bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract Evolution Equations with an Operator Function in the Second Term
Authors: Kukushkin Maksim V.
Published: August 2022

In this paper, having introduced a convergence of a series on the root vectors in the Abel-Lidskii sense, we present a valuable application to the evolution equations. The main issue of the paper is an approach allowing us to principally broaden conditions imposed upon the second term of the evolution equation in the abstract Hilbert space. In this way, we come to the definition of the function of an unbounded non-selfadjoint operator. Meanwhile, considering the main issue we involve an additional concept that is a generalization of the spectral theorem for a non-selfadjoint operator.
Optimality of the Approximation and Learning by the Rescaled Pure Super Greedy Algorithms
Authors: Zhang Wenhui , Ye Peixin , Xing Shuo , Xu Xu
Published: August 2022

We propose the Weak Rescaled Pure Super Greedy Algorithm (WRPSGA) for approximation with respect to a dictionary D in Hilbert space. The WRPSGA is simpler than some popular greedy algorithms. We show that the convergence rate of the RPSGA on the closure of the convex hull of the μ-coherent dictionary D is optimal. Then, we design the Rescaled Pure Super Greedy Learning Algorithm (RPSGLA) for kernel-based supervised learning. We prove that the convergence rate of the RPSGLA can be arbitrarily close to the best rate O(m−1) under some mild assumptions.
Riehl’s Melanosis: A Multimodality, In Vivo, Real-Time Skin Imaging Study with Cellular Resolution Optical Coherence Tomography and Advanced Skin Diagnosis System in a Tertiary Medical Center
Authors: Shen Peng-Chieh , Chan Yu-Pei , Huang Chun-Hsien , Ng Chau Yee
Published: August 2022

Background: Riehl’s melanosis is a psychologically devastating hyperpigmentary disorder that typically occurs on the face and neck. The study of Riehl’s melanosis is limited due to its rarity, variable morphology, and lack of noninvasive diagnostic tools. Recent advances in skin imaging analysis and diagnostic systems improve diagnostic accuracy and enable the noninvasive, real-time evaluation of pigmentary disease. A comprehensive study of Riehl’s melanosis clinical morphology with multimodality and in vivo skin imaging systems has yet to be reported. Objectives: To investigate the clinical features and in vivo advanced skin imaging findings of Riehl’s melanosis. Methods: We retrospectively investigated the clinical characteristics, dermoscopic, and histopathological features of Riehl’s melanosis. We further utilized multimodality skin imaging analysis systems, including a cellular resolution optical coherence tomography (OCT) and new skin diagnosis system, to investigate the features of Riehl’s melanosis. In addition, we compared OCT findings with histopathological features and clinical assessment. Results: We evaluated 30 patients with Riehl’s melanosis at a tertiary medical center from 2010 to 2022. The average age was 47.7 ± 12.3 (mean ± SD) years, predominantly female patients (female: n = 23; male: n = 7). Cellular resolution OCT imaging from lesion skin shows increased melanocyte capping, disrupted basement membrane, telangiectatic blood vessels, and melanophages in the dermis. The advanced skin diagnosis system captured subclinical erythema of the skin, highlighting the inflammatory nature of the disease. The results correlated well with histopathological findings. Limitations: This is a single-center, cross-sectional study. Conclusions: We highlight the features of Riehl’s melanosis through a novel cellular resolution OCT and photographic skin diagnosis system. A multimodality skin diagnosis system can serve as a real-time, in vivo, noninvasive method for evaluating pigmentary disorders.
Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stroma
Authors: Sablatura Lindsey K. , Tellman Tristen V. , Kim Aemin , Farach-Carson Mary C.
Published: August 2022

The bone marrow tumor microenvironment (BMTE) is a complex network of cells, extracellular matrix, and sequestered signaling factors that initially act as a hostile environment for disseminating tumor cells (DTCs) from the cancerous prostate. Three-dimensional (3D) culture systems offer an opportunity to better model these complex interactions in reactive stroma, providing contextual behaviors for cancer cells, stromal cells, and endothelial cells. Using a new system designed for the triculture of osteoblastic prostate cancer (PCa) cells, stromal cells, and microvascular endothelial cells, we uncovered a context-specific pro-apoptotic effect of endothelial cells of the bone marrow different from those derived from the lung or dermis. The paracrine nature of this effect was demonstrated by observations that conditioned medium from bone marrow endothelial cells, but not from dermal or lung endothelial cells, led to PCa cell death in microtumors grown in 3D BMTE-simulating hydrogels. Analysis of the phosphoproteome by reverse phase protein analysis (RPPA) of PCa cells treated with conditioned media from different endothelial cells identified the differential regulation of pathways involved in proliferation, cell cycle regulation, and apoptosis. The findings from the RPPA were validated by western blotting for representative signaling factors identified, including forkhead box M1 (FOXM1; proliferation factor), pRb (cell cycle regulator), and Smac/DIABLO (pro-apoptosis) among treatment conditions. The 3D model presented here thus presents an accurate model to study the influence of the reactive BMTE, including stromal and endothelial cells, on the adaptive behaviors of cancer cells modeling DTCs at sites of bone metastasis. These findings in 3D culture systems can lead to a better understanding of the real-time interactions among cells present in reactive stroma than is possible using animal models.
Research Advances on Molecular Mechanism of Salt Tolerance in Suaeda
Authors: Yu Wancong , Wu Wenwen , Zhang Nan , Wang Luping , Wang Yiheng , Wang Bo , Lan Qingkuo , Wang Yong
Published: August 2022

Plant growth and development are inevitably affected by various environmental factors. High salinity is the main factor leading to the reduction of cultivated land area, which seriously affects the growth and yield of plants. The genus Suaeda is a kind of euhalophyte herb, with seedlings that grow rapidly in moderately saline environments and can even survive in conditions of extreme salinity. Its fresh branches can be used as vegetables and the seed oil is rich in unsaturated fatty acids, which has important economic value and usually grows in a saline environment. This paper reviews the progress of research in recent years into the salt tolerance of several Suaeda species (for example, S. salsa, S. japonica, S. glauca, S. corniculata), focusing on ion regulation and compartmentation, osmotic regulation of organic solutes, antioxidant regulation, plant hormones, photosynthetic systems, and omics (transcriptomics, proteomics, and metabolomics). It helps us to understand the salt tolerance mechanism of the genus Suaeda, and provides a theoretical foundation for effectively improving crop resistance to salt stress environments.
Mesenchymal Stem Cell Studies in the Goat Model for Biomedical Research—A Review of the Scientific Literature
Authors: Dias Inês E. , Viegas Carlos A. , Requicha João F. , Saavedra Maria J. , Azevedo Jorge M. , Carvalho Pedro P. , Dias Isabel R.
Published: August 2022

Mesenchymal stem cells (MSCs) are multipotent cells, defined by their ability to self-renew, while maintaining the capacity to differentiate into different cellular lineages, presumably from their own germinal layer. MSCs therapy is based on its anti-inflammatory, immunomodulatory, and regenerative potential. Firstly, they can differentiate into the target cell type, allowing them to regenerate the damaged area. Secondly, they have a great immunomodulatory capacity through paracrine effects (by secreting several cytokines and growth factors to adjacent cells) and by cell-to-cell contact, leading to vascularization, cellular proliferation in wounded tissues, and reducing inflammation. Currently, MSCs are being widely investigated for numerous tissue engineering and regenerative medicine applications. Appropriate animal models are crucial for the development and evaluation of regenerative medicine-based treatments and eventual treatments for debilitating diseases with the hope of application in upcoming human clinical trials. Here, we summarize the latest research focused on studying the biological and therapeutic potential of MSCs in the goat model, namely in the fields of orthopedics, dermatology, ophthalmology, dentistry, pneumology, cardiology, and urology fields.
A Fuzzy-Based Model to Predict the Spatio-Temporal Performance of the Dolichogenidea gelechiidivoris Natural Enemy against Tuta absoluta under Climate Change
Authors: Agboka Komi Mensah , Tonnang Henri E. Z. , Abdel-Rahman Elfatih M. , Odindi John , Mutanga Onisimo , Mohamed Samira A.
Published: August 2022

The South American tomato pinworm, Tuta absoluta, causes up to 100% tomato crop losses. As Tuta absoluta is non-native to African agroecologies and lacks efficient resident natural enemies, the microgastrine koinobiont solitary oligophagous larval endoparasitoid, Dolichogenidea gelechiidivoris (Marsh) (Syn.: Apanteles gelechiidivoris Marsh) (Hymenoptera: Braconidae) was released for classical biological control. This study elucidates the current and future spatio-temporal performance of D. gelechiidivoris against T. absoluta in tomato cropping systems using a fuzzy logic modelling approach. Specifically, the study considers the presence of the host and the host crop, as well as the parasitoid reproductive capacity, as key variables. Results show that the fuzzy algorithm predicted the performance of the parasitoid (in terms of net reproductive rate (R0)), with a low root mean square error (RMSE) value (<0.90) and a considerably high R2 coefficient (=0.98), accurately predicting the parasitoid performance over time and space. Under the current climatic scenario, the parasitoid is predicted to perform well in all regions throughout the year, except for the coastal region. Under the future climatic scenario, the performance of the parasitoid is projected to improve in all regions throughout the year. Overall, the model sheds light on the varying performance of the parasitoid across different regions of Kenya, and in different seasons, under both current and future climatic scenarios.
Consequences of Oviposition Site Choice for Geckos in Changing Environments
Authors: Abayarathna Theja , Webb Jonathan K.
Published: August 2022

Most lizards lay eggs inside nests where embryos experience daily fluctuations in temperature. As embryos are sensitive to exposure to high temperatures, increases in nest temperatures may pose a risk to lizards. In the velvet gecko Amalosia lesueurii, nest temperatures are positively correlated with air temperatures, so nests may get hotter in future. However, maternal variation in oviposition site choice might buffer populations from future warming. To evaluate the consequences of oviposition site choice, we incubated eggs under two fluctuating temperature regimes that mimicked temperatures experienced inside sun-exposed (“warm”: mean = 25.4 °C; range = 16.5–35.5 °C) and shaded (“cold”: mean = 23.3 °C; 17.5–30.5 °C) communal nests. We measured the phenotypic traits of hatchlings, released them to the wild, and monitored their survival over 6 months. Warm-incubated hatchlings hatched 15 days earlier, on average, and were smaller than their cold-incubated clutch mates. Incubation treatment did not influence the apparent survival of hatchlings. Hence, even if air temperatures increase by 2 °C in future, thermal regimes inside some currently used shaded nests will be suitable for embryo development. Maternal variation in nest site choice may therefore allow southern populations of the velvet gecko to persist in changing environments.
Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art
Authors: della Rocca Giorgia , Re Giovanni
Published: August 2022

ALIAmides are a family of fatty acid amides whose name comes from their mechanism of action, i.e., the Autacoid Local Injury Antagonism (ALIA). Actually, the ALIAmide parent molecule, palmitoylethanolamide (PEA), is locally produced on demand from a cell membrane precursor in order to control immune-inflammatory cell responses, avert chronic non-resolving inflammation, and limit the resulting clinical signs. ALIAmide sister compounds, such as Adelmidrol and palmitoylglucosamine, share mechanisms of action with PEA and may also increase endogenous levels of PEA. Provided that their respective bioavailability is properly addressed (e.g., through decreasing the particle size through micronization), exogenously administered ALIAmides thus mimic or sustain the prohomeostatic functions of endogenous PEA. The aim of the present paper is to review the main findings on the use of ALIAmides in small animals as a tribute to the man of vision who first believed in this “according-to-nature” approach, namely Francesco della Valle. After briefly presenting some key issues on the molecular targets, metabolism, and pharmacokinetics of PEA and related ALIAmides, here we will focus on the preclinical and clinical studies performed in dogs and cats. Although more data are still needed, ALIAmides may represent a novel and promising approach to small animal health.
Single-Stranded DNA Binding Proteins and Their Identification Using Machine Learning-Based Approaches
Authors: Guo Jun-Tao , Malik Fareeha
Published: August 2022

Single-stranded DNA (ssDNA) binding proteins (SSBs) are critical in maintaining genome stability by protecting the transient existence of ssDNA from damage during essential biological processes, such as DNA replication and gene transcription. The single-stranded region of telomeres also requires protection by ssDNA binding proteins from being attacked in case it is wrongly recognized as an anomaly. In addition to their critical roles in genome stability and integrity, it has been demonstrated that ssDNA and SSB–ssDNA interactions play critical roles in transcriptional regulation in all three domains of life and viruses. In this review, we present our current knowledge of the structure and function of SSBs and the structural features for SSB binding specificity. We then discuss the machine learning-based approaches that have been developed for the prediction of SSBs from double-stranded DNA (dsDNA) binding proteins (DSBs).
Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism
Authors: Das Abhijit , Gauthier-Coles Gregory , Bröer Stefan , Rae Caroline D.
Published: August 2022

The cerebellum, or “little brain”, is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to metabolism, providing recycling of carbon backbones and ammonia between cell types. Here, we examined the role of cerebellar amino acid transporters in the cycling of glutamine and alanine in guinea pig cerebellar slices by inhibiting amino acid transporters and examining the resultant metabolism of [1-13C]d-glucose and [1,2-13C]acetate by NMR spectroscopy and LCMS. While the lack of specific inhibitors of each transporter makes interpretation difficult, by viewing results from experiments with multiple inhibitors we can draw inferences about the major cell types and transporters involved. In cerebellum, glutamine and alanine transfer is dominated by system A, blockade of which has maximum effect on metabolism, with contributions from System N. Inhibition of neural system A isoform SNAT1 by MeAIB resulted in greatly decreased metabolite pools and reduced net fluxes but showed little effect on fluxes from [1,2-13C]acetate unlike inhibition of SNAT3 and other glutamine transporters by histidine where net fluxes from [1,2-13C]acetate are reduced by ~50%. We interpret the data as further evidence of not one but several glutamate/glutamine exchange pools. The impact of amino acid transport inhibition demonstrates that the cerebellum has tightly coupled cells and that glutamate/glutamine, as well as alanine cycling, play a major role in that part of the brain.
Matrix Metalloproteinases in Health and Disease 2.0
Authors: Serra Raffaele
Published: August 2022

Matrix metalloproteinases (MMPs) are members of an enzyme family that are critical for maintaining tissue allostasis [...]
Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
Authors: Valenza Marta , Facchinetti Roberta , Steardo Luca , Scuderi Caterina
Published: August 2022

Palmitoylethanolamide (PEA), the naturally occurring amide of ethanolamine and palmitic acid, is an endogenous lipid compound endowed with a plethora of pharmacological functions, including analgesic, neuroprotective, immune-modulating, and anti-inflammatory effects. Although the properties of PEA were first characterized nearly 65 years ago, the identity of the receptor mediating these actions has long remained elusive, causing a period of research stasis. In the last two decades, a renewal of interest in PEA occurred, and a series of interesting studies have demonstrated the pharmacological properties of PEA and clarified its mechanisms of action. Recent findings showed the ability of formulations containing PEA in promoting oligodendrocyte differentiation, which represents the first step for the proper formation of myelin. This evidence opens new and promising research opportunities. White matter defects have been detected in a vast and heterogeneous group of diseases, including age-related neurodegenerative disorders. Here, we summarize the history and pharmacology of PEA and discuss its therapeutic potential in restoring white matter defects.
The Role of Diet in Regulation of Macrophages Functioning
Authors: Varaeva Yurgita R. , Kirichenko Tatiana V. , Shaposhnikova Nataliya N. , Nikityuk Dmitry B. , Starodubova Antonina V.
Published: August 2022

The great importance of diet for health and high life-expectancy is established. The impact of nutrients on immune system is a point of growing research interest. Recent studies have found pro- and anti-inflammatory properties of some diet patterns and nutrients that can be used from the bench to the bedside for chronic low-grade inflammatory status correction. In this regard, the assessment of potential effects of nutrition on macrophage differentiation, proliferation, and functioning in health and disease is highly demanded. In this review, we present current data on the effects of nutrients on the macrophage functioning.
Ribosome-Directed Therapies in Cancer
Authors: Temaj Gazmend , Chichiarelli Silvia , Eufemi Margherita , Altieri Fabio , Hadziselimovic Rifat , Farooqi Ammad Ahmad , Yaylim Ilhan , Saso Luciano
Published: August 2022

The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation.
Atherosclerosis Specific Features in Chronic Kidney Disease (CKD)
Authors: Poznyak Anastasia V. , Sadykhov Nikolay K. , Kartuesov Andrey G. , Borisov Evgeny E. , Sukhorukov Vasily N. , Orekhov Alexander N.
Published: August 2022

Atherosclerosis is the major cause of cardiovascular disease, leading to a high mortality rate worldwide. Several risk factors are known to favor atherogenesis, among which are high blood pressure, smoking, diabetes mellitus, and others. Chronic kidney disease is another serious health problem associated with significant health care costs, morbidity, and mortality. Chronic kidney disease shares several risk factors with atherosclerosis and cardiovascular diseases, such as hypertension and diabetes mellitus. Additional risk factors for cardiovascular disease development should be considered in patients with chronic kidney disease. Interestingly, patients suffering from chronic kidney disease are more prone to cardiovascular problems than the general population. Moreover, chronic kidney disease is characterized by an increased atherosclerotic burden from the very early stages. The purpose of this review was to summarize data on atherosclerosis in chronic kidney disease, highlighting the specific features of the disease combination.
Modifiable Innate Biology within the Gut–Brain Axis for Alzheimer’s Disease
Authors: Marcos Pasero Helena , García Tejedor Aurora , Giménez-Bastida Juan Antonio , Laparra Llopis José Moisés
Published: August 2022

Alzheimer’s disease (AD) is a prototypical inflammation-associated loss of cognitive function, with approximately 90% of the AD burden associated with invading myeloid cells controlling the function of the resident microglia. This indicates that the immune microenvironment has a pivotal role in the pathogenesis of the disease. Multiple peripheral stimuli, conditioned by complex and varied interactions between signals that stem at the intestinal level and neuroimmune processes, are involved in the progression and severity of AD. Conceivably, the targeting of critical innate immune signals and cells is achievable, influencing immune and metabolic health within the gut–brain axis. Considerable progress has been made, modulating many different metabolic and immune alterations that can drive AD development. However, non-pharmacological strategies targeting immunometabolic processes affecting neuroinflammation in AD treatment remain general and, at this point, are applied to all patients regardless of disease features. Despite these possibilities, improved knowledge of the relative contribution of the different innate immune cells and molecules comprising the chronically inflamed brain network to AD pathogenesis, and elucidation of the network hierarchy, are needed for planning potent preventive and/or therapeutic interventions. Moreover, an integrative perspective addressing transdisciplinary fields can significantly contribute to molecular pathological epidemiology, improving the health and quality of life of AD patients. This review is intended to gather modifiable immunometabolic processes based on their importance in the prevention and management of AD.
Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis
Authors: Ismaiel Abdulrahman , Ciobanu Oana Sabina , Ismaiel Mohamed , Leucuta Daniel-Corneliu , Popa Stefan-Lucian , David Liliana , Ensar Dilara , Al Srouji Nahlah , Dumitrascu Dan L.
Published: August 2022

(1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is important to look for alternate techniques in detecting and diagnosing NAFLD. NAFLD is associated with atherosclerosis. The purpose of this study was to assess the effectiveness of the atherogenic index of plasma (AIP) as a non-invasive modality for predicting NAFLD. (2) Methods: A search using electronic databases PubMed, EMBASE, and Scopus was carried out to find observational studies, looking at research that had been published up until the date of 11 May 2022. The included studies’ quality, risk of bias, and internal validity were evaluated using the QUADAS-2 quality assessment tool. The key summary outcomes were the mean difference (MD) and area under the curve (AUC). (3) Results: A total of eight studies (81,178 participants) were included in our review, while 17% of the included participants had NAFLD. A sex distribution of 57.8% men and 42.2% women was observed. The AIP between NAFLD and the controls was not significant (MD 0.212 [95% CI 0.231–0.655]). A significant MD in AIP between the males and females with NAFLD was observed (MD 0.246 [95% CI 0.098–0.395]). The AIP predicted NAFLD with an AUC of 0.764 as well as in males (AUC 0.761) and females (AUC 0.733). (4) Conclusions: There was a substantial MD in the AIP between both sexes, but there was no significant difference in the AIP values between patients with NAFLD and the controls. The AIP is a reliable biomarker for the diagnosis of NAFLD since its ability to predict the development of NAFLD was comparable to that of the other biomarkers.
DNAJB9 Is a Reliable Immunohistochemical Marker of Fibrillary Glomerulonephritis: Evaluation of Diagnostic Efficacy in a Large Series of Kidney Biopsies
Authors: Gambella Alessandro , Pitino Chiara , Barreca Antonella , Nocifora Alberto , Giarin Manuela Maria , Bertero Luca , Biancone Luigi , Roccatello Dario , Papotti Mauro , Cassoni Paola
Published: August 2022

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by a challenging diagnostic workup requiring ultrastructural identification of 20 nm-thick randomly oriented fibrillar deposits. However, the recent introduction of DNAJB9 as a putative diagnostic marker of FGN could thoroughly improve this diagnostic scenario. This study aims to assess the DNAJB9 immunohistochemical expression in a large series of FGN cases and to eventually confirm its role as a diagnostic marker of FGN. We evaluated the immunohistochemical expression of DNAJB9 (Rabbit Polyclonal, ThermoFisher) in a series of 77 FGN and 128 non-FGN cases diagnosed between January 1992 and June 2022 at the Pathology Unit of the AOU Città della Salute e della Scienza Hospital. DNAJB9 was expressed in 73 of the 74 evaluable FGN cases, mostly showing a strong glomerular positivity (68 cases). Additionally, DNAJB9 resulted positive in all challenging scenarios [early-stage (6), congophilic (4), combined (4), and uncertain (4) cases of FGN)]. DNAJB9 was negative in all non-FGN cases, eventually resulting in a specificity of 100% and sensitivity of 99%. In conclusion, we confirmed the role of DNAJB9 as a diagnostic marker of FGN. Its adoption in the clinical routine will allow a faster, more feasible, and more accurate FGN diagnosis.
Multilayer Electrospun-Aligned Fibroin/Gelatin Implant for Annulus Fibrosus Repair: An In Vitro and In Vivo Evaluation
Authors: Hu Ming-Hsiao , Yang Kai-Chiang , Chen Chih-Wei , Chu Po-Han , Chang Yun-Liang , Sun Yuan-Hui , Lin Feng-Huei , Yang Shu-Hua
Published: August 2022

Annulus fibrosus (AF) damage is proven to prompt intervertebral disc (IVD) degeneration, and unrepaired AF lesions after surgical discectomy may boost herniation of the nucleus pulposus (NP) which may lead to further compression of neural structures. Moreover, vascular and neural ingrowth may occur within the defect which is known as a possible reason for discogenic pain. Due to a limited healing capacity, an effective strategy to repair and close the AF defect is necessary. In this study, using electrospinning technology, two nature polymers, silk fibroin and gelatin, were linked to imitate the unique lamellae structure of native AF. Our findings revealed that a multilayer electrospun-aligned fibroin/gelatin scaffold with mechanical and morphological properties mimicking those of native AF lamellae have been developed. The average diameter of the nanofiber is 162.9 ± 38.8 nm. The young’s modulus is around 6.70 MPa with an ultimate tensile strength of around 1.81 MP along preferred orientation. The in vitro test confirmed its biocompatibility and ability to maintain cell viability and colonization. Using a porcine model, we demonstrated that the multilayer-aligned scaffold offered a crucial microenvironment to induce collagen fibrous tissue production within native AF defect. In the implant-repaired AF, H&E staining showed homogeneous fibroblast-like cell infiltration at the repaired defect with very little vascular ingrowth, which was confirmed by magnetic resonance imaging findings. Picrosirius red staining and immunohistochemical staining against type I collagen revealed positively stained fibrous tissue in an aligned pattern within the implant-integrated site. Relative to the intact control group, the disc height index of the serial X-ray decreased significantly in both the injury control and implant group at 4 weeks and 8 weeks (p < 0.05) which indicated this scaffold may not reverse the degenerative process. However, the results of the discography showed that the effectiveness of annulus repair of the implant group is much superior to that of the untreated group. The scaffold, composed with nature fibroin/gelatin polymers, could potentially enhance AF healing that could prevent IVD recurrent herniation, as well as neural and neovascular ingrowth after discectomy surgeries.
Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties
Authors: Carrera-Aubesart Adam , Defaus Sira , Pérez-Peinado Clara , Sandín Daniel , Torrent Marc , Jiménez Maria Ángeles , Andreu David
Published: August 2022

Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads.
Injectability, Processability, Drug Loading, and Antibacterial Activity of Gentamicin-Impregnated Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro
Authors: Hu Ming-Hsien , Chu Pei-Yi , Huang Ssu-Meng , Shih Bo-Sin , Ko Chia-Ling , Hu Jin-Jia , Chen Wen-Cheng
Published: August 2022

Calcium phosphate cement (CPC) is similar to bone in composition and has plasticity, while mesoporous bioactive glass (MBG) has the advantage of releasing Si, which can promote osteogenic properties and drug loading capacity. A sol–gel-prepared MBG micro-powder (mMBG) and further impregnated antibiotic gentamicin sulfate (Genta@mMBG: 2, 3, and 4 mg/mL) antibiotic were added to CPC at different weight ratios (5, 10, and 15 wt.%) to study CPC’s potential clinical applications. Different ratios of mMBG/CPC composite bone cement showed good injectability and disintegration resistance, but with increasing mMBG addition, the working/setting time and compressive strength decreased. The maximum additive amount was 10 wt.% mMBG due to the working time of ~5 min, the setting time of ~10 min, and the compressive strength of ~51 MPa, indicating that it was more suitable for clinical surgical applications than the other groups. The 2Genta@mMBG group loaded with 2 mg/mL gentamicin had good antibacterial activity, and the 10 wt.% 2Genta@mMBG/CPC composite bone cement still had good antibacterial activity but reduced the initial release of Genta. 2Genta@mMBG was found to have slight cytotoxicity, so 2Genta@mMBG was composited into CPC to improve the biocompatibility and to endow CPC with more advantages for clinical application.
Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection
Authors: Rescalli Andrea , Varoni Elena Maria , Cellesi Francesco , Cerveri Pietro
Published: August 2022

Diabetes mellitus is a worldwide-spread chronic metabolic disease that occurs when the pancreas fails to produce enough insulin levels or when the body fails to effectively use the secreted pancreatic insulin, eventually resulting in hyperglycemia. Systematic glycemic control is the only procedure at our disposal to prevent diabetes long-term complications such as cardiovascular disorders, kidney diseases, nephropathy, neuropathy, and retinopathy. Glycated albumin (GA) has recently gained more and more attention as a control biomarker thanks to its shorter lifespan and wider reliability compared to glycated hemoglobin (HbA1c), currently the “gold standard” for diabetes screening and monitoring in clinics. Various techniques such as ion exchange, liquid or affinity-based chromatography and immunoassay can be employed to accurately measure GA levels in serum samples; nevertheless, due to the cost of the lab equipment and complexity of the procedures, these methods are not commonly available at clinical sites and are not suitable to home monitoring. The present review describes the most up-to-date advances in the field of glycemic control biomarkers, exploring in particular the GA with a special focus on the recent experimental analysis techniques, using enzymatic and affinity methods. Finally, analysis steps and fundamental reading technologies are integrated into a processing pipeline, paving the way for future point-of-care testing (POCT). In this view, we highlight how this setup might be employed outside a laboratory environment to reduce the time from measurement to clinical decision, and to provide diabetic patients with a brand-new set of tools for glycemic self-monitoring.
A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma
Authors: Yang Ming-Chun , Wu Di , Sun Hui , Wang Lian-Kun , Chen Xiao-Feng
Published: August 2022

Background: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. Methods: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A’s role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. Results: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. Conclusion: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.
Effects of Sport-Based Interventions on Executive Function in Older Adults: A Systematic Review and Meta-Analysis Protocol
Authors: Contreras-Osorio Falonn , Ramirez-Campillo Rodrigo , Cerda-Vega Enrique , Campos-Jara Rodrigo , Martínez-Salazar Cristian , Arellano-Roco Cristián , Campos-Jara Christian
Published: August 2022

Background: Moderate-to-vigorous intensity exercise programs have proven to exert positive effects on the cognitive performance of older people. However, the specific effects sport-based exercise programs have on cognitive performance, upon executive functions, remain unclear. Therefore, the purpose of this study is to clarify the effects of sport-based exercise programs on executive functions in older adults, through a systematic review protocol of the scientific literature, with a meta-analysis. Methods: The search was performed in the Web of Science, PubMed, Scopus, and EBSCO electronic databases by combining keywords and different medical subject headings (MeSH) to identify and evaluate the relevant studies from inception up until June 2022. This study considers longitudinal studies with at least one experimental group and pre- and post-intervention measurements involving healthy older adults of 60 years of age or older. Studies have to consider one or more measures of executive function, including dimensions of working memory, inhibition, and cognitive flexibility, in order to meet the eligibility criteria for inclusion in this report. The Physiotherapy Evidence Database (PEDro) scale was used for methodological quality assessment studies. The DerSimonian and Laird random-effects model was used to compute the meta-analyses and report effect sizes (ES, i.e., Hedges’ g) with 95% confidence intervals (95% CIs), and a statistical significance set at p ≤ 0.05. The ES values were calculated for executive function globally and for each dimension of executive function (e.g., working memory, inhibition, cognitive flexibility) in the experimental and control/comparator groups using the mean and standard deviation values before and after the intervention period. Conclusions: Our systematic review aims to clarify the effects of sport-based exercise programs on executive functions in older adults. The results may help practitioners and stakeholders to provide better evidence-based decisions regarding sport-based exercise program implementation for older adults, and to help them to optimize cognitive functions during the aging process. Ethical permission is not required for this study. Systematic review registration: this systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42022284788).
Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor
Authors: Kackley Madison L. , Buga Alex , Crabtree Chris D. , Sapper Teryn N. , McElroy Craig A. , Focht Brian C. , Kraemer William J. , Volek Jeff S.
Published: August 2022

Brain-Derived Neurotropic Factor (BDNF) expression is decreased in conditions associated with cognitive decline as well as metabolic diseases. One potential strategy to improve metabolic health and elevate BDNF is by increasing circulating ketones. Beta-Hydroxybutyrate (BHB) stimulates BDNF expression, but the association of circulating BHB and plasma BDNF in humans has not been widely studied. Here, we present results from three studies that evaluated how various methods of inducing ketosis influenced plasma BDNF in humans. Study 1 determined BDNF responses to a single bout of high-intensity cycling after ingestion of a dose of ketone salts in a group of healthy adults who were habitually consuming either a mixed diet or a ketogenic diet. Study 2 compared how a ketogenic diet versus a mixed diet impacts BDNF levels during a 12-week resistance training program in healthy adults. Study 3 examined the effects of a controlled hypocaloric ketogenic diet, with and without daily use of a ketone-salt, on BDNF levels in overweight/obese adults. We found that (1) fasting plasma BDNF concentrations were lower in keto-adapted versus non keto-adapted individuals, (2) intense cycling exercise was a strong stimulus to rapidly increase plasma BDNF independent of ketosis, and (3) clinically significant weight loss was a strong stimulus to decrease fasting plasma BDNF independent of diet composition or level of ketosis. These results highlight the plasticity of plasma BDNF in response to lifestyle factors but does not support a strong association with temporally matched BHB concentrations.
Insights into Early Onset Colorectal Cancer through Analysis of Normal Colon Organoids of Familial Adenomatous Polyposis Patients
Authors: Devall Matthew A. , Eaton Stephen , Ali Mourad W. , Powell Steven M. , Li Li , Casey Graham
Published: August 2022

Early onset colorectal cancer (EOCRC) rates have increased in recent decades. While lowering the recommended age for routine colonoscopies to 45 may reduce this burden, such measures do not address those who develop CRC before that age. Additional measures are needed to identify individuals at-risk for CRC. To better define transcriptomic events that precede the development of CRC, we performed RNA-sequencing analysis in colon organoids derived from seven healthy and six familial adenomatous polyposis (FAP) patients. This led to the identification of 2635 significant differentially expressed genes (FDR < 0.05). Through secondary analysis of publicly available datasets, we found that these genes were enriched for significant genes also present in FAP CRC and non-hereditary CRC datasets, including a subset that were unique to EOCRC. By exposing FAP colon organoids to a three-day ethanol treatment, we found that two EOCRC-relevant genes were also targets of CRC related lifestyle factors. Our data provides unique insight into the potential, early mechanisms of CRC development in colon epithelial cells, which may provide biomarkers for patient monitoring. We also show how modifiable lifestyle factors may further alter genes relevant to EOCRC, adding weight to the hypothesis that such factors represent an important contributor to increased EOCRC incidence.
Learn to Estimate Genetic Mutation and Microsatellite Instability with Histopathology H&E Slides in Colon Carcinoma
Authors: Guo Yimin , Lyu Ting , Liu Shuguang , Zhang Wei , Zhou Youjian , Zeng Chao , Wu Guangming
Published: August 2022

Colorectal cancer is one of the most common malignancies and the third leading cause of cancer-related mortality worldwide. Identifying KRAS, NRAS, and BRAF mutations and estimating MSI status is closely related to the individualized therapeutic judgment and oncologic prognosis of CRC patients. In this study, we introduce a cascaded network framework with an average voting ensemble strategy to sequentially identify the tumor regions and predict gene mutations & MSI status from whole-slide H&E images. Experiments on a colorectal cancer dataset indicate that the proposed method can achieve higher fidelity in both gene mutation prediction and MSI status estimation. In the testing set, our method achieves 0.792, 0.886, 0.897, and 0.764 AUCs for KRAS, NRAS, BRAF, and MSI, respectively. The results suggest that the deep convolutional networks have the potential to provide diagnostic insight and clinical guidance directly from pathological H&E slides.
The Effect of Age on Prostate Cancer Survival
Authors: Clark Roderick , Vesprini Danny , Narod Steven A.
Published: August 2022

It is not clear to what extent the age of diagnosis and the attained age impact on cancer mortality rates in men with newly diagnosed prostate cancer. We estimated annual prostate cancer mortality rates and 20-year survival rates according to the age of diagnosis, race, grade and time since diagnosis using data from the Surveillance, Epidemiology and End-Results (SEER) program. We identified 116,796 prostate cancer patients diagnosed between 1992 and 1997 and followed them for 20 years. There were 21,896 deaths from prostate cancer. We calculated actuarial survival rates and annual prostate cancer mortality rates by age of diagnosis and by tumor grade. The risk of a man dying of prostate cancer was 17% for men diagnosed before age 70 and was 21% for those diagnosed after age 70. The mean annual prostate cancer mortality rate calculated over the 20-year period post-diagnosis was 1.5%. The annual rate increased from 0.9% for those diagnosed below age 60 to 2.1% for those diagnosed above age 70. For men with Gleason score ≥ 7 prostate cancer, the annual prostate cancer mortality rate peaked 2–3 years after diagnosis and then declined. For men diagnosed with Gleason score ≤ 6 prostate cancer, the annual prostate cancer mortality rate continued to rise 20 years after diagnosis and peaked after age 85. This suggests that high-grade prostate cancers are aggressive from the outset, but that low-grade prostate cancers may enter a state of dormancy and reactivate as the patient ages.
Clinical Outcomes Following Proton and Photon Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer
Authors: Bae Bong Kyung , Yang Kyungmi , Noh Jae Myung , Pyo Hongryull , Ahn Yong Chan
Published: August 2022

We aimed to report the clinical outcomes following stereotactic body radiation therapy (SBRT) using photon or proton equipment in early-stage lung cancer. We retrospectively reviewed 202 cT1-2N0M0 lung cancer patients who underwent SBRT with 60 Gy in four consecutive fractions between 2010 and 2019 at our institution: 168 photon SBRT and 34 proton SBRT. Patients who underwent proton SBRT had relatively poor baseline lung condition compared to those who underwent photon SBRT. Clinical outcomes were comparable between treatment modalities: 5-year local control (90.8% vs. 83.6%, p = 0.602); progression-free survival (61.6% vs. 57.8%, p = 0.370); overall survival (51.7% vs. 51.9%, p = 0.475); and cause-specific survival (70.3% vs. 62.6%, p = 0.618). There was no statistically significant difference in grade ≥ 2 toxicities: radiation pneumonitis (19.6% vs. 26.4%, p = 0.371); musculoskeletal (13.7% vs. 5.9%, p = 0.264); and skin (3.6% vs. 0.0%, p = 0.604). In the binary logistic regression analysis of grade ≥3 radiation pneumonitis, poor performance status and poor baseline diffusion capacity of lung for carbon monoxide were significant. To summarize, though patients with high risk of developing lung toxicity underwent proton SBRT more frequently, the SBRT techniques resulted in comparable oncologic outcomes with similar toxicity profiles. Proton SBRT could be considered for patients at high risk of radiation pneumonitis.
HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies
Authors: Uy Natalie F. , Merkhofer Cristina M. , Baik Christina S.
Published: August 2022

Human epidermal growth factor receptor 2 (HER2), a member of the ERBB family of tyrosine kinase receptors, has emerged as a therapeutic target of interest for non-small cell lung cancer (NSCLC) in recent years. Activating HER2 alterations in NSCLC include gene mutations, gene amplifications, and protein overexpression. In particular, the HER2 exon 20 mutation is now a well clinically validated biomarker. Currently, there are limited targeted therapies approved for NSCLC patients with HER2 alterations. This remains an unmet clinical need, as HER2 alterations are present in 7–27% of de novo NSCLC and may serve as a resistance mechanism in up to 10% of EGFR mutated NSCLC. There has been an influx of research on antibody–drug conjugates (ADCs), monoclonal antibodies, and tyrosine kinase inhibitors (TKIs) with mixed results. The most promising therapies are ADCs (trastuzumab-deruxtecan) and novel TKIs targeting exon 20 mutations (poziotinib, mobocertinib and pyrotinib); both have resulted in meaningful anti-tumor efficacy in HER2 mutated NSCLC. Future studies on HER2 targeted therapy will need to define the specific HER2 alteration to better select patients who will benefit, particularly for HER2 amplification and overexpression. Given the variety of HER2 targeted drugs, sequencing of these agents and optimizing combination therapies will depend on more mature efficacy data from clinical trials and toxicity profiles. This review highlights the challenges of diagnosing HER2 alterations, summarizes recent progress in novel HER2-targeted agents, and projects next steps in advancing treatment for the thousands of patients with HER2 altered NSCLC.