bluuebunny/crossref_metadata_2025 huggingface dataset:
The [18F]F-FDG PET/CT Radiomics Classifier of Histologic Subtypes and Anatomical Disease Origins across Various Malignancies: A Proof-of-Principle Study
Authors: Hinzpeter Ricarda , Mirshahvalad Seyed Ali , Murad Vanessa , Avery Lisa , Kulanthaivelu Roshini , Kohan Andres , Ortega Claudia , Elimova Elena , Yeung Jonathan , Hope Andrew , Metser Ur , Veit-Haibach Patrick
Published: May 2024

We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients’ histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT.
The Value of PET/CT in Particle Therapy Planning of Various Tumors with SSTR2 Receptor Expression: Comparative Interobserver Study
Authors: Lütgendorf-Caucig Carola , Wieland Patricia , Hug Eugen , Flechl Birgit , Tubin Slavisa , Galalae Razvan , Georg Petra , Fossati Piero , Mumot Marta , Harrabi Semi , Pradler Irina , Pelak Maciej J.
Published: May 2024

The overexpression of somatostatin receptor type 2 (SSTR2) is a property of various tumor types. Hybrid imaging utilizing [68Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) may improve the differentiation between tumor and healthy tissue. We conducted an experimental study on 47 anonymized patient cases including 30 meningiomas, 12 PitNET and 5 SBPGL. Four independent observers were instructed to contour the macroscopic tumor volume on planning MRI and then reassess their volumes with the additional information from DOTA-PET/CT. The conformity between observers and reference volumes was assessed. In total, 46 cases (97.9%) were DOTA-avid and included in the final analysis. In eight cases, PET/CT additional tumor volume was identified that was not detected by MRI; these PET/CT findings were potentially critical for the treatment plan in four cases. For meningiomas, the interobserver and observer to reference volume conformity indices were higher with PET/CT. For PitNET, the volumes had higher conformity between observers with MRI. With regard to SBGDL, no significant trend towards conformity with the addition of PET/CT information was observed. DOTA PET/CT supports accurate tumor recognition in meningioma and PitNET and is recommended in SSTR2-expressing tumors planned for treatment with highly conformal radiation.
Historical Perspective and Current Trends in Anticancer Drug Development
Authors: Gach-Janczak Katarzyna , Drogosz-Stachowicz Joanna , Janecka Anna , Wtorek Karol , Mirowski Marek
Published: May 2024

Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and pharmacologists for decades, focusing either on the isolation of compounds with cytotoxic properties from plants or on screening thousands of synthetic molecules. Compounds that could potentially become candidates for new anticancer drugs must have the ability to inhibit proliferation and/or induce apoptosis in cancer cells without causing too much damage to normal cells. Some anticancer compounds were discovered by accident, others as a result of long-term research. In this review, we have presented a brief history of the development of the most important groups of anticancer drugs, pointing to the fact that they all have many side effects.
RETRACTED: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvβ3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780
Authors: Godugu Kavitha , Rajabi Mehdi , Mousa Shaker A.
Published: May 2024

The journal retracts the article, “Anti-Cancer Activities of Thyrointegrin αvβ3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma” [...]
Influence of the Planning Parameters of a New Algorithm on the Dosimetric Quality, Beam-On Time and Delivery Accuracy of Tomotherapy Plans
Authors: Burckbuchler Théo , Dehaynin Nicolas , Niederst Claudine , Bartolucci Laurent , Elazhar Halima , Jarnet Delphine , Arbor Florence , Meyer Philippe
Published: May 2024

Background: This work aimed to determine the optimum VOLOTM Ultra algorithm parameters for tomotherapy treatments. Methods: 1056 treatment plans were generated with VOLOTM Ultra for 36 patients and six anatomical locations. The impact of varying four parameters was studied: the accelerated treatment (AT), leaf open/close time (LOT) cutoff, normal tissue objective (NTO) weight, and number of iterations. The beam-on time and dosimetric metrics were quantified for the target volumes and organs at risk (OARs). Delivery quality assurance measurements were obtained for 36 plans to assess the delivery accuracy. Results: The mean beam-on time for the helical tomotherapy and TomoDirect (TD) plans decreased by 26.6 ± 2.8% and 17.4 ± 4.3%, respectively, when the accelerated treatment parameter was increased from 0 to 10, at the expense of the planning target volume (PTV) coverage (2% lower D98%) and OAR dose (up to 15% increase). For TD plans, it seems preferable to systematically use an AT value of 10. Increasing the number of iterations beyond six seems unnecessary. In this study, an NTO weight of approximately 10 appears to be ideal and eliminates the need to use rings in the treatment plan. Finally, no correlation was found between the leaf open/close time cutoff and the delivery accuracy, while a leaf open/close cutoff of 60 ms seemed to degrade dosimetry quality. Conclusion: Optimal values for the AT, LOT cutoff, NTO weight, and number of optimization rounds were identified and should help improve the management of patients whose tomotherapy treatments are planned with VOLOTM Ultra.
A Gold Standard-Derived Modular Barcoding Approach to Cancer Transcriptomics
Authors: Zhu Yan , Koleilat Mohamad Karim I. , Roszik Jason , Kwong Man Kam , Wang Zhonglin , Maru Dipen M. , Kopetz Scott , Kwong Lawrence N.
Published: May 2024

A challenge with studying cancer transcriptomes is in distilling the wealth of information down into manageable portions of information. In this resource, we develop an approach that creates and assembles cancer type-specific gene expression modules into flexible barcodes, allowing for adaptation to a wide variety of uses. Specifically, we propose that modules derived organically from high-quality gold standards such as The Cancer Genome Atlas (TCGA) can accurately capture and describe functionally related genes that are relevant to specific cancer types. We show that such modules can: (1) uncover novel gene relationships and nominate new functional memberships, (2) improve and speed up analysis of smaller or lower-resolution datasets, (3) re-create and expand known cancer subtyping schemes, (4) act as a “decoder” to bridge seemingly disparate established gene signatures, and (5) efficiently apply single-cell RNA sequencing information to other datasets. Moreover, such modules can be used in conjunction with native spreadsheet program commands to create a powerful and rapid approach to hypothesis generation and testing that is readily accessible to non-bioinformaticians. Finally, we provide tools for users to create and interpret their own modules. Overall, the flexible modular nature of the proposed barcoding provides a user-friendly approach to rapidly decoding transcriptome-wide data for research or, potentially, clinical uses.
Safety and Efficacy of High-Dose Chemotherapy with TreoMel 200 vs. TreoMel 140 in Acute Myeloid Leukemia Patients Undergoing Autologous Stem Cell Transplantation
Authors: Eggimann Matthias , Akhoundova Dilara , Nilius Henning , Hoffmann Michèle , Hayoz Michael , Aebi Yolanda , Largiadèr Carlo R. , Daskalakis Michael , Bacher Ulrike , Pabst Thomas
Published: May 2024

(1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients’ basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit.
Molars to Medicine: A Focused Review on the Pre-Clinical Investigation and Treatment of Secondary Degeneration following Spinal Cord Injury Using Dental Stem Cells
Authors: Jenkner Sandra , Clark Jillian Mary , Gronthos Stan , O’Hare Doig Ryan Louis
Published: May 2024

Spinal cord injury (SCI) can result in the permanent loss of mobility, sensation, and autonomic function. Secondary degeneration after SCI both initiates and propagates a hostile microenvironment that is resistant to natural repair mechanisms. Consequently, exogenous stem cells have been investigated as a potential therapy for repairing and recovering damaged cells after SCI and other CNS disorders. This focused review highlights the contributions of mesenchymal (MSCs) and dental stem cells (DSCs) in attenuating various secondary injury sequelae through paracrine and cell-to-cell communication mechanisms following SCI and other types of neurotrauma. These mechanistic events include vascular dysfunction, oxidative stress, excitotoxicity, apoptosis and cell loss, neuroinflammation, and structural deficits. The review of studies that directly compare MSC and DSC capabilities also reveals the superior capabilities of DSC in reducing the effects of secondary injury and promoting a favorable microenvironment conducive to repair and regeneration. This review concludes with a discussion of the current limitations and proposes improvements in the future assessment of stem cell therapy through the reporting of the effects of DSC viability and DSC efficacy in attenuating secondary damage after SCI.
Cyto- and Histopographic Assessment of CPA3-Positive Testicular Mast Cells in Obstructive and Non-Obstructive Azoospermia
Authors: Atiakshin Dmitrii , Kulchenko Nina , Kostin Andrey , Ignatyuk Michael , Protasov Andrey , Klabukov Ilya , Baranovskii Denis , Faniev Mikhail , Korovyakova Elina , Chekmareva Irina , Buchwalow Igor , Tiemann Markus
Published: May 2024

Infertility is an important personal and society disease, of which the male factor represents half of all causes. One of the aspects less studied in male infertility is the immunological testicular microenvironment. Mast cells (MCs), having high potential for regulating spermatogenesis due to fine-tuning the state of the integrative buffer metabolic environment, are one of the most crucial cellular subpopulations of the testicular interstitium. One important component of the MC secretome is proteases that can act as proinflammatory agents and in extracellular matrix (ECM) remodeling. In the testis, MCs are an important cell component of the testicular interstitial tissue (TIT). However, there are still no studies addressing the analysis of a specific MC protease—carboxypeptidase A3 (CPA3)—in cases with altered spermatogenesis. The cytological and histotopographic features of testicular CPA3+ MCs were examined in a study involving 34 men with azoospermia. As revealed, in cases with non-obstructive azoospermia, a higher content of CPA3+ MCs in the TIT and migration to the microvasculature and peritubular tissue of seminiferous tubules were observed when compared with cases with obstructive azoospermia. Additionally, a high frequency of CPA3+ MCs colocalization with fibroblasts, Leydig cells, and elastic fibers was detected in cases with NOA. Thus, CPA3 seems to be of crucial pathogenetic significance in the formation of a profibrogenic background of the tissue microenvironment, which may have direct and indirect effects on spermatogenesis.
Sex Differences in Visceral Pain and Comorbidities: Clinical Outcomes, Preclinical Models, and Cellular and Molecular Mechanisms
Authors: Tiwari Namrata , Qiao Liya Y.
Published: May 2024

Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.
The Relationship between Coping Strategies and State Anxiety during COVID-19 Lockdown: The Role of Perceived Emotional Intelligence
Authors: Geraci Alessandro , Di Domenico Laura , D’Amico Antonella
Published: May 2024

Background: The outbreak of the COVID-19 pandemic has caused an unprecedented and unexpected change all around the globe. The long-term effects are still ongoing, especially those related to the confinement measures. The study took place during the first COVID-19 lockdown in Italy, where everyone was forced to stay home in order to reduce the spread of the virus. The aim was to investigate the role of perceived emotional intelligence abilities (PEI) in coping with COVID-19-related anxiety. Methods: A cross-sectional study design was employed, and this study used an online survey launched through social networks, inviting adults to participate. The participants anonymously completed a three-scale online measurement of self-reported emotional abilities, coping strategies (approach and avoidance), and state anxiety towards COVID-19. Results: perceived emotional intelligence and approach coping significantly predicted state anxiety. In addition, perceived emotional intelligence mediated the relationship between approach coping and state anxiety. Conclusions: the study highlights the positive role of perceived emotional abilities in dealing with the unprecedented event represented by the COVID-19 pandemic, and in particular, in coping with anxiety related to lockdown and confinement. Their results highlight the importance of fostering emotional intelligence for navigating critical life events.
Towards a Sustainable Laser Powder Bed Fusion Process via the Characterisation of Additively Manufactured Nitinol Parts
Authors: Obeidi Muhannad Ahmed , Healy Paul , Alobaidi Hasan , Bourke Declan , Brabazon Dermot
Published: May 2024

Is additive manufacturing (AM) a sustainable process? Can the process be optimised to produce sustainable AM parts and production techniques? Additive manufacturing offers the production of parts made of different types of materials in addition to the complex geometry that is difficult or impossible to produce by using the traditional subtractive methods. This study is focused on the optimisation of laser powder bed fusion (L-PBF), one of the most common technologies used in additive manufacturing and 3D printing. This research was carried out by modulating the build layer thickness of the deposited metal powder and the input volumetric energy density. The aim of the proposed strategy is to save the build time by maximizing the applied layer thickness of nitinol powder while retrieving the different AM part properties. The saving in the process time has a direct effect on the total cost of the produced part as a result of several components like electric energy, inert gas consumption, and labour. Nickel-rich nitinol (52.39 Ni at.%) was selected for investigation in this study due to its extremely high superplastic and shape memory properties in addition to the wide application in various industries like aerospace, biomedical, and automotive. The results obtained show that significant energy and material consumption can be found by producing near full dens AM parts with limited or no alteration in chemical and mechanical properties.
Diagnostic Endoscopic Ultrasound (EUS) of the Luminal Gastrointestinal Tract
Authors: Impellizzeri Giovanna , Donato Giulio , De Angelis Claudio , Pagano Nico
Published: May 2024

The purpose of this review is to focus on the diagnostic endoscopic ultrasound of the gastrointestinal tract. In the last decades, EUS has gained a central role in the staging of epithelial and sub-epithelial lesions of the gastrointestinal tract. With the evolution of imaging, the position of EUS in the diagnostic work-up and the staging flow-chart has continuously changed with two extreme positions: some gastroenterologists think that EUS is absolutely indispensable, and some think it is utterly useless. The truth is, as always, somewhere in between the two extremes. Analyzing the most up-to-date and strong evidence, we will try to give EUS the correct position in our daily practice.
The Early Childhood Development of Pediatric Burn Patients
Authors: Cuijpers Maxime D. , Akkerman Moniek , Baartmans Martin G. A. , van Zuijlen Paul P. M. , Pijpe Anouk
Published: May 2024

Our study aimed to provide a description of the early childhood development of pediatric burn patients relative to Dutch reference values, using both pre- and post-burn data from the Dutch Development Instrument and the D-score. Data from the Dutch Development Instrument were used to calculate the D-score and age-standardized D-score. Similar to a growth chart, the D-score was used to plot pediatric burn patients’ development relative to Dutch reference values for their age. Pediatric burn patients’ (n = 38) median age at the time of injury was 1.0 (1.0–2.0) years old. Burn size ranged from 1.0% to 36.0% of the total body surface area. Ninety-five percent (± 6.0%) of pediatric burn patients passed each of the age-appropriate developmental milestones at the target age. The mean age-standardized D-score was just above the Dutch average (+0.49 SD [0.18, 0.80]) and did not vary depending on sex (p = 0.06) or burn size (p = 0.41). In conclusion, among pediatric patients aged up to two-and-a-half years old, with non-full thickness burns, development was on track relative to the Dutch reference values. Our findings offer valuable first insights into the early childhood development of pediatric burn patients and may alleviate some parental concerns.
Mitogenome Assembly Reveals Gene Migration and RNA Editing Events in Plateau Hongliu (Myricaria elegans Royle.)
Authors: Li Xue , Wu Hao , Hu Xingyao , Wu Yunhua , Nie Feng , Su Tao , Han Mei , Cao Fuliang
Published: May 2024

The Plateau Hongliu (Myricaria elegans Royle.) is a woody shrub halophyte that thrives in arid areas of western Tibet, in the Himalayan Mountains. It is acclaimed as superior in saline stress acclimation and as a critical pharmaceutical resource of the Tibetan traditional herb. Nevertheless, the mitogenome in the genus Myricaria remains unknown. Here, using the Illumina and PacBio sequencing assays, the first complete mitogenome of the M. elegans revealed a multi-branched skeleton with a total length of 416,354 bp and GC content of 44.33%, comprising two circular molecules (M1 and 2). The complete mitogenome annotates 31 unique protein-encoding genes (PEGs), fifteen tRNAs, and three rRNA genes. The UAA exhibits the most prominent codon usage preference as a termination, followed by UUA codons for leucine. The mitogenome contains 99 simple sequence repeats and 353 pairs of dispersed repeats, displaying the most frequent in palindromic repeats. Gene transfer analyses identified 8438 bp of 18 homologous fragments from the plastome, accounting for 2.03% of the total length. Using the PREP suite, 350 C-U RNA editing sites were predicted, of which nad4 and ccmB were on the top frequency. Syntenic and phylogenetic analyses suggested weakly conserved patterns of M. elegans in Caryophyllales owing to the genome rearrangement. In summary, the deciphered unique features and complexities of the mitogenome in M. elegans provide novel insights into understanding the evolution and biological conservation underlying climate resilience in halophytes.
Estimating Economic and Livelihood Values of the World’s Largest Mangrove Forest (Sundarbans): A Meta-Analysis
Authors: Kanan Akbar Hossain , Masiero Mauro , Pirotti Francesco
Published: May 2024

We explored the state of the art economic and livelihood valuation of ecosystem services (ES) in the Sundarbans mangroves, including a comparative analysis between the Bangladesh and Indian parts of the region. We identified 145 values from 26 studies to estimate the Sundarbans’ economic and livelihood values. The number of ES valuation studies of the Sundarbans is scant, and it has gradually increased over time, focusing mainly on the estimation of provisioning ES (66.2%), followed by regulating and maintenance (25.5%), and cultural (8.3%) ES. However, recently, attention has been paid to estimation, regulating and maintenance, and cultural ES. The number of studies on ES was higher for the Bangladesh (73%) part of the Sundarbans than the Indian (27%) one. The estimated economic values of the Sundarbans’ provisioning, regulating and maintenance, and cultural ES were US $ 713.30 ha−1 yr−1, US $ 2584.46 ha−1 yr−1, and US $ 151.88 ha−1 yr−1, respectively. Except for cultural ES, the identified values for the other two ES categories were about 1.5 to 2.5 times higher for the Bangladesh Sundarbans compared to the Indian ones. The results of the meta-regression model showed that the estimated economic and livelihood values of ES are affected by the associated variables (e.g., type of ES, valuation methods, study area, population, and GDP). Our study also identified some remarkable gaps and limitations in the economic and livelihood valuation of the ES of the Sundarbans, highlighting the need for further research to find out the values of all ES to help with policy decision-making.
Study on the Effect and Enhancement of Near-Natural Integrated Plant Positioning Configuration in the Hilly Gully Region, China
Authors: Zhao Hongsheng , Feng Shuang , Li Wanjiao , Gao Yong
Published: May 2024

The establishment of protective forests plays a crucial role in mitigating soil erosion on slopes within hilly and gully regions. However, in practical applications, the configuration of protective forests on slopes is intricate and diverse, and the suitability and rationality of different configuration patterns for various slope sections have not been thoroughly investigated. This study focuses on a 40-year-old artificial protective forest, examining 16 different configuration patterns on the top, middle, and lower slopes. It compares the growth conditions, community structure stability, and characteristics of the saturated soil’s hydraulic conductivity. The findings indicate that the top slope should be identified as a critical area for slope protection. The optimal configuration for this area is the “tree + grass” pattern with a spacing of 5 m × 5 m, which promotes the optimal growth of tree species and effectively reduces the surface runoff of gravel particles ranging from 1 cm to 3 cm in diameter. On the middle slope, the “tree + shrub + grass” structure proves effective in slowing down the erosive force of slope runoff. The recommended spacing for trees is 5 m × 6 m, and for understory shrubs, it is 1 m × 6 m. This configuration pattern results in the most stable structure for the plant community and maximizes the water conservation potential of forest litter. By analyzing the characteristics of the saturated soil’s hydraulic conductivity, we find that the complexity of the plant configuration on the lower slopes is correlated with a greater coefficient of variation in the saturated soil’s hydraulic conductivity. Nevertheless, there is no significant difference in the average soil saturated hydraulic conductivity per unit area between the different configuration patterns. Consequently, the lower slope can rely on the natural recovery of herbaceous plants. The results of this research contribute valuable scientific and technical insights to the management of soil erosion in hilly and gully areas, both in China and around the world.
Transcriptomic Profiling of Peripheral B Cells in Antibody Positive Sjogren’s Patients Reveals Interferon Signature
Authors: Maleki-Fischbach Mehrnaz , Anderson Kelsey , Fernández Pérez Evans R.
Published: May 2024

Background: Sjögren’s disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. Methods: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). Results: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. Conclusions: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.
Prediction Model for Cognitive Impairment among Disabled Older Adults: A Development and Validation Study
Authors: Cui Xiangyu , Zheng Xiaoyu , Lu Yun
Published: May 2024

Disabled older adults exhibited a higher risk for cognitive impairment. Early identification is crucial in alleviating the disease burden. This study aims to develop and validate a prediction model for identifying cognitive impairment among disabled older adults. A total of 2138, 501, and 746 participants were included in the development set and two external validation sets. Logistic regression, support vector machine, random forest, and XGBoost were introduced to develop the prediction model. A nomogram was further established to demonstrate the prediction model directly and vividly. Logistic regression exhibited better predictive performance on the test set with an area under the curve of 0.875. It maintained a high level of precision (0.808), specification (0.788), sensitivity (0.770), and F1-score (0.788) compared with the machine learning models. We further simplified and established a nomogram based on the logistic regression, comprising five variables: age, daily living activities, instrumental activity of daily living, hearing impairment, and visual impairment. The areas under the curve of the nomogram were 0.871, 0.825, and 0.863 in the internal and two external validation sets, respectively. This nomogram effectively identifies the risk of cognitive impairment in disabled older adults.
Gut–Brain Axis: Focus on Sex Differences in Neuroinflammation
Authors: Caldarelli Mario , Rio Pierluigi , Marrone Andrea , Ocarino Francesca , Chiantore Monica , Candelli Marcello , Gasbarrini Antonio , Gambassi Giovanni , Cianci Rossella
Published: May 2024

In recent years, there has been a growing interest in the concept of the “gut–brain axis”. In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of “neuroinflammation”. The gut microbiota–brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut–brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain–gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut–brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions.
Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies
Authors: Sarrou Styliani , Voulgaridi Ioanna , Fousika Athanasia , Dadouli Katerina , Margaritopoulou Olympia , Kakkas Ioannis , Hadjichristodoulou Christos , Kalala Fani , Speletas Matthaios
Published: May 2024

Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.
Programmed Cell Death Reversal: Polyamines, Effectors of the U-Turn from the Program of Death in Helianthus tuberosus L.
Authors: Serafini-Fracassini Donatella , Del Duca Stefano
Published: May 2024

This review describes a 50-year-long research study on the characteristics of Helianthus tuberosus L. tuber dormancy, its natural release and programmed cell death (PCD), as well as on the ability to change the PCD so as to return the tuber to a life program. The experimentation on the tuber over the years is due to its particular properties of being naturally deficient in polyamines (PAs) during dormancy and of immediately reacting to transplants by growing and synthesizing PAs. This review summarizes the research conducted in a unicum body. As in nature, the tuber tissue has to furnish its storage substances to grow vegetative buds, whereby its destiny is PCD. The review’s main objective concerns data on PCD, the link with free and conjugated PAs and their capacity to switch the destiny of the tuber from a program of death to one of new life. PCD reversibility is an important biological challenge that is verified here but not reported in other experimental models. Important aspects of PA features are their capacity to change the cell functions from storage to meristematic ones and their involvement in amitosis and differentiation. Other roles reported here have also been confirmed in other plants. PAs exert multiple diverse roles, suggesting that they are not simply growth substances, as also further described in other plants.
Novel Acetamide-Based HO-1 Inhibitor Counteracts Glioblastoma Progression by Interfering with the Hypoxic–Angiogenic Pathway
Authors: D’Amico Agata Grazia , Maugeri Grazia , Vanella Luca , Consoli Valeria , Sorrenti Valeria , Bruno Francesca , Federico Concetta , Fallica Antonino Nicolò , Pittalà Valeria , D’Agata Velia
Published: May 2024

Glioblastoma multiforme (GBM) represents the deadliest tumor among brain cancers. It is a solid tumor characterized by uncontrolled cell proliferation generating the hypoxic niches in the cancer core. By inducing the transcription of hypoxic inducible factor (HIF), hypoxia triggers many signaling cascades responsible for cancer progression and aggressiveness, including enhanced expression of vascular endothelial growth factor (VEGF) or antioxidant enzymes, such as heme oxygenase-1 (HO-1). The present work aimed to investigate the link between HO-1 expression and the hypoxic microenvironment of GBM by culturing two human glioblastoma cell lines (U87MG and A172) in the presence of a hypoxic mimetic agent, deferoxamine (DFX). By targeting hypoxia-induced HO-1, we have tested the effect of a novel acetamide-based HO-1 inhibitor (VP18/58) on GBM progression. Results have demonstrated that hypoxic conditions induced upregulation and nuclear expression of HO-1 in a cell-dependent manner related to malignant phenotype. Moreover, our data demonstrated that the HO-1 inhibitor counteracted GBM progression by modulating the HIFα/HO-1/VEGF signaling cascade in cancer cells bearing more malignant phenotypes.
Multiplicative Effects of Essential Oils and Other Active Components on Skin Tissue and Skin Cancers
Authors: Kim Hyeong Jae , Hong Jeong Hee
Published: May 2024

Naturally derived essential oils and their active components are known to possess various properties, ranging from anti-oxidant, anti-inflammatory, anti-bacterial, anti-fungal, and anti-cancer activities. Numerous types of essential oils and active components have been discovered, and their permissive roles have been addressed in various fields. In this comprehensive review, we focused on the roles of essential oils and active components in skin diseases and cancers as discovered over the past three decades. In particular, we opted to highlight the effectiveness of essential oils and their active components in developing strategies against various skin diseases and skin cancers and to describe the effects of the identified essential-oil-derived major components from physiological and pathological perspectives. Overall, this review provides a basis for the development of novel therapies for skin diseases and cancers, especially melanoma.
Functional Analysis of the Major Pilin Proteins of Type IV Pili in Streptococcus sanguinis CGMH010
Authors: Chen Yi-Ywan M. , Yang Yuan-Chen , Shieh Hui-Ru , Lin Yu-Juan , Ke Wan-Ju , Chiu Cheng-Hsun
Published: May 2024

The pil gene cluster for Type IV pilus (Tfp) biosynthesis is commonly present and highly conserved in Streptococcus sanguinis. Nevertheless, Tfp-mediated twitching motility is less common among strains, and the factors determining twitching activity are not fully understood. Here, we analyzed the functions of three major pilin proteins (PilA1, PilA2, and PilA3) in the assembly and activity of Tfp in motile S. sanguinis CGMH010. Using various recombinant pilA deletion strains, we found that Tfp composed of different PilA proteins varied morphologically and functionally. Among the three PilA proteins, PilA1 was most critical in the assembly of twitching-active Tfp, and recombinant strains expressing motility generated more structured biofilms under constant shearing forces compared to the non-motile recombinant strains. Although PilA1 and PilA3 shared 94% identity, PilA3 could not compensate for the loss of PilA1, suggesting that the nature of PilA proteins plays an essential role in twitching activity. The single deletion of individual pilA genes had little effect on the invasion of host endothelia by S. sanguinis CGMH010. In contrast, the deletion of all three pilA genes or pilT, encoding the retraction ATPase, abolished Tfp-mediated invasion. Tfp- and PilT-dependent invasion were also detected in the non-motile S. sanguinis SK36, and thus, the retraction of Tfp, but not active twitching, was found to be essential for invasion.
Latest Review Papers in Molecular Plant Sciences 2023
Authors: Komatsu Setsuko , Smertenko Andrei
Published: May 2024

Success in sustaining food security in the face of global climate change depends on the multi-disciplinary efforts of plant science, physics, mathematics, and computer sciences, whereby each discipline contributes specific concepts, information, and tools [...]
Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis
Authors: Alamoodi Munaser , Wazir Umar , Sakr Rita A. , Venkataraman Janhavi , Mokbel Kinan , Mokbel Kefah
Published: May 2024

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7–94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6–72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3–52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0–188). Conclusions: These findings highlight magnetic seed localisation’s efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.
Dynamic Radial MR Imaging for Endoleak Surveillance after Endovascular Repair of Abdominal Aortic Aneurysms with Inconclusive CT Angiography: A Prospective Study
Authors: Almansour Haidara , Mustafi Migdat , Lescan Mario , Grosse Ulrich , Andic Mateja , Schmehl Jörg , Artzner Christoph , Grözinger Gerd , Walter Sven S.
Published: May 2024

Background/Objectives: To assess free-breathing, dynamic radial magnetic resonance angiography (MRA) for detecting endoleaks post-endovascular aortic repair (EVAR) in cases with inconclusive computed tomography angiography (CTA). Methods: This prospective single-center study included 17 participants (mean age, 70 ± 9 years; 13 males) who underwent dynamic radial MRI (Golden-angle RAdial Sparse Parallel-Volumetric Interpolated BrEath-hold, GRASP-VIBE) after inconclusive multiphasic CT for the presence of endoleaks during the follow-up of EVAR-treated abdominal aortic aneurysms. CT and MRI datasets were independently assessed by two radiologists for image quality, diagnostic confidence, and the presence/type of endoleak. Statistical analyses included interrater and intermethod agreement, and diagnostic performance (sensitivity, specificity, area under the curve (AUC)). Results: Subjective image analysis demonstrated good image quality and interrater agreement (k ≥ 0.6) for both modalities, while diagnostic confidence was significantly higher in MRA (p = 0.03). There was significantly improved accuracy for detecting type II endoleaks on MRA (AUC 0.97 [95% CI: 0.87, 1.0]) compared to CTA (AUC 0.66 [95% CI: 0.41, 0.91]; p = 0.03). Although MRA demonstrated higher values for sensitivity, specificity, AUC, and interrater agreement, none of the other types nor the overall detection rate for endoleaks showed differences in the diagnostic performance over CT (p ≥ 0.12). CTA and MRA revealed slight to moderate intermethod concordance in endoleak detection (k = 0.3–0.64). Conclusions: The GRASP-VIBE MRA characterized by high spatial and temporal resolution demonstrates clinical feasibility with good image quality and superior diagnostic confidence. It notably enhances diagnostic performance in detecting and classifying endoleaks, particularly type II, compared to traditional multiphase CTA with inconclusive findings.
Evaluation and Rehabilitation after Adult Lumbar Spine Surgery
Authors: Sakaguchi Tomoyoshi , Gunjotikar Sharvari , Tanaka Masato , Komatsubara Tadashi , Latka Kajetan , Ekade Shashank J. , Prabhu Shrinivas P. , Takamatsu Kazuhiko , Yasuda Yosuke , Nakagawa Masami
Published: May 2024

Purpose: With an increase in the proportion of elderly patients, the global burden of spinal disease is on the rise. This is gradually expected to increase the number of surgical procedures all over the world in the near future. As we know, rehabilitation following spine surgery is critical for optimal recovery. However, the current literature lacks consensus regarding the appropriate post-operative rehabilitation protocol. The purpose of this review is to evaluate the optimal protocol for rehabilitation after lumbar spine surgery in adults. Materials and Methods: The goals of rehabilitation after lumbar spine surgery are to improve physical and psychosocial function and may include multiple modalities such as physical therapy, cognitive behavioral therapy, specialized instruments, and instructions to be followed during activities of daily living. In recent years, not only are a greater number of spine surgeries being performed, but various different techniques of lumbar spine surgery and spinal fusion have also emerged. (1) Our review summarizes post-operative rehabilitation under the following headings—1. Historical aspects, 2. Subjective functional outcomes, and (3) Actual rehabilitation measures, including balance. Results: Physical therapy programs need to be patient-specific and surgery-specific, such that they consider patient-reported outcome measures and take into consideration the technique of spinal fusion used and the muscle groups involved in these surgeries. By doing so, it is possible to assess the level of functional impairment and then specifically target the strengthening of those muscle groups affected by surgery whilst also improving impaired balance and allowing a return to daily activities. Conclusions: Rehabilitation is a multi-faceted journey to restore mobility, function, and quality of life. The current rehabilitation practice focuses on muscle strengthening, but the importance of spinal balance is less elaborated. We thus equally emphasize muscle strengthening and balance improvement post-lumbar spine surgery.