bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty as a Predictor of Hospitalization and Low Quality of Life in Geriatric Patients at an Internal Medicine Outpatient Clinic: A Cross-Sectional Study
Authors: Limpawattana Panita , Khammak Chudapha , Manjavong Manchumad , So-ngern Apichart
Published: September 2022

Frailty is an aging-associated state that increases patients’ vulnerability to disease, and can lead to various adverse outcomes. It is classified as either physical frailty alone or physical frailty in combination with cognitive impairment (cognitive frailty). There are currently limited data available regarding the prevalence and adverse outcomes of frailty in Thailand. This was a cross-sectional study aimed at determining the prevalence of physical and cognitive frailty and their effects on hospitalization and quality of life. Participants were older patients who attended an internal medicine outpatient clinic. Frailty was diagnosed using the Thai Frailty Index. The Thai version of the MoCA was used to evaluate cognitive status. Univariate and multivariate analyses were performed to compare adverse outcomes in terms of poor quality of life and history of admission to hospital between patients with frailty and non-frail patients, and among patients with physical frailty, cognitive frailty, cognitive impairment, and robust (non-frail and non-cognitively impaired) patients. We enrolled 198 participants. The prevalence of physical and cognitive frailty was 28.78% and 20.70%, respectively. When compared with non-frail patients, frailty was associated with hospitalization (adjusted OR 3.01, p = 0.002) but was not significantly related to quality of life (adjusted OR = 1.98, p = 0.09). However, physical and cognitive frailty were associated with fair quality of life when compared with normal patients (adjusted OR = 4.34, p = 0.04 and adjusted OR = 4.28, p = 0.03, respectively). The prevalence of frailty—particularly cognitive frailty—was high. Frailty was associated with adverse outcomes in terms of hospitalization and quality of life.
Sex-Specific Association between Fasting Plasma Glucose and Serum Selenium Levels in Adults from Southern Mexico
Authors: Rios-Lugo María Judith , Palos-Lucio Ana Gabriela , Victoria-Campos Claudia Inés , Lugo-Trampe Angel , Trujillo-Murillo Karina Del Carmen , López-García Maximiliano Arahon , Espinoza-Ruiz Marisol , Romero-Guzmán Elizabeth Teresita , Hernández-Mendoza Héctor , Chang-Rueda Consuelo
Published: September 2022

Selenium (Se) is an essential trace element that by its antioxidant properties has been studied to elucidate its participation in the development of obesity and type 2 diabetes. We evaluated the association between cardiometabolic traits and serum Se levels in a sample of adults from southern Mexico. In 96 nondiabetic individuals, anthropometric data and clinical biochemistry measurements were analyzed. Serum total Se levels were measured with inductively coupled plasma mass spectrometry (ICP-MS). Serum Se level in the whole sample was 10.309 ± 3.031 μg mL−1 and no difference between the women and men was observed (p = 0.09). Additionally, fasting plasma glucose (FPG) was significantly associated with serum Se level (β = −0.07 ± 0.03, p = 0.02, analysis adjusted for age, sex and BMI). Furthermore, sex shows significant interaction with FPG on the serum Se levels (p = 0.01). A follow-up analysis revealed the particular association between FPG and Se levels in women (β = −0.10 ± 0.04, p = 0.01). In conclusion, our data evidenced a women-specific association between FPG and serum Se levels in a sample of adults from southern Mexico.
Comparative Analysis of Complete Chloroplast Genome and Phenotypic Characteristics of Japanese Apricot Accessions
Authors: Coulibaly Daouda , Huang Xiao , Ting Shi , Iqbal Shahid , Ni Zhaojun , Ouma Kenneth Omondi , Hayat Faisal , Tan Wei , Hu Guofeng , Ma Chengdong , Karikari Benjamin , Magdy Mahmoud , Gao Zhihong
Published: September 2022

Japanese apricot (Prunus mume Sieb. et Zucc.) is among the most valued fruits and flowering plants in eastern Asia. However, few comparative studies have been conducted with respect to its agro-morphological and pomological traits, chloroplast (cp) genome sequences and plastid diversity. Therefore, a comparative study was, conducted to investigate the divergence and geographic distribution of ten Japanese apricot accessions from three Chinese provinces (Zhejiang, Jiangsu and Sichuan). Phenotypic characteristics of the evaluated accessions, such as leaf length, tip leaf length, flower diameter, anther number, fruit weight, longitudinal height, transversal height, lateral height, fruit stone weight, stone longitudinal height, stone transversal height, stone lateral heigh, titratable acid content and total soluble solids, varied significantly (p < 0.05) among the ten investigated accessions. On the other hand, most of the investigated accessions were statistically similar within the same province. Comparing the Cp genomes of P. mume accessions with those of the genus Prunus revealed a similarity in structure and composition with slight differences. “Bayes empirical Bayes” (BEB) analysis in Prunus species, including P. mume, revealed BEB in rps16, rps3, rpoC1(4*), rpl32, rpl16, rbcL, psbF, petB, ndhF, clpP and ccsA genes. The BEB value of the rpoC1 gene is higher than 0.95, indicating that it is potentially under positive selection. Interestingly, the accessions from the same province of origin had the same number of forward repeat sequences. Furthermore, all accessions from Zhejiang province had the same number of simple sequence repeats. Similarly, nucleotide deletion/insertion of the ycf1 sequence and the results of phylogenetic trees revealed that accessions were mainly clustered according to their province of origin. Our comparative study of agronomical traits, chloroplast composition, structure, nucleotide variability of cp genome and phylogeography in Japanese apricot accessions provides valuable information on their diversity and geographic distribution.
I Need to Know: Using the CeHRes Roadmap to Develop a Treatment Feedback Tool for Youngsters with Mental Health Problems
Authors: Bongers Ilja L. , Buitenweg David C. , van Kuijk Romy E. F. M. , van Nieuwenhuizen Chijs
Published: September 2022

Patient-Reported Outcome Measures (PROMs) are often used to monitor treatment outcomes in youth mental health care. Unfortunately, youngsters are rarely informed about the results of their PROMs or, when they are, it is in an insufficient manner. Therefore, a web application was developed—together with youngsters—aimed at giving them feedback about their PROMs. The aim of this study is to describe the development process of the application. An expert panel consisting of youngsters, web designers and researchers, as well as a representative from a client organisation, developed the e-health application INK (short for ‘I Need to Know’) in an iterative process based on the Centre for eHealth Research roadmap (CeHRes roadmap). Youngsters prefer, among other aspects, a simple, easy-to-use e-health application with a colourful appearance and want to be able to compare their results across different time points and informants. The INK tool provides youngsters with insight into their PROM results. Based on the youngsters’ preferences, INK users can choose which feedback information is visible. INK facilitates youngsters’ active participation in their treatment as well as shared decision-making with their professional caregivers.
Dementia-Associated Compulsive Singing (DACS): Presentation of Unpublished Clinical Cases Miniseries
Authors: De Masi Roberto , Orlando Stefania , Costa Maria Carmela
Published: September 2022

Dementia-associated compulsive singing (DACS) is a neurotransmettitorial-based behavioral disturbance, characterized by an unabating melodic expression, occurring in patients that suffer from evolved dementia. Previously described only as a “punding” aspect of the dopamine dysregulation syndrome (DDS) in the Parkinson’s disease (PD), compulsive singing has now been described, for the first time, in four non-PD patients effectively treated with Haloperidol or Quetiapine. Unlike the DDS-associated conditions, in our cases DACS is not pharmacologically induced, being that all patients were L-dopa-free. We detected a diffuse hyperintensity of the white matter and brain atrophy, with insular shrinkage as well as ventricular system and/or sub-arachnoid space enlargement in our DACS patients. Furthermore, similarly to the other behavioral symptoms of dementia, DACS also seems to be correlated to the degree of cognitive and functional impairment, rather than its subtype. In conclusion, DACS is a non-cognitive, unpublished clinical aspect of evolved dementia, which is interesting due to the involvement of the extra-nigral dopaminergic system, resulting in an unabating altered behavior, but also to the enrichment of our knowledge in the involutional diseases of the central nervous system and their physiopathological manifestations.
A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes
Authors: Malaza Nompumelelo , Masete Matladi , Adam Sumaiya , Dias Stephanie , Nyawo Thembeka , Pheiffer Carmen
Published: September 2022

Pregestational type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gestational diabetes mellitus (GDM) are associated with increased rates of adverse maternal and neonatal outcomes. Adverse outcomes are more common in women with pregestational diabetes compared to GDM; although, conflicting results have been reported. This systematic review aims to summarise and synthesise studies that have compared adverse pregnancy outcomes in pregnancies complicated by pregestational diabetes and GDM. Three databases, Pubmed, EBSCOhost and Scopus were searched to identify studies that compared adverse outcomes in pregnancies complicated by pregestational T1DM and T2DM, and GDM. A total of 20 studies met the inclusion criteria and are included in this systematic review. Thirteen pregnancy outcomes including caesarean section, preterm birth, congenital anomalies, pre-eclampsia, neonatal hypoglycaemia, macrosomia, neonatal intensive care unit admission, stillbirth, Apgar score, large for gestational age, induction of labour, respiratory distress syndrome and miscarriages were compared. Findings from this review confirm that pregestational diabetes is associated with more frequent pregnancy complications than GDM. Taken together, this review highlights the risks posed by all types of maternal diabetes and the need to improve care and educate women on the importance of maintaining optimal glycaemic control to mitigate these risks.
The Appraisal of Self-Care Agency Scale-Revised (ASAS-R): Reliability and Validity among Portuguese Medical Students
Authors: Oliveira Lídia , Teixeira Andreia , Duarte Ivone
Published: September 2022

Self-care agency plays an important role in an individual’s health. Considering the particularities of their education, it can be a protective factor for the mental health of medical students. This study aims to validate the Portuguese version of the Appraisal of Self-care Agency Scale-Revised (ASAS-R) in Portuguese medical students. A cross-sectional, quantitative, and analytical online study was conducted between 23 April 2021, and 15 July 2021. Exploratory factor analysis (EFA) was performed to test the internal structure of the ASAS-R. Correlations with the SHS (Subjective Happiness Scale), SWLS (Satisfaction with Life Scale), and MHI (Mental Health Inventory) were calculated using Pearson’s coefficient so as to test convergent validity. Internal consistency was evaluated using inter-item correlation, corrected item-total correlation, and Cronbach’s alpha. The total sample included 781 individuals. EFA yielded a 3-factor solution accounting for 53.9% of the explained variance. Pearson’s coefficients obtained between the 3 factors of ASAS-R and the total scores of the 3 construct-related scales demonstrated adequate convergent validity. Total Cronbach’s alpha value was 0.85, while the Cronbach’s alpha of the three factors was 0.81, 0.55, and 0.83, respectively. This study demonstrated that ASAS-R is a valid and reliable instrument for measuring self-care agency among Portuguese medical students.
Ageing and Long-Term Informal Care: The Reality of Two Countries in Europe: Denmark and Portugal
Authors: Maia Ana Catarina , Nogueira Paulo , Henriques Maria Adriana , Farinha Carla , Costa Andreia
Published: September 2022

The knowledge of long-term informal care is particularly interesting for social and health measures related to ageing. This study aims to analyze how Portugal differs from Denmark regarding long-term informal care, specifically referring to personal care received by older people. A cross-sectional study was developed in Portugal and Denmark through the Survey of Health, Ageing and Retirement in Europe (SHARE) in 2015, with a total of 2891 participants. Descriptive statistics and logistic regressions were performed. The findings suggest a significant association for older people from Portugal who receive long-term informal care from non-household caregivers and household caregivers. Moreover, as they age and are from Portugal, their availability to receive long-term informal care from non-household caregivers increases. Furthermore, older people in Portugal are more likely to receive long-term informal care from a household caregiver. It is important to take a closer look at long-term informal care in both countries and think about healthy ageing policies in the current context of the ageing population. This study provides knowledge about disaggregated health data on ageing in the European region, helping to fill research gaps related to older people.
Influence of Upper Footwear Material Properties on Foot Skin Temperature, Humidity and Perceived Comfort of Older Individuals
Authors: Li Pui-Ling , Yick Kit-Lun , Yip Joanne , Ng Sun-Pui
Published: September 2022

Studying the in-shoe microclimate of older individuals is important for enhancing their foot comfort and preventing foot diseases. However, there is a lack of scientific work that explores the thermo-physiological wear comfort of older individuals with different footwear. This study aims to examine the effects of upper footwear materials on changes and distributions in the foot skin temperature and relative humidity for older individuals. Forty older individuals are recruited to perform sitting and walking activities under four experimental conditions in a conditioning chamber. The findings indicate that footwear upper constructed of highly permeable mesh fabric with large air holes shows fewer changes in foot skin temperature (ranging from 1.3 to 3.3 °C) and relative humidity (ranging from −13.3 to 5.7%) throughout the entire foot during dynamic walking, as well as higher subjective ratings on perceived thermal comfort when compared to footwear made of synthetic leather and composite layers. The findings serve to enhance current understanding of designing footwear with optimum comfort for older adults.
Grading Nursing Care Study in Integrated Medical and Nursing Care Institution Based on Two-Stage Gray Synthetic Clustering Model under Social Network Context
Authors: Xu Lan , Zhang Yu
Published: September 2022

Establishing a scientific and sustainable grading nursing care evaluation system is the key to realizing the rational distribution of medical and nursing resources in the combined medical and nursing care services. This study establishes a grading nursing care index system for medical and nursing institutions from both medical and nursing aspects, and proposes a grading nursing care evaluation model based on a combination of interval-valued intuitionistic fuzzy entropy and a two- stage gray synthetic clustering model for interval gray number under a social network context. Through case analysis, the proposed method can directly classify the elderly into corresponding grading nursing care grades and realize the precise allocation of medical and nursing resources, which proves the feasibility of the method.
HRV-Guided Training for Elders after Stroke: A Protocol for a Cluster-Randomized Controlled Trial
Authors: Carrasco-Poyatos María , Granero-Gallegos Antonio , López-García Ginés D. , López-Osca Rut
Published: September 2022

There are many consequences associated with having a stroke, all of which are important factors affecting long-term rehabilitation outcomes; these become important health issues for those of advanced age and require dedicated health strategies. High-intensity interval training (HIIT) is an effective training protocol used in cardiac rehabilitation programs; however, owing to the inter-individual variability in physiological responses to training associated with cardiovascular diseases, the exercise regimen given to each patient should be closely controlled and individualized to ensure the safety and efficiency of the exercise program. Heart rate variability (HRV) is currently being used for this purpose, as it is closely linked to parasympathetic nervous system activation, with high HRV scores associated with good cardiovascular adaptation. The objective of this protocol is to determine the effect of HIIT compared to HRV-guided training in terms of cardiorespiratory fitness, heart rate variability, functional parameters, body composition, quality of life, inflammatory markers, and cognitive function in patients who have had a stroke, as well as to assess the feasibility of patients undertaking an 8-week cardiac rehabilitation program, evaluating its safety and their adherence. The proposed protocol involved cluster-randomized controlled design in which the post-stroke patients are assigned either to an HRV-based training group (HRV-G) or a HIIT-based training group (HIIT-G). HIIT-G will train according to a predefined training program, whereas HRV-G will train depending on the patients’ daily HRV. The outcomes considered are peak oxygen uptake (VO2peak), endothelial and work parameters, heart rate variability, functional parameters, relative weight and body fat distribution, quality of life, inflammatory markers and cognitive function, as well as exercise adherence, feasibility, and safety. It is expected that this HRV-guided training protocol will improve functional performance in patients following a stroke and be safer, more feasible, and generate improved adherence relative to HIIT, providing an improved strategy for to optimize cardiac rehabilitation interventions.
Effect Mechanism Research of Carbon Price Drivers in China—A Case Study of Shenzhen
Authors: Chen Jiongwen , Zhang Jinsuo
Published: September 2022

Revealing the effect mechanism of carbon price drivers is the basis to establish the pricing mechanism of carbon emission exchange, which also promotes the development of the carbon emission exchange market and can reduce the investment risk. Based on the previous research, the cointegration test, Granger causality test, and ridge regression estimate are used to analyze the effect mechanism between the domestic carbon price and its drivers. Johansen’s cointegration analysis reveals that there is a long-term equilibrium relationship between the domestic carbon price and energy price, industrial development level, climate change, and financial prosperity. Ridge regression estimates reveal that the international spot price of thermal coal in the ARA port and the spot price of Brent crude oil in Britain are negatively correlated with the domestic carbon price, while CER futures price is positively correlated with the domestic carbon price. There is a linkage between the international carbon price and the domestic carbon price. Since 2017, the domestic carbon price has been lower than the equilibrium value, and the value of carbon emission rights has been underestimated. With the continuous improvement of the domestic carbon market, the carbon price will rise and fluctuate around the equilibrium price in the future.
Relationship between Attention Capacity and Hand–Eye Reaction Time in Adolescents between 15 and 18 Years of Age
Authors: Huerta Ojeda Álvaro , Lizama Tapia Patricio , Pulgar Álvarez Jaime , González-Cruz Claudia , Yeomans-Cabrera María-Mercedes , Contreras Vera Juan
Published: September 2022

Some experiences demonstrate a direct correlation between attention capacity and reaction capacity. However, the evidence from adolescents enrolled in the Chilean school system is scarce. The purpose of this study was to determine the relationship between attention capacity and hand–eye reaction time (RT) in adolescents between 15 and 18 years of age. Thirty-one adolescents participated voluntarily in this study. The variables were: attention capacity, evaluated through the Evalúa-10 battery (item 1.1), and hand–eye RT, assessed through a simple RT test (SRT) and complex RT (CRT). The relationship between the variables was performed through Pearson’s correlation. Comparisons between males and females were performed with the t-test for independent samples (p ˂ 0.05). There was a moderate correlation between attention and CRT (r = −0.43), a very high correlation between attention and SRT in males (r = −0.73), and between attention and CRT in females (r = −0.73). Between males and females, there was no difference in attention (p ˃ 0.05), while males showed better RT in all tests (p ˂ 0.05). Attention positively influences hand–eye RT in both males and females. Likewise, male adolescents present better hand–eye RT than their female peers.
Lack of Associations between Environmental Exposures and Environmental Enteric Dysfunction among 18-Month-Old Children in Rural Malawi
Authors: Liu Zhifei , Fan Yue-Mei , Ashorn Per , Chingwanda Chilungamo , Maleta Kenneth , Hallamaa Lotta , Hyöty Heikki , Chaima David , Ashorn Ulla
Published: September 2022

Environmental enteric dysfunction (EED) is common and contributes to linear growth faltering (stunting) and mortality among children in low-resource settings. A few studies on the environmental causes of EED have been conducted but the exact exposures that cause or predispose children to EED are context-specific and not clear. This study aimed to assess associations between selected environmental exposures and EED markers among 620 18-month-old children. This was a secondary analysis of data from Malawian children who participated in a randomized controlled trial (iLiNS-DYAD, registered at clinicaltrials.gov as NCT01239693) from birth to 18 months of age. Data on environmental exposures, including drinking water source, sanitation, exposure to animals, housing materials, season, residential area, and food insecurity were collected at enrolment. Biomarkers of EED included concentrations of calprotectin, regenerating 1B protein (REG1B), and alpha-1-antitrypsin from stool samples to assess intestinal inflammation, repair, and permeability, respectively. We performed bivariate and multivariable analyses to assess associations between environmental exposures and EED biomarkers. Adjusting for possible confounders, we did not find associations between the selected environmental exposures and the three biomarkers. These results do not provide support for our hypothesis that the studied adverse environmental exposures are associated with increased concentrations of children’s EED markers in rural Malawi.
Proof of Concept for the Detection with Custom Printed Electrodes of Enterobactin as a Marker of Escherichia coli
Authors: Canciu Alexandra , Cernat Andreea , Tertis Mihaela , Botarca Silvia , Bordea Madalina Adriana , Wang Joseph , Cristea Cecilia
Published: September 2022

The rapid and decentralized detection of bacteria from biomedical, environmental, and food samples has the capacity to improve the conventional protocols and to change a predictable outcome. Identifying new markers and analysis methods represents an attractive strategy for the indirect but simpler and safer detection of pathogens that could replace existing methods. Enterobactin (Ent), a siderophore produced by Escherichia coli or other Gram-negative bacteria, was studied on different electrode materials to reveal its electrochemical fingerprint—very useful information towards the detection of the bacteria based on this analyte. The molecule was successfully identified in culture media samples and a future goal is the development of a rapid antibiogram. The presence of Ent was also assessed in wastewater and treated water samples collected from the municipal sewage treatment plant, groundwater, and tap water. Moreover, a custom configuration printed on a medical glove was employed to detect the target in the presence of another bacterial marker, namely pyocyanin (PyoC), that being a metabolite specific of another pathogen bacterium, namely Pseudomonas aeruginosa. Such new mobile and wearable platforms offer considerable promise for rapid low-cost on-site screening of bacterial contamination.
Targeting Lineage-Specific Transcription Factors and Cytokines of the Th17/Treg Axis by Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Attenuates TNBS-Induced Experimental Colitis
Authors: Szandruk-Bender Marta , Wiatrak Benita , Dzimira Stanisław , Merwid-Ląd Anna , Szczukowski Łukasz , Świątek Piotr , Szeląg Adam
Published: September 2022

The pharmacotherapy of inflammatory bowel disease (IBD) is still not fully effective and safe. Attempts to search for new IBD drugs remain an incessant research aim. One of the novel approaches is targeting the developmental pathway molecules and effector cytokines of Th17/Treg axis. This study aimed to elucidate the impact of new pyrrolo[3,4-d]pyridazinone derivatives, compounds 7b, 10b, or 13b, on the course of experimental colitis in rats and to assess whether these new compounds may influence Th17/Treg axis. Rats were pretreated with studied compounds intragastrically before intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid used for colitis induction. Body weight loss, disease activity index, colon index, and colon tissue damage were analyzed to evaluate the severity of colitis. The colonic levels of RORγt, STAT3, CCR6, Foxp3, IL-6, IL-10, IL-17, TNF-α, IL-23, and PGE2 were assessed. Pretreatment with compounds 7b and 13b alleviated the severity of colitis and concomitantly counteracted the increased levels of RORγt, STAT3, CCR6, IL-6, IL-17, IL-23, TNF-α, and PGE2. The beneficial effect of compounds 7b and 13b may be due to the decrease in the levels of Th17-specific transcription factors and cytokines. The studied compounds might therefore constitute a promising therapeutic strategy in Th17/Treg imbalance-driven inflammatory conditions such as IBD.
Gene Expression Landscape of Chronic Myeloid Leukemia K562 Cells Overexpressing the Tumor Suppressor Gene PTPRG
Authors: Lombardi Giulia , Latorre Roberta Valeria , Mosca Alessandro , Calvanese Diego , Tomasello Luisa , Boni Christian , Ferracin Manuela , Negrini Massimo , Dewik Nader Al , Yassin Mohamed , Ismail Mohamed A. , Carpentieri Bruno , Sorio Claudio , Lecca Paola
Published: September 2022

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context.
HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells
Authors: Beteta-Göbel Roberto , Miralles Marc , Fernández-Díaz Javier , Rodríguez-Lorca Raquel , Torres Manuel , Fernández-García Paula , Escribá Pablo V. , Lladó Victoria
Published: September 2022

Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.
OsRAD51 Plays a Vital Role in Promoting Homologous Recombination in Rice Meiosis
Authors: Liu Xiaofei , Cao Yiwei , Du Guijie , Zhang Chao , Xu Meng , Cheng Zhukuan , Shen Yi , Yu Hengxiu
Published: September 2022

Meiotic recombination plays a pivotal role in achieving accurate chromosomal segregation and increasing genetic diversity. In the homologous recombination pathway, the detailed mechanisms of how OsRAD51 and OsDMC1 work in rice meiosis remain to be explored. Here, we obtained different types of mutants for Osrad51a1, Osrad51a2, Osdmc1a, and Osdmc1b through CRISPR/Cas9. Both Osrad51a1 and Osrad51a2 exhibited normal vegetative growth and fertility. Osrad51 (Osrad51a1 Osrad51a2) mutant plants show normal vegetative growth but exhibit complete sterility, indicating that OsRAD51A1 and OsRAD51A2 are functionally redundant in rice fertility. In contrast to the wild type, Osrad51 chromosomes are not paired perfectly at pachytene and synaptonemal complex (SC) formation is deficient. Moreover, univalents and multivalent associations were observed at metaphase I, chromosome fragments presented at anaphase I, and crossover formation is basically suppressed in Osrad51 pollen mother cells (PMCs). OsRAD51 foci emerge at leptotene and disappear from late pachytene and chromosome localization of OsRAD51 depends on the formation of double-strand breaks (DSBs). Most OsRAD51 foci can co-localize with OsDMC1 signals. OsRAD51 is essential for the loading of OsDMC1 onto chromosomes, and vice versa. In addition, both OsRAD51 and OsDMC1 can interact with OsFIGL1 and OsBRCA2, two important components in rice meiosis. Moreover, the Osrad51 Osdmc1 (Osrad51a1 Osrad51a2 Osdmc1a Osdmc1b) quadruple mutant PMCs exhibited similar defective phenotypes as Osrad51 in homologous pairing, synapsis, and DSB repair. Taken together, our results suggest that the recombinases DMC1 and RAD51 may functionally depend on each other and play important roles in meiotic recombination during meiosis in rice.
Characterization of Vemurafenib-Resistant Melanoma Cell Lines Reveals Novel Hallmarks of Targeted Therapy Resistance
Authors: Radić Martina , Vlašić Ignacija , Jazvinšćak Jembrek Maja , Horvat Anđela , Tadijan Ana , Sabol Maja , Dužević Marko , Herak Bosnar Maja , Slade Neda
Published: September 2022

Regardless of the significant improvements in treatment of melanoma, the majority of patients develop resistance whose mechanisms are still not completely understood. Hence, we generated and characterized two melanoma-derived cell lines, primary WM793B and metastatic A375M, with acquired resistance to the RAF inhibitor vemurafenib. The morphology of the resistant primary WM793B melanoma cells showed EMT-like features and exhibited a hybrid phenotype with both epithelial and mesenchymal characteristics. Surprisingly, the vemurafenib-resistant melanoma cells showed a decreased migration ability but also displayed a tendency to collective migration. Signaling pathway analysis revealed the reactivation of MAPK and the activation of the PI3K/AKT pathway depending on the vemurafenib-resistant cell line. The acquired resistance to vemurafenib caused resistance to chemotherapy in primary WM793B melanoma cells. Furthermore, the cell-cycle analysis and altered levels of cell-cycle regulators revealed that resistant cells likely transiently enter into cell cycle arrest at the G0/G1 phase and gain slow-cycling cell features. A decreased level of NME1 and NME2 metastasis suppressor proteins were found in WM793B-resistant primary melanoma, which is possibly the result of vemurafenib-acquired resistance and is one of the causes of increased PI3K/AKT signaling. Further studies are needed to reveal the vemurafenib-dependent negative regulators of NME proteins, their role in PI3K/AKT signaling, and their influence on vemurafenib-resistant melanoma cell characteristics.
A Study of the Buffer Capacity of Polyelectrolyte Microcapsules Depending on Their Concentration and the Number of Layers of the Polyelectrolyte Shell
Authors: Musin Egor V. , Dubrovskii Alexey V. , Kim Aleksandr L. , Tikhonenko Sergey A.
Published: September 2022

Polyelectrolyte microcapsules are used in the development of new forms of targeted delivery systems, self-healing materials, sensors, and smart materials. Nevertheless, their buffer capacity has not been practically studied, although that characteristic makes it possible to estimate the change in the state of protonation of the entire polyelectrolyte system. This is necessary both for creating a buffer barrier system for pH-sensitive compounds (metals, enzymes, polyelectrolytes, drugs) and for the correct interpretation of the results of research and studying of the PMC structure. The buffer capacity of a PMC can be affected by the concentration of microcapsules in solution and the number of shell layers since the listed parameters affect other physicochemical properties of the PMC shell. This includes, for example, the electrical conductivity, permeability (of ions), osmotic pressure, charge density, etc. In this regard, we studied the change in the buffer capacity of polyelectrolyte microcapsules depending on their concentration and the number of shell layers. As a result, it was found that with an increasing concentration of microcapsules, the buffering capacity of the PMC increases, but at the same time, in the pH range from 4 to 5.5, the calculated buffering capacity of 1 billion capsules decreases with increasing their concentration. This effect may be associated with a decrease in the available -NH2 groups of the PMC’s shell. In addition, it was found that the main contribution to the buffer capacity of a PMC is made by the entire shell of the microcapsule and not just its surface. At the same time, the buffer capacity of the capsules has non-linear growth with an increase in the number of PMC shell layers. It is presumably associated either with a decrease in the polyelectrolyte layer with an increase in their number or with a decrease in the permeability of hydrogen protons.
Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP/PS1 Mice by Upregulating AdipoR1 Levels
Authors: Jian Ye , Yuan Shunling , Yang Jialun , Lei Yong , Li Xuan , Liu Wenfeng
Published: September 2022

Abnormalities in autophagy are associated with Alzheimer’s disease (AD)-like lesions. Studies have shown that exercise can significantly improve AD autophagy abnormalities, but the mechanism underlying this phenomenon remains unclear. APN not only has an important regulatory effect on AD autophagy abnormalities, but also is affected by exercise. Therefore, this study aims to reveal the pathway by which exercise regulates abnormal autophagy in AD using the APN–AdipoR1 signaling pathway as an entry point. The results of the study showed that APP/PS1 double transgenic AD model mice (24 weeks) showed decreased AdipoR1 levels in the brain, abnormal autophagy, increased Aβ deposition, and increased cell apoptosis, and dendritic spines and cognitive function were reduced. Twelve weeks of aerobic exercise enhanced lysosomes and alleviated abnormal autophagy by activating the AdipoR1/AMPK/TFEB signaling pathway in the brains of AD mice, thereby alleviating Aβ deposition and its associated AD-like abnormalities. These findings suggest that the AdipoR1 plays an important role in aerobic exercise’s alleviation of abnormal autophagy in AD brain cells and alleviation of AD-like lesions.
Integrated Transcriptome and Targeted Metabolite Analysis Reveal miRNA-mRNA Networks in Low-Light-Induced Lotus Flower Bud Abortion
Authors: Ren Huihui , Xu Yingchun , Lixie Hongsheng , Kuang Jiaying , Wang Yanjie , Jin Qijiang
Published: September 2022

Most Nelumbo nucifera (lotus) flower buds were aborted during the growing season, notably in low-light environments. How lotus produces so many aborted flower buds is largely unknown. An integrated transcriptome and targeted metabolite analysis was performed to reveal the genetic regulatory networks underlying lotus flower bud abortion. A total of 233 miRNAs and 25,351 genes were identified in lotus flower buds, including 68 novel miRNAs and 1108 novel genes. Further enrichment analysis indicated that sugar signaling plays a potential central role in regulating lotus flower bud abortion. Targeted metabolite analysis showed that trehalose levels declined the most in the aborting flower buds. A potential regulatory network centered on miR156 governs lotus flower bud abortion, involving multiple miRNA-mRNA pairs related to cell integrity, cell proliferation and expansion, and DNA repair. Genetic analysis showed that miRNA156-5p-overexpressing lotus showed aggravated flower bud abortion phenotypes. Trehalose-6-P synthase 1 (TPS1), which is required for trehalose synthase, had a negative regulatory effect on miR156 expression. TPS1-overexpression lotus showed significantly decreased flower bud abortion rates both in normal-light and low-light environments. Our study establishes a possible genetic basis for how lotus produces so many aborted flower buds, facilitating genetic improvement of lotus’ shade tolerance.
Exosomes in Cancer Diagnosis and Therapy
Authors: Ahmad Aamir
Published: September 2022

Cancer affects millions of people worldwide every year [...]
Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks
Authors: Godoy César A. , Pardo-Tamayo Juan S. , Barbosa Oveimar
Published: September 2022

Processes involving lipases in obtaining active pharmaceutical ingredients (APIs) are crucial to increase the sustainability of the industry. Despite their lower production cost, microbial lipases are striking for their versatile catalyzing reactions beyond their physiological role. In the context of taking advantage of microbial lipases in reactions for the synthesis of API building blocks, this review focuses on: (i) the structural origins of the catalytic properties of microbial lipases, including the results of techniques such as single particle monitoring (SPT) and the description of its selectivity beyond the Kazlauskas rule as the “Mirror-Image Packing” or the “Key Region(s) rule influencing enantioselectivity” (KRIE); (ii) immobilization methods given the conferred operative advantages in industrial applications and their modulating capacity of lipase properties; and (iii) a comprehensive description of microbial lipases use as a conventional or promiscuous catalyst in key reactions in the organic synthesis (Knoevenagel condensation, Morita–Baylis–Hillman (MBH) reactions, Markovnikov additions, Baeyer–Villiger oxidation, racemization, among others). Finally, this review will also focus on a research perspective necessary to increase microbial lipases application development towards a greener industry.
Perfluorobutanoic Acid (PFBA) Induces a Non-Enzymatic Oxidative Stress Response in Soybean (Glycine max L. Merr.)
Authors: Omagamre Eguono W. , Mansourian Yeganeh , Liles Diamond , Tolosa Tigist , Zebelo Simon A. , Pitula Joseph S.
Published: September 2022

Short-chain perfluoroalkyl substances (PFAS) are generally considered to be of less environmental concern than long-chain analogues due to their comparatively shorter half-lives in biological systems. Perfluorobutanoic acid (PFBA) is a short-chain PFAS with the most root–shoot transfer factor of all PFAS. We investigated the impact of extended exposure of soybean plants to irrigation water containing environmentally relevant (100 pg–100 ng/L) to high (100 µg–1 mg/L) concentrations of PFBA using phenotypical observation, biochemical characterization, and transcriptomic analysis. The results showed a non-monotonous developmental response from the plants, with maximum stimulation and inhibition at 100 ng/L and 1 mg/L, respectively. Higher reactive oxygen species and low levels of superoxide dismutase (SOD) and catalase (CAT) activity were observed in all treatment groups. However transcriptomic analysis did not demonstrate differential expression of SOD and CAT coding genes, whereas non-enzymatic response genes and pathways were enriched in both groups (100 ng/L and 1 mg/L) with glycine betaine dehydrogenase showing the highest expression. About 18% of similarly downregulated genes in both groups are involved in the ethylene signaling pathway. The circadian rhythm pathway was the only differentially regulated pathway between both groups. We conclude that, similar to long chain PFAS, PFBA induced stress in soybean plants and that the observed hormetic stimulation at 100 ng/L represents an overcompensation response, via the circadian rhythm pathway, to the induced stress.
Delving into the Heterogeneity of Different Breast Cancer Subtypes and the Prognostic Models Utilizing scRNA-Seq and Bulk RNA-Seq
Authors: Xu Jieyun , Qin Shijie , Yi Yunmeng , Gao Hanyu , Liu Xiaoqi , Ma Fei , Guan Miao
Published: September 2022

Background: Breast cancer (BC) is the most common malignancy in women with high heterogeneity. The heterogeneity of cancer cells from different BC subtypes has not been thoroughly characterized and there is still no valid biomarker for predicting the prognosis of BC patients in clinical practice. Methods: Cancer cells were identified by calculating single cell copy number variation using the inferCNV algorithm. SCENIC was utilized to infer gene regulatory networks. CellPhoneDB software was used to analyze the intercellular communications in different cell types. Survival analysis, univariate Cox, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were used to construct subtype specific prognostic models. Results: Triple-negative breast cancer (TNBC) has a higher proportion of cancer cells than subtypes of HER2+ BC and luminal BC, and the specifically upregulated genes of the TNBC subtype are associated with antioxidant and chemical stress resistance. Key transcription factors (TFs) of tumor cells for three subtypes varied, and most of the TF-target genes are specifically upregulated in corresponding BC subtypes. The intercellular communications mediated by different receptor–ligand pairs lead to an inflammatory response with different degrees in the three BC subtypes. We establish a prognostic model containing 10 genes (risk genes: ATP6AP1, RNF139, BASP1, ESR1 and TSKU; protective genes: RPL31, PAK1, STARD10, TFPI2 and SIAH2) for luminal BC, seven genes (risk genes: ACTR6 and C2orf76; protective genes: DIO2, DCXR, NDUFA8, SULT1A2 and AQP3) for HER2+ BC, and seven genes (risk genes: HPGD, CDC42 and PGK1; protective genes: SMYD3, LMO4, FABP7 and PRKRA) for TNBC. Three prognostic models can distinguish high-risk patients from low-risk patients and accurately predict patient prognosis. Conclusions: Comparative analysis of the three BC subtypes based on cancer cell heterogeneity in this study will be of great clinical significance for the diagnosis, prognosis and targeted therapy for BC patients.
NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth
Authors: Xu Ke , Chu Yanhao , Liu Qin , Fan Wenguo , He Hongwen , Huang Fang
Published: September 2022

Protein ubiquitination is a precisely controlled enzymatic cascade reaction belonging to the post-translational modification of proteins. In this process, E3 ligases catalyze the binding of ubiquitin (Ub) to protein substrates and define specificity. The neuronally expressed developmentally down-regulated 4 (NEDD4) subfamily, belonging to the homology to E6APC terminus (HECT) class of E3 ligases, has recently emerged as an essential determinant of multiple cellular processes in different tissues, including bone and tooth. Here, we place special emphasis on the regulatory role of the NEDD4 subfamily in the molecular and cell biology of osteogenesis. We elucidate in detail the specific roles, downstream substrates, and upstream regulatory mechanisms of the NEDD4 subfamily. Further, we provide an overview of the involvement of E3 ligases and deubiquitinases in the development, repair, and regeneration of another mineralized tissue—tooth.