bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroclimate and vegetation variability of high Andean ecosystems
Authors: Carilla Julieta , Aráoz Ezequiel , Foguet Javier , Casagranda Elvira , Halloy Stephan , Grau Alfredo
Published: January 2023

Mountain ecosystems are sensitive to climate fluctuations; however, the scarcity of instrumental data makes necessary the use of complementary information to study the effect of climate change on these systems. Remote sensing permits studying the dynamics of vegetation productivity and wetlands in response to climate variability at different scales. In this study we identified the main climate variables that control vegetation dynamics and water balance in Cumbres Calchaquíes, NW Argentina. For this, we built annual time series from 1986 to 2019 of Soil Adjusted Vegetation Index (SAVI, to quantify spare vegetation productivity), lake area, and snow-ice cover of peatlands, as indicators of mountain productivity and hydrology. We used a decompose function to explore trend, seasonality and random signal of the three-time series, and explored for significant changes in the mean value of consecutive periods. We used correlational analysis to explore their associations with climate records at local, regional, and global scales. The results showed that, SAVI and hydrological indicators presented different fluctuation patterns more pronounced since 2012, when they showed divergent trends with increasing SAVI and decreasing lake area and snow-ice cover. The three indicators responded differently to climate; SAVI increased in warmer years and lake area reflected the water balance of previous years. Snow-ice cover of peatlands was highly correlated with lake area. La Niña had a positive effect on lake area and snow-ice cover and a negative on SAVI, while El Niño had a negative effect on SAVI. Fluctuations of lake areas were synchronized with lake area in the nearby Argentinian puna, suggesting that climate signals have regional extent. The information provided by the three hydroclimate indicators is complementary and reflects different climate components and processes; biological processes (SAVI), physical processes (snow ice cover) and their combination (lake area). This study provides a systematic accessible replicable tool for mountain eco-hydrology long-term monitoring.
To approach or to avoid: The quadripolar model of achievement motivation revisited in a Confucian-heritage context
Authors: Li Guan Ying , Fwu Bih-Jen , Yang Tong-Rong , Chen Yi-Kai
Published: January 2023

Academic challenges and failure are inevitable in pursuit of higher education. According to the self-worth theory, trying hard but failing implies low ability that would be a threat to personal worth, thus preventing students from approaching academic challenges. Nevertheless, previous studies have shown that students in the Confucian-heritage contexts (CHCs) tend to persist rather than quit in the face of academic failure. According to the role obligation theory of self-cultivation (ROT), the CHC learners would perceive academic failure from personal and interpersonal perspectives. The former refers to personal obligations to exert oneself toward the ultimate good, and the latter refers to fulfilling filial obligations to parents by achieving academic excellence. Given the fundamental differences in learners’ perceptions of academic failure between the CHCs and the Western, Educated, Industrialized, Rich, and Democratic (WEIRD) contexts, this study examined the applicability of the quadripolar model of achievement motivation based on the self-worth theory in a CHC higher education institution. Results of confirmatory factor analysis (CFA) supported a two-factor model of fear of failure, including a personal and an interpersonal subfactor. Latent class analysis (LCA) showed that apart from the four existing categories of the quadripolar model, two additional CHC categories emerged and constituted half of the sample. The two CHC categories demonstrated different learner characteristics compared with their corresponding quadripolar categories in terms of levels of emotional distress and academic risk-taking tendency. The results may help debunk the myth that learner characteristics in the CHCs are identical to those observed in the WEIRD contexts. The fundamental differences in fear of failure further indicated the inadequacy of the self-worth theory in explaining achievement motivation in the CHCs where relationalism and role obligations are significant parts of the cultural traditions.
Mental healthcare for young and adolescent LGBTQ+ individuals in the Indian subcontinent
Authors: Gaur Prithvi Sanjeevkumar , Saha Sreoshy , Goel Ashish , Ovseiko Pavel , Aggarwal Shelley , Agarwal Vikas , Haq Atiq Ul , Danda Debashish , Hartle Andrew , Sandhu Nimrat Kaur , Gupta Latika
Published: January 2023

The coronavirus disease (COVID-19) pandemic has led to a significant change in the way healthcare is dispensed. During the pandemic, healthcare inequities were experienced by various sections of society, based on gender, ethnicity, and socioeconomic status. The LGBTQ individuals were also affected by this inequity. There is a lack of information on this topic especially in the developing countries. Hence this issue requires further exploration and understanding. Previous literature briefly explored the mental, physical, and emotional turmoil faced by the LGBTQ community on a regular basis. They feared rejection by family and friends, bullying, physical assault, and religious biases. These issues prevented them from publicly speaking about their sexual orientation thereby making it difficult to collect reliable data. Although they require medical and psychological treatment, they are afraid to ask for help and access healthcare and mental health services. Being mindful of these difficulties, this article explores the various underlying causes of the mental health problems faced by LGBTQ individuals, especially, in the Indian subcontinent. The article also examines the status of healthcare services available to Indian sexual minorities and provides recommendations about possible remedial measures to ensure the well-being of LGBTQ individuals.
Adherence and effectiveness of an emotion-based psychodynamic online self-help during and after inpatient and day-care psychotherapy: Results of a naturalistic study
Authors: Becker Jan , Kreis Adina , Schorch Theresa , Mayer Anna , Tsiouris Angeliki , Beutel Manfred E. , Zwerenz Rüdiger
Published: January 2023

Background

Internet-based mental health interventions are considered effective in providing low-threshold support for people with mental health disorders. However, there is a lack of research investigating the transferability of such online programs into routine care settings. Low treatment adherence and problems with technical implementation often limit a successful transfer into clinical routines. This naturalistic study aims to identify influencing factors on program adherence in patients who participated in an online intervention during inpatient or day-clinic psychotherapeutic treatment.

Methods and findings

In a naturalistic study, we investigated the transferability of the transdiagnostic psychodynamic online self-help program KEN-Online, which includes eight consecutive units. Between May 2017 and October 2018, patients who received inpatient or day-clinic psychotherapeutic treatment at the Department of Psychosomatic Medicine and Psychotherapy in the University Medical Center Mainz have been offered to use KEN-Online. Of the n = 749 patients who were admitted to the clinic, n = 239 patients (32%) registered for participation in KEN-Online. While 46.9% of the participants did not complete any unit (inactive participants), 53.1% completed at least the first unit (active participants). Age, number of diagnoses, and symptom severity were associated with (in)active participation. Adherence decreased over time resulting in only 17 participants (7.6%) who completed all units. None of the sociodemographic and medical characteristics proved to be significant predictors of adherence. Analyses of effectiveness showed a significant reduction of anxiety and depression in active participants in the course of participation, with higher improvements in participants that completed more than half of the units.

Conclusion

Adherence to the online self-help program KEN-Online was lower in the naturalistic setting than in a previous clinical trial, but was still associated with greater program effectiveness. Adherence-promoting measures are crucial to increase the effectiveness of such interventions in clinical settings.
Agile Delphi methodology: A case study on how technology impacts burnout syndrome in the post-pandemic era
Authors: Medina-Dominguez Fuensanta , Sanchez-Segura Maria-Isabel , de Amescua-Seco Antonio , Dugarte-Peña Germán-Lenin , Villalba Arranz Santiago
Published: January 2023

Introduction

In the post-pandemic era, many habits in different areas of our lives have changed. The exponential growth in the use of technology to perform work activities is one of them. At the same time, there has been a marked increase in burnout syndrome. Is this a coincidence? Could they be two interconnected developments? What if they were? Can we use technology to mitigate this syndrome? This article presents the agile Delphi methodology (MAD), an evolved version of the Delphi method, adapted to the needs of modern-day society.

Methods

To drive Occupational Health and Safety (OHS) experts to reach a consensus on what technological and non-technological factors could be causing the burnout syndrome experienced by workers in the post-pandemic era, MAD has been used in a specific case study. This study formally presents MAD and describes the stages enacted to run Delphi experiments agilely.

Results

MAD is more efficient than the traditional Delphi methodology, reducing the time taken to reach a consensus and increasing the quality of the resulting products.

Discussion

OHS experts identified factors that affect and cause an increase in burnout syndrome as well as mechanisms to mitigate their effects. The next step is to evaluate whether, as the experts predict, burnout syndrome decreases with the mechanisms identified in this case study.
Adding a polyphenol-rich fiber bundle to food impacts the gastrointestinal microbiome and metabolome in dogs
Authors: Fritsch Dale A. , Jackson Matthew I. , Wernimont Susan M. , Feld Geoffrey K. , Badri Dayakar V. , Brejda John J. , Cochrane Chun-Yen , Gross Kathy L.
Published: January 2023

Introduction

Pet foods fortified with fermentable fibers are often indicated for dogs with gastrointestinal conditions to improve gut health through the production of beneficial post-biotics by the pet's microbiome.

Methods

To evaluate the therapeutic underpinnings of pre-biotic fiber enrichment, we compared the fecal microbiome, the fecal metabolome, and the serum metabolome of 39 adult dogs with well-managed chronic gastroenteritis/enteritis (CGE) and healthy matched controls. The foods tested included a test food (TF1) containing a novel pre-biotic fiber bundle, a control food (CF) lacking the fiber bundle, and a commercially available therapeutic food (TF2) indicated for managing fiber-responsive conditions. In this crossover study, all dogs consumed CF for a 4-week wash-in period, were randomized to either TF1 or TF2 and fed for 4 weeks, were fed CF for a 4-week washout period, and then received the other test food for 4 weeks.

Results

Meaningful differences were not observed between the healthy and CGE dogs in response to the pre-biotic fiber bundle relative to CF. Both TF1 and TF2 improved stool scores compared to CF. TF1-fed dogs showed reduced body weight and fecal ash content compared to either CF or TF2, while stools of TF2-fed dogs showed higher pH and lower moisture content vs. TF1. TF1 consumption also resulted in unique fecal and systemic metabolic signatures compared to CF and TF2. TF1-fed dogs showed suppressed signals of fecal bacterial putrefactive metabolism compared to either CF or TF2 and increased saccharolytic signatures compared to TF2. A functional analysis of fecal tryptophan metabolism indicated reductions in fecal kynurenine and indole pathway metabolites with TF1. Among the three foods, TF1 uniquely increased fecal polyphenols and the resulting post-biotics. Compared to CF, consumption of TF1 largely reduced fecal levels of endocannabinoid-like metabolites and sphingolipids while increasing both fecal and circulating polyunsaturated fatty acid profiles, suggesting that TF1 may have modulated gastrointestinal inflammation and motility. Stools of TF1-fed dogs showed reductions in phospholipid profiles, suggesting fiber-dependent changes to colonic mucosal structure.

Discussion

These findings indicate that the use of a specific pre-biotic fiber bundle may be beneficial in healthy dogs and in dogs with CGE.
Case report: Large-size intramuscular nodular fasciitis, a challenging histopathologic diagnosis confirmed by molecular detection of USP6 gene rearrangement: Case report and literature review
Authors: Wang Changrong , Wang Wei , Xu Rujun , Xiang Jingjing
Published: January 2023

The intramuscular subtype of nodular fasciitis (NF) is rare with lesions normally not more than 2 cm in size and characterized by pseudosarcomatous morphology. We report a case of a 27-year-old man with a large-size intramuscular NF. The patient came for treatment complaining of an increasingly enlarged mass in the left upper arm for 4 months. Magnetic resonance imaging (MRI) confirmed the presence of a well-defined tumor measuring 5 cm within the outer edge of the middle humerus. Microscopically, the neoplasm was rich in fibroblasts and myofibroblasts in an interlaced pattern with high mitotic index and evident multinuclear giant cells. Erythrocyte extravasation was easily seen in the stroma. The tumor border was infiltrative. Immunohistochemically, the tumor cells were positive for smooth muscle actin (SMA) and negative for cytokeratin, desmin, H-Caldesmon, CD34, S100, ALK, and β-catenin. Fibrosarcoma was highly suspected by histopathological and immunohistochemical examination. Molecular detection demonstrated evidence of ubiquitin-specific peptidase 6 (USP6) gene rearrangement in this tumor. Based on the findings, the tumor was diagnosed as intramuscular NF. At 56 months after the initial surgery, the patient had recovered with no evidence of recurrence or metastasis. Large-size intramuscular NF is very rare and easily overdiagnosed as malignant tumor due to its obvious pseudosarcomatoid pathological features. USP6 gene rearrangement detection can effectively avoid this major misdiagnosis.
Ipsilateral Aorto-Iliac Calcification is Not Directly Associated With eGFR After Kidney Transplantation: A Prospective Cohort Study Analyzed Using a Linear Mixed Model
Authors: Rijkse Elsaline , Roodnat Joke I. , Baart Sara J. , Bijdevaate Diederik C. , Dijkshoorn Marcel L. , Kimenai Hendrikus J. A. N. , van de Wetering Jacqueline , IJzermans Jan N. M. , Minnee Robert C.
Published: January 2023

Aorto-iliac calcification (AIC) is a well-studied risk factor for post-transplant cardiovascular events and mortality. Its effect on graft function remains unknown. The primary aim of this prospective cohort study was to assess the association between AIC and estimated glomerular filtration rate (eGFR) in the first year post-transplant. Eligibility criteria were: ≥50 years of age or ≥30 years with at least one risk factor for vascular disease. A non-contrast-enhanced CT-scan was performed with quantification of AIC using the modified Agatston score. The association between AIC and eGFR was investigated with a linear mixed model adjusted for predefined variables. One-hundred-and-forty patients were included with a median of 31 (interquartile range 26–39) eGFR measurements per patient. No direct association between AIC and eGFR was found. We observed a significant interaction between follow-up time and ipsilateral AIC, indicating that patients with higher AIC scores had lower eGFR trajectory over time starting 100 days after transplant (p = 0.014). To conclude, severe AIC is not directly associated with lower post-transplant eGFR. The significant interaction indicates that patients with more severe AIC have a lower eGFR trajectory after 100 days in the first year post-transplant.
Everolimus Based Immunosuppression Strategies in Adult Lung Transplant Recipients: Calcineurin Inhibitor Minimization Versus Calcineurin Inhibitor Elimination
Authors: Ivulich Steven , Paul Eldho , Kirkpatrick Carl , Dooley Michael , Snell Greg
Published: January 2023

Everolimus (EVE) provides an alternative to maintenance immunosuppression when conventional immunosuppression cannot be tolerated. EVE can be utilized with a calcineurin inhibitor (CNI) minimization or elimination strategy. To date, clinical studies investigating EVE after lung transplant (LTx) have primarily focused on the minimization strategy to preserve renal function. The primary aim was to determine the preferred method of EVE utilization for lung transplant recipients (LTR). To undertake this aim, we compared the safety and efficacy outcomes of EVE as part of minimization and elimination immunosuppressant regimens. Single center retrospective study of 217 LTR initiated on EVE (120 CNI minimization and 97 CNI elimination). Survival outcomes were calculated from the date of EVE commencement. On multivariate analysis, LTR who received EVE as part of the CNI elimination strategy had poorer survival outcomes compared to the CNI minimization strategy [HR 1.61, 95% CI: 1.11–2.32, p=0.010]. Utilization of EVE for renal preservation was associated with improved survival compared to other indications [HR 0.64, 95% CI: 0.42–0.97, p=0.032]. EVE can be successfully utilized for maintenance immunosuppression post LTx, particularly for renal preservation. However, immunosuppressive regimens containing low dose CNI had superior survival outcomes, highlighting the importance of retaining a CNI wherever possible.
Acknowledgment to the Reviewers of CivilEng in 2022
Authors:   CivilEng Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Assessing the Functional Accessibility, Actionability, and Quality of Patient Education Materials from Canadian Cancer Agencies
Authors: van Ballegooie Courtney , Heroux Devon , Hoang Peter , Garg Sarthak
Published: January 2023

Patient education materials (PEM)s were extracted from provincial cancer agencies to determine their organizational health literacy by evaluating the quality, actionability, and functional accessibility (e.g., readability and understandability) of their PEMs. PEMs from 10 provincial agencies were assessed for their grade reading level (GRL), using eight numerical and two graphical readability scales, and underwent a difficult word analysis. The agencies were assessed for PEM quality using two methods (JAMA benchmarks and DISCERN), while actionability and understandability were assessed using the Patient Education Materials Assessment Tool (PEMAT). Seven hundred and eighty-six PEMs were analyzed. The overall average GRL was 9.3 ± 2.1, which is above the recommended 7th GRL for health information. The difficult word analysis showed that 15.4% ± 5.1% of texts contained complex words, 35.8% ± 6.8% of texts contained long words, and 24.2% ± 6.6% of texts contained unfamiliar words. Additionally, there was high overlap between the most frequently identified difficult words in the PEMs and the most frequently misunderstood words by cancer patients identified in the literature. Regarding quality indicators, no agency displayed all four indicators according to the JAMA benchmarks and DISCERN scores ranged between 38 (poor) to 66 (excellent). PEMAT scores ranged between 68% to 88% for understandability and 57% to 88% for actionability. PEMs continue to be written at a level above the recommended GRL across all provinces, and there was overall high variability in the quality, understandability, and actionability of PEMs among provincial agencies. This represents an opportunity to optimize materials, thus ensuring understanding by a wider audience and improving health literacy among Canadian cancer patients.
Seismic Diffraction Attribute Fusion for Geological Discontinuities in Hot Dry Rock Resources
Authors: Yang Jie , Peng Suping , Zhao Jingtao
Published: January 2023

For the safe development and utilization of hot dry rock resources, it is essential to understand the distribution characteristics of underground faults. However, the commonly used reflection attribute analysis method has an insufficient resolution, and the diffraction attribute analysis method is affected by multiple solutions. Moreover, both are highly dependent on the interpreters’ experience and take a long time. Therefore, based on the classical U-Net model, a diffraction attribute fusion model (DAF-U-Net) with 27-layer convolution is proposed. The DAF-U-Net network takes four-channel diffracted attributes as an input and underground fracture distribution as an output. The new network adds a spatial attention and channel attention mechanism to improve the positioning and extraction ability of the U-Net model for the attribute characteristics of diffractions. After optimizing the diffraction attributes of hot dry rock slices in the Gonghe basin, Qinghai, the slices are input into the network to train the model. According to the prediction and identification results of the network model, the DAF-U-Net network has a high reliability in predicting fracture distributions. It has a specific reference role in the subsequent exploitation of hot dry rock.
A Brief Review of Hydrogen Production Methods and Their Challenges
Authors: Dash Santanu Kumar , Chakraborty Suprava , Elangovan Devaraj
Published: January 2023

Hydrogen is emerging as a new energy vector outside of its traditional role and gaining more recognition internationally as a viable fuel route. This review paper offers a crisp analysis of the most recent developments in hydrogen production techniques using conventional and renewable energy sources, in addition to key challenges in the production of Hydrogen. Among the most potential renewable energy sources for hydrogen production are solar and wind. The production of H2 from renewable sources derived from agricultural or other waste streams increases the flexibility and improves the economics of distributed and semi-centralized reforming with little or no net greenhouse gas emissions. Water electrolysis equipment driven by off-grid solar or wind energy can also be employed in remote areas that are away from the grid. Each H2 manufacturing technique has technological challenges. These challenges include feedstock type, conversion efficiency, and the need for the safe integration of H2 production systems with H2 purification and storage technologies.
A Three-Stage Model to Manage Energy Communities, Share Benefits and Provide Local Grid Services
Authors: Rocha Rogério , Silva Ricardo , Mello João , Faria Sérgio , Retorta Fábio , Gouveia Clara , Villar José
Published: January 2023

This paper proposes a three-stage model for managing energy communities for local energy sharing and providing grid flexibility services to tackle local distribution grid constraints. The first stage addresses the minimization of each prosumer’s individual energy bill by optimizing the schedules of their flexible resources. The second stage optimizes the energy bill of the whole energy community by sharing the prosumers’ energy surplus internally and re-dispatching their batteries, while guaranteeing that each prosumer’s new energy bill is always be equal to or less than the bill that results for this prosumer from stage one. This collective optimization is designed to ensure an additional collective benefit, without loss for any community member. The third stage, which can be performed by the distribution system operator (DSO), aims to solve the local grid constraints by re-dispatching the flexible resources and, if still necessary, by curtailing local generation or consumption. Stage three minimizes the impact on the schedule obtained at previous stages by minimizing the loss of profit or utility for all prosumers, which are furthermore financially compensated accordingly. This paper describes how the settlement should be performed, including the allocation coefficients to be sent to the DSO to determine the self-consumed and supplied energies of each peer. Finally, some case studies allow an assessment of the performance of the proposed methodology. Results show, among other things, the potential benefits of allowing the allocation coefficients to take negative values to increase the retail market competition; the importance of stage one or, alternatively, the need for a fair internal price to avoid unfair collective benefit sharing among the community members; or how stage three can effectively contribute to grid constraint solving, profiting first from the existing flexible resources.
Prediction of Pyrolysis Gas Composition Based on the Gibbs Equation and TGA Analysis
Authors: Wardach-Świȩcicka Izabela , Kardaś Dariusz
Published: January 2023

Conventional methods used to determine pyrolysis gas composition are based on chemical kinetics. The mechanism of those reactions is often unknown, which makes the calculations more difficult. Solving complex chemical reactions’ kinetics involving a nonlinear set of equations is CPU time demanding. An alternative approach is based on the Gibbs free energy minimization method. It requires only the initial composition and operation parameters as the input data, for example, temperature and pressure. In this paper, the method for calculating the pyrolytic gas composition from biogenic fuels has been presented, and the thermogravimetric experimental results have been adopted to determine the total gas yield. The studied problem has been reduced to the optimization method with the use of the Lagrange multipliers. This solution procedure is advantageous since it does not require knowledge of the reaction mechanism. The obtained results are in good agreement with experimental data, demonstrating the usefulness of the proposed method.
Applying Energy Justice Principles to Renewable Energy Trading and Allocation in Multi-Unit Buildings
Authors: Mohammadi Sara , Eliassen Frank , Jacobsen Hans-Arno
Published: January 2023

Although rooftop PV panels and battery energy storage systems have been well established for detached residential buildings, there is still a lack of access to the advantages of onsite renewable energy generation and consumption for residents of multi-unit buildings. To understand the effects of developing distributed renewable energy sources for multi-unit buildings, a new fair energy-sharing model in which different groups of residents can gain benefit from the shared energy systems is proposed. Despite the potential benefits of developing renewable technologies in multi-unit buildings, the energy trading and allocation processes in the buildings can be unfair for some groups of residents. Accordingly, this work studies the main principles of energy justice and analyses how these principles can be applied in the energy trading and allocation processes to achieve fair energy sharing. In addition to fairness and justice, the experimental results show that our method increases the sellers’ profit by 59.7–127% and decreases the buyers’ cost by 8–21%, compared to the baseline methods. Moreover, applying the energy justice principles in the proposed sharing models acts as an efficient incentive for the residents of the multi-unit buildings to invest in the shared distributed renewable energy sources.
Evaluation of the Possibility of Increasing the Energy Absorption Efficiency of Fender Devices Using the Example of Cylindrical Fenders with Additional Structural Elements Applied
Authors: Tuleja Joanna , Kędzierska Katarzyna , Sowa Mariusz , Galor Przemysław
Published: January 2023

The providers of transport services in ports must ensure there is adequate protection of the quays against the hulls of vessels. Highly elastic fenders mounted on the wharfs or on the hulls of vessels are used to absorb the energy of an impact. The structure of the fender, and the highly elastic material used to make it, are designed to ensure the highest possible absorption energy with minimized reaction force. In this work, the efficiency of energy absorption by cylindrical fenders into which additional structural elements were introduced in the form of holes of various diameters, was determined numerically using the finite element method. It was found that the features of such structural elements affect the efficiency of their energy absorption. In order to confirm the accuracy of the numerical calculations, they were verified based on experimental determination of the functional parameters of the cylindrical fenders. The reaction force and absorption energy values determined numerically and experimentally for the cylindrical fender were shown to be consistent. The verified numerical calculation methodology was used to evaluate the energy absorption efficiency and the reaction force in cylindrical fenders with additional structural elements.
Enhanced IRE1α Phosphorylation/Oligomerization-Triggered XBP1 Splicing Contributes to Parkin-Mediated Prevention of SH-SY5Y Cell Death under Nitrosative Stress
Authors: Chiu Tsung-Lang , Huang Hsin-Yi , Chang Hui-Fen , Wu Hsin-Rong , Wang Mei-Jen
Published: January 2023

Mutations in parkin, a neuroprotective protein, are the predominant cause of autosomal recessive juvenile Parkinson’s disease. Neuroinflammation-derived nitrosative stress has been implicated in the etiology of the chronic neurodegeneration. However, the interactions between genetic predisposition and nitrosative stress contributing to the degeneration of dopaminergic (DA) neurons remain incompletely understood. Here, we used the SH-SY5Y neuroblastoma cells to investigate the function of parkin and its pathogenic mutants in relation to cell survival under nitric oxide (NO) exposure. The results showed that overexpression of wild-type parkin protected SH-SY5Y cells from NO-induced apoptosis in a reactive oxygen species-dependent manner. Under nitrosative stress conditions, parkin selectively upregulated the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) signaling axis, an unfolded protein response signal through the sensor IRE1α, which controls the splicing of XBP1 mRNA. Inhibition of XBP1 mRNA splicing either by pharmacologically inhibiting IRE1α endoribonuclease activity or by genetically knocking down XBP1 interfered with the protective activity of parkin. Furthermore, pathogenic parkin mutants with a defective protective capacity showed a lower ability to activate the IRE1α/XBP1 signaling. Finally, we demonstrated that IRE1α activity augmented by parkin was possibly mediated through interacting with IRE1α to regulate its phosphorylation/oligomerization processes, whereas mutant parkin diminished its binding to and activation of IRE1α. Thus, these results support a direct link between the protective activity of parkin and the IRE1α/XBP1 pathway in response to nitrosative stress, and mutant parkin disrupts this function.
PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy
Authors: Golderman Valery , Goldberg Zehavit , Gofrit Shany Guly , Dori Amir , Maggio Nicola , Chapman Joab , Sher Ifat , Rotenstreich Ygal , Shavit-Stein Efrat
Published: January 2023

Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.
Biological Activity of Novel Organotin Compounds with a Schiff Base Containing an Antioxidant Fragment
Authors: Antonenko Taisiya A. , Gracheva Yulia A. , Shpakovsky Dmitry B. , Vorobyev Mstislav A. , Mazur Dmitrii M. , Tafeenko Victor A. , Oprunenko Yury F. , Shevtsova Elena F. , Shevtsov Pavel N. , Nazarov Alexey A. , Milaeva Elena R.
Published: January 2023

A series of novel organotin(IV) complexes on the base of 2-(N-3′,5′-di-tert-butyl-4′-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 μM for complex 2). Furthermore, compounds 1–5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.
Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development
Authors: Sarkar Chayna , Das Biswadeep , Rawat Vikram Singh , Wahlang Julie Birdie , Nongpiur Arvind , Tiewsoh Iadarilang , Lyngdoh Nari M. , Das Debasmita , Bidarolli Manjunath , Sony Hannah Theresa
Published: January 2023

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has been facilitated by the employment of classified big data, in concert with strikingly reinforced computing prowess and cloud storage, across all fields. AI has energized computer-facilitated drug discovery. An unrestricted espousing of machine learning (ML), especially DL, in many scientific specialties, and the technological refinements in computing hardware and software, in concert with various aspects of the problem, sustain this progress. ML algorithms have been extensively engaged for computer-facilitated drug discovery. DL methods, such as artificial neural networks (ANNs) comprising multiple buried processing layers, have of late seen a resurgence due to their capability to power automatic attribute elicitations from the input data, coupled with their ability to obtain nonlinear input-output pertinencies. Such features of DL methods augment classical ML techniques which bank on human-contrived molecular descriptors. A major part of the early reluctance concerning utility of AI in pharmaceutical discovery has begun to melt, thereby advancing medicinal chemistry. AI, along with modern experimental technical knowledge, is anticipated to invigorate the quest for new and improved pharmaceuticals in an expeditious, economical, and increasingly compelling manner. DL-facilitated methods have just initiated kickstarting for some integral issues in drug discovery. Many technological advances, such as “message-passing paradigms”, “spatial-symmetry-preserving networks”, “hybrid de novo design”, and other ingenious ML exemplars, will definitely come to be pervasively widespread and help dissect many of the biggest, and most intriguing inquiries. Open data allocation and model augmentation will exert a decisive hold during the progress of drug discovery employing AI. This review will address the impending utilizations of AI to refine and bolster the drug discovery operation.
The Intertwined Role of 8-oxodG and G4 in Transcription Regulation
Authors: Gorini Francesca , Ambrosio Susanna , Lania Luigi , Majello Barbara , Amente Stefano
Published: January 2023

The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) when exposed to reactive oxygen species. In double-helix DNA, 8-oxodG can pair with adenine; hence, it may cause a G > T (C > A) mutation; it is frequently referred to as a form of DNA damage and promptly corrected by DNA repair mechanisms. Moreover, 8-oxodG has recently been redefined as an epigenetic factor that impacts transcriptional regulatory elements and other epigenetic modifications. It has been proposed that 8-oxodG exerts epigenetic control through interplay with the G-quadruplex (G4), a non-canonical DNA structure, in transcription regulatory regions. In this review, we focused on the epigenetic roles of 8-oxodG and the G4 and explored their interplay at the genomic level.
Octafluoro-Substituted Phthalocyanines of Zinc, Cobalt, and Vanadyl: Single Crystal Structure, Spectral Study and Oriented Thin Films
Authors: Sukhikh Aleksandr , Klyamer Darya , Bonegardt Dmitry , Basova Tamara
Published: January 2023

In this work, octafluoro-substituted phthalocyanines of zinc, vanadyl, and cobalt (MPcF8, M = Zn(II), Co(II), VO) were synthesized and studied. The structures of single crystals of the obtained phthalocyanines were determined. To visualize and compare intermolecular contacts in MPcF8, an analysis of Hirshfeld surfaces (HS) was performed. MPcF8 nanoscale thickness films were deposited by organic molecular beam deposition technique and their structure and orientation were studied using X-ray diffraction. Comparison of X-ray diffraction patterns of thin films with the calculated diffractograms showed that all three films consisted of a single crystal phase, which corresponded to a phase of single crystals. Only one strong diffraction peak corresponding to the plane (001) was observed on the diffraction pattern of each film, which indicated a strong preferred orientation with the vast majority of crystallites oriented with a (001) crystallographic plane parallel to the substrate surface. The effect of the central metals on the electronic absorption and vibrational spectra of the studied phthalocyanines as well as on the electrical conductivity of their films is also discussed.
Spotlight on CYP4B1
Authors: Röder Annika , Hüsken Saskia , Hutter Michael C. , Rettie Allan E. , Hanenberg Helmut , Wiek Constanze , Girhard Marco
Published: January 2023

The mammalian cytochrome P450 monooxygenase CYP4B1 can bioactivate a wide range of xenobiotics, such as its defining/hallmark substrate 4-ipomeanol leading to tissue-specific toxicities. Similar to other members of the CYP4 family, CYP4B1 has the ability to hydroxylate fatty acids and fatty alcohols. Structural insights into the enigmatic role of CYP4B1 with functions in both, xenobiotic and endobiotic metabolism, as well as its unusual heme-binding characteristics are now possible by the recently solved crystal structures of native rabbit CYP4B1 and the p.E310A variant. Importantly, CYP4B1 does not play a major role in hepatic P450-catalyzed phase I drug metabolism due to its predominant extra-hepatic expression, mainly in the lung. In addition, no catalytic activity of human CYP4B1 has been observed owing to a unique substitution of an evolutionary strongly conserved proline 427 to serine. Nevertheless, association of CYP4B1 expression patterns with various cancers and potential roles in cancer development have been reported for the human enzyme. This review will summarize the current status of CYP4B1 research with a spotlight on its roles in the metabolism of endogenous and exogenous compounds, structural properties, and cancer association, as well as its potential application in suicide gene approaches for targeted cancer therapy.
The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis
Authors: Andrzejczak Anna , Tupikowski Krzysztof , Tomkiewicz Anna , Małkiewicz Bartosz , Ptaszkowski Kuba , Domin Aleksandra , Szydełko Tomasz , Karabon Lidia
Published: January 2023

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS–PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS.
Key Genes of Immunity Associated with Pterygium and Primary Sjögren’s Syndrome
Authors: Liu Yumeilan , Chen Hao , Cui Hongping
Published: January 2023

Pterygium and primary Sjögren’s Syndrome (pSS) share many similarities in clinical symptoms and ocular pathophysiological changes, but their etiology is unclear. To identify the potential genes and pathways related to immunity, two published datasets, GSE2513 containing pterygium information and GSE176510 containing pSS information, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of pterygium or pSS patients compared with healthy control conjunctiva, and the common DEGs between them were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted for common DEGs. The protein–protein interaction (PPI) network was constructed using the STRING database to find the hub genes, which were verified in clinical samples. There were 14 co-upregulated DEGs. The GO and KEGG analyses showed that these common DEGs were enriched in pathways correlated with virus infection, antigen processing and presentation, nuclear factor-kappa B (NF-κB) and Th17 cell differentiation. The hub genes (IL1R1, ICAM1, IRAK1, S100A9, and S100A8) were selected by PPI construction. In the era of the COVID-19 epidemic, the relationship between virus infection, vaccination, and the incidence of pSS and pterygium growth deserves more attention.
Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
Authors: Sabe Sharif A. , Xu Cynthia M. , Potz Brittany A. , Malhotra Akshay , Sabra Mohamed , Harris Dwight D. , Broadwin Mark , Abid M. Ruhul , Sellke Frank W.
Published: January 2023

We have previously shown that normoxia serum-starved extracellular vesicle (EV) therapy improves myocardial function, perfusion, and angiogenesis in a swine model of chronic myocardial ischemia. Hypoxia-modified EVs have increased abundance of anti-oxidant, pro-angiogenic, and pro-survival proteins. The purpose of this study is to investigate the differential effects of normoxia serum-starved EVs and hypoxia-modified EVs on myocardial function, perfusion, and microvascular density in chronically ischemic myocardium. Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs underwent intramyocardial injection of either normoxia serum-starved EVs (NOR, n = 10) or hypoxia-modified EVs (HYP, n = 7). Five weeks later, pigs were euthanized, and ischemic myocardium was harvested. Hypoxia EV treatment was associated with improved contractility compared to NOR, as well as improved capillary density, without changes in arteriolar density. There were trends towards improved perfusion at rest and during pacing in the HYP group compared to NOR. Ischemic myocardium in the HYP group had increased pro-angiogenic Akt and ERK signaling and decreased expression of anti-angiogenic markers compared to the NOR group. In the setting of chronic myocardial ischemia, hypoxia-modified EVs may enhance contractility, capillary density, and angiogenic signaling pathways compared to normoxia serum-starved EVs.
Microdialysis Reveals Anti-Inflammatory Effects of Sulfated Glycosaminoglycanes in the Early Phase of Bone Healing
Authors: Schulze Sabine , Neuber Christin , Möller Stephanie , Pietzsch Jens , Schaser Klaus-Dieter , Rammelt Stefan
Published: January 2023

Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase. Sulfated glycosaminoglycanes (sGAG) are known to interact with cytokines, chemokines and growth factors and, thus, alter the availability, duration and impact of those mediators on the local molecular level. sGAG-coated polycaprolactone-co-lactide (PCL) scaffolds were inserted into critical-size femur defects in adult male Wistar rats. The femur was stabilized with a plate, and the defect was filled with either sGAG-containing PCL scaffolds or autologous bone (positive control). Wound fluid samples obtained by microdialysis were characterized regarding alterations of cytokine concentrations over the first 24 h after surgery. The analyses revealed the inhibition of the pro-inflammatory cytokines IL-1β and MIP-2 in the sGAG-treated groups compared to the positive control. A simultaneous increase of IL-6 and TNF-α indicated advanced regenerative capacity of sGAG, suggesting their potential to improve bone healing.