bluuebunny/crossref_metadata_2025 huggingface dataset:
The Crystal Structure of Tyrosinase from Verrucomicrobium spinosum Reveals It to Be an Atypical Bacterial Tyrosinase
Authors: Fekry Mostafa , Dave Khyati K. , Badgujar Dilip , Hamnevik Emil , Aurelius Oskar , Dobritzsch Doreen , Danielson U. Helena
Published: September 2023

Tyrosinases belong to the type-III copper enzyme family, which is involved in melanin production in a wide range of organisms. Despite similar overall characteristics and functions, their structures, activities, substrate specificities and regulation vary. The tyrosinase from the bacterium Verrucomicrobium spinosum (vsTyr) is produced as a pre-pro-enzyme in which a C-terminal extension serves as an inactivation domain. It does not require a caddie protein for copper ion incorporation, which makes it similar to eukaryotic tyrosinases. To gain an understanding of the catalytic machinery and regulation of vsTyr activity, we determined the structure of the catalytically active “core domain” of vsTyr by X-ray crystallography. The analysis showed that vsTyr is an atypical bacterial tyrosinase not only because it is independent of a caddie protein but also because it shows the highest structural (and sequence) similarity to plant-derived members of the type-III copper enzyme family and is more closely related to fungal tyrosinases regarding active site features. By modelling the structure of the pre-pro-enzyme using AlphaFold, we observed that Phe453, located in the C-terminal extension, is appropriately positioned to function as a “gatekeeper” residue. Our findings raise questions concerning the evolutionary origin of vsTyr.
Comparative Analysis of pH and Target-Induced Conformational Changes of an Oxytetracycline Aptamer in Solution Phase and Surface-Immobilized Form
Authors: Jakab Kristóf , Melios Nikitas , Tsekenis George , Shaban Abdul , Horváth Viola , Keresztes Zsófia
Published: September 2023

To date, numerous aptamer-based biosensing platforms have been developed for sensitive and selective monitoring of target analytes, relying on analyte-induced conformational changes in the aptamer for the quantification of the analyte and the conversion of the binding event into a measurable signal. Despite the impact of these conformational rearrangements on sensor performance, the influence of the environment on the structural conformations of aptamers has rarely been investigated, so the link between parameters directly influencing aptamer folding and the ability of the aptamer to bind to the target analyte remains elusive. Herein, the effect a number of variables have on an aptamer’s 3D structure was examined, including the pH of the buffering medium, as well as the anchoring of the aptamer on a solid support, with the use of two label-free techniques. Circular dichroism spectroscopy was utilized to study the conformation of an aptamer in solution along with any changes induced to it by the environment (analyte binding, pH, composition and ionic strength of the buffer solution), while quartz crystal microbalance with dissipation monitoring was employed to investigate the surface-bound aptamer’s behavior and performance. Analysis was performed on an aptamer against oxytetracycline, serving as a model system, representative of aptamers selected against small molecule analytes. The obtained results highlight the influence of the environment on the folding and thus analyte-binding capacity of an aptamer and emphasize the need to deploy appropriate surface functionalization protocols in sensor development as a means to minimize the steric obstructions and undesirable interactions of an aptamer with a surface onto which it is tethered.
Acyl-Carnitines Exert Positive Effects on Mitochondrial Activity under Oxidative Stress in Mouse Oocytes: A Potential Mechanism Underlying Carnitine Efficacy on PCOS
Authors: Placidi Martina , Vergara Teresa , Casoli Giovanni , Flati Irene , Capece Daria , Artini Paolo Giovanni , Virmani Ashraf , Zanatta Samuele , D’Alessandro Anna Maria , Tatone Carla , Di Emidio Giovanna
Published: September 2023

Carnitines play a key physiological role in oocyte metabolism and redox homeostasis. In clinical and animal studies, carnitine administration alleviated metabolic and reproductive dysfunction associated with polycystic ovarian syndrome (PCOS). Oxidative stress (OS) at systemic, intraovarian, and intrafollicular levels is one of the main factors involved in the pathogenesis of PCOS. We investigated the ability of different acyl-carnitines to act at the oocyte level by counteracting the effects of OS on carnitine shuttle system and mitochondrial activity in mouse oocytes. Germinal vesicle (GV) oocytes were exposed to hydrogen peroxide and propionyl-l-carnitine (PLC) alone or in association with l-carnitine (LC) and acetyl-l-carnitine (ALC) under different conditions. Expression of carnitine palmitoyltransferase-1 (Cpt1) was monitored by RT-PCR. In in vitro matured oocytes, metaphase II (MII) apparatus was assessed by immunofluorescence. Oocyte mitochondrial respiration was evaluated by Seahorse Cell Mito Stress Test. We found that Cpt1a and Cpt1c isoforms increased under prooxidant conditions. PLC alone significantly improved meiosis completion and oocyte quality with a synergistic effect when combined with LC + ALC. Acyl-carnitines prevented Cpt1c increased expression, modifications of oocyte respiration, and ATP production observed upon OS. Specific effects of PLC on spare respiratory capacity were observed. Therefore, carnitine supplementation modulated the intramitochondrial transfer of fatty acids with positive effects on mitochondrial activity under OS. This knowledge contributes to defining molecular mechanism underlying carnitine efficacy on PCOS.
Exploring Astrocyte-Mediated Mechanisms in Sleep Disorders and Comorbidity
Authors: Li Yujuan , Que Mengxin , Wang Xuan , Zhan Gaofeng , Zhou Zhiqiang , Luo Xiaoxiao , Li Shiyong
Published: September 2023

Astrocytes, the most abundant cells in the brain, are integral to sleep regulation. In the context of a healthy neural environment, these glial cells exert a profound influence on the sleep-wake cycle, modulating both rapid eye movement (REM) and non-REM sleep phases. However, emerging literature underscores perturbations in astrocytic function as potential etiological factors in sleep disorders, either as protopathy or comorbidity. As known, sleep disorders significantly increase the risk of neurodegenerative, cardiovascular, metabolic, or psychiatric diseases. Meanwhile, sleep disorders are commonly screened as comorbidities in various neurodegenerative diseases, epilepsy, and others. Building on existing research that examines the role of astrocytes in sleep disorders, this review aims to elucidate the potential mechanisms by which astrocytes influence sleep regulation and contribute to sleep disorders in the varied settings of brain diseases. The review emphasizes the significance of astrocyte-mediated mechanisms in sleep disorders and their associated comorbidities, highlighting the need for further research.
Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats
Authors: Stratos Ioannis , Schleese Svenja , Rinas Ingmar , Vollmar Brigitte , Mittlmeier Thomas
Published: September 2023

Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. The injured left soleus muscle of the rats was treated for the first four days after trauma with local injections of either calcitriol, VDRM2, or a 10% ethanol solution (control). Although muscle strength significantly decreased post-injury, all groups showed gradual improvement but did not achieve full recovery. By the 14th day, calcitriol-treated rats significantly outperformed the control group in the incomplete tetanic force, with VDRM2-treated rats showing muscle strength values that fell between the control and calcitriol groups. Similar trends were observed in complete tetanic contractions and were confirmed histologically via muscle cell width quantification. Additionally, histological analysis showed increased cellular turnover on the fourth postoperative day in the calcitriol group, as indicated by elevated cell proliferation rates and fewer apoptotic cells. VDRM2-treated animals showed only an increased proliferative activity on day 4 after injury. No noticeable differences between the groups for CAE-positive cells or visible muscle tissue area were found. In conclusion, predominantly calcitriol positively influenced post-trauma muscle recovery, where VDRM2 had substantially lower biological activity.
Clinical Perspectives of Gut Microbiota in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: Where Do We Stand?
Authors: Pantazi Alexandru Cosmin , Kassim Mustafa Ali Kassim , Nori Wassan , Tuta Liliana Ana , Mihai Cristina Maria , Chisnoiu Tatiana , Balasa Adriana Luminita , Mihai Larisia , Lupu Ancuta , Frecus Corina Elena , Lupu Vasile Valeriu , Chirila Sergiu Ioachim , Badescu Anca Gabriela , Hangan Laurentiu-Tony , Cambrea Simona Claudia
Published: September 2023

The gut microbiota (GM) plays a vital role in human health, with increasing evidence linking its imbalance to chronic kidney disease and end-stage kidney disease. Although the exact methods underlying kidney-GM crosstalk are not fully understood, interventions targeting GM were made and lay in three aspects: diagnostic, predictive, and therapeutic interventions. While these interventions show promising results in reducing uremic toxins and inflammation, challenges remain in the form of patient-specific GM variability, potential side effects, and safety concerns. Our understanding of GMs role in kidney disease is still evolving, necessitating further research to elucidate the causal relationship and mechanistic interactions. Personalized interventions focusing on specific GM signatures could enhance patient outcomes. However, comprehensive clinical trials are needed to validate these approaches’ safety, efficacy, and feasibility.
A Neurosurgical Perspective on Brain Metastases from Renal Cell Carcinoma: Multi-Institutional, Retrospective Analysis
Authors: Semenescu Liliana Eleonora , Tataranu Ligia Gabriela , Dricu Anica , Ciubotaru Gheorghe Vasile , Radoi Mugurel Petrinel , Rodriguez Silvia Mara Baez , Kamel Amira
Published: September 2023

Background: While acknowledging the generally poor prognostic features of brain metastases from renal cell carcinoma (BM RCC), it is important to be aware of the fact that neurosurgery still plays a vital role in managing this disease, even though we have entered an era of targeted therapies. Notwithstanding their initial high effectiveness, these agents often fail, as tumors develop resistance or relapse. Methods: The authors of this study aimed to evaluate patients presenting with BM RCC and their outcomes after being treated in the Neurosurgical Department of Clinical Emergency Hospital “Bagdasar-Arseni”, and the Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania. The study is based on a thorough appraisal of the patient’s demographic and clinicopathological data and is focused on the strategic role of neurosurgery in BM RCC. Results: A total of 24 patients were identified with BM RCC, of whom 91.6% had clear-cell RCC (ccRCC) and 37.5% had a prior nephrectomy. Only 29.1% of patients harbored extracranial metastases, while 83.3% had a single BM RCC. A total of 29.1% of patients were given systemic therapy. Neurosurgical resection of the BM was performed in 23 out of 24 patients. Survival rates were prolonged in patients who underwent nephrectomy, in patients who received systemic therapy, and in patients with a single BM RCC. Furthermore, higher levels of hemoglobin were associated in our study with a higher number of BMs. Conclusion: Neurosurgery is still a cornerstone in the treatment of symptomatic BM RCC. Among the numerous advantages of neurosurgical intervention, the most important is represented by the quick reversal of neurological manifestations, which in most cases can be life-saving.
A Comprehensive Review on Neuroimmunology: Insights from Multiple Sclerosis to Future Therapeutic Developments
Authors: Eva Lucian , Pleș Horia , Covache-Busuioc Razvan-Adrian , Glavan Luca Andrei , Bratu Bogdan-Gabriel , Bordeianu Andrei , Dumitrascu David-Ioan , Corlatescu Antonio Daniel , Ciurea Alexandru Vlad
Published: September 2023

This review delves into neuroimmunology, focusing on its relevance to multiple sclerosis (MS) and potential treatment advancements. Neuroimmunology explores the intricate relationship between the immune system and the central nervous system (CNS). Understanding these mechanisms is vital for grasping the pathophysiology of diseases like MS and for devising innovative treatments. This review introduces foundational neuroimmunology concepts, emphasizing the role of immune cells, cytokines, and blood–brain barrier in CNS stability. It highlights how their dysregulation can contribute to MS and discusses genetic and environmental factors influencing MS susceptibility. Cutting-edge research methods, from omics techniques to advanced imaging, have revolutionized our understanding of MS, offering valuable diagnostic and prognostic tools. This review also touches on the intriguing gut–brain axis, examining how gut microbiota impacts neuroimmunological processes and its potential therapeutic implications. Current MS treatments, from immunomodulatory drugs to disease-modifying therapies, are discussed alongside promising experimental approaches. The potential of personalized medicine, cell-based treatments, and gene therapy in MS management is also explored. In conclusion, this review underscores neuroimmunology’s significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes.
RiPa-Net: Recognition of Rice Paddy Diseases with Duo-Layers of CNNs Fostered by Feature Transformation and Selection
Authors: Attallah Omneya
Published: September 2023

Rice paddy diseases significantly reduce the quantity and quality of crops, so it is essential to recognize them quickly and accurately for prevention and control. Deep learning (DL)-based computer-assisted expert systems are encouraging approaches to solving this issue and dealing with the dearth of subject-matter specialists in this area. Nonetheless, a major generalization obstacle is posed by the existence of small discrepancies between various classes of paddy diseases. Numerous studies have used features taken from a single deep layer of an individual complex DL construction with many deep layers and parameters. All of them have relied on spatial knowledge only to learn their recognition models trained with a large number of features. This study suggests a pipeline called “RiPa-Net” based on three lightweight CNNs that can identify and categorize nine paddy diseases as well as healthy paddy. The suggested pipeline gathers features from two different layers of each of the CNNs. Moreover, the suggested method additionally applies the dual-tree complex wavelet transform (DTCWT) to the deep features of the first layer to obtain spectral–temporal information. Additionally, it incorporates the deep features of the first layer of the three CNNs using principal component analysis (PCA) and discrete cosine transform (DCT) transformation methods, which reduce the dimension of the first layer features. The second layer’s spatial deep features are then combined with these fused time-frequency deep features. After that, a feature selection process is introduced to reduce the size of the feature vector and choose only those features that have a significant impact on the recognition process, thereby further reducing recognition complexity. According to the results, combining deep features from two layers of different lightweight CNNs can improve recognition accuracy. Performance also improves as a result of the acquired spatial–spectral–temporal information used to learn models. Using 300 features, the cubic support vector machine (SVM) achieves an outstanding accuracy of 97.5%. The competitive ability of the suggested pipeline is confirmed by a comparison of the experimental results with findings from previously conducted research on the recognition of paddy diseases.
EEG Emotion Recognition by Fusion of Multi-Scale Features
Authors: Du Xiuli , Meng Yifei , Qiu Shaoming , Lv Yana , Liu Qingli
Published: September 2023

Electroencephalogram (EEG) signals exhibit low amplitude, complex background noise, randomness, and significant inter-individual differences, which pose challenges in extracting sufficient features and can lead to information loss during the mapping process from low-dimensional feature matrices to high-dimensional ones in emotion recognition algorithms. In this paper, we propose a Multi-scale Deformable Convolutional Interacting Attention Network based on Residual Network (MDCNAResnet) for EEG-based emotion recognition. Firstly, we extract differential entropy features from different channels of EEG signals and construct a three-dimensional feature matrix based on the relative positions of electrode channels. Secondly, we utilize deformable convolution (DCN) to extract high-level abstract features by replacing standard convolution with deformable convolution, enhancing the modeling capability of the convolutional neural network for irregular targets. Then, we develop the Bottom-Up Feature Pyramid Network (BU-FPN) to extract multi-scale data features, enabling complementary information from different levels in the neural network, while optimizing the feature extraction process using Efficient Channel Attention (ECANet). Finally, we combine the MDCNAResnet with a Bidirectional Gated Recurrent Unit (BiGRU) to further capture the contextual semantic information of EEG signals. Experimental results on the DEAP dataset demonstrate the effectiveness of our approach, achieving accuracies of 98.63% and 98.89% for Valence and Arousal dimensions, respectively.
Beliefs about the Nature of Forgiveness and Avoidance of an Offender among Chinese College Students
Authors: Yi Zhaoyue , Wu Di , Deng Mianlin
Published: September 2023

Previous research on beliefs about the nature of forgiveness (unconditional and conditional) has focused on their effects on health and well-being. However, little is known about how they influence victims’ responses to interpersonal offenses. Given that avoidance is a common response to offenses during early adulthood, this study investigated the relationships between beliefs in unconditional and conditional forgiveness and avoidance of an offender among Chinese college students, the mediating role of forgiveness, and the moderating role of whether or not the offender explains the offense. Participants were 423 Chinese college students. They were asked to recall an unforgettable incident in which another person had offended them, and then completed the following measures: the offender’s explanation, the belief in unconditional/conditional forgiveness, forgiveness, and avoidance of the offender. The study found that: (1) Victims’ belief in unconditional forgiveness negatively predicts their avoidance of an offender, whereas their belief in conditional forgiveness positively predicts the avoidance of an offender. (2) Forgiveness mediates the relationships between beliefs in unconditional and conditional forgiveness and avoidance of an offender. (3) The offender’s explanation moderates the relationships between the belief in conditional forgiveness and forgiveness, as well as avoidance of an offender.
Model Test Study on the Response of Two Different Shallow-Foundation Framed Buildings under Tunnel Volume Loss
Authors: Liu Yang , Zhang Qinghua , Liu Wei , Wang Tianzuo , Liang Zhu , Liu Zhifang , Liu Guochao , Xu Hansheng
Published: September 2023

In order to study the influence of tunnel volume loss on adjacent framed buildings with different shallow foundations, this paper carried out physical model experiments with two common types of footings (isolated and strip footings) under different working conditions based on the digital image correlation (DIC) technique. The main finding of the present paper is that the increase in formation loss rate will aggravate the deformation and damage of the structure, and the strip foundation shows stronger integrity and stability compared with the isolated foundation in this process. With the increase in the eccentricity of the frames with respect to the tunnel, the overall tilt and damage degree of structural elements increases first and then decreases for both foundations, reaching the maximum value with the eccentric distance of one multiple of the tunnel diameter. Interestingly, when the isolated footings are located directly above the tunnel, the damage in the inner panels is the most severe and gradually decreases with eccentricity, changing from a sagging mode to a hogging mode for the frame form. While the strip footings always maintain slight hogging, and the trend of the damage degree of panels is similar to that of elements, with the eccentric distance reaching two times the tunnel diameter, the strip foundation structure tends to be stable, while the isolated one still needs attention for its potential possibility of damage in panels. The research results have reference value for the impact assessment of adjacent shallow-foundation framed buildings in subway tunnel construction.
Thermodynamic Performance Analysis of High Thermal Conductivity Materials in Borehole Heat Exchangers in the European Climate
Authors: Khattak Sanober , Badenes Borja , Urchueguia Javier , Sanner Burkhard
Published: September 2023

While heat pumps have been acknowledged as a key enabling technology to achieve Net Zero goals, their uptake is limited by their performance and cost. In this paper, a simulation-based study is conducted to analyse the performance of ground source heat pumps (GSHPs) utilising high thermal conductivity materials for the borehole heat exchanger (BHE) pipe (1 W/mK) and grouting (3 W/mK) developed in the GEOCOND project. Exergy analysis is conducted to account for energy quantity and quality with a focus on BHE performance. An annual hourly simulation was performed using DesignBuilder V5.4 and Earth Energy Designer (EED4) for representative cool and hot locations in Europe—Stockholm and Valencia, respectively. For a constant BHE length, the results for Stockholm show that the high conductivity materials result in an increase of about 13% BHE exergy extraction compared to the standard grout and pipe, but no such improvement was observed for Valencia. The difference between outdoor temperature and its dynamic variation from the indoor setpoint is identified as a key factor in the overall GSHP exergetic performance. In future research, we propose a thorough life cycle analysis across diverse locations and varying indoor comfort criteria to pinpoint areas where the high thermal conductivity material can enable cost-effective, sustainable heating and cooling.
Quality of Life, Clinical, and Patient-Reported Outcomes after Pencil Beam Scanning Proton Therapy Delivered for Intracranial Grade WHO 1–2 Meningioma in Children and Adolescents
Authors: García-Marqueta Marta , Vázquez Miriam , Krcek Reinhardt , Kliebsch Ulrike L. , Baust Katja , Leiser Dominic , van Heerden Michelle , Pica Alessia , Calaminus Gabriele , Weber Damien C.
Published: September 2023

Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT). Material and methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years. Median age was 13.9 years (range, 3.2–17.2). Six (60%) children were treated as primary treatment (postoperative PT, n = 4; exclusive PT, n = 2) and four (40%) at the time of tumor recurrence. Acute and late toxicities were registered according to Common Terminology Criteria of Adverse Events (CTCAE). Quality of life (QoL) before PBS-PT was assessed using PEDQOL questionnaires. Educational, functional, and social aspects after PT were assessed through our in-house developed follow-up surveys. Median follow-up time was 71.1 months (range, 2.5–249.7), and median time to last questionnaire available was 37.6 months (range, 5.75–112.6). Results: Five (50%) children developed local failure (LF) at a median time of 32.4 months (range, 17.7–55.4) after PBS-PT and four (80%) were considered in-field. One patient died of T-cell lymphoma 127.1 months after PBS-PT. Estimated 5-year local control (LC) and overall survival (OS) rates were 19.4% and 100.0%, respectively. Except for one patient who developed a cataract requiring surgery, no grade ≥3 late toxicities were reported. Before PT, patients rated their QoL lower than their parents in most domains. During the first year after PT, one child required educational support, one needed to attend to a special school, one had social problems and another three children required assistance for daily basic activities (DBA). Three years after PT, only one child required assistance for DBA. Conclusions: The outcome of children with intracranial meningioma treated with PBS-PT is in line with other centers who have reported results of radiation therapy delivered to this particular patient group. This therapy provides acceptable functional status profiles with no high-grade adverse radiation-induced events.
Morphea, Eosinophilic Fasciitis and Cancer: A Scoping Review
Authors: Joly-Chevrier Maxine , Gélinas Alexa , Ghazal Stephanie , Moussa Sarah , McCuaig Catherine C. , Piram Maryam , Mereniuk Alexandra , Litvinov Ivan V. , Osman Mohammed , Pehr Kevin , Netchiporouk Elena
Published: September 2023

Morphea is an autoimmune fibrotic skin disease. Eosinophilic fasciitis (EF) is considered to belong to the severe spectrum of morphea. We conducted a scoping review assessing the risk of secondary cancer among morphea/EF patients, paraneoplastic morphea/EF and morphea/EF developing secondary to cancer therapy. The search was conducted using MEDLINE, Embase, Cochrane databases for articles published from inception to September 2022 following the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines with no language or date restrictions. Two hundred and one studies were included. Of these, 32 studies reported on secondary cancer in morphea/EF patients, 45 on paraneoplastic morphea/EF and 125 on cancer-treatment-induced morphea/EF. While the current evidence remains limited, data suggest an increased risk of secondary cutaneous and possibly pancreatic malignancy in morphea patients, particularly the generalized subtype. There were insufficient data for EF. On the other hand, paraneoplastic morphea was anecdotal, whereas several observational studies suggested that ~10% of EF cases may be paraneoplastic, primarily in the context of hematologic malignancies. Radiotherapy-induced morphea is rare, seen in ~0.2% of treated patients and is usually localized to the treatment site, except in patients with pre-existing autoimmunity. While chemotherapy-induced cases are reported, immunotherapy morphea/EF cases are emerging and are preferentially seen with PD-1 and not CTLA-4 inhibitors. This study is limited by the type of articles included (case reports, case series and observational studies), and hence, additional research on this important topic is needed.
Non-Invasive Assessment of Isocitrate Dehydrogenase-Mutant Gliomas Using Optimized Proton Magnetic Resonance Spectroscopy on a Routine Clinical 3-Tesla MRI
Authors: de Godoy Laiz Laura , Lim Kheng Choon , Rajan Archith , Verma Gaurav , Hanaoka Mauro , O’Rourke Donald M. , Lee John Y. K. , Desai Arati , Chawla Sanjeev , Mohan Suyash
Published: September 2023

Purpose: The isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis. IDH mutations confer neomorphic activity leading to the conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2HG). The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (1H-MRS) in identifying IDH-mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites. Materials and Methods: Thirty-two patients with suspected infiltrative glioma underwent a single-voxel (SVS, n = 17) and/or single-slice-multivoxel (1H-MRSI, n = 15) proton MR spectroscopy (1H-MRS) sequence with an optimized echo-time (97 ms) on 3T-MRI. Spectroscopy data were analyzed using the linear combination (LC) model. Cramér–Rao lower bound (CRLB) values of <40% were considered acceptable for detecting 2HG and <20% for other metabolites. Immunohistochemical analyses for determining IDH mutational status were subsequently performed from resected tumor specimens and findings were compared with the results from spectral data. Mann–Whitney and chi-squared tests were performed to ascertain differences in metabolite levels between IDH-mutant and IDH-wild-type gliomas. Receiver operating characteristic (ROC) curve analyses were also performed. Results: Data from eight cases were excluded due to poor spectral quality or non-tumor-related etiology, and final data analyses were performed from 24 cases. Of these cases, 9/12 (75%) were correctly identified as IDH-mutant or IDH-wildtype gliomas through SVS and 10/12 (83%) through 1H-MRSI with an overall concordance rate of 79% (19/24). The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 77%, 86%, and 70%, respectively. The metabolite 2HG was found to be significant in predicting IDH-mutant gliomas through the chi-squared test (p < 0.01). The IDH-mutant gliomas also had a significantly higher NAA/Cr ratio (1.20 ± 0.09 vs. 0.75 ± 0.12 p = 0.016) and lower Glx/Cr ratio (0.86 ± 0.078 vs. 1.88 ± 0.66; p = 0.029) than those with IDH wild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively. Conclusions: Noninvasive optimized 1H-MRS may be useful in predicting IDH mutational status and 2HG may serve as a valuable diagnostic and prognostic biomarker in patients with gliomas
Innovation in Actinic Keratosis Assessment: Artificial Intelligence-Based Approach to LC-OCT PRO Score Evaluation
Authors: Daxenberger Fabia , Deußing Maximilian , Eijkenboom Quirine , Gust Charlotte , Thamm Janis , Hartmann Daniela , French Lars , Welzel Julia , Schuh Sandra , Sattler Elke
Published: September 2023

Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically assess the PRO score of AKs based on the dermo-epidermal junction’s (DEJ’s) protrusion on LC-OCT images. A dataset of 19.898 LC-OCT images from 80 histologically confirmed AK lesions was used to test the performance of a previous validated artificial intelligence (AI)-based LC-OCT assessment algorithm. AI-based PRO score assessment was compared to the imaging experts’ visual score. Additionally, undulation of the DEJ, the number of protrusions detected within the image, and the maximum depth of the protrusions were computed. Our results show that AI-automated PRO grading is highly comparable to the visual score, with an agreement of 71.3% for the lesions evaluated. Furthermore, this AI-based assessment was significantly faster than the regular visual PRO score assessment. The results confirm our previous findings of the pilot study in a larger cohort that the AI-based grading of LC-OCT images is a reliable and fast tool to optimize the efficiency of visual PRO score grading. This technology has the potential to improve the accuracy and speed of AK diagnosis and may lead to better clinical outcomes for patients.
The Relative Dose Intensity Changes during Cycles of Standard Regimens in Patients with Diffuse Large B-Cell Lymphoma
Authors: Lee Shin , Fujita Kei , Morishita Tetsuji , Negoro Eiju , Tsukasaki Hikaru , Oiwa Kana , Hara Takeshi , Tsurumi Hisashi , Ueda Takanori , Yamauchi Takahiro
Published: September 2023

No studies have focused on the trajectory of the average relative dose intensity (ARDI) during cycles of first-line chemotherapy for patients with diffuse large B-cell lymphoma. To evaluate the impact of attenuating ARDI during cycles on overall survival, we conducted a multi-centre, longitudinal, observational retrospective study. A total of 307 analysable patients were enrolled. Multivariate Cox hazards modelling with restricted cubic spline models revealed prognostic benefits of higher ARDI up to, but not after, cycle 6. According to group-based trajectory modelling, patients were classified into five groups depending on the pattern of ARDI changes. Among these, two groups in which ARDI had fallen significantly to less than 50% by cycles 4–6 displayed significantly poorer prognosis, despite increased ARDI in the second half of the treatment period (log-rank p = 0.02). The Geriatric Nutritional Risk Index offered significant prediction of unfavourable ARDI changes (odds ratio 2.540, 95% confidence interval 1.020–6.310; p = 0.044). Up to cycle 6, maintenance of ARDI in all cycles (but particularly in the early cycles) is important for prognosis. Malnutrition is a significant factor that lets patients trace patterns of ARDI changes during cycles of chemotherapy associated with untoward prognosis.
Colorectal Cancer Survival in German–Danish Border Regions—A Registry-Based Cohort Study
Authors: Rudolph Christiane , Engholm Gerda , Pritzkuleit Ron , Storm Hans H. , Katalinic Alexander
Published: September 2023

The aim of this study was (i) to update the reporting of colorectal cancer survival differences over time in the German–Danish border region (Schleswig-Holstein, Southern Denmark, and Zealand) and (ii) to assess the extent to which it can be explained by stage and primary treatment. Incident invasive colorectal cancer cases diagnosed from 2004 to 2016 with a follow-up of vital status through 31 December 2017 were extracted from cancer registries. Analyses were conducted by anatomical subsite and for four consecutive periods. Kaplan–Meier curves and log-rank tests were computed. Cox regression models using data from Schleswig-Holstein from 2004 to 2007 as the reference category were run while controlling for age, sex, stage, and treatment. The cox regression models showed decreasing hazard ratios of death for all three regions over time for both anatomical subsites. The improvement was stronger in the Danish regions, and adjustment for age, sex, stage, and treatment attenuated the results only slightly. In 2014–2016, colon cancer survival was similar across regions, while rectal cancer survival was significantly superior in the Danish regions. Regional survival differences can only partially be explained by differing stage distribution and treatment and may be linked additionally to healthcare system reforms and screening efforts.
Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist’s Perspective
Authors: Angelico Giuseppe , Broggi Giuseppe , Tinnirello Giordana , Puzzo Lidia , Vecchio Giada Maria , Salvatorelli Lucia , Memeo Lorenzo , Santoro Angela , Farina Jessica , Mulé Antonino , Magro Gaetano , Caltabiano Rosario
Published: September 2023

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0–10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting.
Flexibility and Function of Distal Substrate-Binding Tryptophans in the Blue Mussel β-Mannanase MeMan5A and Their Role in Hydrolysis and Transglycosylation
Authors: Birgersson Simon , Morrill Johan , Stenström Olof , Wiemann Mathias , Weininger Ulrich , Söderhjelm Pär , Akke Mikael , Stålbrand Henrik
Published: September 2023

β-Mannanases hydrolyze β-mannans, important components of plant and microalgae cell walls. Retaining β-mannanases can also catalyze transglycosylation, forming new β-mannosidic bonds that are applicable for synthesis. This study focused on the blue mussel (Mytilus edulis) GH5_10 β-mannanase MeMan5A, which contains two semi-conserved tryptophans (W240 and W281) in the distal subsite +2 of its active site cleft. Variants of MeMan5A were generated by replacing one or both tryptophans with alanines. The substitutions reduced the enzyme’s catalytic efficiency (kcat/Km using galactomannan) by three-fold (W281A), five-fold (W240A), or 20-fold (W240A/W281A). Productive binding modes were analyzed by 18O labeling of hydrolysis products and mass spectrometry. Results show that the substitution of both tryptophans was required to shift away from the dominant binding mode of mannopentaose (spanning subsites −3 to +2), suggesting that both tryptophans contribute to glycan binding. NMR spectroscopy and molecular dynamics simulations were conducted to analyze protein flexibility and glycan binding. We suggest that W240 is rigid and contributes to +2 subsite mannosyl specificity, while W281 is flexible, which enables stacking interactions in the +2 subsite by loop movement to facilitate binding. The substitutions significantly reduced or eliminated transglycosylation with saccharides as glycosyl acceptors but had no significant effect on reactions with alcohols.
Social Stigma in Children with Long COVID
Authors: Buonsenso Danilo , Camporesi Anna , Morello Rosa , De Rose Cristina , Fracasso Matteo , Chieffo Daniela Pia Rosaria , Valentini Piero
Published: September 2023

There is growing evidence that adults with Long COVID suffer from different sets of stigmata related to their condition. In children with Long COVID, this aspect has never been investigated. This study aims to investigate if children with Long COVID also experience stigma. Methods: Children with a previous SARS-CoV-2 infection evaluated at 3 month follow-ups in a pediatric post COVID unit were asked to fill in an online Long COVID Stigma Scale survey before they were assessed by a pediatrician. Doctors were unaware of children’s responses when they performed a diagnosis of Long COVID or full recovery from previous infection, according to the World Health Organization definition of pediatric Long COVID. Responses to the Stigma scale were then compared in the two cohorts of children. Results: 224 patients responded to the questionnaire; 40 patients were diagnosed with Long COVID. Children with Long COVID significantly more frequently felt embarrassed about having Long COVID (p 0.035), felt embarrassed about having physical limitations (p < 0.001), felt they were valued less due to Long COVID (p 0.003), felt they were different from other peers due to Long COVID (p 0.033), felt significantly more frequently that people behaved differently towards them because they might be lying since the diagnosis of Long COVID (p 0.006), that they were less respected by others due to Long COVID (p 0.017), that other people thought that Long COVID is not a real disease (p 0.007), that other people thought that developing Long COVID is a sign of weakness (p 0.008), and that other people might judge them negatively due to their diagnosis of Long COVID (p < 0.001). Conclusions: Children with Long COVID, similar to adults, are suffering from stigmata due to their condition,. These data may have implication and should be used by the public, policy makers, and healthcare professionals regarding pediatric Long COVID.
Modeling Approaches for Residential Energy Consumption: A Literature Review
Authors: Nacht Thomas , Pratter Robert , Ganglbauer Johanna , Schibline Amanda , Aguayo Armando , Fragkos Panagiotis , Zisarou Eleftheria
Published: September 2023

The interest in sustainability and energy efficiency is constantly increasing, and the noticeable effects of climate change and rising energy prices are fueling this development. The residential sector is one of the most energy-intensive sectors and plays an important role in shaping future energy consumption. In this context, modeling has been extensively employed to identify relative key drivers, and to evaluate the impact of different strategies to reduce energy consumption and emissions. This article presents a detailed literature review relative to modeling approaches and techniques in residential energy use, including case studies to assess and predict the energy consumption patterns of the sector. The purpose of this article is not only to review the research to date in this field, but to also identify the possible challenges and opportunities. Mobility, electrical devices, cooling and heating systems, and energy storage and energy production technologies will be the subject of the presented research. Furthermore, the energy upgrades of buildings, their energy classification, as well as the energy labels of the electric appliances will be discussed. Previous research provided valuable insights into the application of modeling techniques to address the complexities of residential energy consumption. This paper offers a thorough resource for researchers, stakeholders, and other parties interested in promoting sustainable energy practices. The information gathered can contribute to the development of effective strategies for reducing energy use, facilitating energy-efficient renovations, and helping to promote a greener and more sustainable future in the residential domain.
Unveiling Nature’s Resilience: Exploring Vegetation Dynamics during the COVID-19 Era in Jharkhand, India, with the Google Earth Engine
Authors: Ahmad Tauseef , Gupta Saurabh Kumar , Singh Suraj Kumar , Meraj Gowhar , Kumar Pankaj , Kanga Shruti
Published: September 2023

The Severe Acute Respiratory Syndrome Coronavirus Disease 2019 (COVID-19) pandemic has presented unprecedented challenges to global health and economic stability. Intriguingly, the necessary lockdown measures, while disruptive to human society, inadvertently led to environmental rejuvenation, particularly noticeable in decreased air pollution and improved vegetation health. This study investigates the lockdown’s impact on vegetation health in Jharkhand, India, employing the Google Earth Engine for cloud-based data analysis. MODIS-NDVI data were analyzed using spatio-temporal NDVI analyses and time-series models. These analyses revealed a notable increase in maximum vegetation greenery of 19% from April 2019 to 2020, with subsequent increases of 13% and 3% observed in March and May of the same year, respectively. A longer-term analysis from 2000 to 2020 displayed an overall 16.7% rise in vegetation greenness. While the maximum value remained relatively constant, it demonstrated a slight increment during the dry season. The Landsat data Mann–Kendall trend test reinforced these findings, displaying a significant shift from a negative NDVI trend (1984–2019) to a positive 17.7% trend (1984–2021) in Jharkhand’s north-west region. The precipitation (using NASA power and Merra2 data) and NDVI correlation were also studied during the pre- and lockdown periods. Maximum precipitation (350–400 mm) was observed in June, while July typically experienced around 300 mm precipitation, covering nearly 85% of Jharkhand. Interestingly, August 2020 saw up to 550 mm precipitation, primarily in Jharkhand’s southern region, compared to 400 mm in the same month in 2019. Peak changes in NDVI value during this period ranged between 0.6–0.76 and 0.76–1, observed throughout the state. Although the decrease in air pollution led to improved vegetation health, these benefits began to diminish post-lockdown. This observation underscores the need for immediate attention and intervention from scientists and researchers. Understanding lockdown-induced environmental changes and their impact on vegetation health can facilitate the development of proactive environmental management strategies, paving the way towards a sustainable and resilient future.
A Formulation for a New Environmentally Friendly Varnish for Paintings
Authors: Pieralli Irene , Salvini Antonella , Angelin Eva Mariasole , Pamplona Marisa , Cocchetti Valeria , Bartolozzi Giovanni , Picollo Marcello
Published: September 2023

Laropal® A81 is a urea-aldehyde resin used as a varnish for paintings requiring 30%–40% of aromatic solvents to be dissolved. Considering the dangers of aromatic solvents for the environment and health, an attempt was made to replace them with less impactful and low-toxic solvents. The present research investigates a new formulation with aliphatic hydrocarbons and esters (isobutyl isobutyrate, IBIB) as an alternative to traditional aromatics mixture. Traditional and alternative varnish formulations of Laropal® A81 were studied on an inert support and paint samples to test the resin by itself and in interaction with paint film, respectively. This study aims to compare the two different formulations of Laropal® A81 by evaluating their optical, colorimetric, and stability proprieties before and after natural and accelerated ageing. Colorimetry and spectroscopic techniques (transmittance and reflectance UV-VIS-NIR, FORS, transmittance and total reflectance FT-IR, and 1H-NMR) were used for the assessment. Very promising results have been obtained with the application of the alternative formulation, with data comparable to those of the traditional formulation, paving the way for the replacement of the aromatic-based solvents traditionally used with IBIB. This allows a safer and more sustainable conservation practice with considerable benefits for the health of the operators and the environment.