bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability and validity of the Shona version of the Exercise Benefits and Barriers Scale in Zimbabwean adult people living with HIV/AIDS
Authors: Dambi Jermaine M. , Domingue Ben , Abas Melanie , Chibanda Dixon , Esterhuizen Tonya M.
Published: August 2023

Introduction

Despite the widely known benefits of physical activity (PA), only 25% of people living with HIV (PLHIV) meet the WHO-recommended minimum PA levels. Consequently, it is essential to understand PA barriers and facilitators using objective measures. Although the Exercise Benefits and Barriers Scale (EBBS) is extensively used, its psychometric evidence is fragmented and has not been previously validated in PLHIV. This study aimed to translate and validate the EBBS Shona version in Zimbabwean PLHIV.

Methods

A cross-sectional study was used to recruit 567 PLHIV from four (4/9) randomly selected polyclinics (primary healthcare facilities) in urban Harare, Zimbabwe. We recruited adult patients (aged ≥18 years) with a confirmed diagnosis of HIV. Participants had to be willing to provide informed consent, not acutely unwell, and proficient in the Shona language. We used a forward-backwards translation method to translate the EBBS from English to Shona, a native Zimbabwean language. After cross-cultural adaptation, we pretested the draft version in 10 PLHIV to assess the face validity, understandability and cultural appropriateness using semi-structured interviews. Thereafter, the EBBS was administered to 567 consecutively-selected PLHIV. Factor analyses were performed for construct validity evaluation.

Results

Most participants were female (72.5%) and reached secondary/high school (78.8%), with a mean age of 39.9 (SD 12.1) years. The EBBS-Shona version yielded a four-factor solution consisting of three benefits factors and one barrier factor against the originally postulated six-factor structure. The EBBS-Shona yielded α = 0.85 and intraclass correlation coefficient = 0.86, demonstrating excellent reliability. Increased perception of exercise benefits was positively correlated with increased reports of physical activity, higher health-related quality of life and lower psychiatric morbidity; evidence for construct validity.

Discussion

This study demonstrates the validity and reliability of the EBBS-Shona version in Zimbabwean PLHIV. The EBBS-Shona version can be used for research and clinical purposes to glean data to inform the development, implementation, and evaluation of bespoke PA interventions for PLHIV.
On the trail of Sisyphus – addiction as an existential neurosis?
Authors: Unterrainer Human-Friedrich
Published: August 2023

In Greek mythology, Sisyphus, king of the Corinthians, dared to deceive the gods and was condemned to roll a boulder to the top of a mountain for all eternity. Shortly before reaching the summit, however, the boulder rolled back down into the valley, and the arduous task had to begin anew. Many of the contents of this classic myth are reminiscent of the therapeutic approach to addictive disorders. In addiction therapy, too, it is often a long and rocky road that ends with a relapse. The therapeutic effort was not entirely in vain, but one often begins to doubt its usefulness. In terms of Sisyphus and a Bio-Psycho-Social Model (BPSM) of health and disease, addiction can be located at the end of a downward spiral. By extension of the BPSM, can addictive disease be considered an expression of existential neurosis? The results of our own research speak in favor of this and show a clearly reduced experience of sense and meaning, but also diminished feelings of hope and forgiveness in addiction patients. However, positive correlations between various parameters of existential well-being and mental health or more appropriate stress coping are also found for the addiction group. These results are supported by neuronal correlates and are mirrored in the general population. Based on this, the consideration of existential issues in addiction therapy can be discussed. Finally, the use of art therapy and work training are proposed as examples of a meaning based therapeutic intervention in dealing with people with addictive diseases.
The pharmacy as a primary care provider
Authors: Mor Nachiket , Sen Dyuti , Zaheen Sarah , Khan Rubayat , Naik Priya , Basu Nayonika
Published: August 2023

Introduction

Primary care is an essential component of any health system, but building high-quality primary care has proven to be a challenge for most developing countries. Among the multiplicity of providers in South Asia, one of the most ubiquitous channels through which not only medicines are obtained but also primary care advice is sought is the neighborhood pharmacy. There are widespread availability of pharmacies in South Asia. There is also good evidence that working with pharmacies in this way is a globally accepted idea, and there are several examples of countries, such as France and Nigeria, that have integrated pharmacies into their primary care systems and entrusted them with significant responsibilities.

Methods

In this paper, we explore the potential of this channel as a formal primary care provider, with a particular focus on the South Asian context, by examining how pharmacies perform against the seven Starfield attributes of (i) first contact care, (ii) continuity of care, (iii) comprehensiveness, (iv) coordination, (v) family centredness, (vi) cultural competency, and (vii) community orientation. In the paper, we use data on pharmacies from four pharmacy-related interventions, one from Bangladesh and three from India, to carry out our analysis using the Qualitative Comparative Analysis (QCA) framework.

Results

We find that even in the South Asian context, pharmacies provide several components of good primary care. As expected, they demonstrate a strong orientation toward the community in which they are located and are able to provide first-contact care. However, we find no direct evidence that they are able to offer continuity of care or bring to bear family-centredness and cultural competency when dealing with their patients. It is encouraging, however, that while there is no formal evidence of this in any of the interventions, multiple anecdotal examples suggest that pharmacists do indeed do much of this, but perhaps in an informal and inconsistent manner.

Discussion

The evidence from these studies provides support for the view that pharmacies have many of the inherent characteristics needed to become an effective primary care channel and already play an important role in providing access to health information and care. However, it is also clear from the research that without additional training and access to tools, pharmacies will not have the competency or knowledge necessary to provide these services or even act as an effective gateway to other healthcare providers. To fully unlock this opportunity, therefore, any organization that wishes to engage with them will need to have the vision and patience to work with this network for an extended period of time and not merely aspire for incremental improvements but have a strategy in place that fundamentally changes the capabilities and the roles that pharmacies can play.
Young sociologists in the mirror: digital ethnographies of young people online
Authors: Crescenzo Nadia
Published: August 2023

The aim of the paper is to analyze how the qualitative method represents a tool capable of analyzing the youth experience in the digital context. The contribution takes as a starting point the results of a didactic exercise experimented in the course of “Sociology of youth cultures” by the students of the University of Salerno in which the qualitative method of netnography was applied to study some youth practices online. During the work carried out, the qualitative method represented a way to study the universe of young people, entering the “new digital habitats,” where young people create and reproduce relationships, identities and spaces for socializing. The results showed, first of all, how the method of netnography made it possible to analyze the contours and transformations of youth practices in digital spaces, and secondly it allowed to arouse “reflexivity” in young people, it allowed to activate a process in which young people have looked at themselves “in the mirror,” entering the folds of the virtual worlds of youth and are amazed at the way in which they represent themselves, becoming observers and observers of that same reality. The qualitative approach has therefore allowed the students to grasp the youth practices in which they are immersed in their daily life from another point of view and have had the opportunity to analyze them from the inside and develop a high degree of reflexivity that it helped to reach a different awareness of being young today and of being able to read the cultural dynamics of youth with a critical eye.
Assessing the impact of drum drying on the nutritional properties of pineapple pomace-fortified crispy mushroom sheets
Authors: Suthiluk Phunsiri , Naradisorn Matchima , Setha Sutthiwal
Published: August 2023

The processing of ‘Phulae’ pineapple fruit for juice generates a significant by-product called pineapple pomace (PAP) that has attracted interest from the functional snack industry. Pineapple pomace (PAP) is rich source of dietary fiber and antioxidants, which make it suitable for incorporating into mushroom products that are rich in high protein content. To investigate the impact of drum drying parameters on the physicochemical properties of PAP, response surface methodology (RSM) was employed for optimization of processing parameters such as steaming temperature (130 to 170°C) and rotation speed (1 to 3 rpm). The aim was to determine the optimal conditions for achieving the highest yield of diphenylpicrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and soluble dietary fiber (SDF), which are important indicators of antioxidant activity and dietary fiber content. These optimal conditions would be used in the production of crispy Pleurotus sajor-caju (PS-PAP) and Lentinus squarrosulus (LS-PAP) sheets both of which were supplemented with PAP. The response of PS-PAP and LS-PAP to the independent variables (steaming temperature and rotation speed) was adequately described by a second-order polynomial equation. The equations demonstrated a high degree of fit with respect to DPPH (R2 = 0.9693 for PS-PAP sheet and R2 = 0.9966 for LS-PAP sheet), FRAP (R2 = 0.9908 for PS-PAP sheet and R2 = 0.9877 for LS-PAP sheet), and SDF (R2 = 0.9689 for PS-PAP sheet and R2 = 0.9598 for LS-PAP sheet). Moreover, the experimental values of the dependent variables closely matched the predicted values, indicating the reliability of the generated models. It was evident that both steaming temperature and rotation speed significantly influenced DPPH, FRAP, and SDF contents and the optimized conditions could be employed for the production of functional crispy mushroom sheets. In conclusion, the study’s novelty lies in the optimization of PAP drum drying parameters for the production of functional crispy mushroom sheets. The research creates opportunities for sustainable and nutritious products, and future perspectives could include sensory evaluation, nutritional analysis, shelf-life studies, market potential and environmental impact assessment. Overall, this research contributes to the development of healthier and eco-friendly food options.
Delayed surgical management of rectovaginal fistula: a case report highlighting challenges and lessons learned
Authors: Drusany Starič Kristina , Distefano Rosario Emanuele Carlo , Campo Giorgia , Norčič Gregor
Published: August 2023

Background

Rectovaginal fistulas following an obstetric anal sphincter injury's repair are rare in developed country and their management could be challenging, particularly in cases of delayed repair. This study emphasizes the importance of accurately diagnosing and promptly repairing such fistulas for optimal patient well-being.

Case

A 30-year-old patient presented with gas incontinence and a greenish discharge from the vagina, 6 months after delivering her baby. Examination revealed a small pinhole lesion on the posterior vaginal wall, and an endoanal ultrasound confirmed the presence of a rectovaginal fistula. Surgical repair was delayed for 9 months due to the patient's breastfeeding. The fistula was eventually repaired through a transrectal approach, with excision of the fistulous tract and closure of both the rectum and vagina. A laparoscopic protective ileostomy was also performed due to the delayed repair. However, a recurrence of the fistula was detected 8 months later, requiring a second repair. The patient underwent physiotherapy for the anal sphincter and achieved optimal sphincter function. After 6 months, the ileostomy was successfully closed, and the patient remained continent.

Conclusions

This case highlights the importance of early recognition and prompt repair of rectovaginal fistulas following obstetric anal sphincter injury. Delayed repairs pose greater challenges and increase the risk of recurrence. Individualized surgical approaches, skilled pelvic floor repair, and a multidisciplinary approach are crucial for successful outcomes. This case underscores the need for careful planning and consideration of patient characteristics in the management of rectovaginal fistulas, aiming to achieve optimal outcomes and patient well-being.
Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation: A Novel Strategy?
Authors: Veltkamp Denise M. J. , Nijhoff Michiel F. , van den Broek Dennis A. J. , Buntinx Maren , Kers Jesper , Engelse Marten A. , Huurman Volkert A. L. , Roelen Dave L. , Heidt Sebastiaan , Alwayn Ian P. J. , de Koning Eelco J. P. , de Vries Aiko P. J.
Published: August 2023

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation. The pancreas allograft was removed because of progressively painful pancreatic panniculitis from clinically uncontrolled chronic rejection. The endocrine function was preserved. Induction treatment for this “islet alloautotransplantation” consisted of plasmapheresis, IVIg and alemtuzumab. At 1 year, the patient retained islet graft function with good glycemic control and absence of severe hypoglycemia, despite persistent low-grade HLA donor-specific antibodies. His panniculitis had resolved completely. In our point of view, islet alloautotransplantation derived from a chronically rejecting pancreas allograft is a potential option to salvage (partial) islet function, despite preformed donor-specific antibodies, in order to maintain stable glycemic control. Thereby it protects against severe hypoglycemia, and it potentially mitigates kidney graft dysfunction and other diabetes-related complications in patients with continued need for immunosuppression and who are otherwise difficult to retransplant.
Distribution of Alien and Translocated Freshwater Fish Species in Bulgarian Lotic Ecosystems, according to the WFD Classification
Authors: Apostolou Apostolos
Published: August 2023

The terms ‘non-native’, ‘non-indigenous’, ‘alien’, and ‘exotic’ refer to species or races that do not occur naturally in an area, i.e., they have not previously existed there, or their dispersal into the area has been mediated by humans. In a broad sense, these terms can refer to species that may originate within the same region or country but not occur naturally in a particular water body until colonization is facilitated by humans. In Bulgaria, some efforts have been made to summarize the distribution of alien fish species, but nothing is known about the translocated species. Here, both groups are considered according to the Water Framework Directive’s (WFD) classification of lotic ecosystems: the main ichthyogeographical regions, the river typology, and the ecological status of the Biological Quality Element (BQE) “Fish”. In total, 7 alien species and 15 translocated species were established, with approximately the same total number of specimens. In general, even though the relative abundance of non-native species reaches 100% in single cases, their total numbers are low, compared to native species. Concerning certain basins/river types, these percentages are slightly higher, due to a complex of parameters determining their distribution: environmental factors (hydromorphological) reflecting the ecological (species’ requirements and tolerance) factors. Some river types are more vulnerable to colonization. The relative abundances of the non-native fish species per sampling site showed a weak connection with the ecological status of the BQE “Fish”. As the distribution of organisms is affected by environmental parameters and biotic interactions, standardized multiannual data, as viewed by the WFD, could become a solid basis for elucidating various aspects of this complex issue.
Memory Effects, Multiple Time Scales and Local Stability in Langevin Models of the S&P500 Market Correlation
Authors: Wand Tobias , Heßler Martin , Kamps Oliver
Published: August 2023

The analysis of market correlations is crucial for optimal portfolio selection of correlated assets, but their memory effects have often been neglected. In this work, we analyse the mean market correlation of the S&P500, which corresponds to the main market mode in principle component analysis. We fit a generalised Langevin equation (GLE) to the data whose memory kernel implies that there is a significant memory effect in the market correlation ranging back at least three trading weeks. The memory kernel improves the forecasting accuracy of the GLE compared to models without memory and hence, such a memory effect has to be taken into account for optimal portfolio selection to minimise risk or for predicting future correlations. Moreover, a Bayesian resilience estimation provides further evidence for non-Markovianity in the data and suggests the existence of a hidden slow time scale that operates on much slower times than the observed daily market data. Assuming that such a slow time scale exists, our work supports previous research on the existence of locally stable market states.
Design Consideration on a Low-Cost Permanent Magnetization Remanufacturing Method for Low-Efficiency Induction Motors
Authors: Zhou Peng , Xu Yanliang , Zhang Wenji
Published: August 2023

At present, a large number of inefficient induction motors (IMs) are still being used in various industrial fields, resulting in a huge waste of energy. Obviously, it is expensive to replace all these machines with high-efficiency motors. Therefore, this paper will investigate the method of low-cost modification of inefficient IMs and propose a low-cost permanent magnetization remanufacturing (PMR) method that can make full use of the original structure of IMs. The PMR method converts the IM’s rotor into a permanent magnet (PM) rotor by directly milling slots in the original rotor and embedding PMs, thus improving the efficiency of the original motor to meet the IE4 standard. Firstly, this paper proposes the PMR process of IM, and based on this process, a Y2-132M1-6 IM is designed for remanufacturing, and the performance of the motor before and after the PMR is compared through finite-element analysis. Then, this paper researches the factors that may affect the starting performance and rated performance of the motor in the PMR design. Finally, based on the PMR design scheme, the Y2-132M1-6 IM is remanufactured into an experimental prototype. The total cost of the PMR is calculated and the performance improvement is tested through experiments.
Integrating Electric Vehicles to Power Grids: A Review on Modeling, Regulation, and Market Operation
Authors: Jia Heping , Ma Qianxin , Li Yun , Liu Mingguang , Liu Dunnan
Published: August 2023

Fossil energy consumption and environmental protection issues have pushed electric vehicles (EVs) to become one of the alternatives to traditional fossil-fuel vehicles. EV refers to a vehicle that uses electric energy as power and is driven by an electric motor. The electric energy of EVs is stored in batteries. When the EV is not traveling, the battery can provide power for other loads. Therefore, with the increase in the number of EVs and the load of the power grid, the EV-to-grid (V2G) mode, which uses EVs to supply power to the power grid, has gradually entered the field of vision of researchers. The physical connection mode, charge and discharge technology, and energy management strategy are the main topics of the current review papers; however, there is a lack of systematic research on V2G modeling, framework, and business models. This paper describes the concepts of the spatio-temporal distribution model and the adjustable capacity of EVs. In addition, common constraints and methods in optimization are introduced. Moreover, this paper introduces the interactive relationship among power grids, load aggregators, and EV users. Furthermore, the business model of V2G is introduced and analyzed from various perspectives. Finally, the future development of V2G is pointed out. This paper’s goal is to provide an overview of the present V2G application scenarios and to identify any challenges that must be overcome.
Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves
Authors: Rahman Aminur , Roy Kumar Jyotirmoy , Deb Gautam Kumar , Ha Taehyeong , Rahman Saifur , Aktar Mst. Khudishta , Ali Md. Isahak , Kafi Md. Abdul , Choi Jeong-Woo
Published: August 2023

This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and the development of antiviral nanomaterials with physical antagonistic features of viral replication checkpoints as such a solution. Our detailed discussion of SARS-CoV-2 replication and pathogenesis highlights four distinct checkpoints, the S protein (ACE2 receptor coupling), the RBD motif (ACE2 receptor coupling), ACE2 coupling, and the S protein cleavage site, as targets for the development of nano-enabled solutions that, for example, prevent viral attachment and fusion with the host cell by either blocking viral RBD/spike proteins or cellular ACE2 receptors. As proof of this concept, we highlight applications of several nanomaterials, such as metal and metal oxide nanoparticles, carbon-based nanoparticles, carbon nanotubes, fullerene, carbon dots, quantum dots, polymeric nanoparticles, lipid-based, polymer-based, lipid–polymer hybrid-based, surface-modified nanoparticles that have already been employed to control viral infections. These nanoparticles were developed to inhibit receptor-mediated host–virus attachments and cell fusion, the uncoating of the virus, viral gene expression, protein synthesis, the assembly of progeny viral particles, and the release of the virion. Moreover, nanomaterials have been used as antiviral drug carriers and vaccines, and nano-enabled sensors have already been shown to enable fast, sensitive, and label-free real-time diagnosis of viral infections. Nano-biosensors could, therefore, also be useful in the remote testing and tracking of patients, while nanocarriers probed with target tissue could facilitate the targeted delivery of antiviral drugs to infected cells, tissues, organs, or systems while avoiding unwanted exposure of non-target tissues. Antiviral nanoparticles can also be applied to sanitizers, clothing, facemasks, and other personal protective equipment to minimize horizontal spread. We believe that the nanotechnology-enabled solutions described in this review will enable us to control repeated SAR-CoV-2 waves caused by antibody escape mutations.
Influence of Bruton’s Tyrosine Kinase (BTK) on Epithelial–Mesenchymal Transition (EMT) Processes and Cancer Stem Cell (CSC) Enrichment in Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Leichtle Franziska , Betzler Annika C. , Eizenberger Carlotta , Lesakova Kristina , Ezić Jasmin , Drees Robert , Greve Jens , Schuler Patrick J. , Laban Simon , Hoffmann Thomas K. , Cordes Nils , Lavitrano Marialuisa , Grassilli Emanuela , Brunner Cornelia
Published: August 2023

Constitutively active kinases play a crucial role in carcinogenesis, and their inhibition is a common target for molecular tumor therapy. We recently discovered the expression of two oncogenic isoforms of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC), Btk-p80 and BTK-p65. However, the precise role of BTK in HNSCC remains unclear. Analyses of a tissue microarray containing benign and malignant as well as inflammatory tissue samples of the head and neck region revealed the preferential expression of BTK-p80 in malignant tissue, whereas BTK-p65 expression was confirmed in over 80% of analyzed metastatic head and neck tumor cases. Therefore, processes associated with metastasis, like cancer stem cell (CSC) enrichment and the epithelial–mesenchymal transition (EMT), which in turn depend on an appropriate cytokine milieu, were analyzed. Treatment of HNSCC-derived cell lines cultured under 3D conditions with the BTK inhibitor AVL-292 caused reduced sphere formation, which was accompanied by reduced numbers of ALDH1A1+ CSCs as well as biological changes associated with the EMT. Moreover, we observed reduced NF-κB expression as well as altered NF-κB dependent pro-tumorigenic and EMT-associated cytokine release of IL-6, IFNγ, and TNFα when BTK activity was dampened. Therefore, an autocrine regulation of the oncogenic BTK-dependent process in HNSCC can be suggested, with BTK inhibition expected to be an effective treatment option for HNSCC.
Identification of Potential Gene Targets for Suppressing Oviposition in Holotrichia parallela Using Comparative Transcriptome Analysis
Authors: Gong Zhongjun , Zhang Jing , Li Yanmin , Li Huiling , Zhang Ziqi , Qin Yifan , Jiang Yueli , Duan Yun , Li Tong , Miao Jin , Wu Yuqing
Published: August 2023

Holotrichia parallela is an important plant pest. Comparative feeding experiments showed that the egg production, oviposition duration and survival rate of H. parallela beetles were significantly higher when they fed on elm leaves than when they fed on willow or purpus privet leaves. RNA sequencing was used to determine transcriptomic changes associated with oviposition. Comparative transcriptome analysis revealed that the beetles that fed on elm and willow had a total of 171 genes with differential expression. When the beetles fed on elm and purpus privet, 3568 genes had differential expression. The vitellogenesis, ovarian serine protease, odorant-binding proteins, acyl-CoA synthetase and follicle cell proteins were commonly upregulated genes in elm-fed beetles compared with those fed on willow/purpus privet leaves. The involvement of the follicle cell protein 3C gene in the regulation of oviposition was confirmed using RNA interference. The results provide insights into the molecular mechanisms underlying oviposition in H. parallela feeding on different host plants. This study also describes a method for identifying potentially effective genes for pest control.
Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion
Authors: Valero-Aracama Maria Jesus , Zheng Fang , Alzheimer Christian
Published: August 2023

The functional and neurophysiological distinction between the dorsal and ventral hippocampus affects also GABAergic inhibition. In line with this notion, ventral CA1 pyramidal cells displayed a more dynamic and effective response to inhibitory input compared to their dorsal counterparts. We posit that this difference is effected by the dorsal–ventral gradient of activin A, a member of the transforming growth factor-β family, which is increasingly recognized for its modulatory role in brain regions involved in cognitive functions and affective behavior. Lending credence to this hypothesis, we found that in slices from transgenic mice expressing a dominant-negative mutant of activin receptor IB (dnActRIB), inhibitory transmission was enhanced only in CA1 neurons of the dorsal hippocampus, where the basal activin A level is much higher than in the ventral hippocampus. We next asked how a rise in endogenous activin A would affect GABAergic inhibition along the longitudinal axis of the hippocampus. We performed ex vivo recordings in wild-type and dnActRIB mice after overnight exposure to an enriched environment (EE), which engenders a robust increase in activin A levels in both dorsal and ventral hippocampi. Compared to control mice from standard cages, the behaviorally induced surge in activin A produced a decline in ventral inhibition, an effect that was absent in slices from dnActRIB mice. Underscoring the essential role of activin in the EE-associated modulation of ventral inhibition, this effect was mimicked by acute application of recombinant activin A in control slices. In summary, both genetic and behavioral manipulations of activin receptor signaling affected the dorsal–ventral difference in synaptic inhibition, suggesting that activin A regulates the strength of GABAergic inhibition in a region-specific fashion.
Memantine Improves the Disturbed Glutamine and γ-Amino Butyric Acid Homeostasis in the Brain of Rats Subjected to Experimental Autoimmune Encephalomyelitis
Authors: Dąbrowska-Bouta Beata , Strużyńska Lidia , Sidoryk-Węgrzynowicz Marta , Sulkowski Grzegorz
Published: August 2023

Glutamine (Gln), glutamate (Glu), and γ-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocyte-derived Gln is the precursor for the two most important neurotransmitters in the central nervous system (CNS), which are the excitatory neurotransmitter Glu and the inhibitory neurotransmitter GABA. In addition to their roles in neurotransmission, these amino acids can be used as alternative substrates in brain metabolism that enable metabolic coupling between astrocytes and neurons in the glutamate–glutamine cycle (GGC). The disturbed homeostasis of these amino acids within the tripartite synapse may be involved in the pathogenesis of various neurological diseases. Interactions between astrocytes and neurons in terms of Gln, Glu, and GABA homeostasis were studied in different phases of experimental allergic encephalomyelitis (EAE) in Lewis rats. The results of the study showed a decrease in the transport (uptake and release) of Gln and GABA in both neuronal and astrocyte-derived fractions. These effects were fully or partially reversed when the EAE rats were treated with memantine, a NMDA receptor antagonist. Changes in the expression and activity of selected glutamine/glutamate metabolizing enzymes, such as glutamine synthase (GS) and phosphate-activated glutaminase (PAG), which were affected by memantine, were observed in different phases of EAE. The results suggested perturbed homeostasis of Gln, Glu, and GABA during EAE, which may indicate alterations in neuron–astrocyte coupling and dysfunction of the tripartite synapse. Memantine appears to partially regulate the disturbed relationships between Gln, Glu, and GABA.
Biological Liquid–Liquid Phase Separation, Biomolecular Condensates, and Membraneless Organelles: Now You See Me, Now You Don’t
Authors: Uversky Vladimir N.
Published: August 2023

Liquid–liquid phase separation (LLPS, also known as biomolecular condensation) and the related biogenesis of various membraneless organelles (MLOs) and biomolecular condensates (BMCs) are now considered fundamental molecular mechanisms governing the spatiotemporal organization of the intracellular space [...]
Preferential Tissue Sites of Different Cancer-Risk Groups of Human Papillomaviruses
Authors: Okodo Mitsuaki , Okayama Kaori , Sasagawa Toshiyuki , Teruya Koji , Settsu Rei , Mizuno Shuichi , Ishii Yasuyoshi , Oda Mizue
Published: August 2023

The oncogenic potential of human papillomavirus (HPV) may be used to determine the tissue tropism of each HPV type. Cervical cancer develops in the squamo-columar junction of the cervices, and most lesions are induced by high-risk (HR) HPV types. This suggests that HR types preferentially infect the cervix, whereas the preferential infection site for low-risk (LR) types is not well defined. The determination of HPV tropism when using cytology samples can be uncertain since it is difficult to avoid contamination of cell samples between the cervix and the vagina. Herein, cell samples were carefully collected by independently scraping the cervix and vagina, after which the HPV types were determined. HPV tissue tropism was determined by considering what HPV types were positive at only one of the sites (the cervix or the vagina) as the viruses that preferentially infected that site. This method revealed that all LR types were only identified in vaginal samples, whereas 87% of HR types were identified in cervical sites. Thus, LR types may preferentially infect the vagina, whereas HR types infect the cervix. These findings suggest that preferential tissue tropism of certain HPV types is a probable factor for malignant progression.
Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1
Authors: Barroso Madalena , Gertzen Marcus , Puchwein-Schwepcke Alexandra F. , Preisler Heike , Sturm Andreas , Reiss Dunja D. , Danecka Marta K. , Muntau Ania C. , Gersting Søren W.
Published: August 2023

Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of GCDH missense variants using different biochemical and biophysical methodologies. Thirteen GCDH variants were investigated in regard to protein stability, hydrophobicity, oligomerization, aggregation, and activity. An altered oligomerization, loss of protein stability and solubility, as well as an augmented susceptibility to aggregation were observed. GA1 variants led to a loss of enzymatic activity, particularly when present at the N-terminal domain. The reduced cellular activity was associated with loss of tetramerization. Our results also suggest a correlation between variant sequence location and cellular protein stability (p < 0.05), with a more pronounced loss of protein observed with variant proximity to the N-terminus. The broad panel of variant-mediated conformational changes of the GCDH protein supports the classification of GA1 as a protein-misfolding disorder. This work supports research toward new therapeutic strategies that target this molecular disease phenotype.
A Citrus and Pomegranate Complex Reduces Methylglyoxal in Healthy Elderly Subjects: Secondary Analysis of a Double-Blind Randomized Cross-Over Clinical Trial
Authors: Bednarska Katarzyna , Fecka Izabela , Scheijen Jean L. J. M. , Ahles Sanne , Vangrieken Philippe , Schalkwijk Casper G.
Published: August 2023

Reactive α-dicarbonyls (α-DCs), such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are potent precursors in the formation of advanced glycation end products (AGEs). In particular, MGO and MGO-derived AGEs are thought to be involved in the development of vascular complications in diabetes. Experimental studies showed that citrus and pomegranate polyphenols can scavenge α-DCs. Therefore, the aim of this study was to evaluate the effect of a citrus and pomegranate complex (CPC) on the α-DCs plasma levels in a double-blind, placebo-controlled cross-over trial, where thirty-six elderly subjects were enrolled. They received either 500 mg of Citrus sinensis peel extract and 200 mg of Punica granatum concentrate in CPC capsules or placebo capsules for 4 weeks, with a 4-week washout period in between. For the determination of α-DCs concentrations, liquid chromatography tandem mass spectrometry was used. Following four weeks of CPC supplementation, plasma levels of MGO decreased by 9.8% (−18.7 nmol/L; 95% CI: −36.7, −0.7 nmol/L; p = 0.042). Our findings suggest that CPC supplementation may represent a promising strategy for mitigating the conditions associated with MGO involvement. This study was registered on clinicaltrials.gov as NCT03781999.
Bipolar Membrane Electrodialysis for Direct Conversion of L-Ornithine Monohydrochloride to L-Ornithine
Authors: He Jinfeng , Liu Wenlong , Hao Jianrong , Ma Xixi , Zheng Zhiyi , Fang Yinghan , Liang Yuxin , Tian Zhihao , Sun Li , Li Chuanrun , Yan Haiyang
Published: August 2023

In this study, bipolar membrane electrodialysis was proposed to directly convert L-ornithine monohydrochloride to L-ornithine. The stack configuration was optimized in the BP-A (BP, bipolar membrane; A, anion exchange membrane) configuration with the Cl− ion migration through the anion exchange membrane rather than the BP-A-C (C, cation exchange membrane) and the BP-C configurations with the L-ornithine+ ion migration through the cation exchange membrane. Both the conversion ratio and current efficiency follow BP-A > BP-A-C > BP-C, and the energy consumption follows BP-A < BP-A-C < BP-C. Additionally, the voltage drop across the membrane stack (two repeating units) and the feed concentration were optimized as 7.5 V and 0.50 mol/L, respectively, due to the low value of the sum of H+ ions leakage (from the acid compartment to the base compartment) and OH− ions migration (from the base compartment to the acid compartment) through the anion exchange membrane. As a result, high conversion ratio (96.1%), high current efficiency (95.5%) and low energy consumption (0.31 kWh/kg L-ornithine) can be achieved. Therefore, bipolar membrane electrodialysis is an efficient, low energy consumption and environmentally friendly method to directly convert L-ornithine monohydrochloride to L-ornithine.
Construction of a Matrix Cancer-Associated Fibroblast Signature Gene-Based Risk Prognostic Signature for Directing Immunotherapy in Patients with Breast Cancer Using Single-Cell Analysis and Machine Learning
Authors: Huang Biaojie , Chen Qiurui , Ye Zhiyun , Zeng Lin , Huang Cuibing , Xie Yuting , Zhang Rongxin , Shen Han
Published: August 2023

Cancer-associated fibroblasts (CAFs) are heterogeneous constituents of the tumor microenvironment involved in the tumorigenesis, progression, and therapeutic responses of tumors. This study identified four distinct CAF subtypes of breast cancer (BRCA) using single-cell RNA sequencing (RNA-seq) data. Of these, matrix CAFs (mCAFs) were significantly associated with tumor matrix remodeling and strongly correlated with the transforming growth factor (TGF)-β signaling pathway. Consensus clustering of The Cancer Genome Atlas (TCGA) BRCA dataset using mCAF single-cell characteristic gene signatures segregated samples into high-fibrotic and low-fibrotic groups. Patients in the high-fibrotic group exhibited a significantly poor prognosis. A weighted gene co-expression network analysis and univariate Cox analysis of bulk RNA-seq data revealed 17 differential genes with prognostic values. The mCAF risk prognosis signature (mRPS) was developed using 10 machine learning algorithms. The clinical outcome predictive accuracy of the mRPS was higher than that of the conventional TNM staging system. mRPS was correlated with the infiltration level of anti-tumor effector immune cells. Based on consensus prognostic genes, BRCA samples were classified into the following two subtypes using six machine learning algorithms (accuracy > 90%): interferon (IFN)-γ-dominant (immune C2) and TGF-β-dominant (immune C6) subtypes. Patients with mRPS downregulation were associated with improved prognosis, suggesting that they can potentially benefit from immunotherapy. Thus, the mRPS model can stably predict BRCA prognosis, reflect the local immune status of the tumor, and aid clinical decisions on tumor immunotherapy.
Special Issue “Centenarians—A Model to Study the Molecular Basis of Lifespan and Healthspan 2.0”
Authors: Caruso Calogero , Puca Annibale Alessandro
Published: August 2023

The global population is experiencing an increase in ageing and life expectancy [...]
Proteome-Level Investigation of Vitis amurensis Calli Transformed with a Constitutively Active, Ca2+-Independent Form of the Arabidopsis AtCPK1 Gene
Authors: Veremeichik Galina N. , Bulgakov Dmitry V. , Konnova Yuliya A. , Brodovskaya Evgenia V. , Grigorchuk Valeria P. , Bulgakov Victor P.
Published: August 2023

Calcium-dependent protein kinases (CDPKs) are one of the main Ca2+ decoders in plants. Among them, Arabidopsis thaliana AtCPK1 is one of the most studied CDPK genes as a positive regulator of plant responses to biotic and abiotic stress. The mutated form of AtCPK1, in which the autoinhibitory domain is inactivated (AtCPK1-Ca), provides constitutive kinase activity by mimicking a stress-induced increase in the Ca2+ flux. In the present study, we performed a proteomic analysis of Vitis amurensis calli overexpressing the AtCPK1-Ca form using untransformed calli as a control. In our previous studies, we have shown that the overexpression of this mutant form leads to the activation of secondary metabolism in plant cell cultures, including an increase in resveratrol biosynthesis in V. amurensis cell cultures. We analyzed upregulated and downregulated proteins in control and transgenic callus cultures using two-dimensional gel electrophoresis, and Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF). In calli transformed with AtCPK1-Ca, an increased amounts of pathogenesis-related proteins were found. A quantitative real-time PCR analysis confirmed this result.
Novel Function of Nogo-A as Negative Regulator of Endothelial Progenitor Cell Angiogenic Activity: Impact in Oxygen-Induced Retinopathy
Authors: Ruknudin Pakiza , Nazari Ali Riza , Wirth Maelle , Lahaie Isabelle , Bajon Emmanuel , Rivard Alain , Chemtob Sylvain , Desjarlais Michel
Published: August 2023

Endothelial Progenitor Cells (EPCs) can actively participate in revascularization in oxygen-induced retinopathy (OIR). Yet the mechanisms responsible for their dysfunction is unclear. Nogo-A, whose function is traditionally related to the inhibition of neurite function in the central nervous system, has recently been documented to display anti-angiogenic pro-repellent properties. Based on the significant impact of EPCs in retinal vascularization, we surmised that Nogo-A affects EPC function, and proceeded to investigate the role of Nogo-A on EPC function in OIR. The expression of Nogo-A and its specific receptor NgR1 was significantly increased in isolated EPCs exposed to hyperoxia, as well as in EPCs isolated from rats subjected to OIR compared with respective controls (EPCs exposed to normoxia). EPCs exposed to hyperoxia displayed reduced migratory and tubulogenic activity, associated with the suppressed expression of prominent EPC-recruitment factors SDF-1/CXCR4. The inhibition of Nogo-A (using a Nogo-66 neutralizing antagonist peptide) or siRNA-NGR1 in hyperoxia-exposed EPCs restored SDF-1/CXCR4 expression and, in turn, rescued the curtailed neovascular functions of EPCs in hyperoxia. The in vivo intraperitoneal injection of engineered EPCs (Nogo-A-inhibited or NgR1-suppressed) in OIR rats at P5 (prior to exposure to hyperoxia) prevented retinal and choroidal vaso-obliteration upon localization adjacent to vasculature; coherently, the inhibition of Nogo-A/NgR1 in EPCs enhanced the expression of key angiogenic factors VEGF, SDF-1, PDGF, and EPO in retina; CXCR4 knock-down abrogated suppressed NgR1 pro-angiogenic effects. The findings revealed that hyperoxia-induced EPC malfunction is mediated to a significant extent by Nogo-A/NgR1 signaling via CXCR4 suppression; the inhibition of Nogo-A in EPCs restores specific angiogenic growth factors in retina and the ensuing vascularization of the retina in an OIR model.
Therapeutic Potentials of Microalgae and Their Bioactive Compounds on Diabetes Mellitus
Authors: Tamel Selvan Kartthigeen , Goon Jo Aan , Makpol Suzana , Tan Jen Kit
Published: August 2023

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to impaired insulin secretion, insulin resistance, or both. Oxidative stress and chronic low-grade inflammation play crucial roles in the pathophysiology of diabetes mellitus. There has been a growing interest in applying natural products to improve metabolic derangements without the side effects of anti-diabetic drugs. Microalgae biomass or extract and their bioactive compounds have been applied as nutraceuticals or additives in food products and health supplements. Several studies have demonstrated the therapeutic effects of microalgae and their bioactive compounds in improving insulin sensitivity attributed to their antioxidant, anti-inflammatory, and pancreatic β-cell protective properties. However, a review summarizing the progression in this topic is lacking despite the increasing number of studies reporting their anti-diabetic potential. In this review, we gathered the findings from in vitro, in vivo, and human studies to discuss the effects of microalgae and their bioactive compounds on diabetes mellitus and the mechanisms involved. Additionally, we discuss the limitations and future perspectives of developing microalgae-based compounds as a health supplement for diabetes mellitus. In conclusion, microalgae-based supplementation has the potential to improve diabetes mellitus and be applied in more clinical studies in the future.
Smartphone-Based High-Throughput Fluorimetric Assay for Histidine Quantification in Human Urine Using 96-Well Plates
Authors: Baltzis Dimitrios , Tsogas George , Zacharis Constantinos , Tzanavaras Paraskevas
Published: August 2023

A high-throughput fluorimetric assay for histidine was developed, using a 96-well plates platform. The analyte reacts selectively with o-phthalaldehyde under mild alkaline conditions to form a stable derivative. Instrumental-free detection was carried out using a smartphone after illumination under UV light (365 nm). The method was proved to be linear up to 100 μM histidine, with an LLOQ (lower limit of quantification) of 10 μM. The assay was only prone to interference from glutathione and histamine that exist in the urine samples at levels that are orders of magnitude lower compared to histidine. Human urine samples were analyzed following minimum treatment and were found to contain histidine in the range of 280 to 1540 μM. The results were in good agreement with an HPLC corroborative method.