bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy of intra-articular infusion of cocktail combined with tranexamic acid in the treatment of middle-age and older patients with frozen shoulder following arthroscopic capsular release
Authors: Bai Xiaojin , Bai Fan , Wang Zhi , Zhang Yan , Liu Fuying , Wang Qibing
Published: May 2023

Objective

To investigate the clinical efficacy of arthroscopic capsular release and postoperative intra-articular infusion of cocktail combined with tranexamic acid (TXA) in the treatment of patients with frozen shoulder.

Method

A total of 85 middle-aged and older patients with frozen shoulder who underwent arthroscopic capsular release and received intra-articular infusion of TXA alone (n = 28), cocktail alone (n = 26), and cocktail plus TXA (n = 31) after surgery were retrospective analyzed. The drainage volume within 24 h after surgery, postoperative length of hospital stay, postoperative complications, visual analog scale (VAS), Neer shoulder assessment scale, ASES score, and range of motion (ROM) of the shoulder joint at 1 day, 1 week, 1 month, and 3 months after surgery in all three groups were recorded and compared.

Results

Postoperative length of hospital stay was significantly shorter in the cocktail + TXA and cocktail groups than that in the TXA group. Postoperative drainage volume was significantly higher in the cocktail group compared with TXA + cocktail group (P < 0.05). At 1 day and 1 week after surgery, pain was more pronounced in the TXA group, which was significantly relieved in the cocktail and the cocktail + TXA groups (P < 0.05). Pain was significantly relieved in all the three groups at 1 and 3 months after surgery. Significant functional improvement of the shoulder was achieved in all three groups at 1 week after surgery, the improvement was apparent in the cocktail + TXA groups (P < 0.05), followed by the cocktail group. At 1 month after surgery, patients in the cocktail + TXA groups obtained excellent functional recovery of the shoulder joint. At 3 months after surgery, patients in all the three groups both obtained good recovery of the shoulder joint function, and the recovery was apparent in the cocktail + TXA groups (P < 0.05).

Conclusion

Arthroscopic capsular release and postoperative intra-articular infusion of cocktail combined with TXA has good safety and efficacy in the treatment of middle-age and older patients with frozen shoulder, which can reduce postoperative pain and intra-articular bleeding, promote early postoperative functional exercises and accelerate early postoperative recovery.
Concepts in soft-tissue reconstruction of the contracted hand and upper extremity after burn injury
Authors: McNamara Colin T. , Iorio Matthew L. , Greyson Mark
Published: May 2023

Burns and their subsequent contracture result in devastating functional and aesthetic consequences which disproportionally affect the upper extremity. By focusing on reconstruction with analogous tissue and utilizing the reconstructive elevator, function can be restored concomitantly with form and aesthetic appearance. General concepts for soft-tissue reconstruction after burn contracture are presented for different sub-units and joints.
Substantiate a read-across hypothesis by using transcriptome data—A case study on volatile diketones
Authors: Drake Christina , Wehr Matthias M. , Zobl Walter , Koschmann Jeannette , De Lucca David , Kühne Britta A. , Hansen Tanja , Knebel Jan , Ritter Detlef , Boei Jan , Vrieling Harry , Bitsch Annette , Escher Sylvia E.
Published: May 2023

This case study explores the applicability of transcriptome data to characterize a common mechanism of action within groups of short-chain aliphatic α-, β-, and γ-diketones. Human reference in vivo data indicate that the α-diketone diacetyl induces bronchiolitis obliterans in workers involved in the preparation of microwave popcorn. The other three α-diketones induced inflammatory responses in preclinical in vivo animal studies, whereas beta and gamma diketones in addition caused neuronal effects. We investigated early transcriptional responses in primary human bronchiolar (PBEC) cell cultures after 24 h and 72 h of air-liquid exposure. Differentially expressed genes (DEGs) were assessed based on transcriptome data generated with the EUToxRisk gene panel of Temp-O-Seq®. For each individual substance, genes were identified displaying a consistent differential expression across dose and exposure duration. The log fold change values of the DEG profiles indicate that α- and β-diketones are more active compared to γ-diketones. α-diketones in particular showed a highly concordant expression pattern, which may serve as a first indication of the shared mode of action. In order to gain a better mechanistic understanding, the resultant DEGs were submitted to a pathway analysis using ConsensusPathDB. The four α-diketones showed very similar results with regard to the number of activated and shared pathways. Overall, the number of signaling pathways decreased from α-to β-to γ-diketones. Additionally, we reconstructed networks of genes that interact with one another and are associated with different adverse outcomes such as fibrosis, inflammation or apoptosis using the TRANSPATH-database. Transcription factor enrichment and upstream analyses with the geneXplain platform revealed highly interacting gene products (called master regulators, MRs) per case study compound. The mapping of the resultant MRs on the reconstructed networks, visualized similar gene regulation with regard to fibrosis, inflammation and apoptosis. This analysis showed that transcriptome data can strengthen the similarity assessment of compounds, which is of particular importance, e.g., in read-across approaches. It is one important step towards grouping of compounds based on biological profiles.
Gender-Specific and U-Shaped Relationship Between Serum Uric Acid and All-Cause Mortality Among Chinese Older Adults: A National Population-Based Longitudinal Study
Authors: Dong Yinqiao , Wang Zhiqiang , Wang Suping , Chang Ruijie , Liu Yujie , Wang Rongxi , Chen Hui , Liu Shangbin , Qian Changlin , Cai Yong , Hu Fan
Published: May 2023

Objectives: This study aimed to prospectively investigate gender-specific relationship between hyperuricemia and all-cause mortality among Chinese older adults.

Methods: The study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2008–2018, a prospective nationwide cohort of older adults in China. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for all-cause mortality. Restricted cubic splines (RCS) were conducted to explore the dose-response relationship between SUA levels and all-cause mortality.

Results: For older women, compared to the participants in the third quartile of SUA level, those in the highest quartile of SUA was associated with significantly higher risk of all-cause mortality in the fully adjusted model (HR: 1.41, 95% CI: 1.03–1.92). No significant associations between SUA levels and all-cause mortality were observed in older men. The present study further found a U-shaped non-linear relationship between SUA levels and all-cause mortality in both sexes of older population (P for non-linear <0.05).

Conclusions: This study provided prospective epidemiological evidence for the predictive role of SUA on all-cause mortality among the Chinese aging population over 10 years of follow-up, while revealing considerable gender-related differences.
A new method for investigating bioequivalence of inhaled formulations: A pilot study on salbutamol
Authors: Rezaei Homa , Khoubnasabjafari Maryam , Jouyban-Gharamaleki Vahid , Hamishehkar Hamed , Afshar Mogaddam Mohammad Reza , Rahimpour Elaheh , Mehvar Reza , Jouyban Abolghasem
Published: May 2023

Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations.

Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. Salbutamol concentrations in the samples were determined using liquid and gas chromatographic methods.

Results: The MDI-1 inhaler induced slightly higher EBC concentrations of salbutamol when compared with MDI-2. The geometric MDI-2/MDI-1 mean ratios (confidence intervals) were 0.937 (0.721–1.22) for maximum concentration and 0.841 (0.592–1.20) for area under the EBC-time profile, indicating a lack of BE between the two formulations. In agreement with the in vivo data, the in vitro data indicated that the fine particle dose (FPD) of MDI-1 was slightly higher than that for the MDI-2 formulation. However, the FPD differences between the two formulations were not statistically significant.

Conclusion: EBC data of the present work may be considered as a reliable source for assessment of the BE studies of orally inhaled drug formulations. However, more detailed investigations employing larger sample sizes and more formulations are required to provide more evidence for the proposed method of BE assay.
Using AI to Detect Pain through Facial Expressions: A Review
Authors: De Sario Gioacchino D. , Haider Clifton R. , Maita Karla C. , Torres-Guzman Ricardo A. , Emam Omar S. , Avila Francisco R. , Garcia John P. , Borna Sahar , McLeod Christopher J. , Bruce Charles J. , Carter Rickey E. , Forte Antonio J.
Published: May 2023

Pain assessment is a complex task largely dependent on the patient’s self-report. Artificial intelligence (AI) has emerged as a promising tool for automating and objectifying pain assessment through the identification of pain-related facial expressions. However, the capabilities and potential of AI in clinical settings are still largely unknown to many medical professionals. In this literature review, we present a conceptual understanding of the application of AI to detect pain through facial expressions. We provide an overview of the current state of the art as well as the technical foundations of AI/ML techniques used in pain detection. We highlight the ethical challenges and the limitations associated with the use of AI in pain detection, such as the scarcity of databases, confounding factors, and medical conditions that affect the shape and mobility of the face. The review also highlights the potential impact of AI on pain assessment in clinical practice and lays the groundwork for further study in this area.
The Role of Platelet-Activating Factor and Magnesium in Obstetrics and Gynecology: Is There Crosstalk between Pre-Eclampsia, Clinical Hypertension, and HELLP Syndrome?
Authors: Chawla Nidhi , Shah Hinal , Huynh Kathleen , Braun Alex , Wollocko Hanna , Shah Nilank C.
Published: May 2023

Clinical hypertension is a complex disease of the cardiovascular system that can affect the body’s ability to physiologically maintain homeostasis. Blood pressure is measured as systolic pressure of the heart and diastolic pressure. When the systolic pressure exceeds values of 130–139 and diastolic exceeds 80–89, the body is in stage 1 hypertension. A pregnant woman with hypertension is predisposed to developing pre-eclampsia during gestation between the 1st and 2nd trimester. If the symptoms and changes in the mother’s body are not controlled, this can progress to hemolysis, elevated liver enzymes, and low platelet count also known as HELLP syndrome. The onset of HELLP syndrome generally begins before the 37th week of pregnancy. Magnesium is one of the most used cations in clinical medicine with various implications in the body. With a critical role in vascular smooth muscle, endothelium, and myocardial excitability it is used in treatment of clinical hypertension, pre-eclampsia in gestational periods, and HELLP syndrome. Platelet-activating factor (PAF) is an endogenous phospholipid proinflammatory mediator that is released in response to various biological and environmental stressors. When released it causes platelets to aggregate, further exacerbating hypertension. The purpose of this literature review is to investigate the role that magnesium and platelet-activating factors have on clinical hypertension, pre-eclampsia, and HELLP syndrome while focusing on the interplay between these molecules.
Image-Guided Proton Therapy: A Comprehensive Review
Authors: Lane Shelby A. , Slater Jason M. , Yang Gary Y.
Published: May 2023

Image guidance for radiation therapy can improve the accuracy of the delivery of radiation, leading to an improved therapeutic ratio. Proton radiation is able to deliver a highly conformal dose to a target due to its advantageous dosimetric properties, including the Bragg peak. Proton therapy established the standard for daily image guidance as a means of minimizing uncertainties associated with proton treatment. With the increasing adoption of the use of proton therapy over time, image guidance systems for this modality have been changing. The unique properties of proton radiation present a number of differences in image guidance from photon therapy. This paper describes CT and MRI-based simulation and methods of daily image guidance. Developments in dose-guided radiation, upright treatment, and FLASH RT are discussed as well.
Will Absolute Risk Estimation for Time to Next Screen Work for an Asian Mammography Screening Population?
Authors: Ho Peh Joo , Lim Elaine Hsuen , Mohamed Ri Nur Khaliesah Binte , Hartman Mikael , Wong Fuh Yong , Li Jingmei
Published: May 2023

Personalized breast cancer risk profiling has the potential to promote shared decision-making and improve compliance with routine screening. We assessed the Gail model’s performance in predicting the short-term (2- and 5-year) and the long-term (10- and 15-year) absolute risks in 28,234 asymptomatic Asian women. Absolute risks were calculated using different relative risk estimates and Breast cancer incidence and mortality rates (White, Asian-American, or the Singapore Asian population). Using linear models, we tested the association of absolute risk and age at breast cancer occurrence. Model discrimination was moderate (AUC range: 0.580–0.628). Calibration was better for longer-term prediction horizons (E/Olong-term ranges: 0.86–1.71; E/Oshort-term ranges:1.24–3.36). Subgroup analyses show that the model underestimates risk in women with breast cancer family history, positive recall status, and prior breast biopsy, and overestimates risk in underweight women. The Gail model absolute risk does not predict the age of breast cancer occurrence. Breast cancer risk prediction tools performed better with population-specific parameters. Two-year absolute risk estimation is attractive for breast cancer screening programs, but the models tested are not suitable for identifying Asian women at increased risk within this short interval.
Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer
Authors: Rickard Brittany P. , Overchuk Marta , Chappell Vesna A. , Kemal Ruhi Mustafa , Sinawang Prima Dewi , Nguyen Hoang Tina Thuy , Akin Demir , Demirci Utkan , Franco Walfre , Fenton Suzanne E. , Santos Janine H. , Rizvi Imran
Published: May 2023

Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.
hist2RNA: An Efficient Deep Learning Architecture to Predict Gene Expression from Breast Cancer Histopathology Images
Authors: Mondol Raktim Kumar , Millar Ewan K. A. , Graham Peter H. , Browne Lois , Sowmya Arcot , Meijering Erik
Published: May 2023

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialised platforms, and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA sequencing techniques to predict the expression of 138 genes (incorporated from 6 commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E)-stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n = 335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12–3.06), p < 5 × 10−3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.87 (95% CI 1.30–2.68), p < 5 × 10−3). The proposed strategy achieves superior performance while requiring less training time, resulting in less energy consumption and computational cost compared to patch-based models. Additionally, hist2RNA predicts gene expression that has potential to determine luminal molecular subtypes which correlates with overall survival, without the need for expensive molecular testing.
Experimental Murine Models for Colorectal Cancer Research
Authors: Neto Íris , Rocha João , Gaspar Maria Manuela , Reis Catarina P.
Published: May 2023

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced models (CIMs) and genetically engineered mouse models (GEMMs). CIMs are valuable for assessing colitis-related carcinogenesis and studying chemoprevention. On the other hand, CRC GEMMs have proven to be useful for evaluating the tumor microenvironment and systemic immune responses, which have contributed to the discovery of novel therapeutic approaches. Although metastatic disease can be induced by orthotopic injection of CRC cell lines, the resulting models are not representative of the full genetic diversity of the disease due to the limited number of cell lines suitable for this purpose. On the other hand, patient-derived xenografts (PDX) are the most reliable for preclinical drug development due to their ability to retain pathological and molecular characteristics. In this review, the authors discuss the various murine CRC models with a focus on their clinical relevance, benefits, and drawbacks. From all models discussed, murine CRC models will continue to be an important tool in advancing our understanding and treatment of this disease, but additional research is required to find a model that can correctly reflect the pathophysiology of CRC.
Artificial Intelligence in CT and MR Imaging for Oncological Applications
Authors: Paudyal Ramesh , Shah Akash D. , Akin Oguz , Do Richard K. G. , Konar Amaresha Shridhar , Hatzoglou Vaios , Mahmood Usman , Lee Nancy , Wong Richard J. , Banerjee Suchandrima , Shin Jaemin , Veeraraghavan Harini , Shukla-Dave Amita
Published: May 2023

Cancer care increasingly relies on imaging for patient management. The two most common cross-sectional imaging modalities in oncology are computed tomography (CT) and magnetic resonance imaging (MRI), which provide high-resolution anatomic and physiological imaging. Herewith is a summary of recent applications of rapidly advancing artificial intelligence (AI) in CT and MRI oncological imaging that addresses the benefits and challenges of the resultant opportunities with examples. Major challenges remain, such as how best to integrate AI developments into clinical radiology practice, the vigorous assessment of quantitative CT and MR imaging data accuracy, and reliability for clinical utility and research integrity in oncology. Such challenges necessitate an evaluation of the robustness of imaging biomarkers to be included in AI developments, a culture of data sharing, and the cooperation of knowledgeable academics with vendor scientists and companies operating in radiology and oncology fields. Herein, we will illustrate a few challenges and solutions of these efforts using novel methods for synthesizing different contrast modality images, auto-segmentation, and image reconstruction with examples from lung CT as well as abdome, pelvis, and head and neck MRI. The imaging community must embrace the need for quantitative CT and MRI metrics beyond lesion size measurement. AI methods for the extraction and longitudinal tracking of imaging metrics from registered lesions and understanding the tumor environment will be invaluable for interpreting disease status and treatment efficacy. This is an exciting time to work together to move the imaging field forward with narrow AI-specific tasks. New AI developments using CT and MRI datasets will be used to improve the personalized management of cancer patients.
A Systematic Review of Endoscopic Treatments for Concomitant Malignant Biliary Obstruction and Malignant Gastric Outlet Obstruction and the Outstanding Role of Endoscopic Ultrasound-Guided Therapies
Authors: Rizzo Giacomo Emanuele Maria , Carrozza Lucio , Quintini Dario , Ligresti Dario , Traina Mario , Tarantino Ilaria
Published: May 2023

Background: The treatments for cancer palliation in patients with concomitant malignant biliary obstruction (MBO) and gastric outlet obstruction (MGOO) are still under investigation due to the lack of evidence available in the medical literature. We performed a systematic search and critical review to investigate efficacy and safety among patients with MBO and MGOO undergoing both endoscopic ultrasound-guided biliary drainage (EUS-BD) and MGOO endoscopic treatment. Methods: A systematic literature search was performed in PubMed, MEDLINE, EMBASE, and the Cochrane Library. EUS-BD included both transduodenal and transgastric techniques. Treatment of MGOO included duodenal stenting or EUS-GEA (gastroenteroanastomosis). Outcomes of interest were technical success, clinical success, and rate of adverse events (AEs) in patients undergoing double treatment in the same session or within one week. Results: 11 studies were included in the systematic review for a total number of 337 patients, 150 of whom had concurrent MBO and MGOO treatment, fulfilling the time criteria. MGOO was treated by duodenal stenting (self-expandable metal stents) in 10 studies, and in one study by EUS-GEA. EUS-BD had a mean technical success of 96.4% (CI 95%, 92.18–98.99) and a mean clinical success of 84.96% (CI 95%, 67.99–96.26). The average frequency of AEs for EUS-BD was 28.73% (CI 95%, 9.12–48.33). Clinical success for duodenal stenting was 90% vs. 100% for EUS-GEA. Conclusions: EUS-BD could become the preferred drainage in the case of double endoscopic treatment of concomitant MBO and MGOO in the near future, with the promising EUS-GEA becoming a valid option for MGOO treatment in these patients.
AhR and Wnt/β-Catenin Signaling Pathways and Their Interplay
Authors: Grishanova Alevtina Y. , Klyushova Lyubov S. , Perepechaeva Maria L.
Published: May 2023

As evolutionarily conserved signaling cascades, AhR and Wnt signaling pathways play a critical role in the control over numerous vital embryonic and somatic processes. AhR performs many endogenous functions by integrating its signaling pathway into organ homeostasis and into the maintenance of crucial cellular functions and biological processes. The Wnt signaling pathway regulates cell proliferation, differentiation, and many other phenomena, and this regulation is important for embryonic development and the dynamic balance of adult tissues. AhR and Wnt are the main signaling pathways participating in the control of cell fate and function. They occupy a central position in a variety of processes linked with development and various pathological conditions. Given the importance of these two signaling cascades, it would be interesting to elucidate the biological implications of their interaction. Functional connections between AhR and Wnt signals take place in cases of crosstalk or interplay, about which quite a lot of information has been accumulated in recent years. This review is focused on recent studies about the mutual interactions of key mediators of AhR and Wnt/β-catenin signaling pathways and on the assessment of the complexity of the crosstalk between the AhR signaling cascade and the canonical Wnt pathway.
Genome-Based Species Diversity Assessment in the Pseudomonas chlororaphis Phylogenetic Subgroup and Proposal of Pseudomonas danubii sp. nov. Isolated from Freshwaters, Soil, and Rhizosphere
Authors: Mulet Magdalena , Martínez María José , Gomila Margarita , Dabernig-Heinz Johanna , Wagner Gabriel E. , Kittinger Clemens , Zarfel Gernot , Lalucat Jorge , García-Valdés Elena
Published: May 2023

The Pseudomonas chlororaphis phylogenetic subgroup of species, within the Pseudomonas fluorescens group, currently includes seven bacterial species, all of which have environmental relevance. Phylogenomic analyses help clarify the taxonomy of strains in the group and allow for precise identification. Thirteen antibiotic-resistant strains isolated in a previous study from nine different sampling sites in the Danube River were suspected to represent a novel species and are investigated taxonomically in the present study, together with four other strains isolated from the Woluwe River (Belgium) that were phylogenetically closely related in their rpoD gene sequences. The strains were characterized phenotypically, chemotaxonomically (fatty acid composition and main protein profiles), and phylogenetically. They could not be assigned to any known Pseudomonas species. Three genomes of representative strains were sequenced and analyzed in the context of the genome sequences of closely related strains available in public databases. The phylogenomic analysis demonstrates the need to differentiate new genomic species within the P. chlororaphis subgroup and that Pseudomonas piscis and Pseudomonas aestus are synonyms. This taxonomic study demonstrates that 14 of the characterized isolates are members of the Pseudomonas_E protegens_A species in the GTDB taxonomy and that they represent a novel species in the genus Pseudomonas, for which we propose the name Pseudomonas danubii sp. nov. with strain JDS02PS016T (=CECT 30214T = CCUG 74756T) as the type strain. The other three strains (JDS08PS003, rDWA16, and rDWA64) are members of the species Pseudomonas_E protegens_B in the GTDB taxonomy and need further investigation for proposal as a new bacterial species.
Exports- and Imports-Led Growth: Evidence from a Time Series Analysis, Case of Jordan
Authors: Istaiteyeh Rasha , Najem Farah , Saqfalhait Nahil
Published: May 2023

The purpose of this study is to examine equilibrium relationships and dynamic causality between economic growth (measured as GDP), exports, and imports in Jordan using time-series data between 1976 and 2021. In particular, this research attempts to determine exports-led growth, imports-led growth, growth-led exports, and growth-led imports in both the short-run and long-run. The four time-series datasets, GDP, merchandise exports, merchandise imports, and gross capital formation, were examined using the Dickey–Fuller unit root tests, the Phillips–Perron unit root test, and the Johansen’s trace tests for cointegration. The dynamic properties of the VAR(1) were summarized using Granger causality tests and impulse response functions. The test results showed that the impulse response functions indicated that there might be some short-run relationships among our datasets. The Johansen cointegration tests suggested that the series were not cointegrated, and hence there were no long-term relationships among the time series. It appeared that in the short-run, both GDP and gross capital formation Grangerly caused merchandise exports. A unit shock in merchandise exports, merchandise imports, and gross capital formation caused very small fluctuating responses from GDP, merchandise exports, merchandise imports, and gross capital in the short-run, and the responses approached zero in the long-run.
Analysis of the European Strategy for Hydrogen: A Comprehensive Review
Authors: Vivanco-Martín Begoña , Iranzo Alfredo
Published: May 2023

This review focuses on analysing the strategy and aspirations of the European Union within the hydrogen sector. This aim is achieved through the examination of the European Parliament’s hydrogen strategy, allowing for a study of actions and projects in hydrogen technologies. The Parliament’s hydrogen strategy is the document that provides the guideline of how the EU intends to function in the hydrogen sector and manages to cover a wide range of topics, all of them significant to represent the entirety of the hydrogen sector. It touches on subjects such as hydrogen demand, infrastructure, research, and standards, among others. The review discusses also the aspect that the EU intends to be a leader in the hydrogen sector, including the large-scale industrialization of key elements such as electrolysers, and this purpose is corroborated by the large number of associations, strategies, plans, and projects that are being established and developed by the European Union. The most important conclusions to learn from this analysis are that hydrogen has many of the right characteristics to make it the key to decarbonisation, especially in hard-to-abate sectors, and that it is bound to be one of the main actors in the imminent green transition. Moreover, hydrogen seems to be having its breakthrough, and this field’s development can have benefits not only from an environmental perspective but also from an economical one, enabling the way into the green transition and the fight against climate change.
Insights into the Mechanism of Action of Helianthus annuus (Sunflower) Seed Essential Oil in the Management of Type-2 Diabetes Mellitus Using Network Pharmacology and Molecular Docking Approaches
Authors: Rampadarath Athika , Balogun Fatai Oladunni , Sabiu Saheed
Published: May 2023

Type-2 diabetes mellitus (T2D) is one of the leading non-communicable diseases of global concern. Knowing the exact mechanism of action of available antidiabetic agents, particularly natural products, may assist in providing effective therapeutic solutions. The antidiabetic action of Helianthus annuus (sunflower) seed has been established; however, the molecular mechanism of action, especially the essential oil, is lacking. The study explored network pharmacology and molecular docking studies to determine the active phytoconstituents, signaling pathways, and probable therapeutic targets to determine the antidiabetic potential of sunflower seed essential oil. Preliminary analysis established 23 target genes with 15 phytoconstituents involved in T2D which all passed Lipinski’s rule of five with no violation. Three pathways were proposed by KEGG analysis as therapeutic targets for T2D development with PPAR as the major route affecting PPARA, FABP4, PPARD, PPARG, and CPT2 genes. Molecular docking investigation confirmed the effectiveness of active SSEO compounds against the identified genes (targets) and established phylloquinone, linoleic acid, tricosylic acid, and lignoceric acid as the probable drug candidates that could offer laudable therapeutic effects in an effort towards T2D management. Thereby, we present an insight toward understanding the mechanism of the antidiabetic action of sunflower seeds via the stimulation of glucose to enhance insulin release.
Isolation and Cultivation of Penicillium citrinum for Biological Control of Spodoptera litura and Plutella xylostella
Authors: Nguyen Hoang , Lin Kuan-Hung , Nguyen Thanh , Le Hong , Ngo Kim , Pham Dinh , Tran Tuyet , Su Chia-Hung , Barrow Colin
Published: May 2023

Biological control agents are a promising substitute for chemical pesticides in agricultural pest management. In this study, Penicillium sp. with high pathogenicity to the agricultural pests oriental leafworm moth (Spodoptera litura) and diamondback moth (Plutella xylostella) were isolated from naturally infected insects and grown on different agricultural residues as an inexpensive substrate for their sporulation. Ten strains of Penicillium (P.01~P.10) were identified as P. citrinum based on morphological features and molecular studies, with sequence analysis using an internal transcribed spacer region. Different fungal isolates exhibited a varying degree of pathogenicity against S. litura and Pl. xylostella, and strains P.04 and P.09 showed the highest pathogenicity to S. litura, with a mortality rate of 92.13% after 7 days of treatments, while strain P.06 resulted in the highest mortality of Pl. xylostella (100%) after 6 days of treatment. Moreover, among ten isolates infected with both S. litura and P. xylostella, P.06 showed potential virulence against S. litura and Pl. xylostella, with lethal time for 50% mortality (LT50) values of 4.5 days and 3.0 days, respectively. The ten isolates showed higher virulence to Pl. xylostella than to S. litura. The agro-industrial-based medium showed efficiency for the cultivation of isolates for sporulation on an industrial scale, suggesting that the newly isolated P. citrinum is a potential biological control agent for controlling insect pests and could be further developed for microbial pesticide production.
Low-Level Clostridial Spores’ Milk to Limit the Onset of Late Blowing Defect in Lysozyme-Free, Grana-Type Cheese
Authors: Carminati Domenico , Bonvini Barbara , Francolino Salvatore , Ghiglietti Roberta , Locci Francesco , Tidona Flavio , Mariut Monica , Abeni Fabio , Zago Miriam , Giraffa Giorgio
Published: May 2023

The growth of clostridial spores during ripening leads to late blowing (LB), which is the main cause of spoilage in Grana Padano Protected Designation of Origin (PDO) cheese and other hard, long-ripened cheeses such as Provolone, Comté, and similar cheeses. This study aimed to verify the cause–effect relationship between the level of clostridial butyric spores (BCS) in milk and the onset of the LB defect. To this end, experimental Grana-type cheeses were produced without lysozyme, using bulk milk with different average BCS content. The vat milk from the so-called “virtuous” farms (L1) contained average levels of BCS of 1.93 ± 0.61 log most probable number (MPN) L−1, while the vat milk from farms with the highest load of spores (L2), were in the order of 2.99 ± 0.69 log MPN L−1. Cheeses after seven months of ripening evidenced a strong connection between BCS level in vat milk and the occurrence of LB defect. In L2 cheeses, which showed an average BCS content of 3.53 ± 1.44 log MPN g−1 (range 1.36–5.04 log MPN g−1), significantly higher than that found in L1 cheeses (p < 0.01), the defect of LB was always present, with Clostridium tyrobutyricum as the only clostridial species identified by species-specific PCR from MPN-positive samples. The L1 cheeses produced in the cold season (C-L1) were free of defects whereas those produced in the warm season (W-L1) showed textural defects, such as slits and cracks, rather than irregular eyes. A further analysis of the data, considering the subset of the cheesemaking trials (W-L1 and W-L2), carried out in the warm season, confirmed the presence of a climate effect that, often in addition to the BCS load in the respective bulk milks (L1 vs. L2), may contribute to explain the significant differences in the chemical composition and some technological parameters between the two series of cheeses. Metagenomic analysis showed that it is not the overall structure of the microbial community that differentiates L1 from L2 cheeses but rather the relative distribution of the species between them. The results of our trials on experimental cheeses suggest that a low-level BCS in vat milk (<200 L−1) could prevent, or limit, the onset of LB in Grana-type and similar cheeses produced without lysozyme.
Historical Mitogenomic Diversity and Population Structuring of Southern Hemisphere Fin Whales
Authors: Buss Danielle L. , Atmore Lane M. , Zicos Maria H. , Goodall-Copestake William P. , Brace Selina , Archer Frederick I. , Baker C. Scott , Barnes Ian , Carroll Emma L. , Hart Tom , Kitchener Andrew C. , Sabin Richard , Sremba Angela L. , Weir Caroline R. , Jackson Jennifer A.
Published: May 2023

Fin whales Balaenoptera physalus were hunted unsustainably across the globe in the 19th and 20th centuries, leading to vast reductions in population size. Whaling catch records indicate the importance of the Southern Ocean for this species; approximately 730,000 fin whales were harvested during the 20th century in the Southern Hemisphere (SH) alone, 94% of which were at high latitudes. Genetic samples from contemporary whales can provide a window to past population size changes, but the challenges of sampling in remote Antarctic waters limit the availability of data. Here, we take advantage of historical samples in the form of bones and baleen available from ex-whaling stations and museums to assess the pre-whaling diversity of this once abundant species. We sequenced 27 historical mitogenomes and 50 historical mitochondrial control region sequences of fin whales to gain insight into the population structure and genetic diversity of Southern Hemisphere fin whales (SHFWs) before and after the whaling. Our data, both independently and when combined with mitogenomes from the literature, suggest SHFWs are highly diverse and may represent a single panmictic population that is genetically differentiated from Northern Hemisphere populations. These are the first historic mitogenomes available for SHFWs, providing a unique time series of genetic data for this species.
The Role of Environmental Factors on Health Conditions, General Health and Quality of Life in Persons with Spinal Cord Injuries in South Africa
Authors: Bezuidenhout Lucian , Rhoda Anthea , Moulaee Conradsson David , Mothabeng Joyce , Joseph Conran
Published: May 2023

Objective: The objective was to describe the individual items of the environmental factors and to investigate the relationship between the environmental factors to health conditions, general health and quality of life in people with SCI in South Africa. Methods: Two hundred persons with SCI participated in a cross-sectional survey design. This study formed part of the International Spinal Cord Injury (InSCI) Community Survey. Four major domains, environmental factors, health conditions, general health and quality of life of the survey questionnaire responses, were used for the analysis. Regression models were used to determine the association between the independent variable, which consisted of the specific environmental factors items, and the dependent variables comprising health conditions, general health and quality of life. Results: The commonly reported environmental barriers were public access, lack of short- and long-distance transport and finances. Environmental factors such as public access (p < 0.001), short- (p < 0.001) and long-distance transport (p = 0.001), and friends’ (p = 0.003) and colleagues’ (p < 0.001) attitudes and communication (p = 0.042) were significantly associated with the presence of secondary health conditions. Finances (p = 0.026), family attitudes (p = 0.037) and communication (p = 0.039) had a significant association with worsened mental health. Services (p = 0.022) and communication (p = 0.042) were also significantly associated with decreased general health. Conclusion: The results provide insight into modifiable environmental factors policymakers need to consider or adapt to improve the lives of people with SCI in South Africa with respect to health (secondary health conditions), as well as general and mental health.
MYCN Amplification Is Associated with Reduced Expression of Genes Encoding γ-Secretase Complex and NOTCH Signaling Components in Neuroblastoma
Authors: Agarwal Prasoon , Glowacka Aleksandra , Mahmoud Loay , Bazzar Wesam , Larsson Lars-Gunnar , Alzrigat Mohammad
Published: May 2023

Amplification of the MYCN oncogene is found in ~20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN’s contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the γ-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding γ-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of γ-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of γ-secretase genes and NOTCH-target genes. Chemical inhibition of γ-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the γ-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.
Flavone and Hydroxyflavones Are Ligands That Bind the Orphan Nuclear Receptor 4A1 (NR4A1)
Authors: Lee Miok , Upadhyay Srijana , Mariyam Fuada , Martin Greg , Hailemariam Amanuel , Lee Kyongbum , Jayaraman Arul , Chapkin Robert S. , Lee Syng-Ook , Safe Stephen
Published: May 2023

It was recently reported that the hydroxyflavones quercetin and kaempferol bind the orphan nuclear receptor 4A1 (NR4A1, Nur77) and act as antagonists in cancer cells and tumors, and they inhibit pro-oncogenic NR4A1-regulated genes and pathways. In this study, we investigated the interactions of flavone, six hydroxyflavones, seven dihydroxyflavones, three trihydroxyflavones, two tetrahydroxyflavones, and one pentahydroxyflavone with the ligand-binding domain (LBD) of NR4A1 using direct-binding fluorescence and an isothermal titration calorimetry (ITC) assays. Flavone and the hydroxyflavones bound NR4A1, and their KD values ranged from 0.36 µM for 3,5,7-trihydroxyflavone (galangin) to 45.8 µM for 3′-hydroxyflavone. KD values determined using ITC and KD values for most (15/20) of the hydroxyflavones were decreased compared to those obtained using the fluorescence assay. The results of binding, transactivation and receptor–ligand modeling assays showed that KD values, transactivation data and docking scores for these compounds are highly variable with respect to the number and position of the hydroxyl groups on the flavone backbone structure, suggesting that hydroxyflavones are selective NR4A1 modulators. Nevertheless, the data show that hydroxyflavone-based neutraceuticals are NR4A1 ligands and that some of these compounds can now be repurposed and used to target sub-populations of patients that overexpress NR4A1.
Quantifying the Dissimilarity of Texts
Authors: Shade Benjamin , Altmann Eduardo G.
Published: May 2023

Quantifying the dissimilarity of two texts is an important aspect of a number of natural language processing tasks, including semantic information retrieval, topic classification, and document clustering. In this paper, we compared the properties and performance of different dissimilarity measures D using three different representations of texts—vocabularies, word frequency distributions, and vector embeddings—and three simple tasks—clustering texts by author, subject, and time period. Using the Project Gutenberg database, we found that the generalised Jensen–Shannon divergence applied to word frequencies performed strongly across all tasks, that D’s based on vector embedding representations led to stronger performance for smaller texts, and that the optimal choice of approach was ultimately task-dependent. We also investigated, both analytically and numerically, the behaviour of the different D’s when the two texts varied in length by a factor h. We demonstrated that the (natural) estimator of the Jaccard distance between vocabularies was inconsistent and computed explicitly the h-dependency of the bias of the estimator of the generalised Jensen–Shannon divergence applied to word frequencies. We also found numerically that the Jensen–Shannon divergence and embedding-based approaches were robust to changes in h, while the Jaccard distance was not.