bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genome Sequencing Solves an Atypical Form of Bardet–Biedl Syndrome: Identification of Novel Pathogenic Variants of BBS9
Authors: Stellacci Emilia , Niceta Marcello , Bruselles Alessandro , Straface Emilio , Tatti Massimo , Carvetta Mattia , Mancini Cecilia , Cecchetti Serena , Parravano Mariacristina , Barbano Lucilla , Varano Monica , Tartaglia Marco , Ziccardi Lucia , Cordeddu Viviana
Published: July 2024

Bardet–Biedl syndrome (BBS) is a rare recessive multisystem disorder characterized by retinitis pigmentosa, obesity, postaxial polydactyly, cognitive deficits, and genitourinary defects. BBS is clinically variable and genetically heterogeneous, with 26 genes identified to contribute to the disorder when mutated, the majority encoding proteins playing role in primary cilium biogenesis, intraflagellar transport, and ciliary trafficking. Here, we report on an 18-year-old boy with features including severe photophobia and central vision loss since childhood, hexadactyly of the right foot and a supernumerary nipple, which were suggestive of BBS. Genetic analyses using targeted resequencing and exome sequencing failed to provide a conclusive genetic diagnosis. Whole-genome sequencing (WGS) allowed us to identify compound heterozygosity for a missense variant and a large intragenic deletion encompassing exon 12 in BBS9 as underlying the condition. We assessed the functional impact of the identified variants and demonstrated that they impair BBS9 function, with significant consequences for primary cilium formation and morphology. Overall, this study further highlights the usefulness of WGS in the diagnostic workflow of rare diseases to reach a definitive diagnosis. This report also remarks on a requirement for functional validation analyses to more effectively classify variants that are identified in the frame of the diagnostic workflow.
Advancements of CRISPR-Mediated Base Editing in Crops and Potential Applications in Populus
Authors: Yang Xuefei , Zhu Ping , Gui Jinshan
Published: July 2024

Base editing represents a cutting-edge genome editing technique that utilizes the CRISPR system to guide base deaminases with high precision to specific genomic sites, facilitating the targeted alteration of individual nucleotides. Unlike traditional gene editing approaches, base editing does not require DNA double-strand breaks or donor templates. It functions independently of the cellular DNA repair machinery, offering significant advantages in terms of both efficiency and accuracy. In this review, we summarize the core design principles of various DNA base editors, their distinctive editing characteristics, and tactics to refine their efficacy. We also summarize their applications in crop genetic improvement and explore their potential contributions to forest genetic engineering.
Phage Therapy: An Alternative Approach to Combating Multidrug-Resistant Bacterial Infections in Cystic Fibrosis
Authors: Cocorullo Mario , Stelitano Giovanni , Chiarelli Laurent Robert
Published: July 2024

Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.
Molecular Modification Enhances Xylose Uptake by the Sugar Transporter KM_SUT5 of Kluyveromyces marxianus
Authors: Luo Xiuyuan , Tao Xi , Ran Guangyao , Deng Yuanzhen , Wang Huanyuan , Tan Liyan , Pang Zongwen
Published: July 2024

This research cloned and expressed the sugar transporter gene KM_SUT5 from Kluyveromyces marxianus GX-UN120, which displayed remarkable sugar transportation capabilities, including pentose sugars. To investigate the impact of point mutations on xylose transport capacity, we selected four sites, predicted the suitable amino acid sites by molecular docking, and altered their codons to construct the corresponding mutants, Q74D, Y195K, S460H, and Q464F, respectively. Furthermore, we conducted site-directed truncation on six sites of KM_SUT5p. The molecular modification resulted in significant changes in mutant growth and the D-xylose transport rate. Specifically, the S460H mutant exhibited a higher growth rate and demonstrated excellent performance across 20 g L−1 xylose, achieving the highest xylose accumulation under xylose conditions (49.94 μmol h−1 gDCW-1, DCW mean dry cell weight). Notably, mutant delA554-, in which the transporter protein SUT5 is truncated at position delA554-, significantly increased growth rates in both D-xylose and D-glucose substrates. These findings offer valuable insights into potential modifications of other sugar transporters and contribute to a deeper understanding of the C-terminal function of sugar transporters.
Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain
Authors: Xiong Huan-Yu , Wyns Arne , Campenhout Jente Van , Hendrix Jolien , De Bruyne Elke , Godderis Lode , Schabrun Siobhan , Nijs Jo , Polli Andrea
Published: July 2024

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management.
JAK Inhibitors in Rheumatoid Arthritis: Immunomodulatory Properties and Clinical Efficacy
Authors: Kiełbowski Kajetan , Plewa Paulina , Bratborska Aleksandra Wiktoria , Bakinowska Estera , Pawlik Andrzej
Published: July 2024

Rheumatoid arthritis (RA) is a highly prevalent autoimmune disorder. The pathogenesis of the disease is complex and involves various cellular populations, including fibroblast-like synoviocytes, macrophages, and T cells, among others. Identification of signalling pathways and molecules that actively contribute to the development of the disease is crucial to understanding the mechanisms involved in the chronic inflammatory environment present in affected joints. Recent studies have demonstrated that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway regulates the behaviour of immune cells and contributes to the progression of RA. Several JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, and filgocitinib, have been developed, and their efficacy and safety in patients with RA have been comprehensively investigated in a number of clinical trials. Consequently, JAK inhibitors have been approved and registered as a treatment for patients with RA. In this review, we discuss the involvement of JAK/STAT signalling in the pathogenesis of RA and summarise the potential beneficial effects of JAK inhibitors in cells implicated in the pathogenesis of the disease. Moreover, we present the most important phase 3 clinical trials that evaluated the use of these agents in patients.
Mystery of the Passerini Reaction for the Synthesis of the Antimicrobial Peptidomimetics against Nosocomial Pathogenic Bacteria
Authors: Wavhal Deepak S. , Koszelewski Dominik , Gulko Cezary , Kowalczyk Paweł , Brodzka Anna , Kramkowski Karol , Ostaszewski Ryszard
Published: July 2024

The first example of applying salicylaldehyde derivatives, as well as coumarin with the formyl group at the C8 position in its structure, as carbonyl partners in a three-component Passerini reaction, is presented. As a result of research on the conditions of the Passerini reaction, the important role of the hydroxyl group in the salicylaldehyde used in the course of the multicomponent reaction was revealed. When an aldehyde with an unprotected hydroxyl group is used, only two-component α-hydroxy amide products are obtained. In contrast, the use of acylated aldehyde results in three-component α-acyloxy amide products with high efficiency. The developed protocol gives access to structurally diversified peptidomimetics with good yield. The compounds were also evaluated as antimicrobial agents against selected strains of nosocomial pathogenic bacteria. The structure–activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF3) or the methyl group at the C4 position in an unsaturated lactone ring of the coumarin scaffold. MIC and MBC studies were carried out on eight selected pathogenic bacteria strains (Gram-positive pathogenic Staphylococcus aureus strain (ATCC 23235), as well as on Gram-negative E. coli (K12 (ATCC 25404), R2 (ATCC 39544), R3 (ATCC 11775), and R4 (ATCC 39543)), Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), and Enterobacter cloacae (ATCC 49141) have shown that the tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Additionally, the cytotoxicity of sixteen derivatives was measured with the use of the MTT test on BALB/c3T3 mouse fibroblast cell lines. The cytotoxicity studies revealed that the tested substances exert a similar or lower effect on cell proliferation than that observed for commonly used antibiotics within the range of therapeutic doses. A parallel MTT assay using ciprofloxacin, bleomycin, and cloxacillin showed that these antibiotics are more cytotoxic when tested in mammalian cells, and cell viability is in the range of 85.0–89.9%. Furthermore, we have shown that the studied coumarin-based peptidomimetics, depending on their structural characteristics, are nonselective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients.
Testing the Feasibility of an Agent-Based Model for Hydrologic Flow Simulation
Authors: Simmonds Jose , Gómez Juan Antonio , Ledezma Agapito
Published: July 2024

Modeling streamflow is essential for understanding flow inundation. Traditionally, this involves hydrologic and numerical models. This research introduces a framework using agent-based modeling (ABM) combined with data-driven modeling (DDM) and Artificial Intelligence (AI). An agent-driven model simulates streamflow and its interactions with river courses and surroundings, considering hydrologic phenomena related to precipitation, water level, and discharge as well as channel and basin characteristics causing increased water levels in the Medio River. A five-year dataset of hourly precipitation, water level, and discharge measurements was used to simulate streamflow. The model’s accuracy was evaluated using statistical metrics like correlation coefficient (r), coefficient of determination (R2), root mean squared error (RMSE), and percentage error in peak discharge (Qpk). The ABM’s simulated peak discharge (Qpk) was compared with the measured peak discharge across four experimental scenarios. The best simulations occurred in scenario 3, using only rainfall and streamflow data. Data management and visualization facilitated input, output, and analysis. This study’s ABM combined with DDM and AI offers a novel approach for simulating streamflow and predicting floods. Future studies could extend this framework to other river basins and incorporate advanced sensor data to enhance the accuracy and responsiveness of flood forecasting.
Investigation of the Dislocation Behavior of 6- and 8-Inch AlGaN/GaN HEMT Structures with a Thin AlGaN Buffer Layer Grown on Si Substrates
Authors: Yan Yujie , Huang Jun , Pan Lei , Meng Biao , Wei Qiangmin , Yang Bing
Published: July 2024

Developing cost-effective methods to synthesize large-size GaN films remains a challenge owing to the high dislocation density during heteroepitaxy. Herein, AlGaN/GaN HEMTs were grown on 6- and 8-inch Si(111) substrates using metal–organic chemical vapor deposition, and their basic properties and dislocation evolution characteristics were investigated thoroughly. With the insertion of a 100 nm thin AlGaN buffer layer, bow–warp analysis of the epitaxial wafers revealed excellent stress control for both the 6- and 8-inch wafers. HR-XRD and AFM analyses validated the high crystal quality and step-flow growth mode of GaN. Further, Hall measurements demonstrated the superior transport performance of AlGaN/GaN heterostructures. It is worth noting that dislocations tended to annihilate in the AlN nucleation layer, the thin AlGaN buffer layer, and the GaN buffer layer in the initial thickness range of 200–300 nm, which was indicated by ADF-STEM. To be specific, the heterointerfaces exhibited a significant effect on the annihilation of c-type (b = <0001>) dislocations, which led to the formation of dislocation loops. The thin inserted layers within the AlGaN buffer layer played a key role in promoting the annihilation of c-type dislocations, while they exerted less influence on a-type (b = 1/3<112¯0>) and (a+c)-type (b = 1/3<112¯3>) dislocations. Within an initial thickness of 200–300 nm in the GaN buffer layer, a-type and (a+c)-type dislocations underwent strong interactions, leading to considerable dislocation annihilation. In addition, the EELS results suggested that the V-shaped pits in the AlN nucleation layer were filled with the AlGaN thin layer with a low Al content.
1H NMR Profiling of Honey Bee Brains across Varying Ages and Seasons
Authors: Morfin Nuria , Goodwin Paul H. , Guzman-Novoa Ernesto , Legge Nicole , Longstaffe James
Published: July 2024

Honey bees (Apis mellifera) provide a useful model for studying aging because of the differences in longevity between the relatively short-lived summer and long-lived winter bees, as well as bees lacking signs of cognitive senescence as they age. Bee brains were dissected from newly emerged, 14-day–, and 28-day– old bees in mid- and late summer, as well as brood nest bees in fall, winter, and spring, before, during, and after overwintering, respectively. Brains were examined with nuclear magnetic resonance (NMR) spectroscopy to analyze their metabolome. Nine variable importance in projection (VIP) variables were identified, primarily amino acids and choline derivatives. Differences in metabolite concentrations were found with different ages of summer bees, mostly between newly emerged and 14-day– old bees, such as a decrease in phenylalanine and an increase in β-alanine, but there were also changes in older adults, such as o-phosphocholine that declined in 28-day– old bees. Differences in brood nest bees were observed, including a decline in tryptophan and an increase in β-alanine. These may provide distinct metabolomic signatures with age and season. Such research holds promise for a better understanding of the complex interplays between bee physiology, development, and aging, which has implications for improving bee health and management.
Characterization of the Spatial Distribution of the Pepper Weevil, Anthonomus eugenii Cano (Col.: Curculionidae), in Pepper Fields in South Florida
Authors: Adeleye Victoria O. , Seal Dakshina R. , Martini Xavier , Meru Geoffrey , Liburd Oscar E.
Published: July 2024

The pepper weevil, Anthonomus eugenii Cano, is an economically important pest of cultivated peppers (Capsicum annuum) in tropical and subtropical regions of the world. This study aimed to ascertain the spatial distribution of pepper weevil infestation across various fields in Miami Dade County, South Florida. The spatio-temporal dynamics of pepper weevil were evaluated using 144 sample points within each of seven pepper fields. The data were analyzed using three different geospatial techniques, spatial analysis by distance indices (SADIE), Moran’s I, and Geary’s C, to determine the spatial distribution of pepper weevil. The SADIE analysis revealed a significant aggregation distribution in 18 out of 30 sampling dates across all fields. The results from Geary’s C and Moran’s I indices indicated a positive spatial autocorrelation (spatial clustering/aggregation) of pepper weevil regardless of field or pepper types. Overall, the findings from this study depict an aggregated spatial distribution pattern of pepper weevil populations, characterized by a tendency for aggregation that transitions to a more uniform distribution as the season progresses.
Radiological Landmarks for Joint Line Level in Challenging Total Ankle Arthroplasty
Authors: Zielli Simone Ottavio , Mazzotti Antonio , Artioli Elena , Arceri Alberto , Sgubbi Federico , Langone Laura , Abdi Pejman , Faldini Cesare
Published: July 2024

Background: Although Total Ankle Arthroplasty (TAA) is primarily performed for post-traumatic ankle arthritis with joint disruption, anatomical landmarks for Joint Line (JL) level are typically preserved. However, severe Post-Traumatic Bone Loss (PTBL) or TAA revision may render some landmarks unidentifiable, challenging JL restoration. Methods: Patients undergoing customized TAA for severe PTBL or revision were enrolled. Custom-made implants, based on 3D CT scans, were designed to address bone defects and provide adequate bone support. Evaluated parameters, measured on bilateral ankle weight-bearing radiographs taken preoperatively and 6–8 months postoperatively, included JL Height Ratio (JLHR) and the distances from JL to the Lateral Malleolus apex (LM-JL), the posterior colliculus of the Medial Malleolus (MM-JL), and the Gissane Calcaneal Sulcus (CS-JL). Reproducibility and variability were assessed, and comparisons were made between radiological parameters measured at TAA and those at the contralateral ankle. Results: Thirteen patients were included. Intra- and interobserver reliability demonstrated excellent values. The least variability was observed in the LM-JL distance. Statistically significant correlations were found between CS-JL and MM-JL distances in the operated limb and between the CS-JL of the operated limb and the contralateral ankle. While TAA parameters did not show statistically significant differences compared with the contralateral ankle, a trend toward proximalization of the JL was noted. Conclusions: This study demonstrated good reproducibility of the analyzed parameters for evaluating JL in TAA among patients with severe PTBL or undergoing revision surgery. However, these parameters cannot be deemed fully reliable. Given their potential weaknesses, it is crucial to identify more reproducible values, preferably ratios.
Long-Term Surgical Outcomes of Scleral Flap versus Scleral Pocket Technique for Sutureless Intrascleral One-Piece Lens Fixation
Authors: Marolo Paola , Caselgrandi Paolo , Gaidano Michele , Conte Fabio , Parisi Guglielmo , Borrelli Enrico , Fallico Matteo , Toro Mario Damiano , Ventre Luca , Vaiano Agostino S. , Reibaldi Michele
Published: July 2024

Objectives: This study compared long-term surgical outcomes of the scleral flap versus scleral pocket technique for sutureless intrascleral one-piece intraocular lens (IOL) fixation. Methods: A retrospective comparative study was conducted at a single center, involving consecutive patients undergoing sutureless intrascleral one-piece IOL implantation, between January 2020 and May 2022. Eyes were divided into two groups based on the surgical technique: group 1 underwent scleral flap (n = 64), and group 2 received scleral pocket technique (n = 59). Visual acuity, refractive outcomes, and complications were assessed over a minimum 24-month follow-up period. Results: Both groups showed improvements in best-corrected visual acuity (BCVA), increasing from 0.84 ± 0.56 logMAR at baseline to 0.39 ± 0.23 logMAR (p = 0.042) at 24 months in group 1 and from 0.91 ± 0.63 logMAR at baseline to 0.45 ± 0.38 logMAR (p = 0.039) at 24 months in group 2. No significant differences in BCVA were observed between the groups at baseline (p = 0.991), 12 (p = 0.496) and 24 months (p = 0.557). Mean spherical equivalent (−0.73 ± 1.32 D in group 1 and −0.92 ± 0.99 D in group 2, p = 0.447), refractive prediction error (−0.21 ± 1.1 D in group 1 and −0.35 ± 1.8 D in group 2, p = 0.377), and surgically induced astigmatism (0.74 ± 0.89 D in group 1 and 0.85 ± 0.76 in group 2, p = 0.651) were comparable between the two groups. An IOL tilt of 5.5 ± 1.8 and 5.8 ± 2.0 degrees (p = 0.867) and an IOL decentration of 0.41 ± 0.21 mm and 0.29 ± 0.11 mm (p = 0.955) were obtained, respectively, in group 1 and group 2 at 24 months. Mean endothelial cell density remained stable at 24 months in both groups (p = 0.832 in group 1 and p = 0.443 in group 2), and it was 1747.20 ± 588.03 cells/mm2 in group 1 and 1883.71 ± 621.29 cells/mm2 in group 2 (p = 0.327) at baseline, 1545.36 ± 442.3 cells/mm2 in group 1 and 1417.44 ± 623.40 cells/mm2 in group 2 (p = 0.483) at 24 months. No cases of endophthalmitis were observed. Conclusions: The scleral pocket technique for sutureless intrascleral one-piece IOL fixation is comparable to the traditional scleral flap technique in terms of long-term visual outcomes and safety. The scleral pocket technique offers a simplified approach and a viable option even for less experienced surgeons.
Effect of Stem Design and Positioning on the Leg Axis after Total Hip Arthroplasty: A Secondary Analysis
Authors: Fey Benjamin , Brenneis Marco , Stief Felix , van Drongelen Stefan
Published: July 2024

Background/Objectives: Various parameters, like femoral offset and leg length, are associated with good patient outcomes after total hip arthroplasty. In this prospective study, the effects of stem design, its placement in the proximal femur and the resulting femoral offset on the total leg axis were investigated. Methods: The 27 patients included in this study received biplanar radiography (EOS®, EOS Imaging) with 3D reconstruction using sterEOS® both preoperatively and postoperatively. For all leg alignment parameters obtained from the 3D reconstruction and from measurements using mediCAD, the deltas between the postoperative and preoperative values were determined. Patients were divided into those who received a short-stem prosthesis and those who received a straight-stem prosthesis. Results: The change in femoral offset with the implantation of a short-stem prosthesis was significantly greater than that with the implantation of a straight-stem prosthesis (11.4 ± 5.9 vs. 4.6 ± 7.4 mm, p = 0.014). Compared with the straight-stem implantation, short-stem implantation caused a significantly greater increase in the varus orientation of the leg (−1.4 ± 0.9 vs. −0.4 ± 1.4°, p = 0.048). There was no significant difference in the positioning of the short-stem prosthesis compared to the straight-stem prosthesis in the proximal femur (3.6 ± 3.1 vs. 2.6 ± 1.9°, p = 0.317). Conclusions: These findings substantiate the impact of prosthesis design on offset and leg alignment. The implantation of short-stems is more variable and requires precise planning. Intraoperative non-physiological offset changes and varus deviation of the leg axis should be avoided. Trial registration: This study was retrospectively registered with the German Clinical Trials Register (DRKS) under the number DRKS00015053 on the 1 August 2018.
The Role of Systemic Inflammation in the Pathogenesis of Spontaneous Intracranial Hemorrhage in the Presence or Absence of Effective Cerebral Blood Flow
Authors: Gusev Evgenii , Solomatina Liliya , Bochkarev Peter , Zudova Alevtina , Chereshnev Valeriy
Published: July 2024

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1–3/5–8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood–brain barrier for tissue breakdown products and other neuroinflammatory factors.
Transoral Robotic Surgery and Human Papillomavirus Infection: Impact on Oropharyngeal Cancer Prognosis
Authors: Chen Jingtao , Zhang Xing , Yan Shida , Li Xiyuan , Li Menghua , Zhang Ying , Zhang Shiting , Li Fengjiao , Song Ming
Published: July 2024

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV−) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1–T2 classification (89.3% vs. 72.0%; p = 1.1 × 10−2), stages I–II (92.1% vs. 82.2%; p = 4.6 × 10−2), and stages III–IV (82.8% vs. 62.2%; p = 5.7 × 10−2) and for HPV− patients (85.5% vs. 33.3%; p < 1.0 × 10−6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.
New Frontiers in Locally Advanced Cervical Cancer Treatment
Authors: Massobrio Roberta , Bianco Lavinia , Campigotto Beatrice , Attianese Daniela , Maisto Elisa , Pascotto Maria , Ruo Redda Maria Grazia , Ferrero Annamaria
Published: July 2024

Despite the introduction of targeted vaccines and screening protocols, locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Compared to early stages, it presents significantly lower cure rates, with a 5-year disease-free survival rate of 68% and a 5-year overall survival rate of 74%. According to current guidelines, definitive radiotherapy with concomitant chemotherapy represents the gold standard for locally advanced cervical cancer treatment. However, a significant number of patients relapse and die from metastatic disease. The aim of this narrative review is to examine the recent advancements in treating locally advanced cervical cancer, exploring new frontiers in therapeutic approaches. The PubMed database and clinical trial registries were searched to identify relevant articles published on locally advanced cervical cancer treatment up to March 2024, mainly focusing on papers published in the last decade. Abstracts presented at major international congresses that bring relevant evidence were included. Progress achieved in refining radiotherapy techniques, recent evidence regarding neoadjuvant treatment preceding surgery or concurrent chemoradiotherapy, and key findings concerning adjuvant treatment are thoroughly explored. Furthermore, a comprehensive review of prominent phase II and phase III trials examining the integration of immune checkpoint inhibitors is conducted, analyzing the various contexts in which they are applied. In light of the new evidence that has emerged in recent years and is discussed in this article, the appropriate selection of the most suitable therapeutic approach for each patient remains a complex but crucial issue.
Systemic Inflammatory Index in Polycythemia Vera and Its Prognostic Implications
Authors: Krecak Ivan , Lekovic Danijela , Arsenovic Isidora , Bogdanovic Andrija , Holik Hrvoje , Zekanovic Ivan , Moric Peric Martina , Lucijanic Marko
Published: July 2024

Background: This study aimed to evaluate the clinical and prognostic associations of the systemic inflammatory index (SII) in polycythemia vera (PV) patients. SII integrates information on absolute neutrophil (ANC), lymphocyte (ALC), and platelet counts into one index (calculated as ANCxALC/platelet count) and was previously shown to predict thrombotic and mortality risks in the general population. Methods: A total of 279 PV patients treated in several hematologic centers in Croatia and Serbia was retrospectively evaluated. Results: The median SII for the overall cohort was 1960. Higher SII stratified at the specific cut-off points was significantly associated with shorter time to thrombosis (TTT; p = 0.004) driven by arterial thrombotic events, and shorter overall survival (OS; p < 0.001). Higher SII was able to refine the European Leukemia Net-defined high-risk patient subgroup for both thrombotic and survival risks, especially in individuals over 60 years of age. SII and all other evaluated CBC components and indices (leukocytes, ANC, ALC, platelets, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)) demonstrated low-to-modest prognostic properties, whereas SII outperformed other parameters with respect to TTT and OS prognostications. Discussion: The presented results complement prior studies evaluating the prognostic performance of different CBC components for thrombotic and survival risk predictions and offer more options to personalize PV treatments.
What Is the Link between Attention-Deficit/Hyperactivity Disorder (ADHD) and Dyslipidemia in Adults? A German Retrospective Cohort Study
Authors: Krieg Sarah , Konrad Marcel , Krieg Andreas , Kostev Karel
Published: July 2024

Background: Alterations in the serum lipid profile have been suspected in many psychiatric disorders, such as schizophrenia and depression. However, studies on lipid status in attention-deficit/hyperactivity disorder (ADHD) are sparse and inconsistent. Methods: Using the nationwide, population-based IQVIA Disease Analyzer database, this retrospective cohort study included 5367 outpatients from general practices in Germany aged ≥18 years with a documented first diagnosis of ADHD between January 2005 and December 2021 and 26,835 propensity score-matched individuals without ADHD. Study outcomes were the first diagnosis of lipid metabolism disorders as a function of ADHD within up to 10 years of the index date. The cumulative 10-year incidence was analyzed using Kaplan–Meier curves and compared using the log-rank test. In addition, univariate Cox regression analyses were performed. Results: In the regression analysis, there was no significant association between ADHD and subsequent lipid metabolism disorders in the total population (HR: 0.94; 95% CI: 0.83–1.08), among women (HR: 1.04; 95% CI: 0.84–1.28), and among men (HR: 0.89; 95% CI: 0.74–1.06). In addition, no significant association was observed in the disease-stratified analyses. Conclusions: The findings of this study indicate that ADHD does not exert an influence on lipid metabolism. However, further investigation is warranted, particularly with respect to pharmacological interventions.
Predictivity of the Prognostic Nutritional Index and Systemic Inflammation Index for All-Cause In-Hospital Mortality in Geriatric and Adult COVID-19 Inpatients
Authors: Cavdar Sibel , Savas Sumru , Tasbakan Sezai , Sayıner Abdullah , Basoglu Ozen , Korkmaz Pervin , Akcicek Fehmi
Published: July 2024

Background: The prognostic nutritional index (PNI) and the systemic immune inflammation index (SII) have been used as simple risk-stratification predictors for COVID-19 severity and mortality in the general population. However, the associations between these indices and mortality might differ due to age-related changes such as inflammaging and several comorbid conditions in older patients. Therefore, we aimed to compare the predictivity of the PNI and SII for mortality among hospitalized older patients and patients under 65 years old. Methods: Patients hospitalized with COVID-19 from March 2020 to December 2020 were retrospectively included. The PNI and SII were calculated from hospital records within the first 48 h after admission. Data were evaluated in the whole group and according to age groups (≥65 < years). Receiver operating characteristic curves were drawn to evaluate the predictivity of the PNI and SII. Results: Out of 407 patients included in this study, 48.4% (n = 197) were older patients, and 51.6% (n = 210) were under 65 years old. For mortality, the area under the curve (AUC) of the PNI and SII in the adult group (<65 years) was 0.706 (95% CI 0.583–0.828) (p = 0.003) and 0.697 (95% CI 0.567–0.827) (p < 0.005), respectively. The AUC of the PNI and SII in the older group was 0.515 (95% CI 0.427–0.604) (p = 0.739) and 0.500 (95% CI 0.411–0.590) (p = 0.993). Conclusions: The accuracy of the PNI and SII in predicting mortality in adult COVID-19 patients seemed to be fair, but no association was found in geriatric patients in this study. The predictivity of the PNI and SII for mortality varies according to age groups.
Isolated Intracranial Hypertensions as Onset of Myelin Oligodendrocyte Glycoprotein Antibody Disease
Authors: Papetti Laura , Moltoni Giulia , Longo Daniela , Monte Gabriele , Dellepiane Francesco , Pro Stefano , Bracaglia Giorgia , Ruscitto Claudia , Verrotti Alberto , Valeriani Massimiliano
Published: July 2024

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is characterized by multiple phenotypic conditions such as acute disseminated encephalomyelitis, optic neuritis, and myelitis. MOGAD’s spectrum is expanding, with potential symptoms of increased intracranial pressure that are similar to idiopathic intracranial hypertension (IIH). We report a boy with new-onset continuous headache and a brain MRI at onset suggesting idiopathic intracranial hypertension (IIH). The patient showed resistance to treatment with acetazolamide and, after one month, developed optic neuritis in the left eye. Laboratory tests documented positive MOG antibodies (anti-MOG) in the serum. The final diagnosis was MOGAD, with the initial symptoms resembling IIH.
EMPATHY Life in Psoriasis: Embracing Patients’ Well-Being in Their Journey of Moderate-to-Severe Psoriasis
Authors: Prignano Francesca , Campione Elena , Parodi Aurora , Vegni Elena , Bardazzi Federico , Borroni Riccardo G. , Burlando Martina , Cinotti Elisa , Dini Valentina , Giacchetti Alfredo , Giofrè Claudia , Megna Matteo , Zichichi Leonardo , Fargnoli Maria Concetta
Published: July 2024

Background: Psoriasis is a chronic inflammatory skin condition that affects millions of individuals worldwide, impacting their physical and emotional well-being. The management of psoriasis requires effective communication and a strong physician–patient relationship. Objective: We aim to develop a novel algorithm to enhance patient well-being and care in moderate-to-severe psoriasis, considering the time constraints that dermatologists have in public hospitals. Methods: This project employed a multidisciplinary approach, involving collaboration between 14 experienced dermatologists (referred to as Key Opinion Leaders: KOLs) and a psychologist. During three separate meetings (an initial virtual session, a face-to-face meeting, and a final virtual meeting), an algorithm (Embracing Patients’ Well-being in their Journey of Moderate-to-Severe psoriasis: EMPATHY), describing the patient’s reception through the entire first visit and follow-up visits, was developed and refined. Results: The EMPATHY algorithm provides a step-by-step approach from the moment the patient arrives at reception, through the first visit and on to subsequent visits. This algorithm fills a critical gap in the existing guidelines by specifically addressing how to foster empathy during psoriasis patient visits within time-limited consultations. The algorithm outlines patient-centered strategies at each visit. Key aspects include creating a welcoming environment, active listening, respecting privacy, tailoring communication styles, and managing patient expectations. Conclusions: The EMPATHY algorithm represents a novel and promising approach to improving patient care and well-being in moderate-to-severe psoriasis. Developed together by dermatologists and a psychologist, this algorithm offers healthcare providers practical guidance for managing both initial and follow-up patient visits. While further validation is necessary, the potential for adapting the EMPATHY algorithm to diverse healthcare settings and patient populations holds promise for improving patient outcomes across various chronic conditions.
Diuretic Treatment in Heart Failure: A Practical Guide for Clinicians
Authors: Wu Lingling , Rodriguez Mario , El Hachem Karim , Krittanawong Chayakrit
Published: July 2024

Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction.
SURgical vs. PERcutaneous ACCESS in Transfemoral Transcatheter Aortic Valve Implantation (SU-PER-ACCESS Study)
Authors: Cammardella Antonio Giovanni , Russo Marco , Di Mauro Michele , Romagnoni Claudia , Ceresa Fabrizio , Patanè Francesco , Gelpi Guido , Pollari Francesco , Barili Fabio , Parolari Alessandro , Ranocchi Federico
Published: July 2024

Background: The transfemoral (TF) approach is the most common route in TAVI, but it is still associated with a risk of bleeding and vascular complications. The aim of this study was to compare the clinical outcomes between surgical cut-down (SC) and percutaneous (PC) approach. (2) Methods: Between January 2018 and June 2022, 774 patients underwent a transfemoral TAVI procedure. After propensity matching, 323 patients underwent TAVI in each group. (3) Results: In the matched population, 15 patients (4.6%) in the SC group vs. 34 patients in the PC group (11%) experienced minor vascular complications (p = 0.02), while no difference for major vascular complication (1.5% vs. 1.9%) were reported. The rate of minor bleeding events was higher in the percutaneous group (11% vs. 3.1%, p <.001). The SC group experienced a higher rate of non-vascular-related access complications (minor 8% vs. 1.2%; major 2.2% vs. 1.2%; p < 0.001). (4) Conclusions: SC for TF-TAVI did not alter the mortality rate at 30 days and was associated with reduced minor vascular complication and bleeding. PC showed a lower rate of non-vascular-related access complications and a lower length of stay. The specific approach should be tailored to the patient’s clinical characteristics.
Enhancing the Antimicrobial Properties of Experimental Resin-Based Dental Composites through the Addition of Quaternary Ammonium Salts
Authors: Nowak Joanna , Zalega Maja , Jakubowski Witold , Domarecka Monika , Sokołowski Jerzy , Bociong Kinga
Published: July 2024

Secondary caries is one of the main reasons for dental filling replacement. There is a need to obtain dental restorative material that is able to act against caries-inducing microorganisms. This study explores the antimicrobial properties of cetyltrimethylammonium bromide (CTAB) or dimethyldioctadecylammonium bromide (DODAB)-modified photo-cured experimental dental composites against Escherichia coli, Streptococcus mutans, and Candida albicans. The antimicrobial activity against Escherichia coli, Streptococcus mutans, and Candida albicans was assessed by using an Accuri C6 flow cytofluorimeter, and then analyzed using BD CSampler software (1.0.264). Bacterial/yeast surface colonization was carried out by using an GX71 inverted-optics fluorescence microscope equipped with a DP 73 digital camera. For bactericidal surface analysis of each sample type, simultaneous standardization was performed using a positive control (live cells) and a negative control (dead cells). A positive correlation between the increasing concentration of CTAB or DODAB and the dead cell ratio of Escherichia coli, Streptococcus mutans, and Candida albicans was revealed. In particular, CTAB at a 2.0 wt% concentration exhibits superior efficiency against pathogens (65.0% dead cells of Escherichia coli, 73.9% dead cells of Streptococcus mutans, and 23.9% dead cells of Candida albicans after 60 min). However, Candida albicans is more resistant to used salts than bacteria. A CTAB- or DODAB-modified experimental dental composite exhibits antimicrobial potential against Escherichia coli, Streptococcus mutans, and Candida albicans after 10 and 60 min of incubation, and the antimicrobial efficiency increases with the wt% of QAS in the tested material.
Recent Progress in Artificial Neurons for Neuromodulation
Authors: Jiang Qinkai , Liu Mengwei
Published: July 2024

Driven by the rapid advancement and practical implementation of biomaterials, fabrication technologies, and artificial intelligence, artificial neuron devices and systems have emerged as a promising technology for interpreting and transmitting neurological signals. These systems are equipped with multi-modal bio-integrable sensing capabilities, and can facilitate the benefits of neurological monitoring and modulation through accurate physiological recognition. In this article, we provide an overview of recent progress in artificial neuron technology, with a particular focus on the high-tech applications made possible by innovations in material engineering, new designs and technologies, and potential application areas. As a rapidly expanding field, these advancements have a promising potential to revolutionize personalized healthcare, human enhancement, and a wide range of other applications, making artificial neuron devices the future of brain-machine interfaces.
Verbal Perceptual Prompts Facilitate Children’s Sensitivity to False Beliefs
Authors: Huang Qiyu , Liu Xiuli
Published: July 2024

False belief understanding is always regarded as a milestone of Theory of Mind (ToM), which is an important aspect of social intelligence. Recently, some researchers have suggested the existence of two ToM systems in individuals: one that explicitly guides false belief understanding and another that implicitly directs sensitivity to false beliefs. However, studies on sensitivity to false beliefs have encountered challenges with replicability, and the factors influencing the manifestation of sensitivity to false beliefs remain to be explored. Based on the anticipatory looking task, we investigated whether verbal perceptual prompts could improve children’s performance of sensitivity to false beliefs. Fifty-eight children aged 5 to 6 were randomly assigned tasks with or without verbal perceptual prompts, involving verbal descriptions and explanations of the protagonist’s perceptual state. The findings showed that verbal perceptual prompts could slightly reduce children’s propensity to look at the actual location of the object in false belief situations and increase the likelihood of exhibiting accurate anticipatory looking patterns across false belief and true belief situations. The results suggest that children’s sensitivity to false beliefs may be situation-dependent, yet further investigation is needed to determine which situational factors can most effectively trigger robust sensitivity to false beliefs in children. The results enlighten educational practice, indicating that introducing cues in social environments that convey insights into others’ mental states, akin to the use of learning scaffolding, is advantageous for the development of children’s social cognitive abilities.