bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological, Structural, Thermal, Pasting, and Digestive Properties of Starches Isolated from Different Varieties of Rice: A Systematic Comparative Study
Authors: Lin Xiaojun , Zhang Xuanyi , Du Bin , Xu Baojun
Published: December 2023

The aim of this study was to compare the properties of isolated starches from ten commonly consumed rice varieties in China and to investigate their possible association. In addition, principal component analysis (PCA) and correlation analysis were performed to demonstrate the weight or relevance of different properties. The starch granules had an irregular polyhedral structure. The crystalline structure had an orthogonal arrangement, which is characteristic of A-type starch with nanocrystals with an orthorhombic crystal structure. In addition, higher levels of rapidly digestible starch (72.43 to 74.32%) and resistant starch (2.27 to 2.3%) were found in glutinous rice starch. The highest content of slowly digestible starch (59.48%) was found in starch isolated from black rice, which may be an ideal rice variety for controlling blood glucose and weight. Starch isolated from red Hani terrace rice showed the highest thermal stability during cooking and the highest resistance to a high shear force treatment. In addition, the PCA suggests that the amylose content of starch largely determines the functional properties of starch and positively correlates with the peak viscosity and setback viscosity of the starch pasting. The results of this study will enrich the scientific knowledge of various rice starches and promote their application in the food industry and other industries.
RNA-Sequencing Analysis Revealed Genes Associated with Sweet Potato (Ipomoea batatas (L.) Lam.) Responses to Stem Rot during Different Infection Stages
Authors: Li Chen , Zhang Liang , Ji Honghu , Song Weihan , Zhong Ziyu , Jiang Meiqiao , Zhang Yungang , Li Qiang , Cheng Linrun , Kou Meng
Published: December 2023

The sweet potato, which is an important tuber crop in China, is susceptible to a variety of pathogens and insect pests during cultivation and production. Stem rot is a common sweet potato disease that seriously affects tuber yield and quality. Unfortunately, there have been relatively few studies on the mechanism mediating the stem rot resistance of sweet potatoes. In this study, a transcriptome sequencing analysis was completed using Xushu 48 samples at different stages (T1, T2, and T3) of the stem rot infection. The T1 vs. T2, T1 vs. T3, and T2 vs. T3 comparisons detected 44,839, 81,436, and 61,932 differentially expressed genes (DEGs), respectively. The DEGs encoded proteins primarily involved in alanine, aspartate, and glutamate metabolism (ko00250), carbon fixation in photosynthetic organisms (ko00710), and amino sugar and nucleotide sugar metabolism (ko00520). Furthermore, some candidate genes induced by phytopathogen infections were identified, including gene-encoding receptor-like protein kinases (RLK5 and RLK7), an LRR receptor-like serine/threonine protein kinase (SERK1), and transcription factors (bHLH137, ERF9, MYB73, and NAC053). The results of this study provide genetic insights that are relevant to future explorations of sweet potato stem rot resistance, while also providing the theoretical basis for breeding sweet potato varieties that are resistant to stem rot and other diseases.
Predicting Nurse Turnover for Highly Imbalanced Data Using the Synthetic Minority Over-Sampling Technique and Machine Learning Algorithms
Authors: Xu Yuan , Park Yongshin , Park Ju Dong , Sun Bora
Published: December 2023

Predicting nurse turnover is a growing challenge within the healthcare sector, profoundly impacting healthcare quality and the nursing profession. This study employs the Synthetic Minority Over-sampling Technique (SMOTE) to address class imbalance issues in the 2018 National Sample Survey of Registered Nurses dataset and predict nurse turnover using machine learning algorithms. Four machine learning algorithms, namely logistic regression, random forests, decision tree, and extreme gradient boosting, were applied to the SMOTE-enhanced dataset. The data were split into 80% training and 20% validation sets. Eighteen carefully selected variables from the database served as predictive features, and the machine learning model identified age, working hours, electric health record/electronic medical record, individual income, and job type as important features concerning nurse turnover. The study includes a performance comparison based on accuracy, precision, recall (sensitivity), F1-score, and AUC. In summary, the results demonstrate that SMOTE-enhanced random forests exhibit the most robust predictive power in the classical approach (with all 18 predictive variables) and an optimized approach (utilizing eight key predictive variables). Extreme gradient boosting, decision tree, and logistic regression follow in performance. Notably, age emerges as the most influential factor in nurse turnover, with working hours, electric health record/electronic medical record usability, individual income, and region also playing significant roles. This research offers valuable insights for healthcare researchers and stakeholders, aiding in selecting suitable machine learning algorithms for nurse turnover prediction.
What If the Clinical and Older Adults’ Perspectives about Frailty Converge? A Call for a Mixed Conceptual Model of Frailty: A Traditional Literature Review
Authors: Khalil Asya Hani , Gobbens Robbert J. J.
Published: December 2023

Existing frailty models have enhanced research and practice; however, none of the models accounts for the perspective of older adults upon defining and operationalizing frailty. We aim to propose a mixed conceptual model that builds on the integral model while accounting for older adults’ perceptions and lived experiences of frailty. We conducted a traditional literature review to address frailty attributes, risk factors, consequences, perceptions, and lived experiences of older adults with frailty. Frailty attributes are vulnerability/susceptibility, aging, dynamic, complex, physical, psychological, and social. Frailty perceptions and lived experience themes/subthemes are refusing frailty labeling, being labeled “by others” as compared to “self-labeling”, from the perception of being frail towards acting as being frail, positive self-image, skepticism about frailty screening, communicating the term “frail”, and negative and positive impacts and experiences of frailty. Frailty risk factors are classified into socio-demographic, biological, physical, psychological/cognitive, behavioral, and situational/environmental factors. The consequences of frailty affect the individual, the caregiver/family, the healthcare sector, and society. The mixed conceptual model of frailty consists of interacting risk factors, interacting attributes surrounded by the older adult’s perception and lived experience, and interacting consequences at multiple levels. The mixed conceptual model provides a lens to qualify frailty in addition to quantifying it.
Individual Differences on Wellbeing Indices during the COVID-19 Quarantine in Greece: A National Study
Authors: Pezirkianidis Christos , Parpoula Christina , Athanasiades Christina , Flora Katerina , Makris Nikolaos , Moraitou Despina , Papantoniou Georgia , Vassilopoulos Stephanos , Sini Maria , Stalikas Anastassios
Published: December 2023

The impact of COVID-19 and the associated lockdown measures on people’s physical and mental wellbeing, as well as their daily lives and functioning, has been extensively studied. This study takes the approach of investigating the consequences of COVID-19 on a national scale, considering sociodemographic factors. The main objective is to make a contribution to ongoing research by specifically examining how age, gender, and marital status influence the overall impact of COVID-19 and wellbeing indicators during the second lockdown period that was implemented in response to the COVID-19 pandemic in the Greek population. The study involved a sample of 16,906 individuals of all age groups in Greece who completed an online questionnaire encompassing measurements related to personal wellbeing, the presence and search for meaning in life, positive relationships, as well as symptoms of depression, anxiety, and stress. Additionally, to gauge the levels of the perceived COVID-19-related impact, a valid and reliable scale was developed. The results reveal that a higher perception of COVID-19 consequences is positively associated with psychological symptoms and the search for meaning in life, while being negatively correlated with personal wellbeing and the sense of meaning in life. In terms of individual differences, the findings indicate that unmarried individuals, young adults, and females tend to report higher levels of psychological symptoms, a greater search for meaning in life, and a heightened perception of COVID-19-related impact. These findings are analyzed in depth, and suggestions for potential directions for future research are put forth.
Assessing Ethnic Minority Representation in Fibromyalgia Clinical Trials: A Systematic Review of Recruitment Demographics
Authors: Henley Peter , Martins Tanimola , Zamani Reza
Published: December 2023

The under-representation of non-White participants in Western countries in clinical research has received increased attention, due to recognized physiological differences between ethnic groups, which may affect the efficacy and optimal dosage of some treatments. This review assessed ethnic diversity in pharmaceutical trials for fibromyalgia, a poorly understood chronic pain disorder. We also investigated longitudinal change to non-White participant proportions in trials and non-White participants’ likelihood to discontinue with fibromyalgia research between trial stages (retention). First, we identified relevant trials conducted in the United States and Canada between 2000 and 2022, by searching PubMed, Web of Science, Scopus, and the Cochrane Library databases. In trials conducted both across the United States and Canada, and exclusively within the United States, approximately 90% of participants were White. A longitudinal analysis also found no change in the proportion of non-White participants in trials conducted across the United States and Canada between 2000 and 2022. Finally, we found no significant differences in trial retention between White and non-White participants. This review highlights the low numbers of ethnic minorities in fibromyalgia trials conducted in the United States and Canada, with no change to these proportions over the past 22 years. Furthermore, non-White participants were not more likely to discontinue with the fibromyalgia research once they were recruited.
Satisfaction of Basic Psychological Needs as Predictors of Motivation towards Physical Education in Primary Education: Influence of Gender and Physical Self-Concept
Authors: Prado-Botana Marta , Carretero-García Miriam , Varela-Garrote Lara , Fraguela-Vale Raúl
Published: December 2023

The aims of this study are as follows: (a) to determine the level of physical self-concept, satisfaction with basic psychological needs (BNP), and motivation towards physical education (PE) among primary education school students; (b) to analyze the correlations between the different variables; to (c) identify gender differences in the studied variables; and (d) to examine the capacity of BPN, physical self-concept, and gender as predictors of different types of motivation towards PE. The sample comprises 474 primary school students (average age = 10.58; SD = 0.626) from four educational centers in A Coruña, Spain. A multivariable linear regression analysis was conducted to determine whether independent variables of BPN, gender, and physical self-concept can predict different types of motivation towards PE. The results show that satisfaction with the BPN of autonomy is significantly lower than the other two variables. Moreover, there is a positive and significant correlation between physical self-concept and satisfaction with BPN, as well as with intrinsic, identified, and introjected motivations. Boys outperform girls in physical self-concept, satisfaction with competence and socialization BPNs, and introjected, external, and amotivation motivations. The main conclusion is that BPNs solely forecast the most self-determined motivations (intrinsic and identified), have a restricted influence on introjected motivations, and do not predict external regulation or amotivation. Neither gender nor physical self-concept significantly contributes to predicting any motivation towards PE at these ages.
Arabinose Plays an Important Role in Regulating the Growth and Sporulation of Bacillus subtilis NCD-2
Authors: Fu Yifan , Liu Xiaomeng , Su Zhenhe , Wang Peipei , Guo Qinggang , Ma Ping
Published: December 2023

A microbial fungicide developed from Bacillus subtilis NCD-2 has been registered for suppressing verticillium wilt in crops in China. Spores are the main ingredient of this fungicide and play a crucial role in suppressing plant disease. Therefore, increasing the number of spores of strain NCD-2 during fermentation is important for reducing the cost of the fungicide. In this study, five kinds of carbon sources were found to promote the metabolism of strain NCD-2 revealed via Biolog Phenotype MicroArray (PM) technology. L-arabinose showed the strongest ability to promote the growth and sporulation of strain NCD-2. L-arabinose increased the bacterial concentration and the sporulation efficiency of strain NCD-2 by 2.04 times and 1.99 times compared with D-glucose, respectively. Moreover, L-arabinose significantly decreased the autolysis of strain NCD-2. Genes associated with arabinose metabolism, sporulation, spore resistance to heat, and spore coat formation were significantly up-regulated, and genes associated with sporulation-delaying protein were significantly down-regulated under L-arabinose treatment. The deletion of msmX, which is involved in arabinose transport in the Bacillus genus, decreased growth and sporulation by 53.71% and 86.46% compared with wild-type strain NCD-2, respectively. Complementing the mutant strain by importing an intact msmX gene restored the strain’s growth and sporulation.
Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition
Authors: Ramos Sergio , Vicente-Blázquez Alba , López-Rubio Marta , Gallego-Yerga Laura , Álvarez Raquel , Peláez Rafael
Published: December 2023

Antimitotic agents are one of the more successful types of anticancer drugs, but they suffer from toxicity and resistance. The application of approved drugs to new indications (i.e., drug repurposing) is a promising strategy for the development of new drugs. It relies on finding pattern similarities: drug effects to other drugs or conditions, similar toxicities, or structural similarity. Here, we recursively searched a database of approved drugs for structural similarity to several antimitotic agents binding to a specific site of tubulin, with the expectation of finding structures that could fit in it. These searches repeatedly retrieved frentizole, an approved nontoxic anti-inflammatory drug, thus indicating that it might behave as an antimitotic drug devoid of the undesired toxic effects. We also show that the usual repurposing approach to searching for targets of frentizole failed in most cases to find such a relationship. We synthesized frentizole and a series of analogs to assay them as antimitotic agents and found antiproliferative activity against HeLa tumor cells, inhibition of microtubule formation within cells, and arrest at the G2/M phases of the cell cycle, phenotypes that agree with binding to tubulin as the mechanism of action. The docking studies suggest binding at the colchicine site in different modes. These results support the repurposing of frentizole for cancer treatment, especially for glioblastoma.
Isolation of Pro-Osteogenic Compounds from Euptelea polyandra That Reciprocally Regulate Osteoblast and Osteoclast Differentiation
Authors: Suzuki Ryuichiro , Shirataki Yoshiaki , Tomomura Akito , Bandow Kenjiro , Sakagami Hiroshi , Tomomura Mineko
Published: December 2023

Plants contain a large number of small-molecule compounds that are useful for targeting human health and in drug discovery. Healthy bone metabolism depends on the balance between bone-forming osteoblast activity and bone-resorbing osteoclast activity. In an ongoing study searching for 22 plant extracts effective against osteoporosis, we found that the crude extract of Euptelea polyandra Sieb. et Zucc (E. polyandra) had osteogenic bioactivity. In this study, we isolated two compounds, isoquercitrin (1) and astragalin (2), responsible for osteogenic bioactivity in osteoblastic MC3T3-E1 cells from the leaf of E. polyandra using column chromatography and the spectroscopic technique. This is the first report to isolate astragalin from E. polyandra. Compounds (1) and (2) promoted osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and alizarin red S stain-positive calcium deposition, while simultaneously suppressing tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation in RAW264.7 cells at non-cytotoxic concentrations. Isoquercitrin (1) and astragalin (2) increased the expression of osteoblastic differentiation genes, Osterix, ALP, and Osteoprotegerin in the MC3T3-E1 cells, while suppressing osteoclast differentiation genes, TRAP, Cathepsin K, and MMP 9 in the RAW264.7 cells. These compounds may be ideal targets for the treatment of osteoporosis due to their dual function of promoting bone formation and inhibiting bone resorption.
Selenium Dibromide Click Chemistry: The Efficient Synthesis of Novel Selenabicyclo[3.3.1]nonene-2 and -nonane Derivatives
Authors: Musalov Maxim V. , Amosova Svetlana V. , Potapov Vladimir A.
Published: December 2023

Highly efficient and convenient methods for the preparation of 35 novel derivatives of 9-selenabicyclo[3.3.1]nonane and 9-selenabicyclo[3.3.1]nonene-2 in high yields based on the adduct of the transannular addition of SeBr2 to 1,5-cyclooctadiene were developed. The methods for the amination of the adduct made it possible to obtain both diamino selenabicyclo[3.3.1]nonane derivatives and their dihydrobromide salts in one step in 88–98% yields. The methods meet the criteria of click chemistry. Compounds with high glutathione peroxidase mimetic activity were found among water-soluble dihydrobromide salts. The selective reaction of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane with acetonitrile to form 6-bromo-9-selenabicyclo[3.3.1]nonene-2 was discovered. The latter compound served as a promising starting material to give rise to the new class of selenabicyclo[3.3.1]nonene-2 derivatives, e.g., 6-alkoxy-9-selenabicyclo[3.3.1]nonenes were obtained in 94–99% yields.
The Anti-Inflammatory Effect of Multi-Wavelength Light-Emitting Diode Irradiation Attenuates Dry Eye Symptoms in a Scopolamine-Induced Mouse Model of Dry Eye
Authors: Goo Hyeyoon , Lee Yea-Jin , Lee Sangkeun , Hong Namgue
Published: December 2023

Dry eye disease is a common condition in patients of all ages, causing discomfort and potential visual problems. Current treatments, including artificial tears and anti-inflammatory drugs, have certain limitations, encouraging research into alternative therapies. We investigated the therapeutic potential of multi-wavelength light-emitting diode (LED) irradiation of mice with dry eye. First, we showed that multi-wavelength LED irradiation was non-toxic to human corneal epithelial cells and improved cell viability. We then used a scopolamine-induced mouse model of dry eye to assess the effects of multi-wavelength LED irradiation on various clinical parameters. This treatment increased the tear volume and reduced corneal irregularity, thus improving dry eye. Histological analysis revealed that multi-wavelength LED irradiation protected against corneal epithelial damage and the associated reduction in epithelial thickness and would thus improve the corneal health of dry eye patients. Multi-wavelength LED irradiation significantly reduced the corneal levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; the treatment was thus anti-inflammatory. Our results suggest that multi-wavelength LED irradiation may serve as a safe and effective treatment for dry eye, alleviating symptoms, reducing inflammation, and promoting corneal health.
The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren’s Disease from Non-Sjögren’s Sicca
Authors: George Christopher T. , Kurien Biji T. , Scofield R. Hal
Published: December 2023

Sjögren’s Disease (SjD) is an autoimmune disorder associated with decreased saliva and/or tear secretions, resulting in patients reporting dryness in the mouth and eyes. Serum autoantibodies directed against the Ro60/SS-A and La/SS-B autoantigens are a distinctive feature of the disease. Analysis of the saliva and tear proteomes represents one promising alternative method of both classifying and monitoring the condition, and research into salivary and tear proteomics in patients with SjD, with and without sicca, has shown its efficacy and practicality in both clinical and research settings. Studies analyzing the saliva proteomics of SjD patients have generally shown an overexpression of proteins involved in T-cell activation, the immune response, β-2 microglobulin, and the recruitment of pro-inflammatory agents. These studies also show a decrease in or downregulation of proteins involved in salivary secretion. Studies analyzing the tear proteomics of patients with SjD have generally indicated an upregulation of proteins involved with TNF-α signaling, B-cell survival, and the recruitment of pro-inflammatory agents. Studies also note the differential expression of tear protein folding as a hallmark of ocular involvement in this condition. These findings help to elucidate the biochemical relationship between the proteomes of saliva/tear fluids and the general pathophysiology of the gland involved with the pathogenesis of this condition, giving further credence to the potential role of salivary and tear proteomics in the future of diagnosis and treatment for patients with SjD.
Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice
Authors: Ji Ailing , Trumbauer Andrea C. , Noffsinger Victoria P. , Meredith Luke W. , Dong Brittany , Wang Qian , Guo Ling , Li Xiangan , De Beer Frederick C. , Webb Nancy R. , Tannock Lisa R. , Starr Marlene E. , Waters Christopher M. , Shridas Preetha
Published: December 2023

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.
Macromolecular Crowding and DNA: Bridging the Gap between In Vitro and In Vivo
Authors: Collette Dylan , Dunlap David , Finzi Laura
Published: December 2023

The cellular environment is highly crowded, with up to 40% of the volume fraction of the cell occupied by various macromolecules. Most laboratory experiments take place in dilute buffer solutions; by adding various synthetic or organic macromolecules, researchers have begun to bridge the gap between in vitro and in vivo measurements. This is a review of the reported effects of macromolecular crowding on the compaction and extension of DNA, the effect of macromolecular crowding on DNA kinetics, and protein-DNA interactions. Theoretical models related to macromolecular crowding and DNA are briefly reviewed. Gaps in the literature, including the use of biologically relevant crowders, simultaneous use of multi-sized crowders, empirical connections between macromolecular crowding and liquid–liquid phase separation of nucleic materials are discussed.
Synthetic Nucleic Acid Antigens in Localized Scleroderma
Authors: Khatri Sangita , Bustos Adrian H. , Jørgensen Christian Damsgaard , Torok Kathryn S. , Gjerdrum Lise-Mette Rahbek , Astakhova Kira
Published: December 2023

We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene BRAF, showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools.
KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort
Authors: Habashy Paul , Lea Vivienne , Wilkinson Kate , Wang Bin , Wu Xiao-Juan , Roberts Tara Laurine , Ng Weng , Rutland Tristan , Po Joseph William , Becker Therese , Descallar Joseph , Lee Mark , Mackenzie Scott , Gupta Ruta , Cooper Wendy , Lim Stephanie , Chua Wei , Lee Cheok Soon
Published: December 2023

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014–2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.
Cell Therapy of Vascular and Neuropathic Complications of Diabetes: Can We Avoid Limb Amputation?
Authors: Soria Bernat , Escacena Natalia , Gonzaga Aitor , Soria-Juan Barbara , Andreu Etelvina , Hmadcha Abdelkrim , Gutierrez-Vilchez Ana Maria , Cahuana Gladys , Tejedo Juan R. , De la Cuesta Antonio , Miralles Manuel , García-Gómez Susana , Hernández-Blasco Luis
Published: December 2023

Globally, a leg is amputated approximately every 30 seconds, with an estimated 85 percent of these amputations being attributed to complications arising from diabetic foot ulcers (DFU), as stated by the American Diabetes Association. Peripheral arterial disease (PAD) is a risk factor resulting in DFU and can, either independently or in conjunction with diabetes, lead to recurring, slow-healing ulcers and amputations. According to guidelines amputation is the recommended treatment for patients with no-option critical ischemia of the limb (CTLI). In this article we propose cell therapy as an alternative strategy for those patients. We also suggest the optimal time-frame for an effective therapy, such as implanting autologous mononuclear cells (MNCs), autologous and allogeneic mesenchymal stromal cells (MSC) as these treatments induce neuropathy relief, regeneration of the blood vessels and tissues, with accelerated ulcer healing, with no serious side effects, proving that advanced therapy medicinal product (ATMPs) application is safe and effective and, hence, can significantly prevent limb amputation.
In Vitro and In Vivo Evidence towards Fibronectin’s Protective Effects against Prion Infection
Authors: Garza M. Carmen , Kang Sang-Gyun , Kim Chiye , Monleón Eva , van der Merwe Jacques , Kramer David A. , Fahlman Richard , Sim Valerie L. , Aiken Judd , McKenzie Debbie , Cortez Leonardo M. , Wille Holger
Published: December 2023

A distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrPSc, in the central nervous system of prion-affected humans and animals. PrPSc is also found in peripheral tissues, raising concerns about the potential transmission of pathogenic prions through human food supplies and posing a significant risk to public health. Although muscle tissues are considered to contain levels of low prion infectivity, it has been shown that myotubes in culture efficiently propagate PrPSc. Given the high consumption of muscle tissue, it is important to understand what factors could influence the establishment of a prion infection in muscle tissue. Here we used in vitro myotube cultures, differentiated from the C2C12 myoblast cell line (dC2C12), to identify factors affecting prion replication. A range of experimental conditions revealed that PrPSc is tightly associated with proteins found in the systemic extracellular matrix, mostly fibronectin (FN). The interaction of PrPSc with FN decreased prion infectivity, as determined by standard scrapie cell assay. Interestingly, the prion-resistant reserve cells in dC2C12 cultures displayed a FN-rich extracellular matrix while the prion-susceptible myotubes expressed FN at a low level. In agreement with the in vitro results, immunohistopathological analyses of tissues from sheep infected with natural scrapie demonstrated a prion susceptibility phenotype linked to an extracellular matrix with undetectable levels of FN. Conversely, PrPSc deposits were not observed in tissues expressing FN. These data indicate that extracellular FN may act as a natural barrier against prion replication and that the extracellular matrix composition may be a crucial feature determining prion tropism in different tissues.
Extraciliary OFD1 Is Involved in Melanocyte Survival through Cell Adhesion to ECM via Paxillin
Authors: Kim Nan-Hyung , Lee Chang Hoon , Lee Ai-Young
Published: December 2023

Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral–facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. However, it remains unknown whether primary cilia are involved in the control of melanocyte apoptosis. While both intraflagellar transport 88 (IFT88) and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) are associated with ciliogenesis in melanocytes, only the knockdown of OFD1, but not IFT88 and RPGRIP1L, resulted in increased melanocyte apoptosis. OFD1 knockdown led to a decrease in the expression of proteins involved in cell–extracellular matrix (ECM) interactions, including paxillin. The OFD1 amino acid residues 601-1012 interacted with paxillin, while the amino acid residues 1-601 were associated with ciliogenesis, suggesting that the OFD1 domains responsible for paxillin binding are distinct from those involved in ciliogenesis. OFD1 knockdown, but not IFT88 knockdown, inhibited melanocyte adhesion to the ECM, a defect that was restored by paxillin overexpression. In summary, our findings indicate that the downregulation of OFD1 induces melanocyte apoptosis, independent of any impairment in ciliogenesis, by reducing melanocyte adhesion to the ECM via paxillin.
Akt Is Controlled by Bag5 through a Monoubiquitination to Polyubiquitination Switch
Authors: Bracho-Valdés Ismael , Cervantes-Villagrana Rodolfo Daniel , Beltrán-Navarro Yarely Mabell , Olguín-Olguín Adán , Escobar-Islas Estanislao , Carretero-Ortega Jorge , Olivares-Reyes J. Alberto , Reyes-Cruz Guadalupe , Gutkind J. Silvio , Vázquez-Prado José
Published: December 2023

The serine-threonine kinase Akt plays a fundamental role in cell survival, metabolism, proliferation, and migration. To keep these essential processes under control, Akt activity and stability must be tightly regulated; otherwise, life-threatening conditions might prevail. Although it is well understood that phosphorylation regulates Akt activity, much remains to be known about how its stability is maintained. Here, we characterize BAG5, a chaperone regulator, as a novel Akt-interactor and substrate that attenuates Akt stability together with Hsp70. BAG5 switches monoubiquitination to polyubiquitination of Akt and increases its degradation caused by Hsp90 inhibition and Hsp70 overexpression. Akt interacts with BAG5 at the linker region that joins the first and second BAG domains and phosphorylates the first BAG domain. The Akt-BAG5 complex is formed in serum-starved conditions and dissociates in response to HGF, coincident with BAG5 phosphorylation. BAG5 knockdown attenuated Akt degradation and facilitated its activation, whereas the opposite effect was caused by BAG5 overexpression. Altogether, our results indicate that Akt stability and signaling are dynamically regulated by BAG5, depending on growth factor availability.
Novel Relationship between Mitofusin 2-Mediated Mitochondrial Hyperfusion, Metabolic Remodeling, and Glycolysis in Pulmonary Arterial Endothelial Cells
Authors: Yegambaram Manivannan , Sun Xutong , Flores Alejandro Garcia , Lu Qing , Soto Jamie , Richards Jaime , Aggarwal Saurabh , Wang Ting , Gu Haiwei , Fineman Jeffrey R. , Black Stephen M.
Published: December 2023

The disruption of mitochondrial dynamics has been identified in cardiovascular diseases, including pulmonary hypertension (PH), ischemia-reperfusion injury, heart failure, and cardiomyopathy. Mitofusin 2 (Mfn2) is abundantly expressed in heart and pulmonary vasculature cells at the outer mitochondrial membrane to modulate fusion. Previously, we have reported reduced levels of Mfn2 and fragmented mitochondria in pulmonary arterial endothelial cells (PAECs) isolated from a sheep model of PH induced by pulmonary over-circulation and restoring Mfn2 normalized mitochondrial function. In this study, we assessed the effect of increased expression of Mfn2 on mitochondrial metabolism, bioenergetics, reactive oxygen species production, and mitochondrial membrane potential in control PAECs. Using an adenoviral expression system to overexpress Mfn2 in PAECs and utilizing 13C labeled substrates, we assessed the levels of TCA cycle metabolites. We identified increased pyruvate and lactate production in cells, revealing a glycolytic phenotype (Warburg phenotype). Mfn2 overexpression decreased the mitochondrial ATP production rate, increased the rate of glycolytic ATP production, and disrupted mitochondrial bioenergetics. The increase in glycolysis was linked to increased hypoxia-inducible factor 1α (HIF-1α) protein levels, elevated mitochondrial reactive oxygen species (mt-ROS), and decreased mitochondrial membrane potential. Our data suggest that disrupting the mitochondrial fusion/fission balance to favor hyperfusion leads to a metabolic shift that promotes aerobic glycolysis. Thus, therapies designed to increase mitochondrial fusion should be approached with caution.
Transcriptomic Analyses Reveal the Role of Cytokinin and the Nodal Stem in Microtuber Sprouting in Potato (Solanum tuberosum L.)
Authors: Zhang Xia , Fujino Kaien , Shimura Hanako
Published: December 2023

In potatoes, tuber secondary growth, especially sprouting, deforms the tubers and severely lowers their commercial value. Tuber sprouting is induced by signal substances, such as gibberellin (GA), which are transported to the tuber from the plant body. The molecular mechanism underlying GA-induced sprouting remains ambiguous. Here, we tried to recreate tuber secondary growth using in vitro stemmed microtubers (MTs) (with the nodal stem attached) and MT halves (with the nodal stem entirely removed). Our experiments showed that GA alone could initiate the sprouting of stemmed microtubers; however, GA failed to initiate MT halves unless 6-benzyladenine, a synthetic cytokinin CK, was co-applied. Here, we analyzed the transcriptional profiles of sprouting buds using these in vitro MTs. RNA-seq analysis revealed a downregulation of cytokinin-activated signaling but an upregulation of the “Zeatin biosynthesis” pathway, as shown by increased expression of CYP735A, CISZOG, and UGT85A1 in sprouting buds; additionally, the upregulation of genes, such as IAA15, IAA22, and SAUR50, associated with auxin-activated signaling and one abscisic acid (ABA) negative regulator, PLY4, plays a vital role during sprouting growth. Our findings indicate that the role of the nodal stem is synonymous with CK in sprouting growth, suggesting that CK signaling and homeostasis are critical to supporting GA-induced sprouting. To effectively control tuber sprouting, more effort is required to be devoted to these critical genes.
OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette–Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway
Authors: Alonso João Carlos Cardoso , de Souza Bianca Ribeiro , Reis Ianny Brum , de Arruda Camargo Gabriela Cardoso , de Oliveira Gabriela , de Barros Frazão Salmazo Maria Izabel , Gonçalves Juliana Mattoso , de Castro Roston José Ronaldo , Caria Paulo Henrique Ferreira , da Silva Santos André , de Freitas Leandro Luiz Lopes , Billis Athanase , Durán Nelson , Fávaro Wagner José
Published: December 2023

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients’ mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1–2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.
Alternative Synthesis of MCM-41 Using Inexpensive Precursors for CO2 Capture
Authors: Aquino Guillermo D. , Moreno M. Sergio , Piqueras Cristian M. , Benedictto Germán P. , Pereyra Andrea M.
Published: December 2023

We explore the use of industrial sources of silicon and surfactant for obtaining low-cost MCM-41 materials and evaluate their performances as CO2 adsorbents. All of them presented a high specific surface area with different structural characteristics and textural properties. Interestingly, the MCM-41 manufactured with the most economical reagents presented a SBET of 1602 m2·g−1. The template was removed by using thermal treatments in an air atmosphere or a washing process. Preservation of silanol groups proved to be more effective under washing or mild thermal treatment conditions with the advantage of their lower cost and environmental benefit. Surface reactivity against CO2 was enhanced by anchoring APTS to silanol groups through wet grafting. All amino-functionalized materials showed a performance as CO2 adsorbents comparable to those reported in the literature, reaching values close to 30 cm3·g−1 at 25 °C and 760 mmHg. Samples with a higher concentration of silanol groups showed better performance. Our studies indicate that adsorbed CO2 is retained at least up to 50 °C, and the CO2 is chemisorbed on the silica modified with amine groups. The chemisorbed gas at very low pressures points to the potential use of these materials for CO2 storage.
Overview and Commissioning Status of the UCLA MITHRA Facility
Authors: Williams Oliver , Fukasawa Atsushi , Sakai Yusuke , Andonian Gerard , Bosco Fabio , Carillo Martina , Manwani Pratik , O’Tool Sean , Pan Jessica , Yadav Monika , Rosenzweig James
Published: December 2023

Presented here are the first results of commissioning of the S-Band hybrid photoinjector and laser systems at the new accelerator and light source facility, MITHRA, at UCLA. The radiation bunker and capabilities of the facility are described with motivation for detailed measurement of beam parameters explained. Following thorough characterization of the photoinjector, a 1.5 m linac is to be installed and experiments up to 30 MeV will begin. These will include experiments in basic plasma physics, space plasma, terahertz production in dielectric structures, and inverse Compton scattering and applications for the X-rays produced.
Use of Silicon Photomultipliers in the Detectors of the JEM-EUSO Program
Authors: Bisconti Francesca
Published: December 2023

The JEM-EUSO program aims to study ultra-high energy cosmic rays from space. To achieve this goal, it has realized a series of experiments installed on the ground (EUSO-TA), various on stratospheric balloons (with the most recent one EUSO-SPB2), and inside the International Space Station (Mini-EUSO), in light of future missions such as K-EUSO and POEMMA. At nighttime, these instruments aim to monitor the Earth’s atmosphere measuring fluorescence and Cherenkov light produced by extensive air showers generated both by very high-energy cosmic rays from outside the atmosphere and by neutrino decays. As the two light components differ in duration (order of microseconds for fluorescence light and a few nanoseconds for Cherenkov light) they each require specialized sensors and acquisition electronics. So far, the sensors used for the fluorescence camera are the Multi-Anode Photomultiplier Tubes (MAPMTs), while for the Cherenkov one, new systems based on Silicon PhotoMultipliers (SiPMs) have been developed. In this contribution, a brief review of the experiments is followed by a discussion of the tests performed on the optical sensors. Particular attention is paid to the development, test, and calibration conducted on SiPMs, also in view to optimize the geometry, mass, and weight in light of the installation of mass-critical applications such as balloon- and space-borne instrumentation.
Embolization of Perforated Coronary Artery with a Fragment of Balloon Catheter (Cut Balloon Technique)—Multicenter Study
Authors: Sobieszek Grzegorz , Zięba Bartosz , Dworzański Wojciech , Celiński Rafał , Barbero Umberto , Opolski Maksymilian P.
Published: December 2023

Background: Iatrogenic distal coronary artery perforation can be a life-threatening complication. While there are different dedicated devices for the embolization of distal perforations, there are scarce data about the embolization using the fragmented balloon catheter, the so-called cut balloon technique (CBT). Methods: We included consecutive patients with distal coronary perforations treated with CBT in four cardiac centers between 2017 and 2023. Clinical, angiographic and procedural characteristics as well as in-hospital outcomes were recorded. Results: Twenty-six patients (68% men, mean age: 71 ± 10.6 years) with 25 distal coronary perforations and one septal collateral perforation were included. Eleven patients (42%) had elective percutaneous coronary intervention, while fifteen patients (58%) were treated for acute coronary syndrome. The site of perforation was most frequently distributed in the left anterior descending artery (40%), followed by the circumflex artery (28%) and right coronary artery (24%). The diameter of balloons for CBT ranged from 1.5 to 4.0 mm, with most balloons (76%) being either 2.0 or 2.5 mm in diameter. Most balloons (88%) were previously used for lesion predilatation. The numbers of cut balloons needed to seal the perforation were 1, 2 and ≥3 in 48%, 20% and 32% of cases, respectively. The in-hospital prognosis was favorable, with cardiac tamponade requiring pericardiocentesis in only four (16%) patients. Neither emergency surgery nor cardiac death occurred. Conclusions: CBT is a safe, efficient and easy-to-implement technique for the embolization of coronary perforations. Most distal coronary perforations can be sealed with one or two fragments of cut balloons, obviating the need for additional devices.