bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of joint orientation on passive movement of the dog’s stifle
Authors: Yair Nadav , Yiapanis Christos , Ben-Amotz Ron , Milgram Joshua
Published: June 2023

Introduction

The cranial cruciate ligament (CCL) is one of numerous structures which determine the path of the tibia relative to the femur when passively flexing/extending the stifle of the dog. The effect of cutting the CCL on passive motion with the hind limb in different orientations, is unknown. The aim of this study was to describe passive movement of the tibia relative to the femur in dogs, with the hind limb in three different orientations, and with CCL intact and cut.

Methods

Ten cadaveric hind limbs were obtained from dogs weighing between 20 kg and 25 kg and prepared for testing in a custom-built joint testing machine. Each hind limb was tested in three different orientations with data collected, using an electromagnetic tracking system, during 2 cycles of flexion/extension with the CCL intact and cut. Each cycle was initiated with the stifle in full extension (0°) and data was collected at 0°, 20°, 30°, 40°, 45°, and 55° of stifle flexion/extension.

Results

Flexion of the stifle resulted in caudal translation and internal rotation of the tibia relative to the femur, with cranial translation and external rotation occurring during extension along the identical path. Cutting the cranial cruciate ligament did not result in significant differences in translation or rotation when the stifle was orientated to approximated the standing position of a dog.

Discussion

Isometric points at the origin and insertion of the CCL can potentially be identified in CCL deficient stifles using a technique based on passive motion of an intact stifle.
Imlifidase for Kidney Transplantation of Highly Sensitized Patients With a Positive Crossmatch: The French Consensus Guidelines
Authors: Couzi Lionel , Malvezzi Paolo , Amrouche Lucile , Anglicheau Dany , Blancho Gilles , Caillard Sophie , Freist Marine , Guidicelli Gwenda Line , Kamar Nassim , Lefaucheur Carmen , Mariat Christophe , Koenig Alice , Noble Johan , Thaunat Olivier , Thierry Antoine , Taupin Jean-Luc , Bertrand Dominique
Published: June 2023

Imlifidase recently received early access authorization for highly sensitized adult kidney transplant candidates with a positive crossmatch against an ABO-compatible deceased donor. These French consensus guidelines have been generated by an expert working group, in order to homogenize patient selection, associated treatments and follow-up. This initiative is part of an international effort to analyze properly the benefits and tolerance of this new costly treatment in real-life. Eligible patients must meet the following screening criteria: cPRA ≥ 98%, ≤ 65-year of age, ≥ 3 years on the waiting list, and a low risk of biopsy-related complications. The final decision to use Imlifidase will be based on the two following criteria. First, the results of a virtual crossmatch on recent serum, which shall show a MFI for the immunodominant donor-specific antibodies (DSA) > 6,000 but the value of which does not exceed 5,000 after 1:10 dilution. Second, the post-Imlifidase complement-dependent cytotoxicity crossmatch must be negative. Patients treated with Imlifidase will receive an immunosuppressive regimen based on steroids, rATG, high dose IVIg, rituximab, tacrolimus and mycophenolic acid. Frequent post-transplant testing for DSA and systematic surveillance kidney biopsies are highly recommended to monitor post-transplant DSA rebound and subclinical rejection.
The Role of Intangible Capital Investment and Intangible Assets in Improving Competitiveness
Authors: Csath Magdolna
Published: June 2023

Based on international literature and data, this essay examines the conditions for improving competitiveness in Hungary in relation to intangible assets and capital investment. The link between productivity – as the basis for competitiveness – and intangible capital investment is also discussed. The essay argues that, although there is no consensus on the interpretation of the concepts examined and further analysis and modelling are needed, the relationships presented suggest that higher levels of intangible asset and capital investment would contribute to improving the productivity and competitiveness of the Hungarian economy. First, because this would improve the overall operational efficiency of tangible investments, and second, because it would support the transition to a knowledge economy, the key condition for boosting competitiveness.
Globalisation versus Deglobalisation
Authors: Halmai Péter
Published: June 2023

One of the biggest questions in recent years concerns the future of globalisation. Some argue that the rivalry between the USA and China, certain trade policy restrictions and the repercussions of the coronavirus pandemic that threatened global production and supply chains could mean the end of globalisation. In fact, however, we are witnessing a fundamental transformation of the globalised world economy. Identifying the main directions of change is a crucial task for economists as well as a precondition for prudent economic policy action.
The Concept of Financial Stability in Theory and Law
Authors: Kálmán János
Published: June 2023

State intervention in the functioning of the economy is necessarily based on some public interests, which may serve as a reason for restrictive state action against the individual, or their freedoms and rights. In legislation, financial stability can be identified as a form of public interest, whereby the need to define the substance of the concept is expressed as an expectation towards the legislator, all the more so because it forms the basis of significant administrative intervention of the public authority type. The study analyses how the concept of financial stability appears in the literature, in legislation and in legal enforcement. Although the concept of financial stability is strongly reflected in the theoretical literature and even in legislation and legal enforcement, its substance is difficult to capture and has evolved constantly. In view of the above, the author offers a definition for the general legal concept of financial stability.
Traditional versus AI-Based Fraud Detection: Cost Efficiency in the Field of Automobile Insurance
Authors: Benedek Botond , Nagy Bálint Zsolt
Published: June 2023

Business practice and various industry reports all show that automobile insurance fraud is very common, which is why effective fraud detection is so important. In our study, we investigate whether today’s widespread AI-based fraud detection methods are more effective from a financial (cost-effectiveness) point of view than methods based on traditional statistical-econometric tools. Based on our results, we came to the unexpected conclusion that the current AI-based automobile insurance fraud detection methods tested on a real database found in the literature are less cost-effective than traditional statistical-econometric methods.
The Uptake of Green Finance Tools in Agriculture : Results of a Q-methodology
Authors: Parádi-Dolgos Anett , Bareith Tibor , Vancsura László , Csonka Arnold
Published: June 2023

In this period of climate change, green finance is expected to have complex consequences to address economic and environmental risks by improving the profitability of individual activities. There are clearly identifiable areas of green development in agriculture that require such funding. Our research investigates the effectiveness of green finance tools in financing the sustainable development of the pig sector, a key agricultural sub-sector. The results of a Q-methodology study carried out with actors in the product chain showed that green finance is an unknown area for them. They are uncertain and pessimistic about whether and to what extent green finance tools can contribute to the development of the sector, but all share the view that sustainable investment in the sector may require public intervention. The use of economic policy instruments may therefore be necessary to make a sector-specific green finance programme a success.
Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature
Authors: Cartes Rodrigo , Karim Muneeb Uddin , Tisseverasinghe Steven , Tolba Marwan , Bahoric Boris , Anidjar Maurice , McPherson Victor , Probst Stephan , Rompré-Brodeur Alexis , Niazi Tamim
Published: June 2023

Background: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. Methods: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Findings: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. Interpretation: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.
Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy
Authors: Lode Holger N. , Ladenstein Ruth , Troschke-Meurer Sascha , Struppe Linda , Siebert Nikolai , Zumpe Maxi , Ehlert Karoline , Huber Stefanie , Glogova Evgenia , Hundsdoerfer Patrick , Eggert Angelika , Zaniewska-Tekieli Anna , Balwierz Walentyna , Wieczorek Aleksandra
Published: June 2023

The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines. The treatment did not result in any unexpected severe toxicities or in any major treatment delays. Grade 3/4 pain was reported by 4/25 patients in cycle 1, decreasing to 0/9 patients in cycles 3 and 4. The median follow-up was 0.6 years. The best response in this group was 48% (12/25 patients), which included three patients with minor responses. At 1 year, the estimated event-free survival was 27% (95% confidence interval [CI] 8–47) and overall survival was 44% (95% CI 24–65). Combining long-term infusion of dinutuximab beta with N5 and N6 chemotherapy demonstrated an acceptable safety profile and encouraging objective response rates in heavily pretreated patients with high-risk neuroblastoma, warranting further evaluation in clinical trials.
Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients
Authors: Garrido Castillo Laura Nalleli , Anract Julien , Delongchamps Nicolas Barry , Huillard Olivier , BenMohamed Fatima , Decina Alessandra , Lebret Thierry , Dachez Roger , Paterlini-Bréchot Patrizia
Published: June 2023

Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target.
Impact of COVID-19 on 1-Year Survival Outcomes in Hepatocellular Carcinoma: A Multicenter Cohort Study
Authors: De Souza Shuell , Kahol de Jong Jeffrey , Perone Ylenia , Shetty Shishir , Qurashi Maria , Vithayathil Mathew , Shah Tahir , Ross Paul , Temperley Laura , Yip Vincent S. , Banerjee Abhirup , Bettinger Dominik , Sturm Lukas , Reeves Helen L. , Geh Daniel , Orr James , Allen Benjamin , Jones Robert P. , Sharma Rohini
Published: June 2023

Introduction: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients’ access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. Methods: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. Results: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. Conclusion: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy.
Management of Patients with Lower-Risk Myelodysplastic Neoplasms (MDS)
Authors: Lucero Josephine , Al-Harbi Salman , Yee Karen W. L.
Published: June 2023

Myelodysplastic neoplasms (MDS) are a heterogenous group of clonal hematologic disorders characterized by morphologic dysplasia, ineffective hematopoiesis, and cytopenia. In the past year, the classification of MDS has been updated in the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours and the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemia with incorporation of morphologic, clinical, and genomic data. Furthermore, the more comprehensive International Prognostic Scoring System-Molecular (IPSS-M) allows for improved risk stratification and prognostication. These three developments allow for more tailored therapeutic decision-making in view of the expanding treatment options in MDS. For patients with lower risk MDS, treatment is aimed at improving cytopenias, usually anemia. The recent approval of luspatercept and decitabine/cedazuridine have added on to the current armamentarium of erythropoietic stimulating agents and lenalidomide (for MDS with isolated deletion 5q). Several newer agents are being evaluated in phase 3 clinical trials for this group of patients, such as imetelstat and oral azacitidine. This review provides a summary of the classification systems, the prognostic scores and clinical management of patients with lower risk MDS.
An Agent-Based Statistical Physics Model for Political Polarization: A Monte Carlo Study
Authors: Diep Hung T. , Kaufman Miron , Kaufman Sanda
Published: June 2023

World-wide, political polarization continues unabated, undermining collective decision-making ability. In this issue, we have examined polarization dynamics using a (mean-field) model borrowed from statistical physics, assuming that each individual interacted with each of the others. We use the model to generate scenarios of polarization trends in time in the USA and explore ways to reduce it, as measured by a polarization index that we propose. Here, we extend our work using a more realistic assumption that individuals interact only with “neighbors” (short-range interactions). We use agent-based Monte Carlo simulations to generate polarization scenarios, considering again three USA political groups: Democrats, Republicans, and Independents. We find that mean-field and Monte Carlo simulation results are quite similar. The model can be applied to other political systems with similar polarization dynamics.
Deep Reinforcement Meta-Learning and Self-Organization in Complex Systems: Applications to Traffic Signal Control
Authors: Korecki Marcin
Published: June 2023

We studied the ability of deep reinforcement learning and self-organizing approaches to adapt to dynamic complex systems, using the applied example of traffic signal control in a simulated urban environment. We highlight the general limitations of deep learning for control in complex systems, even when employing state-of-the-art meta-learning methods, and contrast it with self-organization-based methods. Accordingly, we argue that complex systems are a good and challenging study environment for developing and improving meta-learning approaches. At the same time, we point to the importance of baselines to which meta-learning methods can be compared and present a self-organizing analytic traffic signal control that outperforms state-of-the-art meta-learning in some scenarios. We also show that meta-learning methods outperform classical learning methods in our simulated environment (around 1.5–2× improvement, in most scenarios). Our conclusions are that, in order to develop effective meta-learning methods that are able to adapt to a variety of conditions, it is necessary to test them in demanding, complex settings (such as, for example, urban traffic control) and compare them against established methods.
Review of Developments in Plate Heat Exchanger Heat Transfer Enhancement for Single-Phase Applications in Process Industries
Authors: Arsenyeva Olga , Tovazhnyanskyy Leonid , Kapustenko Petro , Klemeš Jiří Jaromír , Varbanov Petar Sabev
Published: June 2023

A plate heat exchanger (PHE) is a modern, effective type of heat transfer equipment capable of increasing heat recuperation and energy efficiency. For PHEs, enhanced methods of heat transfer intensification can be further applied using the analysis and knowledge already available in the literature. A review of the main developments in the construction and exploration of PHEs and in the methods of heat transfer intensification is presented in this paper with an analysis of the main construction modifications, such as plate-and-frame, brazed and welded PHEs. The differences between these construction modifications and their influences on the thermal and hydraulic performance of PHEs are discussed. Most modern PHEs have plates with inclined corrugations on their surface that create a strong, rigid construction with multiple contact points between the plates. The methods of PHE exploration are mostly experimental studies and/or CFD modelling. The main corrugation parameters influencing PHE performance are the corrugation inclination angle in relation to the main flow direction and the corrugation aspect ratio. Optimisation of these parameters is one way to enhance PHE performance. Other methods of heat transfer enhancement, including improving the form of the plate corrugations, use of nanofluids and active methods, are considered. Future research directions are proposed, such as improving fundamental understanding, developing new corrugation shapes and optimisation methods and area and cost estimations.
Discussion on Incentive Compatibility of Multi-Period Temporal Locational Marginal Pricing
Authors: Hyder Farhan , Yan Bing , Luh Peter , Bragin Mikhail , Zhao Jinye , Zhao Feng , Schiro Dane , Zheng Tongxin
Published: June 2023

In real-time electricity markets, locational marginal prices (LMPs) can be determined by solving multi-interval economic dispatch problems to manage inter-temporal constraints (i.e., ramp rates). Under the current practice, the LMPs for the immediate interval are binding, while the prices for the subsequent intervals are advisory signals. However, a generator may miss the opportunity for higher profits, and compensatory uplift payments are needed at the settlement. To address these issues, the “temporal locational marginal pricing (TLMP)” that augments LMP by incorporating multipliers associated with generators’ reported ramp rates was developed. It was demonstrated that it would result in zero uplift payments, showing great potential as a good pricing scheme. Numerical examples also showed that “the generators had incentives to reveal their ramp rates truthfully”. In this paper, the incentive compatibility of TLMP with respect to ramp-rate reporting is discussed. Our idea is to develop numerical examples to investigate whether reporting the true ramp rates is the best option for generators. The results indicate that TLMP is not incentive compatible, and there are market-clearing scenarios where not reporting true ramp rates may be beneficial.
Improving the Energy Performance and Economic Benefits of Aged Residential Buildings by Retrofitting in Hot–Humid Regions of China
Authors: Yang Xiaolin , Chen Zhuoxi , Zou Yukai , Wan Fengdeng
Published: June 2023

The existing building stock faces the challenge of low energy efficiency and requires renovation and upgrading to meet society′s goals of carbon reduction and sustainable development. This study presents an optimization framework utilizing genetic algorithms to develop robust retrofit plans that balance the need for improved energy efficiency, cost-effectiveness considerations for householders, and uncertainties regarding climate conditions. A case study of an aged residential building in a hot and humid region of China is used to demonstrate the proposed method. The optimization results show a potential energy demand reduction of 81.5%. However, due to the relatively long time required to realize economic benefits from high investments, short-term optimization tends to favor solutions with high energy demand and low primary costs. To effectively reduce carbon emissions, it is recommended to consider the long-term economic benefits of retrofits and prioritize solutions with high energy efficiency. However, it is important to acknowledge that the expensive nature of retrofit investments may pose barriers to residents. Society should provide adequate support and guidance to facilitate residential renovation efforts.
Approaching the Theoretical Maximum Performance of Highly Transparent Thermochromic Windows
Authors: Mann Daniel , Calvi Lavinia , Yeung Cindy P. K. , Habets Roberto , Elen Ken , Hardy An , Van Bael Marlies K. , Buskens Pascal
Published: June 2023

Thermochromic window coatings represent a promising technology to improve the energy efficiency of buildings in intermediate climates. With the technology approaching market introduction it is important to investigate its performance limits within smart windows and to identify existing development challenges. Here we analyze the theoretical maximum performance of thermochromic window coatings that modulate IR transmission whilst retaining high visible transparency. The set limitations lead to a theoretical maximum solar modulation of 39.1%. Within an insulated glazing unit (IGU), where at least 2 glass panes and a conventional low-e coating are required, this value is further reduced to 12.9%. We show that by carefully selecting a low-e coating with the highest compatibility to a thermochromic coated glass and by allowing 10% of modulation in the visible spectral range, the theoretical maximum can be increased to 23.1%, illustrating the importance to codesign and match both coatings within a smart window to reach optimum performance. Furthermore, we compared our current best-performing VO2:SiO2 composite coating within an IGU to the theoretical maximum. The analysis shows that with a solar modulation of 13.4%, the coating is currently at 59% of the theoretical maximum. Finally, we propose and discuss several strategies to proceed further toward the theoretical maximum.
Coupling Simulation of Longitudinal Vibration of Rod String and Multi-Phase Pipe Flow in Wellbore and Research on Downhole Energy Efficiency
Authors: Ma Biao , Dong Shimin
Published: June 2023

The wellbore of a sucker–rod pumping well experiences a multi–phase flow consisting of oil, gas, and water. The flow pattern and pump discharge pressure are greatly impacted by oil well production, which in turn significantly affects the simulation results of longitudinal vibration in the sucker–rod string. When calculating the discharge pressure in a hydrostatic column containing both oil and water (HC), the pressure is not affected by the oil well’s production. This thereby avoids interference between vibrations in the sucker–rod string’s longitudinal direction and the flow from the wellbore. Considering the coupling characteristics between the longitudinal vibration of the sucker–rod string and the wellbore flow, a mathematical model of the sucker–rod pumping system (CMSRS) and a mathematical model of the downhole energy efficiency parameters were established. In detail, the CMSRS comprises two parts: the discharge pressure mathematical models of multi–phase flow dynamics (MD) and the wave equation of the longitudinal vibration of the sucker–rod string. A numerical simulation model of the sucker–rod pumping system was constructed based on a mathematical model. We compared the experimental results, the simulation results of the CMSRS and the simulation results of the sucker–rod string based on the oil–water two–phase hydrostatic column (SMSRS) and found good agreement, indicating the feasibility of the CMSRS. The simulation details show the following: (1) The HC model’s discharge pressure exceeds that of the MD model by more than 33.52%. The polished rod load for the CMSRS is 18.01% lower than that of the SMSRS, and the pump input power for the CMSRS is 36.23% lower than that of the SMSRS. (2) The effective power simulation model based on the energy balance relationship is essentially the same as the effective power calculated by the model based on multi–phase flow effective power. This validates the accuracy of the multi–phase flow effective power model. (3) The limitations of the industry standard effective power model are that (i) the effective head is the net lift height of the fluid in the wellbore reduced to the oil and water phases rather than the effective lift height based on the energy balance relationship and (ii) the power of the gas phase delivered by the pumping pump is disregarded, and only the effective power of the pump delivering the oil–water mixture is considered. (4) The influence of the wellbore parameters on the wellbore efficiency and sub–efficiency is systematically analyzed. The analysis results have an important significance in the guidance of energy saving in pumping wells.
Hydrogen Purification through a Membrane–Cryogenic Integrated Process: A 3 E’s (Energy, Exergy, and Economic) Assessment
Authors: Naquash Ahmad , Riaz Amjad , Yehia Fatma , Chaniago Yus Donald , Lim Hankwon , Lee Moonyong
Published: June 2023

Hydrogen (H2) is known for its clean energy characteristics. Its separation and purification to produce high-purity H2 is becoming essential to promoting a H2 economy. There are several technologies, such as pressure swing adsorption, membrane, and cryogenic, which can be adopted to produce high-purity H2; however, each standalone technology has its own pros and cons. Unlike standalone technology, the integration of technologies has shown significant potential for achieving high purity with a high recovery. In this study, a membrane–cryogenic process was integrated to separate H2 via the desublimation of carbon dioxide. The proposed process was designed, simulated, and optimized in Aspen Hysys. The results showed that the H2 was separated with a 99.99% purity. The energy analysis revealed a net-specific energy consumption of 2.37 kWh/kg. The exergy analysis showed that the membranes and multi-stream heat exchangers were major contributors to the exergy destruction. Furthermore, the calculated total capital investment of the proposed process was 816.2 m$. This proposed process could be beneficial for the development of a H2 economy.
Deletion of a Single Lysine Residue at Position 292 of CAMK2A Disrupts Protein Function, Causing Severe Epileptic Encephalopathy and Intellectual Disability
Authors: Lintas Carla , Facchiano Angelo , Azzarà Alessia , Cassano Ilaria , Tabolacci Claudio , Galasso Cinzia , Gurrieri Fiorella
Published: June 2023

Background: The use of NGS technology has rapidly increased during the last decade, and many new monogenic neurodevelopmental disorders have emerged. Pathogenic variants in the neuronal CAMK2A gene have been recently associated with “intellectual developmental disorder, autosomal dominant 53″ (OMIM#617798), a syndrome characterized by variable clinical manifestations including mild to severe intellectual disability, delayed psychomotor development, delayed or absent speech, delayed walking, seizures, dysmorphic features and behavioral psychiatric manifestations as autism spectrum disorders, aggressive behavior, and hyperactivity. CAMK2A (OMIM*114078) encodes for a subunit of the calcium/calmodulin-dependent serine/threonine kinase II (CaMKII), which is predominately expressed in the brain, where it plays critical roles in synaptic plasticity, learning, and memory as well as in neuronal migration. Methods and Results: We hereby describe a thirty-five-year-old woman affected by severe intellectual disability with epileptic encephalopathy. We performed exome sequencing and found a de novo heterozygous variant in the CAMK2A gene (NM_171825.2: c.874_876delCTT; p.Lys292del), which was fully correlated with her phenotype. This is the first report of an inframe single amino acid deletion in a patient affected by intellectual developmental disorder autosomal dominant 53. The variant is predicted to affect protein structure and function and interaction with other proteins and hits a crucial functional site. Discussion: We discuss our variant in relation to previously reported variants and with the objective of delineating possible genotype–phenotype correlations.
A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level
Authors: Kazantseva Anastasiya , Davydova Yuliya , Enikeeva Renata , Mustafin Rustam , Malykh Sergey , Lobaskova Marina , Kanapin Alexander , Prokopenko Inga , Khusnutdinova Elza
Published: June 2023

The risk of depression could be evaluated through its multifactorial nature using the polygenic score (PGS) approach. Assuming a “clinical continuum” hypothesis of mental diseases, a preliminary assessment of individuals with elevated risk for developing depression in a non-clinical group is of high relevance. In turn, epidemiological studies suggest including social/lifestyle factors together with PGS to address the “missing heritability” problem. We designed regression models, which included PGS using 27 SNPs and social/lifestyle factors to explain individual differences in depression levels in high-education students from the Volga–Ural region (VUR) of Eurasia. Since issues related to population stratification in PGS scores may lead to imprecise variant effect estimates, we aimed to examine a sensitivity of PGS calculated on summary statistics of depression and neuroticism GWAS from Western Europeans to assess individual proneness to depression levels in the examined sample of Eastern Europeans. A depression score was assessed using the revised version of the Beck Depression Inventory (BDI) in 1065 young adults (age 18–25 years, 79% women, Eastern European ancestry). The models based on weighted PGS demonstrated higher sensitivity to evaluate depression level in the full dataset, explaining up to 2.4% of the variance (p = 3.42 × 10−7); the addition of social parameters enhanced the strength of the model (adjusted r2 = 15%, p < 2.2 × 10−16). A higher effect was observed in models based on weighted PGS in the women group, explaining up to 3.9% (p = 6.03 × 10−9) of variance in depression level assuming a combined SNPs effect and 17% (p < 2.2 × 10−16)—with the addition of social factors in the model. We failed to estimate BDI-measured depression based on summary statistics from Western Europeans GWAS of clinical depression. Although regression models based on PGS from neuroticism (depression-related trait) GWAS in Europeans were associated with a depression level in our sample (adjusted r2 = 0.43%, p = 0.019—for unweighted model), the effect was mainly attributed to the inclusion of social/lifestyle factors as predictors in these models (adjusted r2 = 15%, p < 2.2 × 10−16—for unweighted model). In conclusion, constructed PGS models contribute to a proportion of interindividual variability in BDI-measured depression in high-education students, especially women, from the VUR of Eurasia. External factors, including the specificity of rearing in childhood, used as predictors, improve the predictive ability of these models. Implementation of ethnicity-specific effect estimates in such modeling is important for individual risk assessment.
Social and Health Beliefs Related to College Students’ COVID-19 Preventive Behavior
Authors: Kim Nam-Yi
Published: June 2023

Coronavirus disease 2019 (COVID-19) infection prevention behaviors vary from individual to individual, and it is necessary to identify factors related to such behaviors. This study investigated how college students’ social beliefs and health beliefs are related to their adherence to COVID-19 precautionary behaviors. An online survey was conducted among 200 Korean college students from 4 March to 30 June 2022. The variables associated with COVID-19 precautionary behaviors were evaluated, with social beliefs as the independent variable, health beliefs as the mediating variable, and COVID-19 precautionary behaviors as the dependent variable. A correlation analysis and confirmatory factor analysis were performed. The model fit was as follows: χ2/degrees of freedom = 1.64 (p < 0.001), Tucker–Lewis Index = 0.92, comparative fit index = 0.93, standardized root mean square residual = 0.06, and root mean square error of approximation = 0.06. Social complexity, as perceived by college students, was related to COVID-19 precautionary behaviors through mediating health beliefs (perceived benefits). To increase college students’ compliance with COVID-19 precautionary behaviors, it is necessary to identify social beliefs and accordingly propose interventions that focus on personal health beliefs.
Experience with Support at Workplaces for People with Young Onset Dementia: A Qualitative Evaluation of Being Open about Dementia
Authors: Omote Shizuko , Ikeuchi Satomi , Okamoto Rie , Takahashi Yutaro , Koyama Yoshiko
Published: June 2023

Young-onset dementia (YOD) occurs at <65 years of age. Individuals with YOD experience social and psychological disturbances, including a loss of employment. This economic toll affects them, their families, and their caregivers. Employers have an increasing role in supporting affected employees in remaining employed, an important component of the “fight for their dignity”. This study aims to clarify the workplace support experiences of employees with YOD. To assess the experiences of employers with at least one affected employee, we interviewed personnel from eight facilities for qualitative analysis. We identified 5 unique categories and 14 subcategories encompassing the following aspects: confusion at the workplace stemming from the uncertainty of the disease, sensitivity when recommending consultation and diagnosis, creating a system that considers safety and security, building consensus among employers, supporting employees with YOD and their families, and assisting the individual with YOD with activities of daily living. Employers should be open to addressing dementia-related issues in the workplace, including obtaining information from employees’ physicians so that appropriate support can be provided. Appropriate support can include work accommodations, needs-based support, and meetings with families to build consensus for continued employment. This information can facilitate the creation of new training materials for employers.
N-Methyl Costaricine and Costaricine, Two Potent Butyrylcholinesterase Inhibitors from Alseodaphne pendulifolia Gamb.
Authors: Husna Hasnan Muhammad Hafiz , Sivasothy Yasodha , Khaw Kooi Yeong , Nafiah Mohd Azlan , Hazni Hazrina , Litaudon Marc , Wan Ruzali Wan Adriyani , Liew Sook Yee , Awang Khalijah
Published: June 2023

Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer’s disease (AD) drugs. The genus Alseodaphne, comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of A. pendulifolia Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, N-methyl costaricine (1), together with costaricine (2), hernagine (3), N-methyl hernagine (4), corydine (5), and oxohernagine (6). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds 1 and 2 were more-potent BChE inhibitors than galantamine with IC50 values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver–Burk plots of compounds 1 and 2 indicated they were mixed-mode inhibitors. Compounds 1 and 2 have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.
Separation of Palladium from Alkaline Cyanide Solutions through Microemulsion Extraction Using Imidazolium Ionic Liquids
Authors: Deng Hui , Liu Chali , Xu Xin , Wu Yuanyuan , Chen Muhan , Huang Zhangjie
Published: June 2023

In this paper, three imidazolium-based ionic liquids, viz., 1-butyl-3-undecyl imidazolium bromide ([BUIm]Br), 1-butyl-3-octyl imidazolium bromide ([BOIm]Br), and 1-butyl-3-hexadecyl imidazolium bromide ([BCIm]Br), were synthesized. Three novel microemulsions systems were constructed and then were used to recover Pd (II) from cyanide media. Key extraction parameters such as the concentration of ionic liquids (ILs), equilibration time, phase ratio (RA/O), and pH were evaluated. The [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system exhibited a higher extraction percentage of Pd (II) than the [BOIm]Br/n-heptane/n-pentanol/sodium chloride and [BCIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion systems. Under the optimal conditions (equilibrium time of 10 min and pH 10), the extraction percentages of these metals were all higher than 98.5% when using the [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system. Pd(CN)42− was separated through a two-step stripping procedure, in which Fe (III) and Co (III) were first separated using KCl solution, then Pd(CN)42− was stripped using KSCN solution (separation factors of Pd from Fe and Co exceeded 103). After five extraction–recovery experiments, the recovery of Pd (II) through the microemulsion system remained over 90%. The Pd (II) extraction mechanism of the ionic liquid [BUIm]Br was determined to occur via anion exchange, as shown by spectral analysis (UV, FTIR), Job’s method, and DFT calculations. The proposed process has potential applications for the comprehensive treatment of cyanide metallurgical wastewater.
Kaempferol and Biomodified Kaempferol from Sophora japonica Extract as Potential Sources of Anti-Cancer Polyphenolics against High Grade Glioma Cell Lines
Authors: dos Santos Jéssica Silva , Suzan Amanda Janaína , Bonafé Gabriel Alves , Fernandes Anna Maria Alves de Piloto , Longato Giovanna Barbarini , Antônio Márcia Aparecida , Carvalho Patrícia de Oliveira , Ortega Manoela Marques
Published: June 2023

The enzymatic hydrolysis of the extract of Sophora japonica by two glycosyl hydrolases (hesperidinase and galactosidase) was performed in order to obtain kaempferol (KPF)-enriched extract with an enhanced anticancer activity. The current study examined the effectiveness of both Sophora japonica extracts (before (KPF-BBR) and after (KPF-ABR) bioconversion reactions) in reducing cell viability and inducing apoptosis in human high-degree gliomas in vitro. Cytotoxicity was determined using an MTT assay. The effects of both compounds on the proliferation of glioma cell lines were measured using trypan blue exclusion, flow cytometry for cell cycle, wound healing (WH), and neurosphere formation assays. Cellular apoptosis was detected by DNA fragmentation and phosphatidylserine exposure. qPCR and luciferase assays evaluated NF-kB pathway inhibition. The survival rate of NG-97 and U-251 cells significantly decreased in a time- and dose-dependent manner after the addition of KPF-BBR or KPF-ABR. Thus, a 50% reduction was observed in NG-97 cells at 800 µM (KPF-BBR) and 600 µM (KPF-ABR) after 72 h. Both compounds presented an IC50 of 1800 µM for U251 after 72 h. The above IC50 values were used in all of the following analyses. Neither of the KPF presented significant inhibitory effects on the non-tumoral cells (HDFa). However, after 24 h, both extracts (KPF-BBR and KPF-ABR) significantly inhibited the migration and proliferation of NG-97 and U-251 cells. In addition, MMP-9 was downregulated in glioma cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) plus KPF-BBR and TPA+KPF-ABR compared with the TPA-treated cells. Both KPF-BBR and KPF-ABR significantly inhibited the proliferation of glioma stem cells (neurospheres) after 24 h. DNA fragmentation assays demonstrated that the apoptotic ratio of KPF-ABR-treated cell lines was significantly higher than in the control groups, especially NG-97, which is not TMZ resistant. In fact, the flow cytometric analysis indicated that KPF-BBR and KPF-ABR induced significant apoptosis in both glioma cells. In addition, both KPF induced S and G2/M cell cycle arrest in the U251 cells. The qPCR and luciferase assays showed that both KPFs downregulated TRAF6, IRAK2, IL-1β, and TNF-α, indicating an inhibitory effect on the NF-kB pathway. Our findings suggest that both KPF-BBR and KPF-ABR can confer anti-tumoral effects on human cell glioma cells by inhibiting proliferation and inducing apoptosis, which is related to the NF-κB-mediated pathway. The KPF-enriched extract (KPF-ABR) showed an increased inhibitory effect on the cell migration and invasion, characterizing it as the best antitumor candidate.
DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases
Authors: Kousparou Christina , Fyrilla Maria , Stephanou Anastasis , Patrikios Ioannis
Published: June 2023

Neurodegenerative diseases are characterized by neuroinflammation, neuronal depletion and oxidative stress. They coincide with subtle chronic or flaring inflammation, sometimes escalating with infiltrations of the immune system cells in the inflamed parts causing mild to severe or even lethal damage. Thus, neurodegenerative diseases show all features of autoimmune diseases. Prevalence of neurodegenerative diseases has dramatically increased in recent decades and unfortunately, the therapeutic efficacy and safety profile of available drugs is moderate. The beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) polyunsaturated fatty acids (omega-3 PUFAs) are nowadays highlighted by a plethora of studies. They play a role in suppression of inflammation, gene expression, cellular membrane fluidity/permeability, immune functionality and intracellular/exocellular signaling. The role of omega-6 polyunsaturated fatty acids, such as linoleic acid (LA), gamma linolenic acid (GLA), and arachidonic acid (AA), on neuroprotection is controversial, as some of these agents, specifically AA, are proinflammatory, whilst current data suggest that they may have neuroprotective properties as well. This review provides an overview of the existing recent clinical studies with respect to the role of omega-3 and omega-6 PUFAs as therapeutic agents in chronic, inflammatory, autoimmune neurodegenerative diseases as well as the dosages and the period used for testing.
Near-Infrared Autofluorescence (NIRAF) in Atherosclerotic Plaque Dissociates from Intraplaque Hemorrhage and Bilirubin
Authors: Chen Weiyu , Nadel James , Tumanov Sergey , Stocker Roland
Published: June 2023

Near-infrared autofluorescence (NIRAF) in unstable atherosclerotic plaque has been suggested as a novel imaging technology for high-risk atherosclerosis. Intraplaque hemorrhage (IPH) and bilirubin, derived from the subsequent degradation of heme, have been proposed as the source of NIRAF, although their roles and the underlying mechanism responsible for NIRAF remain unclear. To test the proposed role of bilirubin as the source of NIRAF in high-risk atherosclerosis, Biliverdin reductase a gene and apolipoprotein E gene double-knockout (Bvra−/−Apoe−/−) mice were subjected to the Western diet and tandem stenosis (TS) surgery, as a model of both bilirubin deficiency and plaque instability. Human coronary arteries containing atherosclerotic plaques were obtained from heart transplant recipients. The NIRAF was determined by in vivo fluorescence emission computed tomography, and ex vivo infrared imaging. The cholesterol content was quantified by HPLC with UV detection. In Bvra+/+Apoe−/− TS mice, the NIRAF intensity was significantly higher in unstable plaque than in stable plaque, yet the NIRAF in unstable plaque was undistinguishable in Bvra+/+Apoe−/− and littermate Bvra−/−Apoe−/− TS mice. Moreover, the unstable plaque in TS mice exhibited a lower NIRAF compared with highly cellular plaque that lacked most of the features of unstable plaque. In human coronary arteries, the NIRAF associated with cholesterol-rich, calcified lesions, rather than just cholesterol-rich lesions. The NIRAF in atherosclerotic plaque can be dissociated from IPH and bilirubin, such that the compositional meaning of an elevated NIRAF remains obscure.