bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper Jurassic Sediments in the Western Side of the Frolovskoye Basin in West Siberia: Diverse Patterns and Environments of Deposition
Authors: Nemova V.D. , Shakhov A.S. , Bazhukova T.A. , Isangulova A.M. , Kim O.O. , Skomorokhova A.D.
Published: March 2024

—The paper presents data on different types of Late Jurassic carbonaceous–siliceous–shale sequences of marine deposits in the western side of the Frolovskoye basin. The diverse sedimentation patterns in the area were presumably controlled by tectonics, sea bottom topography, and currents, with voluminous gas venting through large faults. Recent exploration drilling in the Elizarovo trough and the Vygnlor basin revealed Upper Jurassic sections of a previously unknown type with low-radioactivity lower strata markedly thicker at the account of biogenic radiolarite intercalations affected by postdepositional carbonatization. The lithology of these rocks is described with implications for deposition environments and extent of such sections.
Model of legal regulation of clusters in the Russian Federation
Authors: Gromova E. A.
Published: March 2024

Objective: to create a model of legal regulation of clusters in the Russian Federation.Methods: historical method, formal-legal analysis, statistical and sociological methods, systematization, comparative-legal method, methods of legal modeling and forecasting.Results: based on the analysis of scientific literature, Russian and foreign legislation and legal practice, the paper formulates the definition of a “cluster” concept (a group of business entities (suppliers, manufacturers, etc.) located on the territory of a special economic zone, operating in a certain sphere, producing and/or carrying out complementary goods, works, services), defines its features and types, and identifies the models of incentive legal regimes: (a) “model of derogations” – EPR model; b) “model of guarantees” – model of a legal regime stimulating entrepreneurial activity in the field of digital innovations and technologies in the PPP (MPP) framework; c) “model of support” – model of a legal regime stimulating entrepreneurial activity of SMEs in the field of digital innovations and technologies; d) “model of preferences” – model of a legal regime stimulating entrepreneurial activity within the boundaries of territories and entities with high innovation potential. The author proposes to create a unified legal regime of cluster and cluster activity in the Russian Federation by developing and adopting a relevant federal law and amending the legislation on special economic zones.Scientific novelty: the article is the first to carry out a comprehensive comparative legal analysis of clusters and cluster policy, their legal regulation in Russia and foreign countries.Practical significance: the main provisions and conclusions of the article can be used in scientific, pedagogical and law enforcement activities when considering issues related to the legal regulation of clusters and cluster policy in Russia and foreign countries, as well as legal regimes stimulating entrepreneurial activity in the field of digital innovation and technology.
From theory to empirics and back: A misunderstanding around the Veblenian dichotomy
Authors: Vernikov A. V. , Kurysheva A. A.
Published: March 2024

Objective: to trace the emergence and consolidation of a wrong meaning when moving from an inaccurately interpreted theoretical concept to empirical evidence. The authors suggest the case of Thorstein Veblen’s evolutionary theory and identify how researchers interpret and apply its selected elements.Methods: discourse analysis. The authors rely on Veblen’s original writings, research papers by Russian authors who refer to the so-called Veblenian dichotomy, and own research findings. The latter show the application of Veblen’s concept to study (1) the features of Russian 19th century economic culture, and (2) contemporary techniques of manipulating personal financial decision-making.Results: the authors found that Veblen had distinguished between contrasting analytical categories when describing different human dispositions, or instinctive proclivities, underlying habitual ways of thinking and doing and economic conduct. Some dispositions lead to productive behavior, while others lead to unproductive one. This concept is essential for institutional analysis. Our research discovers its inaccurate interpretations in the research literature. Starting from a distorted understanding of the theoretical concept, empirical studies contribute to the entrenchment and spread of a misconception, thus feeding a particular ideological agenda. The authors separated Veblen’s original concepts, including ethical ones, from subsequent interpretations and elaborations, to monitor the changing treatment of traditional values in research literature as productive or ceremonial ones. Research findings indicate that the articles by Russian institutionalists contain a systematic bias with regard to the treatment of traditional norms and values as merely ceremonial ones, implying backwardness and archaic patterns, which impede technological progress and “modernization”.Scientific novelty: the application of Veblenian analytical tools in an applied institutional study is reconsidered. Authors’ own analytical technique is suggested to assess the norms underlying economic behavior in terms of their productivity. This technique is applied to the Russian empirical material, both historical and contemporary. To our knowledge, the proposed research technique has not been used in the previous literature.Practical significance: the research findings and their interpretation indicate that Veblen’s ethics and his analytical approach remain relevant. This article contributes to the “restoration” of core values and economic culture of the Russian people. Veblen’s evolutionary theory is suggested as an alternative to the widespread trite methods of cross-country and cross-cultural socio-economic comparisons which presume the supremacy of “Western” values.
On predicting the probability of default of credit organizations in the Russian Federation
Authors: Zakirova D. F.
Published: March 2024

Objective: to form a model for predicting the default of credit organizations under the modern conditions of the banking sector functioning.Methods: unidimensional analysis of variance, regression analysis of binary choice models.Results: in the modern economy, the banking system stability largely affects not only the financial sector, but also the economic and investment climate in the country. Understanding of the banks’ influence on the economy necessitates the formation of appropriate effective forecasting systems that allow identifying problem banks before revoking their licenses is necessary. The existing methodology of the Bank of Russia is characterized by subjectivity and inaccuracy of assessment. The analysis of studies on predicting bank defaults showed various approaches to the methodology of assessing the probability of credit institutions’ bankruptcy, though they have a number of shortcomings. Based on the selection of key factors affecting the bank’s financial stability, the logistic regression model for predicting bankruptcy of banks was formed. The methodology proposed in this article includes five predictors, selected on the basis of the improved methodology for selecting logit regression variables, and complements the existing methodologies.Scientific novelty: a methodology for assessing the probability of commercial banks’ bankruptcy in the Russian Federation was developed, which includes five key predictors for assessing the bank’s financial stability: return on assets, unit weight of liquid assets in the balance sheet currency, unit weight of the loan portfolio in the balance sheet currency, share of loans to the real sector in the balance sheet currency, and share of long-term placements in the loan portfolio. The logistic regression model of binary choice proposed in the paper allows distinguishing financially stable credit organizations from problem banks with a forecasting horizon of five months and a classification accuracy of 88,33 %.Practical significance: the relatively high classification accuracy of the model allows its use by the Bank of Russia in controlling the credit organizations functioning, as well as directly by the credit organization’s management, in order to assess the organization’s financial stability and to predict the default probability, as well as to form the bank’s development strategy.
WITHDRAWN: Entrepreneurship and Nigerian Economic Development Nexus in the Digitized Era
Authors: Onyejiaku Chinyere C. , Ngong Chi Aloysius , Onwumere Josaphat Uchechukwu Joe
Published: March 2024

The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
ExaAUAC: Arabic Twitter User Age prediction Corpus based on language and metadata features
Authors: Sadeghi Reyhaneh , Akbari Ahmad , Jaziriyan Mohammad Mehdi
Published: March 2024

Twitter is a rich resource for analyzing the contents of social media and extracting the age groups of users can be beneficial for recommender systems, marketing and advertising, etc. Age detection task is an aspect of demographic information of users. In this study a large-scale corpus of Arabic Twitter users including 181k user profiles with age groups consisting of -18, 18-24, 25-34, 35-49, 50-64, +65 is presented. The corpus is created by various methods, such as collecting publicly available birthday announcement tweets using the Twitter Search application programming interface, manual annotation, augmenting data and fetching verified accounts.Different evaluations are tested to find the model with highest accuracy and efficiency. Number of tweets, regression vs. classification, using metadata of users and tweets, using baseline model vs. BERT are some parts of examinations done.Presented methodology is based on language and metadata features and final model is fine-tuned with BERT on 70k users and evaluated on 8200 manually annotated users. We show that our best model, compared with baseline model and BERT-based similar model yields an improvement of up to 9% in F1-score and increment of 5% in accuracy, respectively. The model achieved macro-averaged F1-score of 44 on six age groups, and F1-score of 58 on three age groups of -25, 25-34, +35. The link of our proposed data is provided here: www.github.com/exaco/ExaAUAC
Assessing climate induced resettlement impacts on livelihood vulnerability in flood-prone areas of Punjab, Pakistan; an application of livelihood vulnerability index
Authors: Ahmad Dilshad , Afzal Muhammad
Published: March 2024

Population living in climate induced disaster vulnerable areas can mitigate risks by preventive resettlement strategies. However, prior to having resettlement risks and particular resettles livelihood impacts it is necessary to investigate those communities whose living have transformed through climate persuaded resettlement. Objective of this research work is to examine prior resettlement and after resettlement climate-based livelihood vulnerability variations of resettled two model villages flood prone community of Muzaffargarh. Livelihood vulnerability changes of resettled households were investigated by application of Livelihood vulnerability index that covers seven major components exposure, finance, water, health, social networks, livelihood strategy and sociodemographic profile. In this study data was collected by well-developed questionnaire from 241 households’ heads which resettled in two model villages from twelve flood prone union council areas. Data collected by direct interaction with respondents where questionnaire consists on some significant perspectives regarding resettlers subsidies receipts, physical conditions, job status, income aspect, socioeconomic perspective and damages of flood disasters prior and after resettlement. Livelihood vulnerability index each indicator values prior and after resettlement were calculated to determine in what way altered household’s livelihood after resettlement. Estimated outcomes of study indicated that vulnerability of health, water, livelihood strategy and exposure components were significantly declined when household moved to less flood prone areas owing to resettlement in well-construction model villages associated with government subsidies. On the other hand, some major components like finance and social networking becomes higher vulnerable owing to loss in economic activity and kinship which were deep rooted in original communities of households. In these resettled areas, proactive stance of concerned authorities or institutions and policy makers need to implement with compacted strategies to reduce financial risks and job vulnerabilities to develop sustainable livelihood of resettled households.
Biochemical Composition and Toxicity Assessment of Seaweeds from the Algerian Coast: Implications for Human Consumption and Marine Pollution
Authors: Ousmer Lila , Madani Zahia , Dahim Mohammed Abdullah , Boussebaa Walid , Adouane Meriem , Ouali Karima Ould , Msela Amine , Dahmoune Farid , Aleya Lotfi , Trabelsi Lamia , houali karim , Kadri Nabil
Published: March 2024

Seaweeds are widely used as food and natural remedies among the Asian population. In this study, the biochemical composition of Cystoseeira amentacea, Cystoseira sedoides, and Sargassum vulgare from the Algerian coast was evaluated. The results indicated that the protein content ranged from 8.62–9.56%, whereas the lipid content varied from 0.77 to 2.35%. The most prevalent unsaturated fatty acid was oleic acid (14.47–18.64%). The seaweeds contain phenolic compounds in varying amounts, LC-MS-MS analysis showed the presence of catechin, p-coumaric acid, caffeic acid, and gallic acid. Moreover, the phaeophyta are rich in potassium and calcium. However, they accumulate high quantities of heavy metals including arsenic (403.92 ± 1.299 to 508.62 ± 1.364 mg/100g of dry matter). The results suggest that these algae are rich in primary and secondary metabolites, however, they cannot serve as human food, due to their toxicity. Consequently, they can used as bioindicators of marine pollution. Keyworlds : Seaweeds, Phenolic compounds, Fatty acids, Proteins, Flavonoids, Heavy metals.
Surgical Approach Selection for Congenital Long-Segment Hirschsprung's Disease
Authors: wu wei , tan kezhe , sheng qingfeng , liu jiangbin , lv zhibao
Published: March 2024

Objective: To investigate the selection of timing and methods for curative surgery in patients with congenital long-segment Hirschsprung's disease with different lesion extents.
Methods: A retrospective analysis was conducted on 22 children with congenital long-segment Hirschsprung's disease who were treated at our hospital from September 2013 to September 2020. Among them, there were 14 males and 8 females, with a median age of 8 months (ranging from 1 month to 6 years). The lesion extents included the proximal descending colon in 10 cases, transverse colon in 8 cases, colonic hepatic flexure in 2 cases, and ascending colon in 2 cases. Regarding the surgical timing, 13 cases underwent colostomy, and 1 case underwent ileostomy (9 cases in stage I surgery, 13 cases in stage II surgery). Follow-up was conducted to assess the complications and bowel function in the mid-to-long-term postoperative period according to different surgical approaches.
Results: Twenty-two patients underwent curative surgery for congenital long-segment Hirschsprung's disease using different surgical methods. The main surgical approaches included stage I surgery (laparoscopic-assisted Soave procedure in 7 cases, laparoscopic modified Duhamel procedure in 2 cases) and stage II surgery (laparoscopic-assisted Soave procedure in 2 cases, laparoscopic or open modified Duhamel procedure in 12 cases). The average duration of stage I surgery was 150 minutes (ranging from 120 to 300 minutes), while that of stage II surgery was 180 minutes (ranging from 160 to 320 minutes). No intraoperative complications or anastomotic leaks occurred. One case experienced postoperative rectal bleeding, which improved with conservative treatment, and two cases had postoperative anal pain, which gradually resolved. The defecation frequency ranged from 2 to 18 times per day within 4 weeks postoperatively and returned to normal (1-3 times per day) with an average time of 4.2 months (ranging from 1.6 to 4.8 months). The average follow-up period was 41 months (ranging from 14 to 83 months). Five cases experienced small bowel colitis postoperatively, and three cases had early constipation symptoms, which improved with conservative treatment. No anorectal malformations or fecal incontinence were observed during the follow-up.
Conclusion: 1. Laparoscopic-assisted or open modified Duhamel procedures are safe and feasible for the treatment of congenital long-segment Hirschsprung's disease. 2. The extent of lesion involvement in congenital long-segment Hirschsprung's disease can range from the sigmoid colon to the cecum, and different management methods should be selected based on the specific lesion extent.
Bio-efficacy of Solanum torvum (Sw.) against agricultural pest Spodoptera litura (Fab.) (Lepidoptera: Noctuidae)
Authors: R Murugesan , K Vasuki , B kaleeswaran
Published: March 2024

The antifeedant, larvicidal and histological effects of Solanum torvum leaf extracts were investigated against Spodoptera litura. The study found that the ethyl acetate leaf extract showed a significant antifeedant effect against S. litura of (86.16%) at 5%, followed by SNP (Solanum torvum based silver nanoparticles synthesis) showed the a good antifeedant activity of 61.33% at 600 ppm. Ethyl acetate extract showed a larvicidal activity against S. litura of 88.21% and the LC50 value was 2.05%. Exposure of larvae to ethyl acetate leaf extract resulted in significant histological damage, particularly affecting epithelial, goblet and digestive cells. The results suggest that the inclusion of these plant extracts in integrated pest management approaches can promote sustainable and environmentally friendly pest control methods in agriculture.
Knowledge, Attitudes and Behaviors of 5th and 6th Grade Medical Students About Testicular Cancer
Authors: Önal Ayşe Emel , Yüce Servet , Koçak Elif Nur
Published: March 2024

Background and Objective:
The aim of this study is to determine the knowledge, attitudes and behaviors of the last two semesters of medical faculty students who will start to practice medicine in the near future and to investigate their beliefs about this subject.
Materials and Methods
This descriptive study conducted between 01-10-2018 and 31-07-2019. The population of the study consisted of 5th and 6th grade students of a medical faculty 278 students.
Results
52.2% of the students had heard of self-testicular examination. 15.5% of male students reported that they performed self-testicular examination. 13.3% of the students reported that they received training in this subject in medical education. The rate of those students who stated that this issue was shown practically in clinics was 2.9%. For Champion's Health Belief Model Scale’s sub-sections, the mean for sensitivity was 11.01 ± 4.36, triviality-seriousness was 20.58 ± 5.92, benefits was 11,46 ± 2,99, barriers was 10,14 ± 4,04, and the mean of self-efficacy was 18.64 ± 5.26.
Conclusion and Recommendations:
According to the Health Belief Model, students' sensitivity to the subject was below the expected average score, the importance was above the expected average score, believing in the benefits of TSE (testicular self-examination) was higher than the average, the TSE barriers were below the average, and the self-efficacy scores were above the average. Medical students should be more sensitive about testicular cancer and their TSE rates should be increased and their behaviors to recommend and teach this examination to their patients should be increased.
Optimization of the solubilization of faecal sludge by microwave treatment
Authors: Md Principal , Pocock Jon , Velkushanova Konstantina
Published: March 2024

This study examined the effects of microwave treatment on the physicochemical characteristics of faecal sludge (FS). FS from Ventilated Improved Pit (VIP) latrines were treated in a microwave oven at varying microwave power levels and treatment times. Changes in total solids (TS), volatile solids (VS), total chemical oxygen demand (TCOD), and soluble chemical oxygen demand (sCOD) were measured. A response surface methodology (RSM) was used to optimize organic matter solubilization during microwave treatment. A central composite design was employed, and the observed responses were used to fit a second-order response surface model. Microwave treatment at 14,000kJ/kg.TS reduced FS volume by 58%. The VS/TS ratios remained similar before and after microwave treatment. The solubilization of organic matter (measured by sCOD/TCOD ratio) increased after microwave treatment, showing an initial linear increase with specific energy, followed by a decrease. The highest solubilization was 38%, achieved at microwave power level of 630W for 3 minutes. It was observed that organic matter solubilization was more sensitive to contact time than microwave power. The optimized conditions were determined by RSM to be 617.7W and 2.4 minutes, which were within the experimental design boundaries. These findings align with similar observations from other studies using wastewater sludge. The results suggest that microwave treatment can achieve multiple FS treatment objectives. Optimal operating conditions should be identified if the aim is to solubilize organic matter in FS.
Exploring the Antimicrobial and Anticancer Potential of Pyocyanin Produced by Pseudomonas aeruginosa Strain ONO14782
Authors: Ibrahim Prof. Dr. Mohamed Khaled , El-Zawhry Prof. Dr. Yehia Ahmed , Esmaiel Prof. Dr. Ahmed Abdel Rahman , Askora Prof. Dr. Ahmed Abdel Rahman , Mostafa Mohga Tohamy Afifi
Published: March 2024

Background
Pseudomonas aeruginosa is a clinically and epidemiologically important bacterium that causes both acute and chronic infections. The pathogenesis of P. aeruginosa depends on the virulence factors, The important virulence factors of P. aeruginosa included biofilm formation, pigment (pyocyanin), cytotoxins, phospholipases, elastases, and proteases. Pyocyanin is a chloroform soluble blue-green pigment produced by P. aeruginosa, has an antibacterial activity against a wide range of drug-resistant bacteria and pathogenic bacteria, also it was exhibited antifungal activity against different species of mycotoxigenic fungi. and we can use it as an anticancer agent is advised .
Methods
In this study, 46 out of 66 P. aeruginosa isolates were selected based on their pigmentation on cetrimide agar. Pseudomonas isolates were collected from urinary tract infection (urine), burned skin infection and diabetic foot wound (pus) and respiratory infections (sputum). Pseudomonas Cetrimide Agar was used as selective media. TLC technique was used for purification, while UV-Vis, FTIR and GC-MS techniques analysis were used for characterization properties for P73 (ONO14782) strain. Anticancerous effect has been determined by MTT assay established against HepG2, MCF-7 and HCT-116 cell lines.
Results
46 pigmented isolates were selected from 66 isolates. TLC plates showed a blue color in visible light with Rf = 0.81 for pyocyanin. A P73 (ONO14782) strain was used as an experimental strain to study the role of antimicrobial activity of pure pyocyanin, revealing resistance of Klebsiella pneumoniae and Staphylococcus aureus, with Escherichia coli showing intermediate sensitivity. Additionally, pyocyanin demonstrated antifungal efficacy against various yeast and fungi. Furthermore, pyocyanin showed promising anticancer activity against tested cancer cell lines, with strain P73 (ONO14782) displaying activity against HepG2, MCF-7, HCT-116, and A-549 cell lines.
Conclusions
The objective of this study is extraction and purification of pyocyanin from local clinical isolates and choose high productivity strain of pyocyanin studying characterization properties produced from P73 ONO14782 strain and studying its antimicrobial and anticancerous effect. Pyocyanin showed a very high cytotoxic effect on cancerous cell lines leads to reduction in viability of these cells.
Inflammatory Chemokines as Potential Reversal Agents for Tamoxifen Resistance in Breast Cancer Cells
Authors: Ashfaq Isbah , Munir Ali , Izza Bint E Javed , Shaukat Huzaifa , Pervaiz Asim , Asghar Muqadas , Tayyeb Asima
Published: March 2024

Tamoxifen therapy stands as a cornerstone in the treatment regimen for estrogen receptor positive breast cancer. However, emergence and management of tamoxifen resistance pose significant clinical hurdles. Hence, comprehending intricate molecular mechanisms of tamoxifen resistance becomes imperative. This study endeavors to decipher molecular mechanisms underlying acquired tamoxifen resistance. Integrated meta-analysis approach was employed on available microarray gene expression datasets to identify potential targets implicated in tamoxifen resistance. In silico findings were experimentally validated using MCF-7TamR cells model. Meta-analysis highlighted involvement of inflammatory pathways mainly up-regulation of chemokines in tamoxifen resistant breast cancer cells compared to control. qPCR analysis further confirmed significant up-regulation of chemokine genes, including CCL2, CCL20, CXCL6, CXCL14, CXCL12, CXCR4, CCR5, and CCL3 in MCF-7TamR cells. To delineate specific roles of these chemokines in tamoxifen resistance, MCF-7TamR cells were subjected, to selected inflammatory/chemokine antagonists, separately. The observed attenuation of cellular growth, induction of DNA damage, apoptosis, and cell cycle arrest, coupled with the down-regulation of chemokine gene expression, suggests a reversal of the resistance phenotype in treated cells compared to untreated resistant cells. In conclusion, our findings propose that inflammatory chemokines hold the potential to reverse tamoxifen resistance and augment drug sensitivity, offering a promising avenue for mitigating and overcoming tamoxifen resistance in breast cancer therapy.
Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy
Authors: Tian Lingling , Duan Qi , Li Rongshan , Li Yafeng
Published: March 2024

Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage kidney disease worldwide. However, therapeutic drugs for DN treatment are still in lack. Inotodiol (INO), a kind of lanostane triterpenoid isolated from INO that has various biological activities. In this study, we employed db/db mice as the spontaneous DN model in vivo, and high glucose treated MPC5 cells in vitro to elucidate the protective effects and underlying mechanisms of INO in DN. Ratio of right kidney weight/body weight was calculated, and levels of FBG, urine albumin/creatinine (UACR), BUN and Scr were measured. The SOD, CAT, GSH-Px and MDA levels in kidney were detected by using commercial kits. The histopathological changes of renal tissues were assessed by HE, PAS and Masson staining. The intracellular ROS was detected by using fluorescence probe DCHF-DA. Cytotoxicity assay was performed using CCK-8 assay kit. The rate of apoptosis was detected by flow cytometry. The expressions of Bax, Bcl-2, Cytc, Cleaved caspase-3, GSK-3β, pSer-GSK-3β, Akt, p-Akt, Synaptopodin, WT-1, Nrf2, NQO1, Keap1, heme HO-1 were measured by western blot. The expressions of Bax, CytC, WT-1, Synaptopodin, Bcl-2, GSK-3β and pSer9-GSK-3β in renal tissues were measured by immunohistochemistry. Our results showed that INO treatment reduced the FBG, BUN, Scr and UACR levels in db/db mice. Moreover, INO increased the expressions of Synaptopodin and WT-1 proteins. Besides, INO treatment also mitigated kidney histopathological changes, reduces kidney oxidative stress as reflected by reduced levels of Keap-1, NOX4 and MDA, but increased levels of kidney antioxidants SOD, CAT, GSH-Px, Nrf2, NQO1 and HO-1. Additionally, kidney apoptosis decreased as reflected by decreased protein levels of Cytc, Bax and Cleaved caspase-3 while its anti-apoptosis Bcl-2 protein levels increased. Mechanistically, INO inhibited GSK-3β activity by activating the PI3K/Akt signaling pathway, increased the level of anti-apoptosis, decreased level of oxidative stress and reduced podocyte injury in vivo and in vitro. Collectively, these results indicated that INO protected against DN through ameliorating oxidative stress and apoptosis via the PI3K/Akt/GSK-3β pathway.
Purification and biochemical characterization of beta-hexosaminidase from freshwater cnidarian Hydra vulgaris Ind-Pune
Authors: Kukkemane Kowshik , Krishnapati Lakshmi Surekha , Vuruputuri Ratna Mahathi , Ranganatha Kavyashree Sakharayapatna , Nadimpalli Siva Kumar
Published: March 2024

Beta-N-acetylhexosaminidase (Hex) is a vital lysosomal hydrolase ubiquitous in living organisms, that plays a crucial role in cellular homeostasis. Dysfunctions in this enzyme are implicated in severe pathological conditions such as Tay-Sachs and Sandhoff diseases in humans. We report the purification and biochemical characterization of hexosaminidase from the soluble extracts obtained from the polyps of Hydra vulgaris Ind Pune. The Hydra Hex was purified by two-step sequential chromatography (hydrophobic interaction and gel filtration). Our results suggested that the enzyme isoform purified from Hydra is HexB, most likely to be a homodimer with a subunit mass of 65 kDa showing characteristic wobbling specificity. The pH optimum was in the range of 5.0 to 6.0 and the temperature optimum in the range of 50 ºC to 60 ºC. pH stability and temperature stability were found to be 5.0 and 40 ºC respectively. The homology modelling studies corroborated the homodimeric nature of Hydra HexB, and indicated its structural resemblance to human HexB. This first study offers significant insights into Hydra HexB, providing a foundational framework for further extensive investigations on this and other different lysosomal hydrolases in Hydra. The purified enzyme then holds promise for applications in glycomics and glycobiology research, offering new avenues for exploring the intricate roles of carbohydrates in biological systems.
Motor Skill Learning Modulates Striatal Extracellular Vesicles’ Content in a Mouse Model of Huntington’s Disease
Authors: Solana-Balaguer Júlia , Garcia-Segura Pol , Campoy-Campos Genís , Chicote-González Almudena , Fernández-Irigoyen Joaquín , Santamaría Enrique , Pérez-Navarro Esther , Masana Mercè , Alberch Jordi , Malagelada Cristina
Published: March 2024

Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.
Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product
Authors: Figueiredo Joana , Mendes Maria , Pais Alberto , Sousa João J. , Vitorino Carla
Published: March 2024

The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However, the drug stability becomes compromised due to the higher free energy and disorder of molecular packing in the amorphous phase, leading to crystallization. To overcome the stability concern, polymers are used as a matrix to form a stable homogeneous amorphous system. The present work aims to design ASD-based formulations under the quality umbrella by design principles for improving oral drug bioavailability, using celecoxib (CXB) as a model drug. ASDs were prepared from selected polymers and tested both individually and in combinations, using various manufacturing techniques: high-shear homogenization, high-pressure homogenization, microfluidic-on-a-chip, and spray-drying. The resulting dispersions were further optimized, resorting to a 32 full-factorial design, considering the API:Polymers ratio and the total solid content as variables. The formulated products were evaluated regarding analytical centrifugation and the influence of the different polymers on the intrinsic dissolution rate of the CXBASDs. Microfluidic-on-a-chip led to amorphous status of the formulation. The in vitro evaluation demonstrated a remarkable 26-fold enhancement in the intrinsic dissolution rate, and the translation of this formulation into tablets as the final dosage form is consistent with the observed performance enhancement. These findings are supported by ex vivo assays, which exhibited a two-fold increase in permeability compared to pure CXB. This study tackles the bioavailability hurdles encountered with diverse active compounds, offering insights into the development of more effective drug delivery platforms.
Low-complexity Continuous-Variable Quantum Key Distribution with true local oscillator using pilot-assisted frequency locking
Authors: Ruiz-Chamorro Andres , Garcia-Callejo Aida , Fernandez Veronica
Published: March 2024

In the domain of Continuous Variable Quantum Key Distribution (CV-QKD), a significant challenge arises in achieving precise frequency synchronization, an issue commonly termed as frequency locking. This involves matching the optical frequencies of both the quantum signal laser and the local oscillator laser for accurate symbol demodulation during the exchange of quantum keys. As such, implementations today still grapple with maintaining precise synchronization between sender and receiver frequencies, occasionally hindering the efficiency and reliability of the information exchange. Addressing this challenge, we present and empirically validate a novel approach to CV-QKD by incorporating a pilot tone-assisted frequency locking algorithm to enhance stability when using a locally generated local oscillator (LLO) at the receiver. The proposed design leverages software-based optimization techniques, thereby eliminating the need for high-speed electronic stabilization devices and achieving efficient performance at typical repetition rates. Specifically, the introduction of the pilot tone algorithm allows us to effectively mitigate phase fluctuations and preserve the integrity of the quantum signals during transmission without resorting to time-multiplexed reference pulses or fast-locking electronics in the lasers. Our results suggest the potential for achieving secure key rates of up to 1 Mb/s over a 50 km single-mode fiber when using these techniques, offering promising insights into the feasibility of high-rate, low-complexity CV-QKD implementations under realistic conditions.
Disposition of emergency department patients presenting with angiotensin-converting enzyme inhibitor-induced angioedema
Authors: Briggs Blake , Cline David , Husain Iltifat
Published: March 2024

Background
Angiotensin-converting enzyme inhibitors (ACEI) are the most common cause of drug-induced angioedema in the United States (US). Our primary objective was to provide descriptive evidence regarding ED disposition of ACEI-induced angioedema patients. Our secondary objective was to evaluate unique patterns in those with ACEI-induced angioedema at a tertiary referral center.
Methods
This was a retrospective study evaluating all cases of ACEI-induced angioedema at a large, regional academic medical center. We performed a medical record review to identify patients with ACEI-induced angioedema who presented to the ED from January 1, 2016, to December 31, 2022. A total of 637 unique patient encounters met potential inclusion. After a substantial, standardized review, 94 patients met inclusion.
Results
During the study period, there were 94 patients presenting to the ED who were diagnosed as having angioedema secondary to an ACEI (90 patients) or ARB (4 patients). The only treatment found to have statistical association with disposition was intramuscular (IM) epinephrine. Overall, 53 patients (56.38%) improved during their ED stay, and of those, 32 patients (60.38%) were discharged home. None of the 12 patients that worsened were sent home from the ED. Only thirteen of 43 ED discharged patients (23.64%) had their ACEI/ARB documented in their allergy listings compared to 42 of 51 patients (76.36%) of admitted patients, p < 0.0001, odds ratio of failure to document was 0.0929 (95% CI, 0.0352 to 0.24512). Only one patient out of the total 94 returned to the ED during our study period and was subsequently discharged.
Conclusion
Our results indicate that at a large, tertiary care referral center, carefully selected patients with ACEI-angioedema were safely discharged home with low risk of return visit to the ED within 72 hours. No particular symptom or sign predicted the need for intubation, but those who were discharged from the ED with a median stay of 4 hours had no increased risk of return to the ED versus those who were admitted. Further, among those admitted, patients in our study had a short inpatient stay and were safely discharged with no documented early return visit to the ED.
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis
Authors: Kim Jisu , Gao Chao , Guo Pengcheng , Sheng Jianyong , Wang Jianxin
Published: March 2024

Introduction: Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity.
Objective: Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with silymarin (SM). Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
Methods: Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
Results: BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
Conclusion: BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death or toxicity. BDEs@lipo-SM can accelerate liver recovery in the APAP-induced acute liver injury model, which highlights thathybrid BDEs represent an attractive delivery vehicle for therapeutic applications.
Shape optimisation of a hydrodynamic separator using expensive and constrained multi-objective computational modelling
Authors: Roberts Andrew Philip , Rahat Alma As-Aad Mohammad , Jarman Daniel Stuart , Fieldsend Jonathan Edward , Tabor Gavin Randal
Published: March 2024

The shape of a hydrodynamic particle separator has been optimised using unsteady computational fluid dynamics, coupled with Lagrangian particle tracking, combined with a parallelised and robust formulation of Bayesian optimisation. The noise present in the models of the separator required the use of the minimum probability of improvement infill criterion for optimisation of the geometry. This allowed direct inclusion of the objective noise via homoscedastic Gaussian process models. The wall clock time for the fluid modelling suggested that the Bayesian sampling should be parallelised. An existing parallelisation strategy was modified for the infill criterion being used and customised to favour exploitation in the decision space in order to deal with the cliff-edge type landscape that the infill criterion created. A new strategy was developed for convergence failures using Voronoi penalisation, while the approach for handling hardware failures was by manual restart. The presence of unsteady flow in the separator was addressed by time-resolving the flow fields in an Eulerian-Lagrangian manner. The optimisation generated an approximate Pareto front of solutions, which included novel and unexpected geometric shapes, demonstrating the value of Bayesian optimisation in producing innovative designs, which resulted in the filing of a patent.
Wavelet integrated multiscale feature fusion network for imbalanced skin lesion classification
Authors: Shi Xin , Dong Xiaofang , Ye Shuhua , Li Wei , Li Haiyan
Published: March 2024

Accurate medical skin lesion classification is crucial for disease diagnosis and treatment planning. However, current methods are challenged by the presence of scattered feature, imbalanced class distributions and adverse effects of noise. To address these issues, a wavelet integrated multi-scale feature fusion network for imbalanced skin lesion classification is proposed. Firstly, a multi-scale feature fusion network (MSFuse) is designed, which contains parallel local and global feature modules to efficiently capture local spatial context features and global semantic information representation of features at different scales, while implementing adaptive hierarchical feature fusion blocks (HFF) to fuse semantic information between features at different scales in each branch. Subsequently, a Multi-Weighted New Loss (MWNL) function is proposed to overcome the challenge of uneven sample size and classification difficulty while reducing the impact of abnormal samples on training. Finally, the discrete wavelet transform (DWT) is incorporated instead of the average pooling of the fusion branch in MSFuse to remove the high-frequency components of the output features and extract the high-level features from the low-frequency components to suppress the effect of noise on the final classification results and improve the classification accuracy. Ablation experiments and comparison experiments are conducted on the ISIC2018 dataset, and the subjective and objective experimental results demonstrate that the proposed network outperforms the state-of-the-art methods and achieves the superior skin lesion classification results with 84.42%, 70.35%, 74.53%, 74.76% and 74.34% for Acc, MCC, F1, Prec, and Recall, respectively.
Dimethyl phthalate exposure induces cognitive impairment through COX2-mediated microglial activation
Authors: Wang Genghuan , Shen Jian , Lin Yingcong , Zhai Liping , Guan Qiaobing , Shen Heping
Published: March 2024

AIM
We investigated the mechanism of action whereby exposure to dimethyl phthalate (DMP), an environmental pollutant, causes cognitive impairment.
METHODS
Network pharmacology was used to analyze the targets and regulatory networks associated with DMP-brain injury-cognitive impairment. The environmental intake of DMP was simulated by DMP exposure, and Morris water maze was adopted to examine cognitive impairment. The tissue levels of inflammatory cytokines were detected. Brain tissue damage was assayed by H&E and Nissl staining, and protein expression was identified by Western blotting. The effects of DMP were observed after separate application of siRNA-COX2 and celecoxib-COX2 inhibitors. In the in vitro experiment, the effects of DMP on microglia activation were investigated.
RESULTS
Network pharmacology revealed that PTGS2 (COX2) was significantly correlated with DMP, which could act through COX2. After exposure to DMP, mice showed significant brain injury and cognitive impairment, along with activation of microglia and upregulation of inflammatory cytokines. The application of siRNA-COX2 and celecoxib-COX2 could inhibit the effects of DMP and ameliorate the cognitive impairment in mice. The in vitro results showed that DMP could activate microglia and cause microglia activation and neuroinflammation.
CONCLUSION
DMP exposure can induce neuroinflammation through COX2-mediated activation of microglia, resulting in cognitive impairment. COX2 is an important target for DMP action.
Multi-response Optimisation Applied on Friction Stir Processing to Enhanced Wear and Corrosion performance in Al-Si Alloys
Authors: Traiano Denner , Nascimento Silvia Rosa , Lourençato Luciano Augusto , Roca Angel Sánchez , Orozco Mario César Sánchez , Fals Hipólito Domingo Carvajal
Published: March 2024

Eutectic (Al12Si) and hyper-eutectic (Al14Si) Al–Si alloys were processed through friction-stir processing (FSP). These Al-Si alloys' microstructure, microhardness, wear, and corrosion behaviour were studied. FSP led to the fragmentation and uniform distribution of Si and Fe-rich intermetallic phases in the Al matrix. Multi-response optimisation of the friction-stir process of Al–Si alloys was investigated. The optimum FSP parameters were a tool rotation speed of 1100 rpm and a 16 mm/min travel speed for Al12Si alloy. The friction stir processed Al12Si samples exhibit the highest microhardness (93 Hv); the most considerable fragmentation of Si particles and Fe-rich intermetallic phases, with average sizes of 2.82 and 2.07 µm, respectively; and optimal values of coefficient of friction (0.60); and corrosion rate (1.28×10− 4 mm/y). This work provided a mathematical model to obtain the optimum FSP parameters for producing surfaces in Al12Si alloys with excellent microstructural characteristics, high hardness, and better wear and corrosion resistance.