in general, whereas industrial and transportation factors demonstrated positive effects to variable degrees, and the effects of policy, location, and population factors were not significant. (ii) Over time, the effects of townships administrative division adjustments changed from positive to negative, and the negative effects displayed an increasing trend, revealing that (iii) the effect of administrative division adjustments in Dalian City was positive and negative over time. This further reveals the objective problem that administrative division adjustment in recent years was effective over the short term, but not over the long term. (iv) During the study period, administrative division adjustments positively affected regional enterprise concentrations and economic development solely during a short time frame and in a small geographical area. However, its negative effects increased extensively, which infers that maintaining a relatively stable administrative division is more beneficial for promoting economic development in Dalian City.
Green and Low-Carbon Commuting Evaluation and Optimization of a Cross-Border Metropolitan Region by the Subway Network: The Case of Shenzhen and Hong Kong, China
Authors: Chen Dening , He Zuxin , Hong Xinyi , Ni Xinxin , Ma Renfeng
Published: July 2022

In the context of the One Country–Two Systems policy, Shenzhen and Hong Kong have rapidly grown into a dual-core international metropolis. However, a huge barrier is the commuting cost incurred by the tariff policy, which blocks the road to the high-quality development of the Guangdong–Hong Kong–Macao Greater Bay Area (GBA). Based on traffic accessibility and kernel density analysis of the subway network and points of interest (POIs) of urban functional areas with ArcGIS, this study analyzed the commute time and convenience level of the functional areas in the two separate tariff zones. The traffic (commute) time in 75 min was taken as the turning point of the efficiency of the Shenzhen–Hong Kong connection, and it was found that both the customs clearance time and the accessible areas show the shape of a parabolic function with an upward opening. It was also found that, in Shenzhen and Hong Kong, the commute time in most of the business, commercial, residential, and industrial areas is 60–75 min. In particular, the comfortable range within 45 min was not achieved. It is necessary to further promote the effectiveness of the Shenzhen–Hong Kong customs clearance system and continuously reduce the customs clearance cost so as to promote the integration of Shenzhen and Hong Kong in order to implement the national strategy of “dual circulation” and innovation-driven development and efficiently drive the coordinated construction of the GBA.
Industrial Carbon Emission Efficiency of Cities in the Pearl River Basin: Spatiotemporal Dynamics and Driving Forces
Authors: Jiang Hongtao , Yin Jian , Qiu Yuanhong , Zhang Bin , Ding Yi , Xia Ruici
Published: July 2022

In the context of green and high-quality development, effectively enhancing industrial carbon emission efficiency is critical for reducing carbon emissions and achieving sustainable economic growth. This study explored this research area using three models: the super-efficient SBM model was used to measure the industrial carbon emission efficiency of 48 cities in the Pearl River Basin from 2009 to 2017; the exploratory spatiotemporal data analysis method was used to reveal the spatiotemporal interaction characteristics of industrial carbon emission efficiency; and the geographical detectors and geographically weighted regression model were employed to explore the influencing factors. The results are as follows: (1) The Pearl River Basin’s industrial carbon emission efficiency steadily increased from 2009 to 2017, with an average annual growth rate of 0.18 percent, but the industrial carbon emission efficiency of some sites remains low; (2) The local spatiotemporal pattern of industrial carbon emission efficiency is solitary and spatially dependent; (3) The spatial variation of industrial carbon emission efficiency is influenced by a number of factors, including the industrialization level, openness to the outside world, the science and technology level, energy consumption intensity, and productivity level, with the productivity level, industrialization level, and openness to the outside world being the most important. Among these factors, the productivity level, science and technology level, openness to the outside world, and industrialization level all have a positive correlation with industrial carbon emission efficiency, but energy consumption intensity has a negative correlation. This study provides an integrated framework using exploratory spatiotemporal analysis and geographically weighted regression to examine carbon emission efficiency among cities. It can serve as a technical support for carbon reduction policies in cities within the Pearl River Basin, as well as a reference for industrial carbon emission studies of other regions of the world.
High-Speed Railway Facilities, Intercity Accessibility and Urban Innovation Level—Evidence from Cities in Three Chinese Megacity Regions
Authors: Li Na , Lu Haiyan , Lv Yongxin
Published: July 2022

This paper investigates the impact of high-speed railways (HSR) on urban innovation levels by improving intercity accessibility. We employ prefecture city-level data within three megacity regions in China from 2009 to 2018. Using the number of invention patents granted as a proxy for the innovation level of a city, we find that HSR facilities significantly improve urban innovation levels through better regional intercity accessibility and that there is a diminishing effect as commuting time increases. The impact mechanisms of innovation improvement can be explained by an ever-increasing potential of interaction activities among talents and technology investment opportunities among cities. We contribute to the literature by highlighting the spatial attenuation impact of HSR on urban innovation levels as well as the underlying mechanisms. Particularly, talent interaction exerts a larger effect on urban innovation levels than technology investment opportunities. Moreover, we unravel the heterogeneous effects that more innovative cities and cities with double first-class universities gain more from the improved intercity accessibility brought by HSR. This research has policy implications that promoting HSR facilities improves innovation levels of cities with different resources.
Analysis Model of the Relationship between Public Spatial Forms in Traditional Villages and Scenic Beauty Preference Based on LiDAR Point Cloud Data
Authors: Chen Guodong , Sun Xinyu , Yu Wenbo , Wang Hao
Published: July 2022

Traditional villages are historically, culturally, scientifically and aesthetically valuable, and a beautiful landscape is the primary embodiment of a traditional village environment. Urbanization and modernization have had a great impact on village landscapes. As an important aspect of traditional village landscapes, creating beautiful public spaces is an effective way to attract tourists and improve the well-being of residents. Landscape aesthetic activities are the result of the interaction between landscape objects and aesthetic subjects. Research on the relationship between the form of traditional village public spaces and subjective aesthetic preferences has long been neglected. This research examined 31 public spaces in traditional villages in the Dongshan and Xishan areas in Lake Taihu, Suzhou. An index system of public spatial forms in traditional villages was created, basic data of spatial forms were collected using a hand-held 3D laser scanner, and the value of the spatial forms index was calculated using R language. The scenic beauty estimation (SBE) method was improved, with the estimation of the beauty of the scenic environment based on VR panorama rather than traditional photo media. Parameter screening was performed using correlation analysis and full subset regression analysis, and four models were used to fit the SBE scores and grades. The results show that the majority of public spaces had lower than average SBE scores, and the four key indicators of average contour upper height, solid-space ratio, vegetation cover, and comprehensive closure predicted SBE. In addition, the linear model (R2 = 0.332, RMSE = 64.774) had the most accurate SBE level prediction and the stochastic forest model (R2 = 0.405, RMSE = 63.311) was better at predicting specific SBE scores. The model provides managers, designers, and researchers with a method for the quantitative evaluation of visual landscape preferences and quantitative landscape spatial forms and provides a reference for the protection and renewal of traditional village landscapes.