bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological analysis of Dirofilaria immitis (Spirurida: Onchocercidae) infecting pet dogs (Canis lupus familiaris, Linnaeus, 1758) in Baixada Fluminense, Rio de Janeiro
Authors: de Andrade Vieira Viviane Marques , da Silva Priscila Pinho , Paulino Érica Tex , do Amaral Fernandes Priscila , Labarthe Norma , Gazêta Gilberto Salles , de Moraes Neto Antonio Henrique Almeida
Published: May 2024

Dirofilaria immitis infection is routinely detected in dogs during veterinary care in tropical and subtropical regions worldwide. Parasitological tests for the detection of this infection are routinely performed only in areas with a high prevalence. Baixada Fluminense, a region in Rio de Janeiro, was considered heartworm-free until local veterinarians began to receive blood exams results indicating the presence of microfilariae (MF). A laboratory database was hence used to collect data from 2017 to 2020 to understand the extent of spread of the parasite in this area. The results of complete blood count analysis and MF or heartworm antigen detection tests conducted on canine samples sent from veterinary clinics in Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti municipalities) were included. In total, the results of 16,314 hematological tests were considered. The overall prevalence of D. immitis was 3.4% (554/16,314), considering that only one test result was obtained per animal on the same day. This study is highly relevant because it indicates the spreading geographic distribution of the worms, heightens awareness among local health professionals and the general population, and encourages compliance with prophylactic measures to prevent further spread of parasite.
Antibiotic resistance spectrums of Escherichia coli and Enterococcus spp. strains against commonly used antimicrobials from commercial meat-rabbit farms in Chengdu City, Southwest China
Authors: Sun Chen , Wang Ziye , Li Yan , Huang Jian
Published: May 2024

Antimicrobial resistance (AMR) is commonly associated with the inappropriate use of antibiotics during meat-rabbit production, posing unpredictable risks to rabbit welfare and public health. However, there is limited research on the epidemiological dynamics of antibiotic resistance among bacteria indicators derived from local healthy meat-rabbits. To bridge the knowledge gap between antibiotic use and AMR distribution, a total of 75 Escherichia coli (E. coli) and 210 Enterococcus spp. strains were successfully recovered from fecal samples of healthy meat-rabbits. The results revealed that diverse AMR phenotypes against seven commonly used antimicrobials, including ampicillin (AMP), amoxicillin-clavulanic acid (A/C), doxycycline (DOX), enrofloxacin (ENR), florfenicol (FFC), gentamicin (GEN), and polymycin B (PMB), were observed among most strains of E. coli and Enterococcus spp. in two rabbit farms, although the distribution pattern of antibiotic resistance between young and adult rabbits was similar. Among them, 66 E. coli strains showed resistance against 6 antimicrobials except for PMB. However, 164 Enterococcus spp. strains only exhibited acquired resistance against DOX and GEN. Notably, the DOX-based AMR phenotypes for E. coli and Enterococcus spp. strains were predominant, indicating the existing environmental stress conferred by DOX exposure. The MICs tests suggested elevated level of antibiotic resistance for resistant bacteria. Unexpectedly, all GEN-resistant Enterococcus spp. strains resistant high-level gentamicin (HLGR). By comparison, the blaTEM, tetA, qnrS and floR were highly detected among 35 multi-resistant E. coli strains, and aac[6']-Ie-aph[2']-Ia genes widely spread among the 40 double-resistant Enterococcus spp. strains. Nevertheless, the presence of ARGs were not concordant with the resistant phenotypes for a portion of resistant bacteria. In conclusion, the distribution of AMR and ARGs are prevalent in healthy meat-rabbits, and the therapeutic antimicrobials use in farming practice may promote the antibiotic resistance transmission among indicator bacteria. Therefore, periodic surveillance of antibiotic resistance in geographic locations and supervisory measures for rational antibiotic use are imperative strategies for combating the rising threats posed by antibiotic resistance, as well as maintaining rabbit welfare and public health.
Investigating the impact of preslaughter handling intensity on goats: a study on behavior, physiology, blood enzymes, and hormonal responses
Authors: Al-Owaimer Abdullah N. , Suliman Gamaleldin M. , Alobre Mohsen M. , Swelum Ayman A. , Al-Badwi Mohammed A. , Ba-Awadh Hani , Sazili Awis Qurni , Kumar Pavan , Kaka Ubedullah
Published: May 2024

Introduction

The present study evaluated the effect of preslaughter stress intensities on the behavioral, physiological, blood biochemicals, and hormonal responses in goats.

Methods

Twenty-seven intact male goats (Ardi breed, 10 months of age, 27 kg liveweight) were divided into three treatment groups viz., the control (C) group, ear pulling (EP) group, and leg pulling (LP) group. Various behavioral, physiological, blood biochemical and hormonal responses were recorded before and after handling.

Results and Discussion

The EP and LP goats had a higher frequency and intensity of vocalization as compared to control goats. The preslaughter handling stress intensities had a significant effect on the before and after handling values of heart rate, respiration rate, rectal temperature, and ear temperature. Further, among groups, the glucose value increased significantly upon preslaughter handling as compared to the baseline value. The LP goats had significantly higher after-handling value for lactate dehydrogenase (LDH) as compared to the before-handling value. The catecholamines (adrenaline and noradrenaline) and β-endorphin concentrations increased significantly upon preslaughter handling. The higher physiological, behavioral, blood biochemical, and hormonal response indicated higher preslaughter stress in EP and LP goats. Both levels of intensity revealed unfavorable responses in goats that may adversely affect animal welfare and meat quality. Thus, to ensure minimal adverse effects on behavior, physiology, blood enzymes, and hormonal responses, it is recommended to follow animal welfare principles when implementing preslaughter handling practices.
Assessment of testicular stiffness in fertile dogs with shear wave elastography techniques: a pilot study
Authors: Zappone Viola , Iannelli Nicola Maria , Sinagra Letizia , Donato Giulia , Quartuccio Marco , Cristarella Santo , De Majo Massimo , Caspanello Tiziana
Published: May 2024

Ultrasound of the testes is important in the evaluation of breeding dogs, and recently advanced techniques such as Shear Wave Elastography (SWE) have been developed. This study focused on evaluation of normal testicular stiffness in healthy and fertile male dogs, employing both qualitative (2D-SWE) and quantitative (pSWE, 2D-SWE) techniques. Nineteen dogs of various medium-large breeds aged 3.39 ± 2.15 years, and with a history of successful reproduction were included after clinical, B-mode and Doppler ultrasound of testes and prostate, and semen macro and microscopic evaluations. pSWE involved square regions of interest (ROIs) placed at six different points in the testicular parenchyma, while 2D-SWE depicted stiffness with a color scale ranging from blue (soft) to red (stiff), allowing a subsequent quantification of stiffness by the application of 4 round ROIs. The results showed a mean Shear Wave Speed (SWS) of 2.15 ± 0.39 m/s using pSWE, with lower values above the mediastinum compared to below, and in the center of the testis compared to the cranial and caudal poles. 2D-SWE demonstrated a uniform blue pattern in the parenchyma, and a mean SWS of 1.65 ± 0.15 m/s. No significant differences were found between left and right testes, above and below the mediastinum, or among breeds. No correlations were observed between mean SWS and body condition score, age, testicular and prostatic volume. Weight was positively correlated with mean SWS only by 2D-SWE. By performing semen analysis and enrolling only healthy and fertile adult dogs, we ensured both structural and functional integrity of the testes. This pilot study represents a valuable baseline data for testicular stiffness by both pSWE and 2D-SWE with a Mindray US machine in medium-large sized healthy and fertile dogs, pointing out the potential role of SWE in the non-invasive fertility assessment and management of breeding dogs.
The Impact of Internet Addiction on Mental Health: Exploring the Mediating Effects of Positive Psychological Capital in University Students
Authors: Zewude Girum Tareke , Bereded Derib Gosim , Abera Endris , Tegegne Goche , Goraw Solomon , Segon Tesfaye
Published: May 2024

Introduction: The widespread use of the internet has brought numerous benefits, but it has also raised concerns about its potential negative impact on mental health, particularly among university students. This study aims to investigate the relationship between internet addiction (IA) and mental health (MH) in university students, as well as explore the mediating effects of positive psychological capital (PsyCap) in this relationship. Objective: The main goal of this study was to examine the psychometric properties of the measures and to determine whether internet addiction could negatively predict university students’ mental health, mediated through PsyCap. Method: A cross-sectional design with an inferential approach was employed to address this objective. The data were collected using the Psychological Capital Questionnaire (PCQ-24), Internet Addiction Scale (IAS), and Keyes’ Mental Health Continuum-Short Form (MHC-SF). The total sample of this study comprised 850 students from two large public higher education institutions in Ethiopia, of whom 334 (39.3%) were female and 516 (60.7%) were male, with a mean age of 22.32 (SD = 4.04). Several analyses were performed to achieve the stated objectives, such as Cronbach’s alpha and composite reliabilities, bivariate correlation, discriminant validity, common method biases, and structural equation modeling (confirmatory factor analysis, path analysis, and mediation analysis). Confirmatory factor analysis was conducted to test the construct validity of IAS, PCQ-24, and MHC-SF. Additionally, the mediating model was examined using structural equation modeling with the corrected biased bootstrap method. Results: The preliminary study results found that the construct validity of IAS, PCQ-24, and MHC-SF was excellent and appropriate. Furthermore, the findings demonstrate that internet addiction had a negative and direct effect on PsyCap and MH. Moreover, PsyCap fully mediated the relationship between IA and MH. Additionally, this study confirmed that all the scales exhibited strong internal consistency and good psychometric properties. Conclusion: This study contributes to a better understanding of the complex interplay between IA, PsyCap, and MH among university students, confirming previous findings. Recommendation: The findings, discussed in relation to the recent and relevant literature, will be valuable for practitioners and researchers aiming to improve mental health and reduce internet addiction by utilizing positive psychological resources as protective factors for university students.
RisDes_Index: An Index for Analysing the Advance of Areas Undergoing Desertification Using Satellite Data
Authors: Silva Thieres George Freire da , Cruz Neto José Francisco da , Jardim Alexandre Maniçoba da Rosa Ferraz , Souza Carlos André Alves de , Araújo Júnior George do Nascimento , Silva Marcos Vinícius da , Silva Jhon Lennon Bezerra da , Carvalho Ailton Alves de , Montenegro Abelardo Antônio de Assunção , de Souza Luciana Sandra Bastos
Published: May 2024

The proposal for a method of identifying the occurrence of desertification that has a strong association with in situ data leads to more assertive results when analysing the contribution of climate and social and economic factors to advancing the process. This study aimed to develop a methodology called the RisDes_Index to evaluate the evolution of the desertification process based on satellite data. The concept of the RisDes_Index method was based on the reflectance variables of the R, B and G bands, albedo and LAI of the Landsat 5/TM and Landsat 8/OLI satellites. Principal component analysis was used to assess the biophysical basis of the RisDes_Index by associating the results with micrometeorological data, physical and chemical properties, and vegetation cover data collected from five experimental sites in the semi-arid region of Brazil. These sites included one from a seasonally dry forest (i.e., the Caatinga), an agricultural cactus plantation, an area undergoing desertification, and two irrigated sugarcane crops (wetlands), one with and one without straw cover. The RisDes_Index was applied to all pixels of the images from 5 December 1991, 14 November 2001, 20 November 2009 and 6 October 2016 of an important desertification nucleus (DN) in the semi-arid region of Brazil, i.e., the DN of Cabrobó. The proposed RisDes_Index was able to identify areas with significant processes of desertification, which mainly occur in areas of sandy, acidic, bare soils with a high β value (Bowen ratio) and high soil temperature. The results of the RisDes_Index showed that in 5 December 1991, desertified areas comprised 38% of the total area of the DN of Cabrobó, expanding to 51% in 2016. Application of the RisDes_Index confirmed the advance of desertification in the DN of Cabrobó. This was due to a consequent increase in the water deficit and intensified deforestation to increase the areas of livestock farming. The RisDes_Index proved to be a robust method, as its estimation based on simple satellite products exhibited a strong association with biophysical variables of areas with different land uses and degradation levels. Thus, it is suggested that the RisDes_Index be applied in various regions of the world, with the idea of directing action to meet the advance of desertification.
Correlation Methodologies between Land Use and Greenhouse Gas emissions: The Case of Pavia Province (Italy)
Authors: De Lotto Roberto , Bellati Riccardo , Moretti Marilisa
Published: May 2024

The authors present an analysis of the correlation between demographic and territorial indicators and greenhouse gas (GHG) emissions, emphasizing the spatial aspect using statistical methods. Particular attention is given to the application of correlation techniques, considering the spatial correlation between the involved variables, such as demographic, territorial, and environmental indicators. The demographic data include factors such as population, demographic distribution, and population density; territorial indicators include land use, particularly settlements, and road soil occupancy. The aims of this study are as follows: (1) to identify the direct relationships between these variables and emissions; (2) to evaluate the spatial dependence between geographical entities; and (3) to contribute to generating a deeper understanding of the phenomena under examination. Using spatial autocorrelation analysis, our study aims to provide a comprehensive framework of the territorial dynamics that influence the quantity of emissions. This approach can contribute to formulating more targeted environmental policies, considering the spatial nuances that characterize the relationships between demographics, territory, and GHGs. The outcome of this research is the identification of a direct formula to obtain greenhouse gas emissions from data about land use starting from the case study of Pavia Province in Italy. In the paper, the authors highlight different methodologies to compare land use and GHG emissions to select the most feasible correlation formula. The proposed procedure has been tested and can be used to promote awareness of the spatial dimension in the analysis of complex interactions between anthropogenic factors and environmental impacts.
Pulmonary Cavitation as a Complication of COVID-19: Case Series and a Brief Review of the Literature
Authors: Aghamohammadi Mehdi , Ghodrati Samad , Etemadi Sh Milad , Sehat Mohammad Soroush , Alizargar Javad
Published: May 2024

The COVID-19 pandemic has led to an unprecedented surge in respiratory illness cases worldwide. Although uncommon, pulmonary cavitation has been reported as a potential complication of COVID-19. This case series report describes four cases of COVID-19 patients with lung cavities, highlighting the various causes and clinical manifestations of this complication, and a review of the literature on the presence of lung cavities in COVID-19 patients. In two cases, the cavities were most likely due to secondary bacterial superinfections, with one case being complicated by multi-drug-resistant bacteria. Another case developed cavities secondary to a fungal infection, while the third case was directly caused by SARS-CoV-2 invasion in the lungs. The presence of cavities with or without air-fluid level or pneumothorax in COVID-19 patients should be considered as a potential complication of this infection, especially in those with respiratory symptoms. Physicians should remain vigilant for the development of pulmonary cavitation in COVID-19 patients, particularly those receiving high doses of steroids. Additionally, spontaneous pneumothorax should be considered an alarming sign in COVID-19 patients.
Near-Infrared Spectroscopy (NIRS) in the Assessment of Cerebral Tissue Oxygenation (rSO2): Methodological Issues and Dilemmas
Authors: Lukaszewski Marceli , Nelke Kamil
Published: May 2024

Introduction: Monitoring cerebral perfusion in patients with brain injury is a major clinical challenge. Monitoring cerebral oxygenation (rSO2) via NIRS was introduced in the early 1980s, and many clinicians believed it to be a valuable method for assessing cerebral perfusion and subsequent measures to optimize cerebral flow. The main problem with the use of NIRS is the presence of intermediate structures—the skin, skull, meninges, cerebrospinal fluid—and their influence on the test result. Therefore, it seems that NIRS assessment performed on a patient during brain death can give an idea of the magnitude of the influence of these intermediate structures on the monitoring result. Case presentation: We present a case study of cerebral oxygenation measurements in a patient undergoing a brain death diagnostic procedure. A clinical situation in which cerebral blood flow is stopped can give an idea of the specificity of this method, in particular of the influence of intermediate structures on the monitoring result. In this case, the result obtained using NIRS is increased by the patient’s oxygenation before the apnea test. The influence of chromophores in the tissues surrounding the CNS and reflections and scattering of the light wave spectrum have a very significant effect on the final result of cerebral saturation measurement. Discussion: The majority of observations in existing research describing changes in cerebral perfusion or its optimization may be burdened by the problem described here, i.e., by the significant influence of measured intermediate structure oxygenation. The specificity of NIRS in assessing cerebral perfusion requires careful analysis. The therapeutic implications of monitoring cerebral oxygenation with NIRS are of great importance, and based on the example presented and the literature provided, this method should be used with caution. It has been shown that in a patient with brain death, the result of NIRS oxygenation measurements depends on the structures surrounding the brain.
Flow Cytometry as a Rapid and Valuable Method in Investigation of Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Isolates
Authors: Uçak Şafak Ceren , Öngen Betigül
Published: May 2024

Rapid detection of antimicrobial resistance is crucial for early initiation of appropriate therapy. The aim of this study was to investigate whether resistance to colistin, the last-resort antibiotic, in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates can be detected accurately and rapidly by flow cytometry (FCM). The VITEK 2 automated system was used to identify 85 K. pneumoniae strains and to determine their resistance to carbapenems. The minimum inhibitory concentration (MIC) values for colistin in 85 CRKP strains were determined by broth microdilution (BMD), which is the reference method. In addition, FCM was used, combined with DiBAC4(3) fluorescent stain, to determine colistin susceptibility. The MIC₅₀ value of the strains, 80% of which were resistant to colistin by the BMD method, was 16 mg/L, and the MIC₉₀ value was 32 mg/L. When FCM was compared with the reference method, it was determined that the specificity was 94.1%, sensitivity was 100% of FCM, and Cohen’s kappa value was 0.96. Colistin susceptibility results with FCM were obtained within an average of 2 h. These findings suggest that FCM holds great promise as a rapid and reliable alternative method for detecting colistin resistance in CRKP strains.
Impact of Lactic Acid Bacteria Fermentation on (Poly)Phenolic Profile and In Vitro Antioxidant and Anti-Inflammatory Properties of Herbal Infusions
Authors: Ozturk Tarik , Ávila-Gálvez María Ángeles , Mercier Sylvie , Vallejo Fernando , Bred Alexis , Fraisse Didier , Morand Christine , Pelvan Ebru , Monfoulet Laurent-Emmanuel , González-Sarrías Antonio
Published: May 2024

Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of Lactiplantibacillus plantarum of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE2) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders.
Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients
Authors: Anguera Georgia , Mulet Maria , Zamora Carlos , Osuna-Gómez Rubén , Barba Andrés , Sullivan Ivana , Serra-López Jorgina , Cantó Elisabet , Vidal Silvia , Majem Margarita
Published: May 2024

PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and its evolution during treatment. One hundred thirteen NSCLC patients, according to their radiological response after 10–12 weeks of treatment, were classified into responders, stable, and progressive disease. Percentages of circulating PD-L1+ leukocytes, PD-L1+ platelets (PLTs), and leukocyte-PLT complexes were assessed using flow cytometry, and plasma concentrations of soluble immunomodulatory factors were quantified by ELISA. Responders exhibited significantly higher pre-treatment percentages of PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs than progressors. The percentages of these populations decreased in responders post-treatment, contrasting with stables and progressors. PLTs notably contributed to PD-L1 expression in CD14+ cells and neutrophils. Plasma cytokine analysis revealed baseline differences only in IL-17 concentration among groups, whereas network analyses highlighted distinct association patterns between plasma molecules and PD-L1+ leukocytes after 10–12 weeks of treatment. Our findings suggest that pre-treatment assessment of circulating PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs may be helpful in identifying NSCLC patients who are potential candidates for anti-PD-(L)1 therapy.
Porous Tantalum Acetabular Cups in Primary and Revision Total Hip Arthroplasty: What Has Been the Experience So Far?—A Systematic Literature Review
Authors: Argyropoulou Evangelia , Sakellariou Evangelos , Galanis Athanasios , Karampinas Panagiotis , Rozis Meletis , Koutas Konstantinos , Tsalimas George , Vasiliadis Elias , Vlamis John , Pneumaticos Spiros
Published: May 2024

Background: The global population, especially in the Western world, is constantly aging and the need for total hip arthroplasties has rocketed, hence there has been a notable increase in revision total hip arthroplasty cases. As time has passed, a considerable developments in science and medicine have been attained which have also resulted in the evolution of both surgical techniques and implants. Continuous improvements have allowed large bore bearings to be utilized which provide an increased range of motion, with ameliorated stability and a very low rate of wear. The trend for almost the last two decades has been the employment of porous tantalum acetabular cups. Several studies exist comparing them with other conventional methods for total hip arthroplasties, exhibiting promising short and midterm results. Methods: The Preferred Reporting Items for Systematic Reviews and a Meta-Analysis (PRISMA) were used to identify published studies in a comprehensive search up to February 2023, and these studies were reviewed by the authors of the article. Specific rigorous pre-determined inclusion and exclusion criteria were implemented. Results: Fifty-one studies met our inclusion criteria and were involved in the systematic review. Sixteen studies examined postoperative clinical and radiological outcomes of using a tantalum cup in primary and revision total hip arthroplasty, whilst four biomechanical studies proved the superiority of tantalum acetabular components. Five articles provided a thorough comparison between tantalum and titanium acetabular cups, while the other studies analyzed long-terms results and complication rates. Conclusions: Porous tantalum acetabular cups appear to be a valuable option in revision total hip arthroplasty, providing clinical improvement, radiological stability, and promising long-term outcomes. However, ongoing research, longer follow-up periods, and careful consideration of patient factors are essential to further validate and refine the use of tantalum in various clinical scenarios.
Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma
Authors: Popov Alexey , Hrudka Jan , Szabó Arpád , Oliverius Martin , Šubrt Zdeněk , Vránová Jana , Ciprová Vanda , Moravcová Jana , Mandys Václav
Published: May 2024

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.
Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus
Authors: Fernández-Cladera Yolanda , García-González María , Hernández-Díaz Marta , Gómez-Bernal Fuensanta , Quevedo-Abeledo Juan C. , González-Rivero Agustín F. , de Vera-González Antonia , Gómez-Moreno Cristina , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: May 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.
Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview
Authors: Biz Carlo , Khamisy-Farah Rola , Puce Luca , Szarpak Lukasz , Converti Manlio , Ceylan Halil İbrahim , Crimì Alberto , Bragazzi Nicola Luigi , Ruggieri Pietro
Published: May 2024

In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system’s structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity–mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of “Sexual Orientation and Gender Identity” (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field.
Transplant Eligible and Ineligible Elderly Patients with AML—A Genomic Approach and Next Generation Questions
Authors: Sackstein Paul , Williams Alexis , Zemel Rachel , Marks Jennifer A. , Renteria Anne S. , Rivero Gustavo
Published: May 2024

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized.
Beyond Chemotherapy: Present and Future Perspectives in the Treatment of Lymphoproliferative Disorders
Authors: Massaro Fulvio , Andreozzi Fabio , Abrassart Tom , Castiaux Julie , Massa Hanne , Rizzo Ornella , Vercruyssen Marie
Published: May 2024

Over the past three decades, the treatment of lymphoproliferative disorders has undergone profound changes, notably due to the increasing availability of innovative therapies with the potential to redefine clinical management paradigms. A major impact is related to the development of monoclonal antibodies, checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapies. This review discusses the current landscape of clinical trials targeting various hematological malignancies, highlighting promising early-phase results and strategies to overcome resistance. Lymphoproliferative disorders encompass a range of conditions: while in Hodgkin lymphoma (HL) the goal is to reduce chemotherapy-related toxicity by integrating immunotherapy into the frontline setting, peripheral T cell lymphoma (PTCL) lacks effective targeted therapies. The review emphasizes a shifting therapeutic landscape towards precision medicine and treatment modalities that are less toxic yet more effective.
Drug-Induced Myopathies: A Comprehensive Review and Update
Authors: Miernik Sebastian , Matusiewicz Agata , Olesińska Marzena
Published: May 2024

Drug-induced myopathies are a common cause of muscle pain, and the range of drugs that can cause muscle side effects is constantly expanding. In this article, the authors comprehensively discuss the diagnostic and therapeutic process in patients with myalgia, and present the spectrum of drug-induced myopathies. The review provides a detailed analysis of the literature on the incidence of myopathy during treatment with hypolipemic drugs, beta-blockers, amiodarone, colchicine, glucocorticosteroids, antimalarials, cyclosporine, zidovudine, and checkpoint inhibitors, a group of drugs increasingly used in the treatment of malignancies. The article considers the clinical course of the different types of myopathies, their pathogenesis, histopathological features, and treatment methods of these disorders. The aim of this paper is to gather from the latest available literature up-to-date information on the course, pathophysiology, and therapeutic options of drug-induced myopathies, to systematize the knowledge of drug-induced myopathies and to draw the attention of internists to the fact that these clinical issues are an important therapeutic problem.
Hepatocyte-Specific PEX16 Abrogation in Mice Leads to Hepatocyte Proliferation, Alteration of Hepatic Lipid Metabolism, and Resistance to High-Fat Diet (HFD)-Induced Hepatic Steatosis and Obesity
Authors: Chen Xue , Wang Long , Denning Krista L. , Mazur Anna , Xu Yujuan , Wang Kesheng , Lawrence Logan M. , Wang Xiaodong , Lu Yongke
Published: May 2024

Obesity results in hepatic fat accumulation, i.e., steatosis. In addition to fat overload, impaired fatty acid β-oxidation also promotes steatosis. Fatty acid β-oxidation takes place in the mitochondria and peroxisomes. Usually, very long-chain and branched-chain fatty acids are the first to be oxidized in peroxisomes, and the resultant short chain fatty acids are further oxidized in the mitochondria. Peroxisome biogenesis is regulated by peroxin 16 (PEX16). In liver-specific PEX16 knockout (Pex16Alb-Cre) mice, hepatocyte peroxisomes were absent, but hepatocytes proliferated, and liver mass was enlarged. These results suggest that normal liver peroxisomes restrain hepatocyte proliferation and liver sizes. After high-fat diet (HFD) feeding, body weights were increased in PEX16 floxed (Pex16fl/fl) mice and adipose-specific PEX16 knockout (Pex16AdipoQ-Cre) mice, but not in the Pex16Alb-Cre mice, suggesting that the development of obesity is regulated by liver PEX16 but not by adipose PEX16. HFD increased liver mass in the Pex16fl/fl mice but somehow reduced the already enlarged liver mass in the Pex16Alb-Cre mice. The basal levels of serum triglyceride, free fatty acids, and cholesterol were decreased, whereas serum bile acids were increased in the Pex16Alb-Cre mice, and HFD-induced steatosis was not observed in the Pex16Alb-Cre mice. These results suggest that normal liver peroxisomes contribute to the development of liver steatosis and obesity.
Olfactory Dysfunction and Glaucoma
Authors: Iannucci Valeria , Bruscolini Alice , Iannella Giannicola , Visioli Giacomo , Alisi Ludovico , Salducci Mauro , Greco Antonio , Lambiase Alessandro
Published: May 2024

Background: Olfactory dysfunction is a well-known phenomenon in neurological diseases with anosmia and hyposmia serving as clinical or preclinical indicators of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Since glaucoma is a neurodegenerative disease of the visual system, it may also entail alterations in olfactory function, warranting investigation into potential sensory interconnections. Methods: A review of the current literature of the last 15 years (from 1 April 2008 to 1 April 2023) was conducted by two different authors searching for topics related to olfaction and glaucoma. Results: three papers met the selection criteria. According to these findings, patients with POAG appear to have worse olfaction than healthy subjects. Furthermore, certain predisposing conditions to glaucoma, such as pseudoexfoliation syndrome and primary vascular dysregulation, could possibly induce olfactory changes that can be measured with the Sniffin Stick test. Conclusions: the scientific literature on this topic is very limited, and the pathogenesis of olfactory changes in glaucoma is not clear. However, if the results of these studies are confirmed by further research, olfactory testing may be a non-invasive tool to assist clinicians in the early diagnosis of glaucoma.
A Novel RP-UHPLC-MS/MS Approach for the Determination of Tryptophan Metabolites Derivatized with 2-Bromo-4′-Nitroacetophenone
Authors: Jankech Timotej , Gerhardtova Ivana , Majerova Petra , Piestansky Juraj , Fialova Lubica , Jampilek Josef , Kovac Andrej
Published: May 2024

Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise and reliable methods for their determination are needed. Variability in their physicochemical properties makes the analytical process challenging. In this case, chemical modification of analyte derivatization could come into play. Here, we introduce a novel fast reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with tandem mass spectrometry (MS/MS) method for the determination of Trp and its ten metabolites in human plasma samples after derivatization with 2-bromo-4′-nitroacetophenone (BNAP). The derivatization procedure was optimized in terms of incubation time, temperature, concentration, and volume of the derivatization reagent. Method development comprises a choice of a suitable stationary phase, mobile phase composition, and gradient elution optimization. The developed method was validated according to the ICH guidelines. Results of all validation parameters were within the acceptance criteria of the guideline, i.e., intra- and inter-day precision (expressed as relative standard deviation; RSD) were in the range of 0.5–8.2% and 2.3–7.4%, accuracy was in the range of 93.3–109.7% and 94.7–110.1%, limits of detection (LODs) were in the range of 0.15–9.43 ng/mL, coefficients of determination (R2) were higher than 0.9906, and carryovers were, in all cases, less than 8.8%. The practicability of the method was evaluated using the blue applicability grade index (BAGI) with a score of 65. Finally, the developed method was used for the analysis of Alzheimer’s disease and healthy control plasma to prove its applicability. Statistical analysis revealed significant changes in picolinic acid (PA), anthranilic acid (AA), 5 hydroxyindole-3-acetic acid (5-OH IAA), and quinolinic acid (QA) concentration levels. This could serve as the basis for future studies that will be conducted with a large cohort of patients.
Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Hydrolyze Recombinant RBD and Nucleocapsid (N) Proteins
Authors: Timofeeva Anna M. , Shayakhmetova Liliya Sh. , Nikitin Artem O. , Sedykh Tatyana A. , Matveev Andrey L. , Shanshin Daniil V. , Volosnikova Ekaterina A. , Merkuleva Iuliia A. , Shcherbakov Dmitriy N. , Tikunova Nina V. , Sedykh Sergey E. , Nevinsky Georgy A.
Published: May 2024

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization.
Study on the Coupled Heat Transfer of Conduction, Convection, and Radiation in Foam Concrete Based on a Microstructure Numerical Model
Authors: Huang Tao , Wang Mengge , Feng Shuang , Peng Zhongqi , Huang Xiaoyu , Song Yaohua
Published: May 2024

Foam concrete is a typical cement-based porous material; its special microstructure endows it with excellent properties, such as light weight, energy efficiency, thermal insulation, and fire resistance. Therefore, it is widely used as a thermal insulation material for buildings. The heat transfer modes of foam concrete include conduction, convection, and radiation. However, previous studies considered conduction to be the dominant mode, often neglecting the effects of convection and radiation. In this study, a stochastic numerical model of the foam concrete microstructure is established based on the statistical parameters of the pore structure. With this model, the heat transfer mechanism of foam concrete is analyzed at the mesoscopic level, and the equivalent thermal conductivity is calculated. By comparing four different working conditions, the influence of conduction, convection, and radiation on the heat transfer of foam concrete is analyzed, and the specific contribution rates of conduction, convection, and radiation are calculated. The results show that the convection effect is weak due to the pore size being smaller than 1 mm; so, the influence of convection can be neglected in the heat transfer analysis of foam concrete. The contribution of radiation increases with the decrease in foam concrete density and the increase in temperature difference. When the temperature difference is 40 °C and the density is 300 kg/m3, the contribution of radiation exceeds 20%. Therefore, for low-density and high-temperature difference situations, the influence of radiation cannot be ignored. The heat transfer in foam concrete is mainly through conduction, but with the decrease in density and the increase in temperature difference, the contribution of conduction shows a downward trend. Nevertheless, the contribution of conduction is still much larger than that of radiation and convection.