bluuebunny/crossref_metadata_2025 huggingface dataset:
Charting Alzheimer’s Disease and Dementia: Epidemiological Insights, Risk Factors and Prevention Pathways
Authors: Contador Israel , Buch-Vicente Bárbara , del Ser Teodoro , Llamas-Velasco Sara , Villarejo-Galende Alberto , Benito-León Julián , Bermejo-Pareja Félix
Published: July 2024

Alzheimer’s disease (AD), the most common cause of dementia, is a complex and multifactorial condition without cure at present. The latest treatments, based on anti-amyloid monoclonal antibodies, have only a modest effect in reducing the progression of cognitive decline in AD, whereas the possibility of preventing AD has become a crucial area of research. In fact, recent studies have observed a decrease in dementia incidence in developed regions such as the US and Europe. However, these trends have not been mirrored in non-Western countries (Japan or China), and the contributing factors of this reduction remain unclear. The Lancet Commission has delineated a constrained classification of 12 risk factors across different life stages. Nevertheless, the scientific literature has pointed to over 200 factors—including sociodemographic, medical, psychological, and sociocultural conditions—related to the development of dementia/AD. This narrative review aims to synthesize the risk/protective factors of dementia/AD. Essentially, we found that risk/protective factors vary between individuals and populations, complicating the creation of a unified prevention strategy. Moreover, dementia/AD explanatory mechanisms involve a diverse array of genetic and environmental factors that interact from the early stages of life. In the future, studies across different population-based cohorts are essential to validate risk/protective factors of dementia. This evidence would help develop public health policies to decrease the incidence of dementia.
Advances and Challenges in Spinal Cord Injury Treatments
Authors: Alvi Mohammed Ali , Pedro Karlo M. , Quddusi Ayesha I. , Fehlings Michael G.
Published: July 2024

Spinal cord injury (SCI) is a debilitating condition that is associated with long-term physical and functional disability. Our understanding of the pathogenesis of SCI has evolved significantly over the past three decades. In parallel, significant advances have been made in optimizing the management of patients with SCI. Early surgical decompression, adequate bony decompression and expansile duraplasty are surgical strategies that may improve neurological and functional outcomes in patients with SCI. Furthermore, advances in the non-surgical management of SCI have been made, including optimization of hemodynamic management in the critical care setting. Several promising therapies have also been investigated in pre-clinical studies, with some being translated into clinical trials. Given the recent interest in advancing precision medicine, several investigations have been performed to delineate the role of imaging, cerebral spinal fluid (CSF) and serum biomarkers in predicting outcomes and curating individualized treatment plans for SCI patients. Finally, technological advancements in biomechanics and bioengineering have also found a role in SCI management in the form of neuromodulation and brain–computer interfaces.
Impact of the COVID-19 and War Migration on HIV/AIDS Epidemiology in Poland
Authors: Genowska Agnieszka , Zarębska-Michaluk Dorota , Parczewski Miłosz , Strukcinskiene Birute , Rzymski Piotr , Flisiak Robert
Published: July 2024

Objectives: This study analyzed trends in HIV/AIDS in Poland over the time period of 2009–2021 and the potential impact of COVID-19 and the migration of war refugees from Ukraine. Methods: Long-term trends were assessed by joinpoint regression using data from Polish HIV/AIDS registries. The HIV/AIDS burden was also compared before and during the pandemic and refugee migration. Results: In 2009–2021, the upward tendency in the rate of new HIV infections until 2017 and decrease after 2017 was accompanied by a downward trend in new HIV/AIDS diagnoses and mortality. From the pandemic’s beginning until March 2022, rates of new HIV/AIDS diagnoses dramatically decreased to later increase to pre-pandemic levels, which partially coincided with the wave of migration of refugees from Ukraine. Conclusions: Long-term analysis of HIV/AIDS in Poland showed a downward trend in new HIV/AIDS diagnoses and related mortality in 2009–2021. While the pandemic has reduced the number of detected HIV/AIDS cases, a subsequent increase in new HIV diagnoses in 2022 may be related to lifting the COVID-19 restrictions and war refugees’ migration. These observations have implications for the WHO European Region, seeking to end AIDS as a public health problem by 2030.
Planned Subtotal Resection following Stereotactic Radiosurgery of Koos 3 and 4 Vestibular Schwannomas
Authors: Turek Grzegorz , Dzierzęcki Sebastian , Obierzyński Paweł , Drożdż Adrian , Mariak Zenon , Zielińska-Turek Justyna , Czyżewski Wojciech , Dżaman Karolina , Ząbek Mirosław
Published: July 2024

Background/Objectives: Surgical resection of medium to large vestibular schwannomas (VSs, Koos grade 3 and 4) is a widely used approach, although stereotactic radiosurgery (SRS) is increasingly proposed as initial treatment. The quality of life-centered approach is challenged in cases where tumor growth control cannot be achieved with SRS, thus necessitating salvage surgery. We present a series of eight consecutive patients who required surgery due to continued tumor growth after SRS. Methods: Of the 146 patients with VS grades 3 and 4 initially treated with SRS, only eight patients (mean age, 54 ± 7.2 years; range, 42–63 years) required subsequent surgery. Their mean tumor volume was 9.9 ± 3.2 cm3. The mean time from SRS to first tumor progression and planned subtotal resection was 23 ± 5.9 months and 45 ± 17.5 months, respectively. SRS was not performed after the surgery in favor of a “wait and rescan” approach. Tumor residue was monitored on follow-up magnetic resonance imaging. In all patients, tumor growth control after planned subtotal resection was maintained at 63 ± 19.8 months. Results: None of the 146 patients had serious complications after SRS. In the eight patients who required surgery, tumor growth between 22% and 212% (mean, 4 cm3) was reported within 26 to 84 months after SRS. Before salvage surgery, they scored 1 point on the House–Brackmann scale. Subtotal excision was performed, and VIIth nerve function was preserved in all patients. At 63 ± 19.8 months, 3 patients had a House–Brackmann score of 1, four patients had a score of 2, and one patient had a score of 3. Conclusions: Surgical excision of medium to large VS after SRS can be relatively safe, provided that a quality of life-centered approach of subtotal resection is used.
Syndecan-1 Levels in Females with Active Rheumatoid Arthritis
Authors: Rodriguez-Jimenez Norma Alejandra , Gonzalez-Ponce Fabiola , Gamez-Nava Jorge Ivan , Ramirez-Villafaña Melissa , Saldaña-Cruz Ana Miriam , Ponce-Guarneros Juan Manuel , Olivas-Flores Eva Maria , Macías-Islas Miguel Angel , Valdivia-Tangarife Edgar Ricardo , Jacobo-Cuevas Heriberto , Ramos-Estrada Luz Gabriela , Totsuka-Sutto Sylvia , Cardona-Muñoz Ernesto German , Gonzalez-Lopez Laura ,   on behalf of the Group for the Assessment of Prognosis Biomarkers in Autoimmune Disorders
Published: July 2024

Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71–93); specificity, 52% (95%CI: 31–72); positive predictive value, 78% (95%CI: 70–84); and negative predictive value, 62% (95%CI: 44–77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.
Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes
Authors: Ribeiro Eduarda , Costa Barbara , Marques Lara , Vasques-Nóvoa Francisco , Vale Nuno
Published: July 2024

Backgroud: This study investigates the potential of vasodilator drugs as additive therapy in the treatment of urological cancers, particularly in combination with the antineoplastic agent 5-fluorouracil (5-FU). Methods: The study evaluated the cytotoxic effects of sildenafil, tezosentan and levosimendan alone and in combination with 5-FU on urological cancer cell lines. The assessment included MTT assays, colony formation assays and wound healing assays to determine cell viability, proliferative capacity, and migratory behavior, respectively. Results: Sildenafil and tezosentan showed limited cytotoxic effects, while levosimendan demonstrated moderate anticancer activity. The combination of levosimendan and 5-FU exhibited an additive interaction, enhancing cytotoxicity against cancer cells while sparing normal cells. Levosimendan also inhibited cell migration and proliferation, potentially through mechanisms involving the modulation of cAMP levels and nitric oxide production. Conclusions: The findings suggest that levosimendan can be used in conjunction with 5-FU to reduce the required dose of 5-FU, thereby minimizing side effects without compromising therapeutic efficacy. This study offers a new perspective for enhancing therapeutic outcomes in patients with urological cancers.
Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review
Authors: Migliorisi Giulia , Mastrorocco Elisabetta , Dal Buono Arianna , Gabbiadini Roberto , Pellegatta Gaia , Spaggiari Paola , Racca Francesca , Heffler Enrico , Savarino Edoardo Vincenzo , Bezzio Cristina , Repici Alessandro , Armuzzi Alessandro
Published: July 2024

Background/Objectives: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. Methods: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. Results: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.
Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective
Authors: Santus Pierachille , Signorello Juan Camilo , Danzo Fiammetta , Lazzaroni Giada , Saad Marina , Radovanovic Dejan
Published: July 2024

N-acetyl-L-cysteine (NAC) was initially introduced as a treatment for mucus reduction and widely used for chronic respiratory conditions associated with mucus overproduction. However, the mechanism of action for NAC extends beyond its mucolytic activity and is complex and multifaceted. Contrary to other mucoactive drugs, NAC has been found to exhibit antioxidant, anti-infective, and anti-inflammatory activity in pre-clinical and clinical reports. These properties have sparked interest in its potential for treating chronic lung diseases, including chronic obstructive pulmonary disease (COPD), bronchiectasis (BE), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF), which are associated with oxidative stress, increased levels of glutathione and inflammation. NAC’s anti-inflammatory activity is noteworthy, and it is not solely secondary to its antioxidant capabilities. In ex vivo models of COPD exacerbation, the anti-inflammatory effects have been observed even at very low doses, especially with prolonged treatment. The mechanism involves the inhibition of the activation of NF-kB and neurokinin A production, resulting in a reduction in interleukin-6 production, a cytokine abundantly present in the sputum and breath condensate of patients with COPD and correlates with the number of exacerbations. The unique combination of mucolytic, antioxidant, anti-infective, and anti-inflammatory properties positions NAC as a safe, cost-effective, and efficacious therapy for a plethora of respiratory conditions.
Retro Mode Imaging for Detection and Quantification of Sub-RPE Drusen and Subretinal Drusenoid Deposits in Age-Related Macular Degeneration
Authors: Saßmannshausen Marlene , Sautbaeva Leyla , von der Emde Leon Alexander , Vaisband Marc , Sloan Kenneth R. , Hasenauer Jan , Holz Frank G. , Ach Thomas
Published: July 2024

Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm2 (deviated left mode (DL)) and 105.4 ± 45.5 mm2 (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm2) and BAF imaging (49.1 ± 42.9 mm2) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD.
Evaluation of Diet and Symptom Severity in Disorder of Gut–Brain Interaction
Authors: Faruga-Lewicka Wioleta , Bielaszka Agnieszka , Staśkiewicz-Bartecka Wiktoria , Opiołka Sabina , Kiciak Agata , Kardas Marek
Published: July 2024

Background: Disorders of gut–brain interaction are chronic or recurrent symptoms originating in the gastrointestinal tract that cannot be substantiated by the results of standard clinical tests, such as radiologic studies, morphologies, or endoscopic examination. The diagnosis of these disorders is mainly based on symptoms and the standardized Rome IV criteria. These criteria classify functional disorders of the gastrointestinal tract according to anatomical location and define each disorder according to a set of symptoms. Methods: This study was conducted between October 2021 and February 2022. Participants in the study were patients of a gastroenterology outpatient clinic with a functional disease diagnosed by a gastroenterologist. A questionnaire was used to conduct the study, with questions regarding perceived functional discomforts of the gastrointestinal tract, dietary changes to alleviate discomforts, and frequency of consumption of various food groups. Results: Based on the study, statistical significance was demonstrated between the gender of the respondents and the severity of gastrointestinal complaints after the consumption of legumes and alcohol. The analysis performed confirmed the correlation between the age of the respondents and the severity of complaints when consuming raw vegetables and fruits, brassica vegetables, legumes, fried products, and spicy products. There was also a significant correlation between the body mass index (BMI) of the respondents and the severity of complaints after alcohol consumption. Conclusions: The results identify abdominal pain, bloating, and constipation as the most commonly reported gastrointestinal symptoms among participants. The association between the consumption of certain foods, such as milk and dairy products, as well as fried and fatty foods, and the severity of disorders of gut–brain interaction symptoms was confirmed. Despite this, the majority of respondents did not eliminate any food products to alleviate the discomfort.
Clinical and Patient Reported Outcomes of an Optimized Trifocal Intraocular Lens
Authors: Cano-Ortiz Antonio , Sánchez-Ventosa Álvaro , Villalba-González Marta , González-Cruces Timoteo , Prados-Carmona Juan José , Díaz-Mesa Vanesa , Piñero David P. , Villarrubia-Cuadrado Alberto
Published: July 2024

Background/Objectives: To evaluate the clinical and patient-reported outcomes (PROMs) obtained with an optimized version of a previously investigated trifocal IOL. Methods: Prospective non-comparative single-center study enrolling 29 patients (55–71 years) undergoing bilateral cataract surgery with implantation of the trifocal diffractive IOL Liberty 677CMY (Medicontur Medical Engineering Ltd., Zsámbék, Hungary). Visual and refractive outcomes as well as PROMs were evaluated during a 3-month follow-up: measurement of uncorrected and corrected distance (UDVA, CDVA), intermediate (UIVA, DCIVA) and near visual acuities (UNVA, DCNVA), defocus curve, patient satisfaction, photic phenomena perception, spectacle independence, and difficulty in performing some vision-related activities. Results: A total of 100%, 92%, and 80% of patients achieved a postoperative binocular UDVA, UIVA, and UNVA of 20/25 or better, respectively. Likewise, 100%, 80%, and 84% of patients achieved a postoperative binocular CDVA, DCIVA, and DCNVA of 20/25 or better, respectively. In the defocus curve, all mean visual acuity values were better than 0.15 logMAR for all defocus levels. A total of 95.8%, 95.8%, and 91.7% of patients referred to be satisfied with their distance, intermediate, and near visual vision, respectively. Mean overall Catquest Rasch calibrated score was −3.12 ± 0.98. Most of the patients were spectacle independent: far (95.8%), intermediate (95.8%) or near vision (91.7%). No bothersome or minimal to moderately bothersome halo, starburst, and glare was perceived by 83.3%, 83.4%, and 83.3% of patients, respectively. Conclusions: The trifocal IOL evaluated provides a visual acuity improvement, with high levels of spectacle independence, patient satisfaction, and perceived visual quality associated.
The Effect of Chopped Carbon Fibers on the Mechanical Properties and Fracture Toughness of 3D-Printed PLA Parts: An Experimental and Simulation Study
Authors: Ogaili Ahmed Ali Farhan , Basem Ali , Kadhim Mohammed Salman , Al-Sharify Zainab T. , Jaber Alaa Abdulhady , Njim Emad Kadum , Al-Haddad Luttfi A. , Hamzah Mohsin Noori , Al-Ameen Ehsan S.
Published: July 2024

The incorporation of fiber reinforcements into polymer matrices has emerged as an effective strategy to enhance the mechanical properties of composites. This study investigated the tensile and fracture behavior of 3D-printed polylactic acid (PLA) composites reinforced with chopped carbon fibers (CCFs) through experimental characterization and finite element analysis (FEA). Composite samples with varying CCF orientations (0°, 0°/90°, +45°/−45°, and 0°/+45°/−45°/90°) were fabricated via fused filament fabrication (FFF) and subjected to tensile and single-edge notched bend (SENB) tests. The experimental results revealed a significant improvement in tensile strength, elastic modulus, and fracture toughness compared to unreinforced PLA. The 0°/+45°/90° orientation exhibited a 3.6% increase in tensile strength, while the +45°/−45° orientation displayed a 29.9% enhancement in elastic modulus and a 29.9% improvement in fracture toughness (259.12 MPa) relative to neat PLA (199.34 MPa√m). An inverse correlation between tensile strength and fracture toughness was observed, attributed to mechanisms such as crack deflection, fiber bridging, and fiber pull-out facilitated by multi-directional fiber orientations. FEA simulations incorporating a transversely isotropic material model and the J-integral approach were conducted using Abaqus, accurately predicting fracture toughness trends with a maximum discrepancy of 8% compared to experimental data. Fractographic analysis elucidated the strengthening mechanisms, highlighting the potential of tailoring CCF orientation to optimize mechanical performance for structural applications.
A 0.064 mm2 16-Channel In-Pixel Neural Front End with Improved System Common-Mode Rejection Exploiting a Current-Mode Summing Approach
Authors: Nicolini Giovanni , Fava Alessandro , Centurelli Francesco , Scotti Giuseppe
Published: July 2024

In this work, we introduce the design of a 16-channel in-pixel neural analog front end that employs a current-based summing approach to establish a common-mode feedback loop. The primary aim of this novel structure is to enhance both the system common-mode rejection ratio (SCMRR) and the common-mode interference (CMI) range. Compared to more conventional designs, the proposed front end utilizes DC-coupled inverter-based main amplifiers, which significantly reduce the occupied on-chip area. Additionally, the current-based implementation of the CMFB loop obviates the need for voltage buffers, replacing them with simple common-gate transistors, which, in turn, decreases both area occupancy and power consumption. The proposed architecture is further examined from an analytical standpoint, providing a comprehensive evaluation through design equations of its performance in terms of gain, common-mode rejection, and noise power. A 50 μm × 65 μm compact layout of the pixel amplifiers that make up the recording channels of the front end was designed using a 180 nm CMOS process. Simulations conducted in Cadence Virtuoso reveal an SCMRR of 80.5 dB and a PSRR of 72.58 dB, with a differential gain of 44 dB and a bandwidth that fully encompasses the frequency range of the bio-signals that can be theoretically captured by the neural probe. The noise integrated in the range between 1 Hz and 7.5 kHz results in an input-referred noise (IRN) of 4.04 μVrms. Power consumption is also tested, with a measured value of 3.77 μW per channel, corresponding to an overall consumption of about 60 μW. To test its robustness with respect to PVT and mismatch variations, the front end is evaluated through extensive parametric simulations and Monte Carlo simulations, revealing favorable results.
Monitoring of the Weld Pool, Keyhole Morphology and Material Penetration State in Near-Infrared and Blue Composite Laser Welding of Magnesium Alloy
Authors: Wei Wei , Liu Yang , Deng Haolin , Wei Zhilin , Wang Tingshuang , Li Guangxian
Published: July 2024

The laser welding of magnesium alloys presents challenges attributed to their low laser-absorbing efficiency, resulting in instabilities during the welding process and substandard welding quality. Furthermore, the complexity of signals during laser welding processes makes it difficult to accurately monitor the molten state of magnesium alloys. In this study, magnesium alloys were welded using near-infrared and blue lasers. By varying the power of the near-infrared laser, the energy absorption pattern of magnesium alloys toward the composite laser was investigated. The U-Net model was employed for the segmentation of welding images to accurately extract the features of the melt pool and keyhole. Subsequently, the penetrating states were predicted using the convolutional neural network (CNN), and the novel approach employing Local Binary Pattern (LBP) features + a backpropagation (BP) neural network was applied for comparison. The extracted images achieved MPA and MIoU values of 89.54% and 81.81%, and the prediction accuracy of the model can reach up to 100%. The applicability of the two monitoring approaches in different scenarios was discussed, providing guidance for the quality of magnesium welding.
The First Observation of the Filamentous Fungus Neurospora crassa Growing in the Roots of the Grass Brachypodium distachyon
Authors: Kollath-Leiß Krisztina , Repnik Urska , Winter Hannes , Winkelmann Heinrich , Freund Anna Sophia , Kempken Frank
Published: July 2024

The model organism Neurospora crassa has been cultivated in laboratories since the 1920s and its saprotrophic lifestyle has been established for decades. However, beyond their role as saprotrophs, fungi engage in intricate relationships with plants, showcasing diverse connections ranging from mutualistic to pathogenic. Although N. crassa has been extensively investigated under laboratory conditions, its ecological characteristics remain largely unknown. In contrast, Brachypodium distachyon, a sweet grass closely related to significant crops, demonstrates remarkable ecological flexibility and participates in a variety of fungal interactions, encompassing both mutualistic and harmful associations. Through a comprehensive microscopic analysis using electron, fluorescence, and confocal laser scanning microscopy, we discovered a novel endophytic interaction between N. crassa and B. distachyon roots, where fungal hyphae not only thrive in the apoplastic space and vascular bundle but also may colonize plant root cells. This new and so far hidden trait of one of the most important fungal model organisms greatly enhances our view of N. crassa, opening new perspectives concerning the fungus‘ ecological role. In addition, we present a new tool for studying plant–fungus interspecies communication, combining two well-established model systems, which improves our possibilities of experimental design on the molecular level.
Antifungal Activity of Sesamol on Pestalotiopsis neglecta: Interfering with Cell Membrane and Energy Metabolism
Authors: Ma Weihu , Ji Jingyu , Zhang Bowen , Sun Wenzhuo , Zhao Jinyan , Zhang Jie , Zhang Guocai
Published: July 2024

This paper investigated the inhibitory effect of Sesamol (Ses) on Pestalotiopsis neglecta. The potential inhibitory mechanisms were explored by observing changes in cell morphology, measuring alterations in cell membrane-related indices, as well as energy metabolism-related indices and changes in enzyme activities related to virulence. The results show that Ses completely inhibited the growth of P. neglecta at 600 μg/mL (minimum inhibitory concentration and minimum fungicidal concentration), with an EC50 of 142 ± 13.22 μg/mL. As observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Ses treatment resulted in the breakage and crumpling of P. neglecta cell membrane and organelle lysis. Ergosterol content and the total lipid in P. neglecta treated with 300 μg/mL Ses was 91.52% and 54% of that in the control groups, respectively. In addition, spores were stained, increased leakage of intracellular constituents at 260 nm, and decreased extracellular pH. This suggests damage to the cell membrane integrity and permeability. Furthermore, Ses decreased the ATP levels and key enzymes in the tricarboxylic acid (TCA) cycle, indicating interference with the fungal energy metabolism. Moreover, the activities of polygalacturonase (PG) and endoglucanase (EG) of P. neglecta treated with 300 μg/mL of Ses were only 28.20% and 29.13% of that in the control groups, respectively, indicating that Ses can reduce the virulence of P. neglecta. In conclusion, our results show that Ses should be considered as a potential plant-derived fungicide due to its ability to disrupt the morphology of P. neglecta, damage cell membrane integrity and permeability in P. neglecta, interfere with energy metabolism, and reduce its virulence, ultimately affecting the fungal growth.
Feasibility of a Randomized, Interventional Pilot Clinical Study of Oral Cannabinoids in People with HIV on Antiretroviral Therapy: CTNPT 028
Authors: Mboumba Bouassa Ralph-Sydney , Needham Judy , Nohynek Dana , Samarani Suzanne , Bobeuf Florian , Del Balso Lina , Paisible Natalie , Vertzagias Claude , Sebastiani Giada , Margolese Shari , Mandarino Enrico , Singer Joel , Klein Marina , Lebouché Bertrand , Cox Joseph , Vulesevic Branka , Müller Alison , Lau Elisa , Routy Jean-Pierre , Jenabian Mohammad-Ali , Costiniuk Cecilia T.
Published: July 2024

Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021–April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a “washout period” for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55–62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.
Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma
Authors: Kühnel Christian , Köhler Alexander , Brachwitz Tim , Seifert Philipp , Gühne Falk , Aschenbach René , Freudenberg Robert , Freesmeyer Martin , Drescher Robert
Published: July 2024

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose–response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.
Dynamics of RAS Mutations in Liquid Biopsies in Metastatic Colorectal Cancer Patients—Case Series and Literature Review
Authors: Popescu Ionut , Croitoru Vlad M. , Croitoru-Cazacu Irina M. , Dudau Ana-Maria , Herlea Vlad , Dima Simona Olimpia , Croitoru Adina Emilia
Published: July 2024

Liquid biopsies can accurately identify molecular alterations in patients with colorectal cancer with high concordance with tissue analysis and shorter turnaround times. Circulating tumor (ct) DNA analysis can be used for diagnosing and monitoring tumor evolution in patients with metastatic colorectal cancer who are treated with EGFR inhibitors. In this article, we reported three clinical cases to illustrate the relevance of RAS mutations identified in ctDNA samples of patients with wild-type metastatic colorectal cancer who received an EGFR inhibitor plus chemotherapy as first-line treatment. The identification of RAS mutations in these patients is one of the most frequently identified mechanisms of acquired resistance. However, detecting a KRAS mutation via liquid biopsy can be caused by inter-tumor heterogeneity or it can be a false positive due to clonal hematopoiesis. More research is needed to determine whether ctDNA monitoring may help guide therapy options in metastatic colorectal cancer patients. We performed a literature review to assess the technologies that are used for analysis of RAS mutations on ctDNA, the degree of agreement between tissue and plasma and the importance of tissue/plasma discordant cases.
Spatial Heterogeneity Analysis of the Multidimensional Characteristics of Urban Green Spaces in China—A Study Based on 285 Prefecture-Level Cities
Authors: Zhao Wei , Liu Dianfeng , Niu Jiqiang , He Jianhua , Xu Feng
Published: July 2024

Quantitative measurement of urban green spaces (UGSs) plays a fundamental role in enhancing their ecological functions and services. Current studies have not adequately analyzed the multifunctional characteristics and the diverse benefits of urban green spaces at the national scale. This study developed a multidimensional indicator system in terms of scale, pattern, and services to measure green spaces in 285 prefecture-level cities in China. The influences of different geographic zones and urban development on UGS characteristics were also investigated. The results showed that per capita area of urban green spaces were significantly different between the two sides of the “Botai Line”, and the UGS structure was mainly dominated by woodlands. Urban green spaces in the central and east had higher fragmentation, lower landscape diversity, and weaker connectivity. The spatial accessibility of green spaces exhibited a “low–high–medium” pattern from north to south in China, with central-eastern China experiencing the worst equity in green space supply. Overall, cities with higher integrated benefits of green spaces were mainly located in Northeast and North China. Type I large cities had higher ratings for UGS characteristics compared with the other types of cities. These findings can serve as solid guidance for cities seeking to build green space systems with highly integrated socio–ecological benefits.
The Effect of High-Standard Farmland Construction Policy on Grain Harvest Losses in China
Authors: Hu Nanyan , Hu Yonghao , Luo Yi , Wu Laping
Published: July 2024

The United Nations included reducing harvest losses as a Sustainable Development Goal in 2015, sparking heightened research and policymaker interest in reducing losses to ensure food security. High-standard farmland construction plays a crucial role in ensuring food security. Few studies have combined high-standard farmland construction with grain harvest losses. Drawing on the data from the 2022 Chinese Post-Harvest Loss Survey (CPHLS 2022), the study utilizes OLS (ordinary least square) and quantile regression models to explore the impact of high-standard farmland construction on grain harvest losses. Empirical results show that high-standard farmland construction can significantly reduce grain harvest losses. The research conclusions are still valid after passing a series of robustness tests. The heterogeneity analysis shows that high-standard farmland construction significantly impacts on grain harvest losses for farmers in major grain-producing areas, plain areas, and eastern regions. Mechanism analysis reveals that high-standard farmland construction mainly reduces grain harvest losses by expanding operational scale and enhancing mechanization application. Based on research findings, the Chinese government should formulate a targeted high-standard farmland construction policy, optimize the agricultural machinery operating environment, and promote appropriate operational scale to ensure national food security.
Haemolytic Anaemia-Related Pulmonary Hypertension
Authors: Karyofyllis Panagiotis , Demerouti Eftychia , Tsetika Eleftheria-Garyfallia , Apostolopoulou Styliani , Tsiapras Panagiotis , Iakovou Ioannis , Tsiapras Dimitrios
Published: July 2024

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension—PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year—100%; 2, 3, 4, 5, and 6 years—96%; 9 years—90%; and 13 years—78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients.
A New Methodology for the Accurate Measurement of Tibiofemoral Kinematics in Human Cadaveric Knees: An Evaluation of the Anterior–Posterior Laxity Pre- and Post-Cruciate Ligament Resection
Authors: Brendle Saskia A. , Krueger Sven , Grifka Joachim , Müller Peter E. , Grupp Thomas M.
Published: July 2024

Anterior–posterior (AP) stability is an important measure of knee performance after total knee arthroplasty (TKA). To improve the stabilizing effect of implants designed to compensate for the loss of the cruciate ligaments, it is important to understand the tibiofemoral contact situation within the native ligamentous situation of the knee and how it changes after cruciate ligament resection. This in vitro study introduces a new approach to accurately measure the tibiofemoral kinematics in a six-degrees-of-freedom joint motion simulator by tracking landmark-based coordinate systems and their corresponding bone geometries. The tibiofemoral contact situation was investigated by projecting the medial and lateral flexion facet centers onto the tibial plateau under AP shear forces across various flexion angles in thirteen knees. Tests were conducted pre- and post-cruciate ligament resection. Post-cruciate ligament resection, the femoral condyles shifted closer to or even exceeded the posterior border of the tibial plateau, but only slightly closer to the anterior border. This study presents a new methodology for measuring the tibiofemoral kinematics that can be applied to multiple loading profiles. It provides a basis for further investigations, including passive or active muscle forces, to enhance the design of total knee protheses and improve surgical outcomes.
Clinical Trends and Novel Research Insights into Testicular and Penile Disorders and Infertility
Authors: Bumbasirevic Uros
Published: July 2024

Due to their great heterogeneity with regard to etiopathogenesis, the clinical presentations, diagnostics, treatment approaches, and potential complications of testicular and penile disorders, despite posing a significant public health burden, constitute an immensely complex, highly fascinating, and continually evolving topic in urology [...]
The Use of Hydroxyapatite Polymer with Curdlan in the Treatment of Bone Defects Associated with Ectopic Tooth Extraction in Dogs—A Case Series
Authors: Misztal-Kunecka Anna , Prządka Przemysław , Dzimira Stanisław
Published: July 2024

Ectopic teeth are an eruption disorder in which teeth are located in anatomical structures where, physiologically, they should not occur. An ectopic tooth is a very rare phenomenon, affecting approximately 0.5% of the canine population, and few descriptions of the treatment of such teeth in dogs can be found in the available literature. This article describes the diagnostic and therapeutic handling of cavities following extraction of ectopic teeth in nine dogs. The cases are subdivided into uncomplicated (when the ectopic tooth was encapsulated in the surrounding connective tissue, without lysis of the bone around the tooth) and complicated (in which, in addition to the presence of the ectopic tooth, a dentigerous cyst had formed). Four cases of complicated ectopic teeth are described in more detail. In this study, special attention was paid not only to the technique of tooth extraction itself but also to the method of securing and healing large bone defects after the extraction using hydroxyapatite curdlan polymer. Owing to the plastic properties of the bone substitute preparation, it was possible to implant the material without enlarging the bone defect created during the tooth extraction. Control radiographs showed features of bone regeneration, and clinical examination at both the early and late stages revealed no postoperative complications.
Influence of Diet on Reproducible Corticosterone Levels in a Mouse Model of Maternal Separation with Early Weaning
Authors: Choe Jamie Y. , Donkor Michael , Thorpe Roland J. , Allen Michael S. , Phillips Nicole R. , Jones Harlan P.
Published: July 2024

Maternal separation with early weaning (MSEW) is a popular early life stress (ELS) model in rodents, which emulates childhood neglect through scheduled mother-offspring separation. Although variations of ELS models, including maternal separation and MSEW, have been published for the mouse species, the reported results are inconsistent. Corticosterone is considered the main stress hormone involved in regulating stress responses in rodents—yet generating a robust and reproducible corticosterone response in mouse models of ELS has been elusive. Considering the current lack of standardization for MSEW protocols, these inconsistent results may be attributed to variations in model methodologies. Here, we compared the effects of select early wean diet sources—which are the non-milk diets used to complete early weaning in MSEW pups—on the immediate stress phenotype of C57BL/6J mice at postnatal day 21. Non-aversive handling was an integral component of our modified MSEW model. The evaluation of body weight and serum corticosterone revealed the early wean diet to be a key variable in the resulting stress phenotype. Interestingly, select non-milk diets facilitated a stress phenotype in which low body weight was accompanied by significant corticosterone elevation. Our data indicate that dietary considerations are critical in MSEW-based studies and provide insight into improving the reproducibility of key stress-associated outcomes as a function of this widely used ELS paradigm.
Fabrication and Characterization of Biomedical Ti-Mg Composites via Spark Plasma Sintering
Authors: Masuda Taisei , Oh Minho , Kobayashi Equo
Published: July 2024

The fabrication of Ti-Mg composite biomaterials was investigated using spark plasma sintering (SPS) with varying Mg contents and sintering pressures. The effects of powder mixing, Mg addition, and sintering pressure on the microstructure and mechanical properties of the composite materials were systematically analyzed. Uniform dispersion of Mg within the Ti matrix was achieved, confirming the efficacy of ethanol-assisted ball milling for consistent mixing. The Young’s modulus of the composite materials exhibited a linear decrease with increasing Mg content, with Ti-30vol%Mg and Ti-50vol%Mg demonstrating reduced modulus values compared to pure Ti. Based on density measurements, compression tests, and Young’s modulus results, it was determined that the sinterability of Ti-30vol%Mg saturates at a sintering pressure of approximately 50 MPa. Moreover, our immersion tests in physiological saline underscore the profound significance of our findings. Ti-30vol%Mg maintained compressive strength above that of cortical bone for 6-to-10 days, with mechanical integrity improving under higher sintering pressures. These findings mark a significant leap towards the development of Ti-Mg composite biomaterials with tailored mechanical properties, thereby enhancing biocompatibility and osseointegration for a wide range of biomedical applications.