bluuebunny/crossref_metadata_2025 huggingface dataset:
Silver nanoparticle interactions with glycated and non-glycated human serum albumin mediate toxicity
Authors: Park Hee-Yon , Chung Christopher , Eiken Madeline K. , Baumgartner Karl V. , Fahy Kira M. , Leung Kaitlyn Q. , Bouzos Evangelia , Asuri Prashanth , Wheeler Korin E. , Riley Kathryn R.
Published: March 2023

Introduction: Biomolecules bind to and transform nanoparticles, mediating their fate in biological systems. Despite over a decade of research into the protein corona, the role of protein modifications in mediating their interaction with nanomaterials remains poorly understood. In this study, we evaluated how glycation of the most abundant blood protein, human serum albumin (HSA), influences the formation of the protein corona on 40 nm silver nanoparticles (AgNPs) and the toxicity of AgNPs to the HepG2 human liver cell line.

Methods: The effects of glycation on AgNP-HSA interactions were quantified using circular dichroism spectroscopy to monitor protein structural changes, dynamic light scattering to assess AgNP colloidal stability, zeta potential measurements to measure AgNP surface charge, and UV-vis spectroscopy and capillary electrophoresis (CE) to evaluate protein binding affinity and kinetics. The effect of the protein corona and HSA glycation on the toxicity of AgNPs to HepG2 cells was measured using the WST cell viability assay and AgNP dissolution was measured using linear sweep stripping voltammetry.

Results and Discussion: Results from UV-vis and CE analyses suggest that glycation of HSA had little impact on the formation of the AgNP protein corona with protein-AgNP association constants of ≈2x107 M-1 for both HSA and glycated HSA (gHSA). The formation of the protein corona itself (regardless of whether it was formed from HSA or glycated HSA) caused an approximate 2-fold decrease in cell viability compared to the no protein AgNP control. While the toxicity of AgNPs to cells is often attributed to dissolved Ag(I), dissolution studies showed that the protein coated AgNPs underwent less dissolution than the no protein control, suggesting that the protein corona facilitated a nanoparticle-specific mechanism of toxicity. Overall, this study highlights the importance of protein coronas in mediating AgNP interactions with HepG2 cells and the need for future work to discern how protein coronas and protein modifications (like glycation) may alter AgNP reactivity to cellular organisms.
The effect of birth weight and time of day on the thermal response of newborn water buffalo calves
Authors: Napolitano Fabio , Bragaglio Andrea , Braghieri Ada , El-Aziz Ayman H. Abd , Titto Cristiane Gonçalves , Villanueva-García Dina , Mora-Medina Patricia , Pereira Alfredo M. F. , Hernández-Avalos Ismael , José-Pérez Nancy , Casas-Alvarado Alejandro , Lezama-García Karina , Domínguez-Oliva Adriana , Rodríguez-González Daniela , Bertoni Aldo , Mota-Rojas Daniel
Published: March 2023

During the 1st days of life, water buffalo calves, especially those with low birth weight, are susceptible to hypothermic mortality due to scarce energy reserves provided by fats. This means that monitoring the thermal state of newborns is essential. The objectives of the present study were to apply infrared thermography (IRT) in 109 buffalo calves to detect differences in the surface temperatures of six thermal windows –lacrimal gland, lacrimal caruncle, periocular region, nostrils, ear canal, pelvic limbs–, and determine their association to birth weight during the first 6 days of life. The calves were divided into four categories according to their weight (Q1, 37.8–41.25 kg; Q2, 41.3–46.3 kg; Q3, 46.4–56.3 kg; Q4, 56.4–60.3 kg). The thermographic images were recorded in the morning and afternoon. Results showed that the animals in Q4 registered the highest temperatures in all the thermal windows, and that these were higher in the afternoon (p < 0.0001). When considering the thermal windows, those located in the facial region recorded the highest temperatures; in contrast, the temperatures at the pelvic limbs remained below the average values of the other windows (33.41 and 33.76°C in the morning and afternoon, respectively). According to these results, the birth weight of water buffaloes is a factor that alters their thermoregulation during the 1st days of life, a condition that can be partially compensated by colostrum intake to promote development of an efficient thermoregulatory mechanism in water buffalo calves.
Malignancy and viral infections in Sub-Saharan Africa: A review
Authors: Diakite Mahamadou , Shaw-Saliba Kathryn , Lau Chuen-Yen
Published: March 2023

The burden of malignancy related to viral infection is increasing in Sub-Saharan Africa (SSA). In 2018, approximately 2 million new cancer cases worldwide were attributable to infection. Prevention or treatment of these infections could reduce cancer cases by 23% in less developed regions and about 7% in developed regions. Contemporaneous increases in longevity and changes in lifestyle have contributed to the cancer burden in SSA. African hospitals are reporting more cases of cancer related to infection (e.g., cervical cancer in women and stomach and liver cancer in men). SSA populations also have elevated underlying prevalence of viral infections compared to other regions. Of 10 infectious agents identified as carcinogenic by the International Agency for Research on Cancer, six are viruses: hepatitis B and C viruses (HBV and HCV, respectively), Epstein-Barr virus (EBV), high-risk types of human papillomavirus (HPV), Human T-cell lymphotropic virus type 1 (HTLV-1), and Kaposi’s sarcoma herpesvirus (KSHV, also known as human herpesvirus type 8, HHV-8). Human immunodeficiency virus type 1 (HIV) also facilitates oncogenesis. EBV is associated with lymphomas and nasopharyngeal carcinoma; HBV and HCV are associated with hepatocellular carcinoma; KSHV causes Kaposi’s sarcoma; HTLV-1 causes T-cell leukemia and lymphoma; HPV causes carcinoma of the oropharynx and anogenital squamous cell cancer. HIV-1, for which SSA has the greatest global burden, has been linked to increasing risk of malignancy through immunologic dysregulation and clonal hematopoiesis. Public health approaches to prevent infection, such as vaccination, safer injection techniques, screening of blood products, antimicrobial treatments and safer sexual practices could reduce the burden of cancer in Africa. In SSA, inequalities in access to cancer screening and treatment are exacerbated by the perception of cancer as taboo. National level cancer registries, new screening strategies for detection of viral infection and public health messaging should be prioritized in SSA’s battle against malignancy. In this review, we discuss the impact of carcinogenic viruses in SSA with a focus on regional epidemiology.
Acoustic Echo Cancellation with the Normalized Sign-Error Least Mean Squares Algorithm and Deep Residual Echo Suppression
Authors: Shachar Eran , Cohen Israel , Berdugo Baruch
Published: March 2023

This paper presents an echo suppression system that combines a linear acoustic echo canceller (AEC) with a deep complex convolutional recurrent network (DCCRN) for residual echo suppression. The filter taps of the AEC are adjusted in subbands by using the normalized sign-error least mean squares (NSLMS) algorithm. The NSLMS is compared with the commonly-used normalized least mean squares (NLMS), and the combination of each with the proposed deep residual echo suppression model is studied. The utilization of a pre-trained deep-learning speech denoising model as an alternative to a residual echo suppressor (RES) is also studied. The results showed that the performance of the NSLMS is superior to that of the NLMS in all settings. With the NSLMS output, the proposed RES achieved better performance than the larger pre-trained speech denoiser model. More notably, the denoiser performed considerably better on the NSLMS output than on the NLMS output, and the performance gap was greater than the respective gap when employing the RES, indicating that the residual echo in the NSLMS output was more akin to noise than speech. Therefore, when little data is available to train an RES, a pre-trained speech denoiser is a viable alternative when employing the NSLMS for the preceding linear AEC.
Influence of Pesticides and Mineral Fertilizers on the Bacterial Community of Arable Soils under Pea and Chickpea Crops
Authors: Khmelevtsova Ludmila , Konstantinova Elizaveta , Karchava Shorena , Klimova Maria , Azhogina Tatiana , Polienko Elena , Khammami Margarita , Sazykin Ivan , Sazykina Marina
Published: March 2023

Fertile Chernozems of Southern Russia are of great value, so it is important to study the impact of agricultural activities on the soil quality. Changes in taxonomic composition and α-diversity of microbial communities of agricultural soils occupied by pea (Pisum sativum L.) and chickpea (Cicer arietinum L.) in response of cropland management were studied. A field experiment was conducted under four different conditions: (1) control, (2) mineral fertilizers (NPK) application alone, (3) pesticides application alone, and (4) fertilization combined with pesticides. The taxonomic composition of the soil bacterial community was studied by amplification and sequencing of the 16S rRNA gene. The predominance of Actinobacteria (17.7–32.3%), Proteobacteria (17.7–28.2%), Planctomycetes (10.1–21.3%), Acidobacteria (5.3–11.1%), Chloroflexi (1.0–7.1%), Gemmatimonadetes (2.5–8.0%), Bacteroidetes (3.6–11.3%), and Verrucomicrobia (3.9–9.2%) was noted. Introduction of pesticides led to an increase in the relative abundance of Chlorobi and Gemmatimonadetes. The time of sampling was the main significant factor determining the differences in the structure of soil microbial communities. All treatments did not have a significant effect on the α-diversity of the studied soils. Thus, treatment with mineral fertilizers and pesticides does not have a significant negative effect on the bacterial community of cultivated soils.
Variance Components, Correlation and Path Coefficient Analysis of Morpho-Physiological and Yield Related Traits in Spider Plant (Gynandropsis gynandra (L.) Briq.) under Water-Stress Conditions
Authors: Chatara Tinashe , Musvosvi Cousin , Houdegbe Aristide Carlos , Sibiya Julia
Published: March 2023

Drought is the most complex abiotic stress for crop production at the global level. Therefore, developing new African spider plant genotypes tolerant to drought stress is one of the best approaches to achieving and optimizing high yield potential with water use efficiency. Advances in the selection of this crop can be determined by an understanding of genetic variability, heritability, and the associations that exist among different traits. The aim of this study was to gather information that will aid in the breeding of African spider plant cultivars with improved drought tolerance. A randomized complete block design (RCBD) experiment with eighteen genotypes and four replications was carried out across three water regimes: severe drought (30% field capacity), intermediate drought (50% field capacity), and well-watered (100% field capacity), in two seasons. Data on twelve morpho-physiological traits were recorded. The analysis of variance showed significant differences among genotypes (p < 0.05) in leaf yield and yield-related traits. The phenotypic coefficient of variation (PCV) was greater than the genotypic coefficient of variation (GCV) for all 12 traits evaluated. High to moderate heritability estimates combined with a high to moderate genetic advance were observed for number of leaves, leaf width, plant height and stem diameter under drought stress conditions, indicating that these traits are controlled by additive gene action. Because of their predominant additive gene effects, correlation with leaf yield and favorable direct and indirect effects via the other yield-attributing traits, number of leaves per plant, plant height, days to 50% flowering, relative water content, net photosynthesis and leaf length could be used as target traits to improve spider plant leaf yield under drought-stressed conditions.
Domestic Waste and Wastewaters as Potential Sources of Pharmaceuticals in Nestling White Storks (Ciconia ciconia)
Authors: Blanco Guillermo , Gómez-Ramírez Pilar , Espín Silvia , Sánchez-Virosta Pablo , Frías Óscar , García-Fernández Antonio J.
Published: March 2023

Information on the exposure of wild birds to pharmaceuticals from wastewater and urban refuse is scarce despite the enormous amount of drugs consumed and discarded by human populations. We tested for the presence of a battery of antibiotics, NSAIDs, and analgesics in the blood of white stork (Ciconia ciconia) nestlings in the vicinity of urban waste dumps and contaminated rivers in Madrid, central Spain. We also carried out a literature review on the occurrence and concentration of the tested compounds in other wild bird species to further evaluate possible shared exposure routes with white storks. The presence of two pharmaceutical drugs (the analgesic acetaminophen and the antibiotic marbofloxacin) out of fourteen analysed in the blood of nestlings was confirmed in 15% of individuals (n = 20) and in 30% of the nests (n = 10). The apparently low occurrence and concentration (acetaminophen: 9.45 ng mL−1; marbofloxacin: 7.21 ng mL−1) in nestlings from different nests suggests the uptake through food acquired in rubbish dumps rather than through contaminated flowing water provided by parents to offspring. As with other synthetic materials, different administration forms (tablets, capsules, and gels) of acetaminophen discarded in household waste could be accidentally ingested when parent storks forage on rubbish to provide meat scraps to their nestlings. The presence of the fluoroquinolone marbofloxacin, exclusively used in veterinary medicine, suggests exposure via consumption of meat residues of treated animals for human consumption found in rubbish dumps, as documented previously at higher concentrations in vultures consuming entire carcasses of large livestock. Control measures and ecopharmacovigilance frameworks are needed to minimize the release of pharmaceutical compounds from the human population into the environment.
Implementation Strategies for Preventing Healthcare-Associated Infections across the Surgical Pathway: An Italian Multisociety Document
Authors: Sartelli Massimo , Bartoli Stefano , Borghi Felice , Busani Stefano , Carsetti Andrea , Catena Fausto , Cillara Nicola , Coccolini Federico , Cortegiani Andrea , Cortese Francesco , Fabbri Elisa , Foghetti Domitilla , Forfori Francesco , Giarratano Antonino , Labricciosa Francesco Maria , Marini Pierluigi , Mastroianni Claudio , Pan Angelo , Pasero Daniela , Scatizzi Marco , Viaggi Bruno , Moro Maria Luisa
Published: March 2023

Healthcare-associated infections (HAIs) result in significant patient morbidity and can prolong the duration of the hospital stay, causing high supplementary costs in addition to those already sustained due to the patient’s underlying disease. Moreover, bacteria are becoming increasingly resistant to antibiotics, making HAI prevention even more important nowadays. The public health consequences of antimicrobial resistance should be constrained by prevention and control actions, which must be a priority for all health systems of the world at all levels of care. As many HAIs are preventable, they may be considered an important indicator of the quality of patient care and represent an important patient safety issue in healthcare. To share implementation strategies for preventing HAIs in the surgical setting and in all healthcare facilities, an Italian multi-society document was published online in November 2022. This article represents an evidence-based summary of the document.
Use of Machine Learning and Remote Sensing Techniques for Shoreline Monitoring: A Review of Recent Literature
Authors: Tsiakos Chrysovalantis-Antonios D. , Chalkias Christos
Published: March 2023

Climate change and its effects (i.e., sea level rise, extreme weather events) as well as anthropogenic activities, determine pressures to the coastal environments and contribute to shoreline retreat and coastal erosion phenomena. Coastal zones are dynamic and complex environments consisting of heterogeneous and different geomorphological features, while exhibiting different scales and spectral responses. Thus, the monitoring of changes in the coastal land classes and the extraction of coastlines/shorelines can be a challenging task. Earth Observation data and the application of spatiotemporal analysis methods can facilitate shoreline change analysis and detection. Apart from remote sensing methods, the advent of machine learning-based techniques presents an emerging trend, being capable of supporting the monitoring and modeling of coastal ecosystems at large scales. In this context, this study aims to provide a review of the relevant literature falling within the period of 2015–2022, where different machine learning approaches were applied for cases of coast-line/shoreline extraction and change analysis, and/or coastal dynamic monitoring. Particular emphasis is given on the analysis of the selected studies, including details about their performances, as well as their advantages and weaknesses, and information about the different environmental data employed.
Background and Blended Spectral Line Reduction in Precision Spectroscopy of EUV and X-ray Transitions in Highly Charged Ions
Authors: Hosier Adam , Dipti  , Yang Yang , Szypryt Paul , Mondeel Grant P. , Naing Aung , Tan Joseph N. , Silwal Roshani , O’Neil Galen , Lapierre Alain , Blundell Steven A. , Gillaspy John D. , Gwinner Gerald , Villari Antonio C. C. , Ralchenko Yuri , Takacs Endre
Published: March 2023

Extreme ultraviolet spectra of Na-like and Mg-like Os and Ir were recorded at the National Institute of Standards and Technology using a grazing incidence spectrometer. We report a method in EBIT spectral analysis that reduces signals from contaminant lines of known or unknown origin. We utilize similar ion charge distributions of heavy highly charged ions that create similar potentials for lighter contaminating background elements. First-order approximations to ion distributions are presented to demonstrate differences between impurity elements with and without heavy ions present.
Review of Active Front-End Rectifiers in EV DC Charging Applications
Authors: Zhaksylyk Assel , Rasool Haaris , Abramushkina Ekaterina , Chakraborty Sajib , Geury Thomas , El Baghdadi Mohamed , Hegazy Omar
Published: March 2023

Active Front-End (AFE) rectifiers have regained momentum as the demand for highpower Electric Vehicle (EV) charging infrastructure increases exponentially. AFE rectifiers have high efficiency and reliability, and they minimize the disturbances that could be generated due to the operation of the EV charging systems by reducing harmonic distortion and operating close to the Unity Power Factor (UPF). The purpose of this review is to present the current state-of-the-art AFE rectifiers used in fast chargers, focusing on the comparison between different AFE topologies and their components, as well as modular AFE solutions. Furthermore, different control strategies of AFE converters are presented and compared. Some of their more widely used control techniques, namely Voltage Oriented Control (VOC), Direct Power Control (DPC), Hysteresis Current Control (HCC), and Model Predictive Control (MPC), have been implemented, and their performance compared. Centralized and distributed control systems are compared for operating parallel AFE rectifiers for modular, fast charging systems. An overview of cooling systems and reliability evaluation tools is also presented. Finally, trends and future outlooks are analyzed.
Strategies and Challenge of Thick Electrodes for Energy Storage: A Review
Authors: Zheng Junsheng , Xing Guangguang , Jin Liming , Lu Yanyan , Qin Nan , Gao Shansong , Zheng Jim P.
Published: March 2023

In past years, lithium-ion batteries (LIBs) can be found in every aspect of life, and batteries, as energy storage systems (ESSs), need to offer electric vehicles (EVs) more competition to be accepted in markets for automobiles. Thick electrode design can reduce the use of non-active materials in batteries to improve the energy density of the batteries and reduce the cost of the batteries. However, thick electrodes are limited by their weak mechanical stability and poor electrochemical performance; these limitations could be classified as the critical cracking thickness (CCT) and the limited penetration depth (LPD). The understanding of the CCT and the LPD have been proposed and the recent works on breaking the CCT and improving the LPD are listed in this article. By comprising these attempts, some thick electrodes could not offer higher mass loading or higher accessible areal capacity that would defeat the purpose.
Amide Proton Transfer-Weighted Imaging Combined with ZOOMit Diffusion Kurtosis Imaging in Predicting Lymph Node Metastasis of Cervical Cancer
Authors: Huang Qiuhan , Wang Yanchun , Meng Xiaoyan , Li Jiali , Shen Yaqi , Hu Xuemei , Feng Cui , Li Zhen , Kamel Ihab
Published: March 2023

Background: The aim of this study is to investigate the feasibility of amide proton transfer-weighted (APTw) imaging combined with ZOOMit diffusion kurtosis imaging (DKI) in predicting lymph node metastasis (LNM) in cervical cancer (CC). Materials and Methods: Sixty-one participants with pathologically confirmed CC were included in this retrospective study. The APTw MRI and ZOOMit diffusion-weighted imaging (DWI) were acquired. The mean values of APTw and DKI parameters including mean kurtosis (MK) and mean diffusivity (MD) of the primary tumors were calculated. The parameters were compared between the LNM and non-LNM groups using the Student’s t-test or Mann–Whitney U test. Binary logistic regression analysis was performed to determine the association between the LNM status and the risk factors. The diagnostic performance of these quantitative parameters and their combinations for predicting the LNM was assessed with receiver operating characteristic (ROC) curve analysis. Results: Patients were divided into the LNM group (n = 17) and the non-LNM group (n = 44). The LNM group presented significantly higher APTw (3.7 ± 1.1% vs. 2.4 ± 1.0%, p < 0.001), MK (1.065 ± 0.185 vs. 0.909 ± 0.189, p = 0.005) and lower MD (0.989 ± 0.195 × 10−3 mm2/s vs. 1.193 ± 0.337 ×10−3 mm2/s, p = 0.035) than the non-LNM group. APTw was an independent predictor (OR = 3.115, p = 0.039) for evaluating the lymph node status through multivariate analysis. The area under the curve (AUC) of APTw (0.807) was higher than those of MK (AUC, 0.715) and MD (AUC, 0.675) for discriminating LNM from non-LNM, but the differences were not significant (all p > 0.05). Moreover, the combination of APTw, MK, and MD yielded the highest AUC (0.864), with the corresponding sensitivity of 76.5% and specificity of 88.6%. Conclusion: APTw and ZOOMit DKI parameters may serve as potential noninvasive biomarkers in predicting LNM of CC.
The Role of Patient-Derived Organoids in Triple-Negative Breast Cancer Drug Screening
Authors: Psilopatis Iason , Mantzari Amalia , Vrettou Kleio , Theocharis Stamatios
Published: March 2023

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, with a grave prognosis and few effective treatment options. Organoids represent revolutionary three-dimensional cell culture models, derived from stem or differentiated cells and preserving the capacity to differentiate into the cell types of their tissue of origin. The current review aims at studying the potential of patient-derived TNBC organoids for drug sensitivity testing as well as highlighting the advantages of the organoid technology in terms of drug screening. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms “organoid” and “triple-negative breast cancer” were employed, and we were able to identify 25 studies published between 2018 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the use of patient-derived organoids for drug sensitivity testing in TNBC. Patient-derived organoids are excellent in vitro study models capable of promoting personalized TNBC therapy by reflecting the treatment responses of the corresponding patients and exhibiting high predictive value in the context of patient survival evaluation.
Countermovement Jumps Detect Subtle Motor Deficits in People with Multiple Sclerosis below the Clinical Threshold
Authors: Geßner Anne , Stölzer-Hutsch Heidi , Trentzsch Katrin , Schriefer Dirk , Ziemssen Tjalf
Published: March 2023

In the early stages of multiple sclerosis (MS), there are currently no sensitive assessments to evaluate complex motor functions. The countermovement jump (CMJ), a high-challenge task in form of a maximal vertical bipedal jump, has already been investigated as a reliable assessment in healthy subjects for lower extremity motor function. The aim was to investigate whether it is possible to use CMJ to identify subthreshold motor deficits in people with multiple sclerosis (pwMS). All participants (99 pwMS and 33 healthy controls) performed three maximal CMJs on a force plate. PwMS with full motor function and healthy controls (HC) did not differ significantly in age, disease duration, Body Mass Index and the Expanded Disability Scale Score. In comparison to HC, pwMS with full motor function demonstrated a significantly decreased CMJ performance in almost all observed kinetic, temporal and performance parameters (p < 0.05). With increasing disability in pwMS, it was also observed that jump performance decreased significantly. This study showed that the CMJ, as a high challenge task, could detect motor deficits in pwMS below the clinical threshold of careful neurological examination. Longitudinal studies are pending to evaluate whether the CMJ can be used as a standardized measure of disease progression.
Gut Microbial Profile Changes in Patients with Gallbladder Stones after UDCA/CDCA Treatment
Authors: Lee Jungnam , Lee Sohee , Kim Hanul , Bae Jaewoong , Park Jin-Seok
Published: March 2023

Background: Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are used to treat patients with asymptomatic or mildly symptomatic gallstone disease. This study was conducted to evaluate the efficacy of gallbladder (GB) stone dissolution by UDCA/CDCA and the impact of treatment on gut microbial profiles. Methods: Fifteen treatment-naive patients with GB stones were initially included, but two dropped out during the treatment period. UDCA/CDCA was administered for 6 months. Abdominal ultrasonography was performed to evaluate response to treatment. In addition, fecal samples were collected before and after treatment for gut microbiome profiling. Then, 16S ribosomal RNA gene sequencing was carried out on fecal samples obtained before and after treatment, and results were compared with those of forty healthy controls. Results: Eight (62%) of the thirteen evaluable patients treated with UDCA/CDCA responded to treatment (four achieved complete GB stone resolution and four partial dissolution). Taxonomic compositions of fecal samples at the phylum level showed a significantly lower relative abundance of the Proteobacteria phylum in the pre-UDCA/CDCA group than in the healthy control group (p = 0.024). At the genus level, the relative abundances of five bacteria (Faecalibacterium, Roseburia, Lachnospira, Streptococcus, and Alistipes) differed in the control and pre-UDCA/CDCA group. Interestingly, the abundance of Roseburia was restored after 6 months of UDCA/CDCA treatment. Conclusion: Gut microbial dysbiosis was observed in GB stone patients and partially reversed by UDCA/CDCA treatment, which also effectively dissolved GB stones.
Measuring Drug Therapy Effect on Osteoporotic Fracture Risk by Trabecular Bone Lacunarity: The LOTO Study
Authors: Zaia Annamaria , Maponi Pierluigi , Sallei Manuela , Galeazzi Roberta , Scendoni Pietro
Published: March 2023

An MRI method providing one parameter (TBLβ: trabecular-bone-lacunarity-parameter-β) that is sensitive to trabecular bone architecture (TBA) changes with aging and osteoporosis is under study as a new tool in the early diagnosis of bone fragility fracture. A cross-sectional and prospective observational study (LOTO: Lacunarity Of Trabecular bone in Osteoporosis) on over-50s women, at risk for bone fragility fracture, was designed to validate the method. From the baseline data, we observed that in women with prevalent vertebral fractures (VF+), TBA was differently characterized by TBLβ when osteoporosis treatment is considered. Here we verify the potential of TBLβ as an index of osteoporosis treatment efficacy. Untreated (N = 156) and treated (N = 123) women were considered to assess differences in TBLβ related to osteoporosis treatment. Prevalent VFs were found in 31% of subjects, 63% of which were under osteoporosis medications. The results show that TBLβ discriminates between VF+ and VF− patients (p = 0.004). This result is mostly stressed in untreated subjects. Treatment, drug therapy in particular (89% Bisphosphonates), significantly counteracts the difference between VF+ and VF− within and between groups: TBLβ values in treated patients are comparable to untreated VF− and statistically higher than untreated VF+ (p = 0.014) ones. These results highlight the potential role of TBLβ as an index of treatment efficacy.
The Role of Glutamate Receptors in Epilepsy
Authors: Chen Tsang-Shan , Huang Tzu-Hsin , Lai Ming-Chi , Huang Chin-Wei
Published: March 2023

Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing.
Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort
Authors: Iseas Soledad , Prost Diego , Bouchereau Sarah , Golubicki Mariano , Robbio Juan , Oviedo Ana , Coraglio Mariana , Kujaruk Mirta , Méndez Guillermo , Carballido Marcela , Roca Enrique , Gros Louis , De Parades Vincent , Baba-Hamed Nabil , Adam Julien , Abba Martín Carlos , Raymond Eric
Published: March 2023

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19–33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25–2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.
Tissue Engineering Supporting Regenerative Strategies to Enhance Clinical Orthodontics and Dentofacial Orthopaedics: A Scoping, Perspective Review
Authors: Abid Mushriq , Jamal Hasan , Alsahafi Elham , Dziedzic Arkadiusz , Kubina Robert
Published: March 2023

The personalized regenerative therapeutic strategies applicable in the structural and functional repair of maxillofacial/dental defects are expected to extend beyond the limits of what is currently possible in the management of dentofacial anomalies and treating malocclusions. The application of undifferentiated stem cells (SCs), including signaling molecule control and individualized tissue engineering based on targeted therapies, has been proposed to overcome therapeutic limitations and complications associated with treatments for craniofacial defects, including severe orthodontic discrepancies. This scoping, prospective review discusses comprehensively the current knowledge and prospects for improving clinical outcomes by the application of novel cell-required and cell-free regenerative strategies in biomedicine. The existing evidence, although scant, suggests that patients receiving an orthodontic treatment could benefit from precise tissue augmentation, allowing enhancement of tooth movement generated by orthognathic forces; faster, more predictable alignment of dental arches; optimal management of periodontal complications; and prevention of external root resorption. Ultimately, enriching orofacial tissues and “customizing” the repair of congenital/acquired defects in the craniofacial region can be vastly enhanced to provide a positive therapeutic outcome and improve patients’ quality of life.
Immortalized B Cells Transfected with mRNA of Antigen Fused to MITD (IBMAM): An Effective Tool for Antigen-Specific T-Cell Expansion and TCR Validation
Authors: Wang Zhe , Zhang Tiantian , Anderson Aaron , Lee Vincent , Szymura Szymon , Dong Zhenyuan , Kuang Benjamin , Oh Elizabeth , Liu Jingwei , Neelapu Sattva S. , Kwak Larry , Cha Soung-chul
Published: March 2023

Peripheral mononuclear blood cells (PBMCs) are the most widely used study materials for immunomonitoring and antigen-specific T-cell identification. However, limited patient PBMCs and low-frequency antigen-specific T cells remain as significant technical challenges. To address these limitations, we established a novel platform comprised of optimized HLA-matched immortalized B cells transfected with mRNA of a prototype viral or tumor antigen conjugated to MHC class-I trafficking domain protein (MITD) to increase the efficiency of epitope expression in antigen-presenting cells (APCs) essential to expanding antigen-specific T cells. When applied to CMV as a model, the IBMAM platform could successfully expand CMV-specific T cells from low-frequency CMV PBMCs from seropositive donors. Additionally, this platform can be applied to the validation of antigen specific TCRs. Together, compared to using APCs with synthesized peptides, this platform is an unlimited, highly efficient, and cost-effective resource in detecting and expanding antigen-specific T cells and validating antigen-specific TCRs.
Sensitivity Analysis for Survival Prognostic Prediction with Gene Selection: A Copula Method for Dependent Censoring
Authors: Yeh Chih-Tung , Liao Gen-Yih , Emura Takeshi
Published: March 2023

Prognostic analysis for patient survival often employs gene expressions obtained from high-throughput screening for tumor tissues from patients. When dealing with survival data, a dependent censoring phenomenon arises, and thus the traditional Cox model may not correctly identify the effect of each gene. A copula-based gene selection model can effectively adjust for dependent censoring, yielding a multi-gene predictor for survival prognosis. However, methods to assess the impact of various types of dependent censoring on the multi-gene predictor have not been developed. In this article, we propose a sensitivity analysis method using the copula-graphic estimator under dependent censoring, and implement relevant methods in the R package “compound.Cox”. The purpose of the proposed method is to investigate the sensitivity of the multi-gene predictor to a variety of dependent censoring mechanisms. In order to make the proposed sensitivity analysis practical, we develop a web application. We apply the proposed method and the web application to a lung cancer dataset. We provide a template file so that developers can modify the template to establish their own web applications.
Use of Graphene and Its Derivatives for the Detection of Dengue Virus
Authors: Dutta Reshmi , Rajendran Kokilavani , Jana Saikat Kumar , Saleena Lilly M. , Ghorai Suvankar
Published: March 2023

Every year, the dengue virus and its principal mosquito vector, Aedes sp., have caused massive outbreaks, primarily in equatorial countries. The pre-existing techniques available for dengue detection are expensive and require trained personnel. Graphene and its derivatives have remarkable properties of electrical and thermal conductivity, and are flexible, light, and biocompatible, making them ideal platforms for biosensor development. The incorporation of these materials, along with appropriate nanomaterials, improves the quality of detection methods. Graphene can help overcome the difficulties associated with conventional techniques. In this review, we have given comprehensive details on current graphene-based diagnostics for dengue virus detection. We have also discussed state-of-the-art biosensing technologies and evaluated the advantages and disadvantages of the same.
Graphene Nanocomposites in Space Sector—Fundamentals and Advancements
Authors: Kausar Ayesha , Ahmad Ishaq , Eisa M. H. , Maaza Malik
Published: March 2023

Graphene is one of the most significant carbon nanomaterials, with a one-atom-thick two-dimensional nanostructure. Like other nanocarbons, graphene has been used as a polymer reinforcement. This review explores the impact of graphene and graphene-based nanocomposites on aerospace applications. The fabrication and indispensable features of graphene-derived nanocomposites have been considered. Numerous polymers and nanocomposites have been employed for aerospace systems such as reinforced thermosetting/thermoplastic polymers and epoxy/graphene nanocomposites. Moreover, graphene-modified carbon-fiber-based composites have been discussed for the space sector. Aerospace nanocomposites with graphene have been investigated for superior processability, structural features, morphology, heat stability, mechanical properties, flame resistance, electrical/thermal conductivity, radiation protection, and adhesion applications. Subsequently, epoxy and graphene-derived nanocomposites have been explored for heat/mechanically stable aerospace engineering structures, radiation-shielding materials, adhesives, coatings, etc.
Orthogonal Optimization, Characterization, and In Vitro Anticancer Activity Evaluation of a Hydrogen Peroxide-Responsive and Oxygen-Reserving Nanoemulsion for Hypoxic Tumor Photodynamic Therapy
Authors: Hong Liang , Wang Jianman , Zhou Yi , Shang Guofu , Guo Tao , Tang Hailong , Li Jiangmin , Luo Yali , Zeng Xiangyu , Zeng Zhu , Hu Zuquan
Published: March 2023

Tumor hypoxia can seriously impede the effectiveness of photodynamic therapy (PDT). To address this issue, two approaches, termed in situ oxygen generation and oxygen delivery, were developed. The in situ oxygen generation method uses catalysts such as catalase to decompose excess H2O2 produced by tumors. It offers specificity for tumors, but its effectiveness is limited by the low H2O2 concentration often present in tumors. The oxygen delivery strategy relies on the high oxygen solubility of perfluorocarbon, etc., to transport oxygen. It is effective, but lacks tumor specificity. In an effort to integrate the merits of the two approaches, we designed a multifunctional nanoemulsion system named CCIPN and prepared it using a sonication-phase inversion composition–sonication method with orthogonal optimization. CCIPN included catalase, the methyl ester of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), photosensitizer IR780, and perfluoropolyether. Perfluoropolyether may reserve the oxygen generated by catalase within the same nanoformulation for PDT. CCIPN contained spherical droplets below 100 nm and showed reasonable cytocompatibility. It presented a stronger ability to generate cytotoxic reactive oxygen species and consequently destroy tumor cells upon light irradiation, in comparison with its counterpart without catalase or perfluoropolyether. This study contributes to the design and preparation of oxygen-supplementing PDT nanomaterials.
Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group
Authors: Thomssen Christoph , Vetter Martina , Kantelhardt Eva J. , Meisner Christoph , Schmidt Marcus , Martin Pierre M. , Clatot Florian , Augustin Doris , Hanf Volker , Paepke Daniela , Meinerz Wolfgang , Hoffmann Gerald , Wiest Wolfgang , Sweep Fred C. G. J. , Schmitt Manfred , Jänicke Fritz , Loibl Sibylle , Minckwitz Gunter von , Harbeck Nadia
Published: March 2023

Background: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. Methods: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), cyclophosphamide (500 mg/m2) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m2 (FEC-Doc). Primary endpoint was disease-free survival (DFS). Results: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1–94.8) with FEC-Doc and 93.7% (91.7–95.3) with FEC. Five-year-overall survival was 97.0% (95.4–98.0) for FEC-Doc and 96.6% % (94.9–97.8) for FEC. Conclusions: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.
Treatment Patterns, Testing Practices, and Outcomes in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer in Poland: A Descriptive Analysis of National, Multicenter, Real-World Data from the REFLECT Study
Authors: Pluzanski Adam , Bryl Maciej , Chmielewska Izabela , Czyzewicz Grzegorz , Luboch-Kowal Joanna , Wrona Anna , Samborska Agnieszka , Krzakowski Maciej
Published: March 2023

Non-small-cell lung cancer (NSCLC) represents 85% of new cases of lung cancer. Over the past two decades, treatment of patients with NSCLC has evolved from the empiric use of chemotherapy to more advanced targeted therapy dedicated to patients with an epidermal growth factor receptor (EGFR) mutation. The multinational REFLECT study analyzed treatment patterns, outcomes, and testing practices among patients with EGFR-mutated advanced NSCLC receiving first-line EGFR tyrosine kinase inhibitor (TKI) therapy across Europe and Israel. The aim of this study is to describe the Polish population of patients from the REFLECT study, focusing on treatment patterns and T790M mutation testing practice. A descriptive, retrospective, non-interventional, medical record-based analysis was performed on the Polish population of patients with locally advanced or metastatic NSCLC with EGFR mutations from the REFLECT study (NCT04031898). A medical chart review with data collection was conducted from May to December 2019.The study involved 110 patients. Afatinib was used as the first-line EGFR-TKI therapy in 45 (40.9%) patients, erlotinib in 41 (37.3%), and gefitinib in 24 (21.8%) patients. The first-line EGFR-TKI therapy was discontinued in 90 (81.8%) patients. The median progression-free survival (PFS) on first-line EGFR-TKI therapy was 12.9 months (95% CI 10.3–15.4). A total of 54 patients started second-line therapy, of whom osimertinib was administered to 31 (57.4%). Among 85 patients progressing on first-line EGFR-TKI therapy, 58 (68.2%) were tested for the T790M mutation. Positive results for the T790M mutation were obtained from 31 (53.4%) tested patients, all of whom received osimertinib in the next lines of therapy. The median overall survival (OS) from the start of first-line EGFR-TKI therapy was 26.2 months (95% CI 18.0–29.7). Among patients with brain metastases, the median OS from the first diagnosis of brain metastases was 15.5 months (95% CI 9.9–18.0). The results of the Polish population from the REFLECT study highlight the need for effective treatment of patients with advanced EGFR-mutated NSCLC. Nearly one-third of patients with disease progression after first-line EGFR-TKI therapy were not tested for the T790M mutation and did not have the opportunity to receive effective treatment. The presence of brain metastases was a negative prognostic factor.
Emerging Therapies in CLL in the Era of Precision Medicine
Authors: Iyer Prajish , Wang Lili
Published: March 2023

Over the past decade, the treatment landscape of CLL has vastly changed from the conventional FC (fludarabine and cyclophosphamide) and FCR (FC with rituximab) chemotherapies to targeted therapies, including inhibitors of Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) as well as inhibitors of BCL2. These treatment options dramatically improved clinical outcomes; however, not all patients respond well to these therapies, especially high-risk patients. Clinical trials of immune checkpoint inhibitors (PD-1, CTLA4) and chimeric antigen receptor T (CAR T) or NK (CAR NK) cell treatment have shown some efficacy; still, long-term outcomes and safety issues have yet to be determined. CLL remains an incurable disease. Thus, there are unmet needs to discover new molecular pathways with targeted or combination therapies to cure the disease. Large-scale genome-wide whole-exome and whole-genome sequencing studies have discovered genetic alterations associated with disease progression, refined the prognostic markers in CLL, identified mutations underlying drug resistance, and pointed out critical targets to treat the disease. More recently, transcriptome and proteome landscape characterization further stratified the disease and revealed novel therapeutic targets in CLL. In this review, we briefly summarize the past and present available single or combination therapies, focusing on potential emerging therapies to address the unmet clinical needs in CLL.