bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Climate Variability on Malaria Transmission in Southern Côte d’Ivoire, West Africa
Authors: Doumbia Madina , Coulibaly Jean Tenena , Silué Dieudonné Kigbafori , Cissé Guéladio , N’Dione Jacques-André , Koné Brama
Published: November 2023

Malaria continues to be a major public health concern with a substantial burden in Africa. Even though it has been widely demonstrated that malaria transmission is climate-driven, there have been very few studies assessing the relationship between climate variables and malaria transmission in Côte d’Ivoire. We used the VECTRI model to predict malaria transmission in southern Côte d’Ivoire. First, we tested the suitability of VECTRI in modeling malaria transmission using ERA5 temperature data and ARC2 rainfall data. We then used the projected climatic data pertaining to 2030, 2050, and 2080 from a set of 14 simulations from the CORDEX-Africa database to compute VECTRI outputs. The entomological inoculation rate (EIR) from the VECTRI model was well correlated with the observed malaria cases from 2010 to 2019, including the peaks of malaria cases and the EIR. However, the correlation between the two parameters was not statistically significant. The VECTRI model predicted an increase in malaria transmissions in both scenarios (RCP8.5 and RCP4.5) for the time period 2030 to 2080. The monthly EIR for RCP8.5 was very high (1.74 to 1131.71 bites/person) compared to RCP4.5 (0.48 to 908 bites/person). These findings call for greater efforts to control malaria that take into account the impact of climatic factors.
Predictors of Phthalate Metabolites Exposure among Healthy Pregnant Women in the United States, 2010–2015
Authors: Siddiq Shabnaz , Clemons Autumn M. , Meeker John D. , Gennings Chris , Rauh Virginia , Leisher Susannah Hopkins , Llanos Adana A. M. , McDonald Jasmine A. , Wylie Blair J. , Factor-Litvak Pam
Published: November 2023

Phthalate use and the concentrations of their metabolites in humans vary by geographic region, race, ethnicity, sex, product use and other factors. Exposure during pregnancy may be associated with detrimental reproductive and developmental outcomes. No studies have evaluated the predictors of exposure to a wide range of phthalate metabolites in a large, diverse population. We examined the determinants of phthalate metabolites in a cohort of racially/ethnically diverse nulliparous pregnant women. We report on urinary metabolites of nine parent phthalates or replacement compounds—Butyl benzyl phthalate (BBzP), Diisobutyl phthalate (DiBP), Diethyl phthalate (DEP), Diisononyl phthalate (DiNP), D-n-octyl phthalate (DnOP), Di-2-ethylhexyl terephthalate (DEHTP), Di-n/i-butyl phthalate (DnBP), Di-isononyl phthalate (DiNP) and Di-(2-ethylhexyl) phthalate (DEHP) from urine collected up to three times from 953 women enrolled in the Nulliparous Mothers To Be Study. Phthalate metabolites were adjusted for specific gravity. Generalized estimating equations (GEEs) were used to identify the predictors of each metabolite. Overall predictors include age, race and ethnicity, education, BMI and clinical site of care. Women who were Non-Hispanic Black, Hispanic or Asian, obese or had lower levels of education had higher concentrations of selected metabolites. These findings indicate exposure patterns that require policies to reduce exposure in specific subgroups.
Exploring Frailty in the Intersection of Cardiovascular Disease and Cancer in Older People
Authors: Amsalu Erkihun , Zhang Ying , Harrison Christopher , Nguyen Tan Van , Nguyen Tu Ngoc
Published: November 2023

Advances in cardiovascular therapies and cancer treatments have resulted in longer patient survival. The coexistence of cancer and cardiovascular disease has been recognized as a complex clinical scenario. In addition to cardiovascular disease, older people with cancer are at greater risk of experiencing multimorbidity and geriatric syndromes, such as frailty. In older people, the concurrent presence of cancer and cardiovascular disease increases the risk of mortality, and the presence of frailty can exacerbate their conditions and hinder treatment effectiveness. Given the significant intersection among frailty, cardiovascular disease, and cancer in older people, this paper aims to provide an overview of the current research in this field and identifies gaps in the research to understand the burden and impact of frailty in these populations. While many studies have examined the prevalence and impact of frailty on adverse outcomes in patients with cancer or cardiovascular disease, evidence of frailty in individuals with both conditions is lacking. There is no universally accepted definition of frailty, which leads to inconsistencies in identifying and measuring frailty in older adults with cardiovascular disease and cancer. The frailty index seems to be a preferred frailty definition in studies of patients with cancer, while the frailty phenotype seems to be more commonly used in cardiovascular research. However, differences in how the frailty index was categorized and in how patients were classified as ‘frail’ depending on the cut points may have a negative effect on understanding the impact of frailty in the studied populations. This makes it challenging to compare findings across different studies and limits our understanding of the prevalence and impact of frailty in these populations. Addressing these research gaps will contribute to our understanding of the burden of frailty in older people with cardiovascular disease and cancer, and improve clinical care protocols in this vulnerable population.
Ceramides Mediate Insulin-Induced Impairments in Cerebral Mitochondrial Bioenergetics in ApoE4 Mice
Authors: Carr Sheryl T. , Saito Erin R. , Walton Chase M. , Saito Jeremy Y. , Hanegan Cameron M. , Warren Cali E. , Trumbull Annie M. , Bikman Benjamin T.
Published: November 2023

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here, we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice, an oft-used model of AD research, were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography–mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.
Host Transcriptional Regulatory Genes and Microbiome Networks Crosstalk through Immune Receptors Establishing Normal and Tumor Multiomics Metafirm of the Oral-Gut-Lung Axis
Authors: Otálora-Otálora Beatriz Andrea , López-Rivera Juan Javier , Aristizábal-Guzmán Claudia , Isaza-Ruget Mario Arturo , Álvarez-Moreno Carlos Arturo
Published: November 2023

The microbiome has shown a correlation with the diet and lifestyle of each population in health and disease, the ability to communicate at the cellular level with the host through innate and adaptative immune receptors, and therefore an important role in modulating inflammatory process related to the establishment and progression of cancer. The oral cavity is one of the most important interaction windows between the human body and the environment, allowing the entry of an important number of microorganisms and their passage across the gastrointestinal tract and lungs. In this review, the contribution of the microbiome network to the establishment of systemic diseases like cancer is analyzed through their synergistic interactions and bidirectional crosstalk in the oral-gut-lung axis as well as its communication with the host cells. Moreover, the impact of the characteristic microbiota of each population in the formation of the multiomics molecular metafirm of the oral-gut-lung axis is also analyzed through state-of-the-art sequencing techniques, which allow a global study of the molecular processes involved of the flow of the microbiota environmental signals through cancer-related cells and its relationship with the establishment of the transcription factor network responsible for the control of regulatory processes involved with tumorigenesis.
Polysaccharides and Phenolic Compounds Recovered from Red Bell Pepper, Tomato and Basil By-Products Using a Green Extraction by Extractor Timatic®
Authors: Khatib Mohamad , Cecchi Lorenzo , Bellumori Maria , Zonfrillo Beatrice , Mulinacci Nadia
Published: November 2023

Fruits and vegetables processing produces significant amounts of by-products rich in valuable bioactive compounds such as polyphenols and dietary fiber. Food by-product re-use promotes the eco-sustainability of several crops. This study aimed to apply green extractions of bioactive compounds from by-products of basil, tomato, and red bell pepper production. Tests were performed by applying extraction procedures both at laboratory scale and using the Timatic® extractor. Water and ethanol 10% and 20% were used for extraction of red bell pepper and tomato, testing different temperatures (30, 50, and 90 °C; water at 90 °C and ethanol 20% were applied for basil. The obtained phenolic extracts were analyzed by HPLC-DAD-MS. Polysaccharides of tomato and red bell pepper were extracted at laboratory scale and chemically characterized using 1H-NMR to define the methylation and acylation degree, and DLS to estimate the hydrodynamic volume. Laboratory extraction tests allowed efficient scaling-up of the process on the Timatic® extractor. Phenolic content in the dried extracts (DE) ranged 8.0–11.2 mg/g for tomato and red bell pepper and reached 240 mg/g for basil extracts. Polysaccharide yields (w/w on DM) reached 6.0 and 10.4% for dried tomato and red bell pepper, respectively. Dry extracts obtained using the Timatic® extractor and water can be useful sources of bioactive phenols. The study provided new data on tomato and red bell pepper polysaccharides that may be useful for future applications.
Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation?
Authors: Nestorovich Ekaterina M. , Bezrukov Sergey M.
Published: November 2023

Ion channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primarily found in excitable cell membranes. In contrast, there exists another group of larger, and less selective, β-barrel channels of a different origin, which are not directly associated with cell excitability. Remarkably, these channels can also undergo closing, or “gating”, induced by sufficiently strong electric fields. Once the field is removed, the channels reopen, preserving a memory of the gating process. In this study, we explored the hypothesis that the voltage-induced closure of the β-barrel channels can be seen as a form of reversible protein denaturation by the high electric fields applied in model membranes experiments—typically exceeding twenty million volts per meter—rather than a manifestation of functional gating. Here, we focused on the bacterial outer membrane channel OmpF reconstituted into planar lipid bilayers and analyzed various characteristics of the closing-opening process that support this idea. Specifically, we considered the nearly symmetric response to voltages of both polarities, the presence of multiple closed states, the stabilization of the open conformation in channel clusters, the long-term gating memory, and the Hofmeister effects in closing kinetics. Furthermore, we contemplate the evolutionary aspect of the phenomenon, proposing that the field-induced denaturation of membrane proteins might have served as a starting point for their development into amazing molecular machines such as voltage-gated channels of nerve and muscle cells.
Zn2+ Differentially Influences the Neutralisation of Heparins by HRG, Fibrinogen, and Fibronectin
Authors: Sobczak Amélie I. S. , Ajjan Ramzi A. , Stewart Alan J.
Published: November 2023

For coagulation to be initiated, anticoagulant glycosaminoglycans (GAGs) such as heparins need to be neutralised to allow fibrin clot formation. Platelet activation triggers the release of several proteins that bind GAGs, including histidine-rich glycoprotein (HRG), fibrinogen, and fibronectin. Zn2+ ions are also released and have been shown to enhance the binding of HRG to heparins of a high molecular weight (HMWH) but not to those of low molecular weight (LMWH). The effect of Zn2+ on fibrinogen and fibronectin binding to GAGs is unknown. Here, chromogenic assays were used to measure the anti-factor Xa and anti-thrombin activities of heparins of different molecular weights and to assess the effects of HRG, fibrinogen, fibronectin, and Zn2+. Surface plasmon resonance was also used to examine the influence of Zn2+ on the binding of fibrinogen to heparins of different molecular weights. Zn2+ had no effect on the neutralisation of anti-factor Xa (FXa) or anti-thrombin activities of heparin by fibronectin, whereas it enhanced the neutralisation of unfractionated heparin (UFH) and HMWH by both fibrinogen and HRG. Zn2+ also increased neutralisation of the anti-FXa activity of LMWH by fibrinogen but not HRG. SPR showed that Zn2+ increased fibrinogen binding to both UFH and LMWH in a concentration-dependent manner. The presented results reveal that an increase in Zn2+ concentration has differential effects upon anticoagulant GAG neutralisation by HRG and fibrinogen, with implications for modulating anti-coagulant activity in plasma.
Biofilms in Periprosthetic Orthopedic Infections Seen through the Eyes of Neutrophils: How Can We Help Neutrophils?
Authors: Arciola Carla Renata , Ravaioli Stefano , Mirzaei Rasoul , Dolzani Paolo , Montanaro Lucio , Daglia Maria , Campoccia Davide
Published: November 2023

Despite advancements in our knowledge of neutrophil responses to planktonic bacteria during acute inflammation, much remains to be elucidated on how neutrophils deal with bacterial biofilms in implant infections. Further complexity transpires from the emerging findings on the role that biomaterials play in conditioning bacterial adhesion, the variety of biofilm matrices, and the insidious measures that biofilm bacteria devise against neutrophils. Thus, grasping the entirety of neutrophil–biofilm interactions occurring in periprosthetic tissues is a difficult goal. The bactericidal weapons of neutrophils consist of the following: ready-to-use antibacterial proteins and enzymes stored in granules; NADPH oxidase-derived reactive oxygen species (ROS); and net-like structures of DNA, histones, and granule proteins, which neutrophils extrude to extracellularly trap pathogens (the so-called NETs: an allusive acronym for “neutrophil extracellular traps”). Neutrophils are bactericidal (and therefore defensive) cells endowed with a rich offensive armamentarium through which, if frustrated in their attempts to engulf and phagocytose biofilms, they can trigger the destruction of periprosthetic bone. This study speculates on how neutrophils interact with biofilms in the dramatic scenario of implant infections, also considering the implications of this interaction in view of the design of new therapeutic strategies and functionalized biomaterials, to help neutrophils in their arduous task of managing biofilms.
Aerococcus viridans Phage Lysin AVPL Had Lytic Activity against Streptococcus suis in a Mouse Bacteremia Model
Authors: Xi Hengyu , Fu Yao , Chen Chong , Feng Xin , Han Wenyu , Gu Jingmin , Ji Yalu
Published: November 2023

Streptococcus suis (S. suis) is a swine pathogen that can cause sepsis, meningitis, endocarditis, and other infectious diseases; it is also a zoonotic pathogen that has caused a global surge in fatal human infections. The widespread prevalence of multidrug-resistant S. suis strains and the decline in novel antibiotic candidates have necessitated the development of alternative antimicrobial agents. In this study, AVPL, the Aerococcus viridans (A. viridans) phage lysin, was found to exhibit efficient bactericidal activity and broad lytic activity against multiple serotypes of S. suis. A final concentration of 300 μg/mL AVPL reduced S. suis counts by 4–4.5 log10 within 1 h in vitro. Importantly, AVPL effectively inhibited 48 h S. suis biofilm formation and disrupted preformed biofilms. In a mouse model, 300 μg/mouse AVPL protected 100% of mice from infection following the administration of lethal doses of multidrug-resistant S. suis type 2 (SS2) strain SC19, reduced the bacterial load in different organs, and effectively alleviated inflammation and histopathological damage in infected mice. These data suggest that AVPL is a valuable candidate antimicrobial agent for treating S. suis infections.
Effect of Low Concentration of Nitroxides on SH-SY5Y Cells Transfected with the Tau Protein
Authors: Bartosz Grzegorz , Pieńkowska Natalia , Kut Kacper , Cieniek Bogumił , Stefaniuk Ireneusz , Sadowska-Bartosz Izabela
Published: November 2023

Nitroxides, stable synthetic free radicals, are promising antioxidants, showing many beneficial effects both at the cellular level and in animal studies. However, the cells are usually treated with high millimolar concentrations of nitroxides which are not relevant to the concentrations that could be attained in vivo. This paper aimed to examine the effects of low (≤10 μM) concentrations of three nitroxides, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), 4-hydroxy-TEMPO (TEMPOL) and 4-amino-TEMPO (TEMPAMINE), in pure chemical systems and on SH-SY5Y cells transfected with the human tau protein (TAU cells), a model of chronic cellular oxidative stress, and transfected with the empty plasmid (EP cells). All nitroxides were active in antioxidant-activity tests except for the 2,2′-azinobis-(3-ethylbenzthiazolin-6-sulfonate) radical (ABTS•) decolorization assay and reduced Fe3+, inhibited autoxidation of adrenalin and pyrogallol and oxidation of dihydrorhodamine123 by 3-morpholino-sydnonimine SIN-1. TEMPO protected against fluorescein bleaching from hypochlorite, but TEMPAMINE enhanced the bleaching. Nitroxides showed no cytotoxicity and were reduced by the cells to non-paramagnetic derivatives. They decreased the level of reactive oxygen species, depleted glutathione, and increased mitochondrial-membrane potential in both types of cells, and increased lipid peroxidation in TAU cells. These results demonstrate that even at low micromolar concentrations nitroxides can affect the cellular redox equilibrium and other biochemical parameters.
The PolitiFact-Oslo Corpus: A New Dataset for Fake News Analysis and Detection
Authors: Põldvere Nele , Uddin Zia , Thomas Aleena
Published: November 2023

This study presents a new dataset for fake news analysis and detection, namely, the PolitiFact-Oslo Corpus. The corpus contains samples of both fake and real news in English, collected from the fact-checking website PolitiFact.com. It grew out of a need for a more controlled and effective dataset for fake news analysis and detection model development based on recent events. Three features make it uniquely placed for this: (i) the texts have been individually labelled for veracity by experts, (ii) they are complete texts that strictly correspond to the claims in question, and (iii) they are accompanied by important metadata such as text type (e.g., social media, news and blog). In relation to this, we present a pipeline for collecting quality data from major fact-checking websites, a procedure which can be replicated in future corpus building efforts. An exploratory analysis based on sentiment and part-of-speech information reveals interesting differences between fake and real news as well as between text types, thus highlighting the importance of adding contextual information to fake news corpora. Since the main application of the PolitiFact-Oslo Corpus is in automatic fake news detection, we critically examine the applicability of the corpus and another PolitiFact dataset built based on less strict criteria for various deep learning-based efficient approaches, such as Bidirectional Long Short-Term Memory (Bi-LSTM), LSTM fine-tuned transformers such as Bidirectional Encoder Representations from Transformers (BERT) and RoBERTa, and XLNet.
Shallow Whole-Genome Sequencing of Aedes japonicus and Aedes koreicus from Italy and an Updated Picture of Their Evolution Based on Mitogenomics and Barcoding
Authors: Zadra Nicola , Tatti Alessia , Silverj Andrea , Piccinno Riccardo , Devilliers Julien , Lewis Clifton , Arnoldi Daniele , Montarsi Fabrizio , Escuer Paula , Fusco Giuseppe , De Sanctis Veronica , Feuda Roberto , Sánchez-Gracia Alejandro , Rizzoli Annapaola , Rota-Stabelli Omar
Published: November 2023

Aedes japonicus and Aedes koreicus are two invasive mosquitoes native to East Asia that are quickly establishing in temperate regions of Europe. Both species are vectors of arboviruses, but we currently lack a clear understanding of their evolution. Here, we present new short-read, shallow genome sequencing of A. japonicus and A. koreicus individuals from northern Italy, which we used for downstream phylogenetic and barcode analyses. We explored associated microbial DNA and found high occurrences of Delftia bacteria in both samples, but neither Asaia nor Wolbachia. We then assembled complete mitogenomes and used these data to infer divergence times estimating the split of A. japonicus from A. koreicus in the Oligocene, which was more recent than that previously reported using mitochondrial markers. We recover a younger age for most other nodes within Aedini and other Culicidae. COI barcoding and phylogenetic analyses indicate that A. japonicus yaeyamensis, A. japonicus amamiensis, and the two A. koreicus sampled from Europe should be considered as separate species within a monophyletic species complex. Our studies further clarify the evolution of A. japonicus and A. koreicus, and indicate the need to obtain whole-genome data from putative species in order to disentangle their complex patterns of evolution.
The Early Diagnosis of Lung Cancer: Critical Gaps in the Discovery of Biomarkers
Authors: Gasparri Roberto , Sabalic Angela , Spaggiari Lorenzo
Published: November 2023

Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of noninvasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction in lung cancer mortality. However, it is not particularly suitable for clinical practice because of its costs, radiation, and false-positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. In this paper, we provide an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main objective is to highlight the limitations and strengths of studies on predictive lung cancer biomarkers to stimulate further investigation for early diagnosis. Finally, we discuss future perspectives on managing clinical trials for biomarker research and their integration into clinical practice.
COVID-19 and the Concept of Thrombo-Inflammation: Review of the Relationship between Immune Response, Endothelium and Coagulation
Authors: de Maistre Emmanuel , Savard Philippe , Guinot Pierre-Gregoire
Published: November 2023

COVID-19, caused by the SARS-CoV-2 virus, has revealed a complex interplay between inflammation and coagulation, leading to the emergence of the concept of thrombo-inflammation. This concept recognizes that COVID-19 is not solely a respiratory illness, but a systemic disease with significant vascular and hematological components. COVID-19 is associated with an unusual prothrombotic state, with intense endothelial activation leading to vasculopathy, cytokine storm, complement system activation and a hypercoagulability state (the activation of platelets and the coagulation cascade, impaired fibrinolysis). The aim of this review is to discuss the different pathological pathways described in COVID-19 that lead to thromboembolic events. Widespread vaccination and post-COVID-19 immunization allows control over the severity of this pandemic. A better understanding of the pathophysiology of COVID-19 can improve the management of frail patients who are hospitalized in intensive care units.
Hematological Composite Scores in Patients with Inflammatory Bowel Disease
Authors: Carrillo-Palau Marta , Vera-Santana Belén , Morant-Domínguez Andrea , Hernández-Camba Alejandro , Ramos Laura , Alonso-Abreu Inmaculada , Hernández Álvarez-Buylla Noemi , Arranz Laura , Vela Milagros , Hernández-Guerra Manuel , Gómez-Moreno Cristina , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: November 2023

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients—130 Crohn’s (CD) disease and 67 ulcerative colitis (UC)—and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.
Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction
Authors: Saef Joshua , Martyn Trejeeve , Ray Dey Anusha , Khedraki Rola , Ives Lauren , Collier Patrick , Jaber Wael A. , Estep Jerry D. , Hanna Mazen , Tang Wai Hong Wilson
Published: November 2023

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is classically thought of as a progressive disease with preserved systolic function. The longitudinal clinical trajectories of ATTR-CM with impaired left ventricular ejection fraction (LVEF) remain unclear. Methods: This is a single-center retrospective cohort study of consecutive patients with ATTR-CM who underwent two or more echocardiograms with baseline LVEF < 50%. Patients were stratified according to the presence of ≥5% change in LVEF. A Cox proportional hazard model examined hazard of a composite outcome of death, transplant, or LVAD insertion over the two years following diagnosis. Results: In our study cohort of 179 patients, 62 patients (34.6%) experienced an increase in LVEF while 33 (18.4%) experienced a decrease in LVEF. After adjusting for covariates, patients with a decrease in EF experienced increased hazard of death (HR 2.15, 95% CI 1.05–4.40, p = 0.038) compared to those with stable or an increase in LVEF. Changes in LVEF corresponded with significant differences in NT proBNP trajectories, but initial biomarker levels or clinical staging were not predictive of LVEF trajectory. Conclusions: in ATTR-CM patients with impaired LVEF, over a third demonstrated improved LVEF over time, while those with a decrease in LVEF had worse long-term outcomes.
Reactive Hypoglycemia: A Trigger for Nutrient-Induced Endocrine and Metabolic Responses in Polycystic Ovary Syndrome
Authors: Karakas Sidika E.
Published: November 2023

Polycystic ovary syndrome (PCOS) is an insulin-resistant state compensated for by the body via hyperinsulinemia. More than 50% of women with PCOS are obese and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Energy/caloric content as well as the nutrient composition of one’s diet may also be important. This article will present a series of studies from our research comparing the effects of dietary protein vs. simple carbohydrates (CHOs). The results of the acute challenge studies demonstrate that simple CHO intake causes reactive hypoglycemia in one third of women with PCOS, especially among obese and insulin-resistant individuals. Symptoms of hypoglycemia are associated with secretion of cortisol and adrenal androgens. Simple CHOs suppress the hunger signal ghrelin for a shorter period. During weight loss, women who receive protein supplementation achieve more significant weight and fat mass losses. The amino acid compositions of the protein supplements do not affect the improvements in weight and insulin resistance. It is plausible that simple CHO intake leads to weight gain, or interferes with weight loss, by causing reactive hypoglycemia, triggering adrenal steroid secretion and thus leading to snacking. Since obese women with PCOS are more susceptible to reactive hypoglycemia, a vicious cycle is established. Restriction of simple CHOs may break this cycle.
Chronotropic Response and Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Cross-Sectional Study
Authors: Osailan Ahmad M. , Metsios George S. , Duda Joan L. , Kitas George D. , Veldhuijzen van Zanten Jet J. C. S. , Elnaggar Ragab K.
Published: November 2023

Background: Individuals with rheumatoid arthritis (RA) are at a high risk of cardiovascular diseases (CVD). A reduced chronotropic response (CR), which produces exercise intolerance, is known to be a contributing factor to CVD and mortality. Studies have shown that patients with RA have a reduced CR. However, knowledge of CR-related factors in patients with RA is limited. This study aimed to explore CR-related factors, including CVD risk factors, inflammatory markers, and cardiorespiratory fitness (VO2PEAK). Methods: A total of 106 RA patients underwent a treadmill test, heart rate monitoring, and various assessments, including serological CVD risk factors, inflammatory markers, and VO2PEAK. Results: A total of 34% of participants demonstrated a reduced CR (≤80%). Body mass index, HOMA, hsCRP, and fibrinogen were inversely related to CR, while HDL, QUICKi, VO2PEAK, and RER exhibited a positive association. HDL and VO2PEAK emerged as independent CR-related factors in regression analysis. Conclusions: The current findings suggest that reduced CR in RA is associated with several CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Future studies should investigate the effects of controlling these associated variables on CR in patients with RA.
Coronary Revascularization after Transcatheter and Surgical Aortic Valve Replacement
Authors: Gabbieri Davide , Giorgi Federico , Mascheroni Greta , Chiarabelli Matteo , D’Anniballe Giuseppe , Meli Marco , Labia Clorinda , Ghidoni Italo
Published: November 2023

Introduction: Due to the selective criteria and short-term follow-up of previous transcatheter aortic valve implantation (TAVI) trials, the coronary revascularization incidence after TAVI has been difficult to determine. This study investigated the epidemiology of coronary revascularization after surgical aortic valve replacement (SAVR) and TAVI in patients with severe aortic valve stenosis (AS), with and without coronary artery disease (CAD), in a mid-term follow-up, single-center, real-world setting. Methods: Between 2010 to 2020, 1486 patients with AS underwent SAVR or TAVI with balloon-expandable Edwards® transcatheter heart valves (THVs). Using hospital discharge records, we could estimate for each patient resident in Emilia Romagna the rate of ischemic events treated with percutaneous coronary intervention (PCI). A subgroup without CAD was also analyzed. Results: The 5-year overall survival was 78.2%. Freedom from PCI after AVR and TAVI at 5 years was 96.9% and 96.9%, respectively, with previous PCI as a predictor (HR 4.86, 95% CI 2.57–9.21 p < 0.001). The freedom from PCI curves were not significantly different. Conclusions: Notwithstanding the aged population, the revascularization incidence was only 2.4%, requiring further evaluation even in younger patients with longer follow-up. Despite the profile frame raise due to the evolution of Edwards® balloon-expandable THVs, PCI or coronarography feasibility were not compromised in our population.
Clinical and Functional Outcomes of Kinematic Aligned Total Knee Arthroplasty with a Medial Pivot Design: Two-Year Follow-Up
Authors: Sosio Corrado , Rossi Nicolò , Sirtori Paolo , Ciliberto Ricardo , Lombardo Michele Davide Maria , Peretti Giuseppe Michele , Mangiavini Laura
Published: November 2023

Background: Kinematic alignment (KA) restores native limb alignment following total knee arthroplasty (TKA). The association of this technique with a medial pivot implant design attempts to re-establish the physiological kinematics of the knee. This study aims to analyze the clinical and radiological outcomes of patients undergoing MP-TKA with kinematic alignment and to assess the effect of limb alignment on the clinical outcomes. Methods: We retrospectively analyzed 55 patients who underwent kinematic aligned medial pivot TKA from September 2018 to January 2020. Patient-related outcomes (PROMs) were collected at baseline, 3, 12, and 24 months after surgery. Long-standing weight-bearing radiographs were performed three months after surgery. Results: We demonstrated a significant improvement in clinical outcomes from 3 months after surgery up to 24 months of follow-up. This clinical improvement was independent of limb alignment. The radiological analysis showed that the patient’s native limb alignment was restored and that their joint line orientation was parallel to the floor. Conclusion: The association of kinematic alignment and a medial pivot TKA implant allows for a fast recovery, with good clinical and functional outcomes up to a minimum of 2 years of follow-up, independent of the final limb alignment.
Comparison of the iStent Inject® versus the iStent Inject® W—Both in Combination with Cataract Surgery—In Open-Angle Glaucoma
Authors: Deneri Steffen , Merté Ralph-Laurent , Eter Nicole , Brücher Viktoria C.
Published: November 2023

We compare the short- and mid-term postoperative outcomes of the iStent inject® with its successor, the iStent inject® W. A retrospective monocentric study was performed to compare the iStent inject® used for cataract surgery with the iStent inject® W, also used for cataract surgery. The primary study endpoint was intraocular pressure (IOP) reduction six months after surgery. Six-month follow-up results were available for 35 eyes from 27 patients in the iStent inject® group and for 32 eyes from 25 patients in the iStent inject® W group. IOP reduction at six months post surgery was significantly greater in the iStent inject® W group (−2.2 mmHg [iStent inject® W] vs. −0.06 mmHg [iStent inject®], p = 0.037). There was a statistically greater decrease in glaucoma medication administration at six months in the iStent inject® group than in the iStent inject® W group (−1.28 agents vs. −0.62 agents, p = 0.007). These findings support the hypothesis that the superior positioning of the iStent inject® W (due to its larger base diameter) compared to the iStent Inject® leads to greater IOP reduction. Because of the short follow-up period, small study cohort, and differences in the number of glaucoma patients, the study results must be interpreted carefully.
Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes
Authors: Cipriani Cristiana , Lauriero Gabriella , Tripepi Giovanni , Ferrari Serge , Bover Jordi , Ravera Maura , Barbuto Simona , Cianciolo Giuseppe , De Nicola Luca , Brandi Maria Luisa , Minisola Salvatore , Mereu Maria Cristina , Corrao Giovanni , Del Vecchio Lucia , Fusaro Maria
Published: November 2023

Among the metabolic changes occurring during the course of type 2 diabetes (T2DM) and diabetic kidney disease (DKD), impaired bone health with consequent increased fracture risk is one of the most complex and multifactorial complications. In subjects with diabetic kidney disease, skeletal abnormalities may develop as a consequence of both conditions. In the attempt to define a holistic approach to diabetes, potential effects of various classes of antidiabetic drugs on the skeleton should be considered in the setting of normal kidney function and in DKD. We reviewed the main evidence on these specific topics. Experimental studies reported potential beneficial and harmful effects on bone by different antidiabetics, with few data available in DKD. Clinical studies specifically designed to evaluate skeletal effects of antidiabetics have not been performed; notwithstanding, data gleaned from randomized controlled trials and intervention studies did not completely confirm observations made by basic research. In the aggregate, evidence from meta-analyses of these studies suggests potential positive effects on fracture risk by metformin and glucagon-like peptide-1 receptor agonists, neutral effects by dipeptidyl peptidase-4 inhibitors, sodium–glucose cotransporter-2 inhibitors, and sulfonylureas, and negative effects by insulin and thiazolidinediones. As no clinical recommendations on the management of antidiabetic drugs currently include fracture risk assessment among the main goal of therapy, we propose an integrated approach with the aim of defining a patient-centered management of diabetes in chronic kidney disease (CKD) and non-CKD patients. Future clinical evidence on the skeletal effects of antidiabetics will help in optimizing the approach to a personalized and more effective therapy of diabetes.
Fatigue Damage Assessment and Lifetime Prediction of Short Fiber Reinforced Polymer Composites—A Review
Authors: Bogdanov Alexey A. , Panin Sergey V. , Kosmachev Pavel V.
Published: November 2023

This paper reviews the findings in the area of fatigue damage assessment and lifetime prediction of short fiber reinforced polymer composites (SFRPs) under cyclic loading. It is shown that the direct methods of microstructure/damage inspection are the most sensitive and informative, while micro-computed tomography (μ-CT) is more laborious and possesses limitations in sample dimensions. Although the sensitivity of the indirect methods can vary, the most common one is based on stiffness reduction. It is shown that developing models of fatigue processes is impossible without assessing the degree of damage. The latter can be determined by stiffness reduction, the development of creep, or energy dissipation. Since fatigue mechanisms can differ, the most complete information can be obtained by combining these methods. The prediction results for fatigue life models based on plastic strain development showed the greatest agreement with the experimental results in comparison with other prediction models. In addition, some tasks are highlighted as the priority directions for the development of SFRPs and non-destructive testing (NDT) methods for their monitoring under fatigue.
Differences in Body Composition and Maturity Status in Young Male Volleyball Players of Different Levels
Authors: Grigoletto Alessia , Mauro Mario , Toselli Stefania
Published: November 2023

Volleyball is an intermittent team sport that requires specific anthropometrical and physical characteristics for winning performance. The present study aimed to evaluate the maturity status of the young male players of eight volleyball teams, and to observe differences in anthropometric characteristics and body composition. Ninety-four male adolescent volleyball players were recruited during a national tournament carried out in Treviso (Italy). Anthropometric characteristics such as weight, stature, skinfold thicknesses, circumferences and diameters, and bioelectrical impedance were measured. The biological maturation was estimated for all players. Each team was classified as a higher or lower lever according to its tournament ranking. A two-way ANOVA compared team levels and players’ maturity status. Considering the maturity offset, 62 boys were classified as “on time”, 20 as “late”, and 12 as “early”. Three clubs presented many boys with “early” as the maturity offset, and two of these finished the tournament in the first position. Young volleyball players classified as “early” seemed to show anthropometric characteristics linked to better performance at the tournament (higher height, upper arm and calf muscle area, fat mass percentage, and total fat-free mass). The results of the present study could have practical implications for talent selection, but further studies are needed to better evaluate the effect of maturity status on the characteristics of volleyball players.
An AI Approach to Identifying Novel Therapeutics for Rheumatoid Arthritis
Authors: Rajan Jency R. , McDonald Stephen , Bjourson Anthony J. , Zhang Shu-Dong , Gibson David S.
Published: November 2023

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that has a significant impact on quality of life and work capacity. Treatment of RA aims to control inflammation and alleviate pain; however, achieving remission with minimal toxicity is frequently not possible with the current suite of drugs. This review aims to summarise current treatment practices and highlight the urgent need for alternative pharmacogenomic approaches for novel drug discovery. These approaches can elucidate new relationships between drugs, genes, and diseases to identify additional effective and safe therapeutic options. This review discusses how computational approaches such as connectivity mapping offer the ability to repurpose FDA-approved drugs beyond their original treatment indication. This review also explores the concept of drug sensitisation to predict co-prescribed drugs with synergistic effects that produce enhanced anti-disease efficacy by involving multiple disease pathways. Challenges of this computational approach are discussed, including the availability of suitable high-quality datasets for comprehensive analysis and other data curation issues. The potential benefits include accelerated identification of novel drug combinations and the ability to trial and implement established treatments in a new index disease. This review underlines the huge opportunity to incorporate disease-related data and drug-related data to develop methods and algorithms that have strong potential to determine novel and effective treatment regimens.
Laparoscopic versus Ultrasound-Guided Transversus Abdominis Plane Block for Postoperative Analgesia Management after Radical Prostatectomy: Results from a Single Center Study
Authors: Civitella Angelo , Prata Francesco , Papalia Rocco , Citriniti Vincenzo , Tuzzolo Piergiorgio , Pascarella Giuseppe , Forastiere Ester Maria Alba , Ragusa Alberto , Tedesco Francesco , Prata Salvatore Mario , Anceschi Umberto , Simone Giuseppe , Muto Giovanni , Scarpa Roberto Mario , Cataldo Rita
Published: November 2023

(1) Background: Regional anesthesia, achieved through nerve blocks, has gained widespread acceptance as an effective pain management approach. This research aimed to evaluate the efficacy of laparoscopic (LAP) transversus abdominis plane (TAP) block in patients undergoing laparoscopic radical prostatectomy. (2) Methods: From January 2023 to July 2023, 60 consecutive patients undergoing minimally invasive radical prostatectomy were selected. Patients were split into two groups receiving ultrasound-guided (US) or laparoscopic-guided TAP block. The primary outcome was a pain score expressed by a 0−10 visual analog scale (VAS) during the first 72 h after surgery. (3) Results: Both LAP-TAP and US-TAP block groups were associated with lower pain scores postoperatively. No statistically significant differences were observed between the two groups in surgery time, blood loss, time to ambulation, length of stay, and pain after surgery (all p > 0.2). In the LAP-TAP block group, the overall operating room time was significantly shorter than in the US-TAP block group (140 vs. 152 min, p = 0.04). (4) Conclusions: The laparoscopic approach, compared to the US-TAP block, was equally safe and not inferior in reducing analgesic drug use postoperatively. Moreover, the intraoperative LAP-TAP block seems to be a time-sparing procedure that could be recommended when patient-controlled analgesia cannot be delivered.
Urban Land Expansion Simulation Considering the Increasing versus Decreasing Balance Policy: A Case Study in Fenghua, China
Authors: Jin Yaya , Ding Jiahe , Chen Yue , Zhang Chaozheng , Hou Xianhui , Zhang Qianqian , Liu Qiankun
Published: November 2023

Under the political dominance of urbanization, the policy of increasing versus decreasing balance (IVDB) between urban and rural construction land has had a profound influence on urban land expansion in China. The purpose of this study is to reveal the impact of the IVDB policy on the process of urban land expansion. Considering the transition process among different land use types under the IVDB policy, this study proposes two situations of urban land expansion. A future land use simulation (FLUS) model is applied to simulate the expansion process over three steps. A case study of Fenghua District in Ningbo City, China, shows the following: (1) In the first situation of village land directly transformed into urban land, the transformation is concentrated in the northern and western parts of Fenghua District. The expansion trends are particularly pronounced along existing urban land and main traffic lines. (2) In the second situation of village land reclamation for agricultural land and urban land occupation for agricultural land, the spatial differences in village land conversion to arable land or other agricultural land are relatively small, and the degree of concentration of arable land is significantly increased after reclamation. Urban land expansion mainly occurs close to Ningbo City. With the help of transfer quotas “produced” by other areas, expansion land can be balanced within Fenghua District. This research helps to shed light on the urban land use growth process and provides beneficial insights for stock spatial planning in China.