bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway
Authors: Li Jing , Zhang Jianchao , Zhu Yan , Afolabi Lukman O. , Chen Liang , Feng Xuesong
Published: May 2023

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.
Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
Authors: Almomani Rowida , Sopacua Maurice , Marchi Margherita , Ślęczkowska Milena , Lindsey Patrick , de Greef Bianca T. A. , Hoeijmakers Janneke G. J. , Salvi Erika , Merkies Ingemar S. J. , Ferdousi Maryam , Malik Rayaz A. , Ziegler Dan , Derks Kasper W. J. , Boenhof Gidon , Martinelli-Boneschi Filippo , Cazzato Daniele , Lombardi Raffaella , Dib-Hajj Sulayman , Waxman Stephen G. , Smeets Hubert J. M. , Gerrits Monique M. , Faber Catharina G. , Lauria Giuseppe ,   on behalf of the PROPANE Study Group
Published: May 2023

Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (n = 237), painless-DPN (n = 309), painful-SFN (n = 547) and painless-SFN (n = 32), recruited in four different centers, were analyzed for SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of SCN3A, SCN7A-SCN11A, and SCN1B-SCN4B revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, n = 194/1125). A potential pathogenic variant was present in 18.1% (n = 142/784) of painful neuropathy patients vs. 15.2% (n = 52/341) of painless neuropathy patients (17.3% (n = 41/237) for painful-DPN patients, 14.9% (n = 46/309) for painless-DPN patients, 18.5% (n = 101/547) for painful-SFN patients, and 18.8% (n = 6/32) for painless-SFN patients). Of the variants detected, 70% were in SCN7A, SCN9A, SCN10A and SCN11A. The frequency of SCN9A and SCN11A variants was the highest in painful-SFN patients, SCN7A variants in painful-DPN patients, and SCN10A variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.
In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model
Authors: Giovannini Daniela , De Angelis Cinzia , Astorino Maria Denise , Fratini Emiliano , Cisbani Evaristo , Bazzano Giulia , Ampollini Alessandro , Piccinini Massimo , Nichelatti Enrico , Trinca Emiliano , Nenzi Paolo , Mancuso Mariateresa , Picardi Luigi , Marino Carmela , Ronsivalle Concetta , Pazzaglia Simonetta
Published: May 2023

Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a “full-linac” proton-therapy accelerator.
Overview of Avian Sex Reversal
Authors: Zhang Xiuan , Li Jianbo , Chen Sirui , Yang Ning , Zheng Jiangxia
Published: May 2023

Sex determination and differentiation are processes by which a bipotential gonad adopts either a testicular or ovarian cell fate, and secondary sexual characteristics adopt either male or female developmental patterns. In birds, although genetic factors control the sex determination program, sex differentiation is sensitive to hormones, which can induce sex reversal when disturbed. Although these sex-reversed birds can form phenotypes opposite to their genotypes, none can experience complete sex reversal or produce offspring under natural conditions. Promising evidence indicates that the incomplete sex reversal is associated with cell autonomous sex identity (CASI) of avian cells, which is controlled by genetic factors. However, studies cannot clearly describe the regulatory mechanism of avian CASI and sex development at present, and these factors require further exploration. In spite of this, the abundant findings of avian sex research have provided theoretical bases for the progress of gender control technologies, which are being improved through interdisciplinary co-operation and will ultimately be employed in poultry production. In this review, we provide an overview of avian sex determination and differentiation and comprehensively summarize the research progress on sex reversal in birds, especially chickens. Importantly, we describe key issues faced by applying gender control systems in poultry production and chronologically summarize the development of avian sex control methods. In conclusion, this review provides unique perspectives for avian sex studies and helps scientists develop more advanced systems for sex regulation in birds.
Chicken Erythrocyte: Epigenomic Regulation of Gene Activity
Authors: Beacon Tasnim H. , Davie James R.
Published: May 2023

The chicken genome is one-third the size of the human genome and has a similarity of sixty percent when it comes to gene content. Harboring similar genome sequences, chickens’ gene arrangement is closer to the human genomic organization than it is to rodents. Chickens have been used as model organisms to study evolution, epigenome, and diseases. The chicken nucleated erythrocyte’s physiological function is to carry oxygen to the tissues and remove carbon dioxide. The erythrocyte also supports the innate immune response in protecting the chicken from pathogens. Among the highly studied aspects in the field of epigenetics are modifications of DNA, histones, and their variants. In understanding the organization of transcriptionally active chromatin, studies on the chicken nucleated erythrocyte have been important. Through the application of a variety of epigenomic approaches, we and others have determined the chromatin structure of expressed/poised genes involved in the physiological functions of the erythrocyte. As the chicken erythrocyte has a nucleus and is readily isolated from the animal, the chicken erythrocyte epigenome has been studied as a biomarker of an animal’s long-term exposure to stress. In this review, epigenomic features that allow erythroid gene expression in a highly repressive chromatin background are presented.
ROS Consumers or Producers? Interpreting Transcriptomic Data by AlphaFold Modeling Provides Insights into Class III Peroxidase Functions in Response to Biotic and Abiotic Stresses
Authors: New James , Barsky Daniel , Uhde-Stone Claudia
Published: May 2023

Participating in both biotic and abiotic stress responses, plant-specific class III peroxidases (PERs) show promise as candidates for crop improvement. The multigenic PER family is known to take part in diverse functions, such as lignin formation and defense against pathogens. Traditionally linked to hydrogen peroxide (H2O2) consumption, PERs can also produce reactive oxygen species (ROS), essential in tissue development, pathogen defense and stress signaling. The amino acid sequences of both orthologues and paralogues of PERs are highly conserved, but discovering correlations between sequence differences and their functional diversity has proven difficult. By combining meta-analysis of transcriptomic data and sequence alignments, we discovered a correlation between three key amino acid positions and gene expression in response to biotic and abiotic stresses. Phylogenetic analysis revealed evolutionary pressure on these amino acids toward stress responsiveness. Using AlphaFold modeling, we found unique interdomain and protein–heme interactions involving those key amino acids in stress-induced PERs. Plausibly, these structural interactions may act as “gate keepers” by preventing larger substrates from accessing the heme and thereby shifting PER function from consumption to the production of ROS.
Synergistic Nanomedicine: Photodynamic, Photothermal and Photoimmune Therapy in Hepatocellular Carcinoma: Fulfilling the Myth of Prometheus?
Authors: Ailioaie Laura Marinela , Ailioaie Constantin , Litscher Gerhard
Published: May 2023

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, with high morbidity and mortality, which seriously threatens the health and life expectancy of patients. The traditional methods of treatment by surgical ablation, radiotherapy, chemotherapy, and more recently immunotherapy have not given the expected results in HCC. New integrative combined therapies, such as photothermal, photodynamic, photoimmune therapy (PTT, PDT, PIT), and smart multifunctional platforms loaded with nanodrugs were studied in this review as viable solutions in the synergistic nanomedicine of the future. The main aim was to reveal the latest findings and open additional avenues for accelerating the adoption of innovative approaches for the multi-target management of HCC. High-tech experimental medical applications in the molecular and cellular research of photosensitizers, novel light and laser energy delivery systems and the features of photomedicine integration via PDT, PTT and PIT in immuno-oncology, from bench to bedside, were introspected. Near-infrared PIT as a treatment of HCC has been developed over the past decade based on novel targeted molecules to selectively suppress cancer cells, overcome immune blocking barriers, initiate a cascade of helpful immune responses, and generate distant autoimmune responses that inhibit metastasis and recurrences, through high-tech and intelligent real-time monitoring. The process of putting into effect new targeted molecules and the intelligent, multifunctional solutions for therapy will bring patients new hope for a longer life or even a cure, and the fulfillment of the myth of Prometheus.
Continuous User Authentication on Multiple Smart Devices
Authors: Wang Yajie , Zhang Xiaomei , Hu Haomin
Published: May 2023

Recent developments in the mobile and intelligence industry have led to an explosion in the use of multiple smart devices such as smartphones, tablets, smart bracelets, etc. To achieve lasting security after initial authentication, many studies have been conducted to apply user authentication through behavioral biometrics. However, few of them consider continuous user authentication on multiple smart devices. In this paper, we investigate user authentication from a new perspective—continuous authentication on multi-devices, that is, continuously authenticating users after both initial access to one device and transfer to other devices. In contrast to previous studies, we propose a continuous user authentication method that exploits behavioral biometric identification on multiple smart devices. In this study, we consider the sensor data captured by accelerometer and gyroscope sensors on both smartphones and tablets. Furthermore, multi-device behavioral biometric data are utilized as the input of our optimized neural network model, which combines a convolutional neural network (CNN) and a long short-term memory (LSTM) network. In particular, we construct two-dimensional domain images to characterize the underlying features of sensor signals between different devices and then input them into our network for classification. In order to strengthen the effectiveness and efficiency of authentication on multiple devices, we introduce an adaptive confidence-based strategy by taking historical user authentication results into account. This paper evaluates the performance of our multi-device continuous user authentication mechanism under different scenarios, and extensive empirical results demonstrate its feasibility and efficiency. Using the mechanism, we achieved mean accuracies of 99.8% and 99.2% for smartphones and tablets, respectively, in approximately 2.3 s, which shows that it authenticates users accurately and quickly.
Enhancing Organizational Data Security on Employee-Connected Devices Using BYOD Policy
Authors: AlShalaan Manal Rajeh , Fati Suliman Mohamed
Published: May 2023

To address a business need, most organizations allow employees to use their own devices to enhance productivity and job satisfaction. For this purpose, the Bring Your Own Device (BYOD) policy provides controllable access for employees to organize data through their personal devices. Although the BYOD practice implies plenty of advantages, this also opens the door to a variety of security risks. This study investigates these security risks and proposes a complementary encryption approach with a digital signature that uses symmetric and asymmetric algorithms, depending on the organization’s digital certificate, to secure sensitive information stored in employees’ devices within the framework of BYOD policies. The method uses Advanced Encryption System (AES), Blowfish, RSA and ElGamal with a digital signature to achieve strong encryption and address critical security considerations such as user authentication, confidentiality and data integrity. The proposed encryption approach offers a robust and effective cryptographic solution for securing sensitive information in organizational settings that involve BYOD policies. The study includes experimental results demonstrating the proposed approach’s efficiency and performance, with reasonable encryption and decryption times for different key and file sizes. The results of the study revealed that AES and Blowfish have the best execution time. AES has a good balance of security and performance. RSA performs better than ElGamal in encryption and signature verification, while RSA is slower than ElGamal in decryption. The study also provides a comparative analysis with previous studies of the four encryption algorithms, highlighting the strengths and weaknesses of each approach.
Clinical Characteristics of Acute Appendicitis in Pregnancy: 10-Year Experience at a Single Institution in South Korea
Authors: Choi Yun Suk , Seo Ji Hyun , Yi Jin Wook , Choe Yun-Mee , Heo Yoon Seok , Choi Sun Keun
Published: May 2023

Background: Acute appendicitis is the most common cause of non-obstetric surgical disease in pregnant women. The diagnosis and treatment of appendicitis during pregnancy are very important because it can cause life-threatening morbidity to the fetus and mother. We evaluated the clinical characteristics of acute appendicitis in pregnant women. Methods: We retrospectively reviewed a medical database that included patients who underwent surgery for acute appendicitis at our hospital from January 2013 through December 2022. We compared non-pregnant women of reproductive age with pregnant women. We classified the pregnant women according to gestational age. Result: A total of 828 patients were reproductive-aged women between 15 and 44 years old. There were 759 non-pregnant patients and 69 pregnant patients. ASA (American Society of Anesthesiologists) physical status classes were significantly higher and hospital stays were significantly longer in the pregnant group. There was no significant intergroup difference in terms of the proportions of complicated appendicitis, extended surgery, or complications. When the enrolled pregnant women were divided into three subgroups according to gestational age, the mean operation time was longest in the third-trimester subgroup. There were no differences among the subgroups in terms of the proportions of complicated appendicitis, extended surgery, or complications, nor were there differences among the subgroups in terms of laboratory findings. Preterm labor and stillbirth occurred in two pregnant women with complicated appendicitis in the second trimester. Conclusion: Immediate surgical treatment should be strongly considered in pregnant women with appendicitis. Efforts for more accurate diagnosis are needed for pregnant women with appendicitis.
Vision-Related Quality of Life following Combined Cataract and Minimally Invasive Glaucoma Surgery or Cataract Surgery Alone in Glaucoma Patients
Authors: Yuasa Yuki , Hirooka Kazuyuki , Okada Naoki , Onoe Hiromitsu , Murakami Yumiko , Okumichi Hideaki , Kiuchi Yoshiaki
Published: May 2023

This study examined glaucoma patients after undergoing combined cataract and minimally invasive glaucoma surgery (MIGS), microhook ab interno trabeculotomy and goniotomy with the Kahook Dual Blade (KDB), or cataract surgery alone, and it then evaluates their vision-related quality of life (VR-QOL) following the procedure. A total of 75 eyes of 75 consecutive glaucoma patients in this prospective cohort study underwent phacoemulsification (Phaco) or phaco and MIGS (Phaco-TLO) between October 2019 and March 2022. In all cases, the National Eye Institute Visual Function Questionnaire (VFQ-25) was used to evaluate the 20 eyes in the Phaco group and the 55 eyes in the Phaco-TLO group before and at 2 months after surgery. There was a significant increase in the visual acuity (logMAR) at 2 months post-operatively (Phaco group; 0.34 ± 0.10 to −0.07 ± 0.1, p < 0.0001, Phaco-TLO group; 0.37 ± 0.43 to 0.09 ± 0.32, p < 0.0001). The median (25–75th percentile) total VFQ scores in the Phaco group before and at 2 months after surgery were 71.1 (62.4–80.6) and 79.4 (69.0–84.0), respectively. (p = 0.006). The median (25–75th percentile) total VFQ scores in the Phaco-TLO group before and at 2 months after surgery were 69.8 (55.3–78.6) and 74.7 (65.1–83.3), respectively. (p = 0.005). Glaucoma patients who underwent not only cataract surgery alone but also combined cataract surgery and MIGS exhibited significant improvement in the VR-QOL.
Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review
Authors: Palacios-García José , Porras-González Cristina , Moreno-Luna Ramón , Maza-Solano Juan , Polo-Padillo Juan , Muñoz-Bravo José Luis , Sánchez-Gómez Serafín
Published: May 2023

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nose and paranasal sinuses characterized by the presence of nasal polyps. The symptoms produced by the presence of nasal polyps such as nasal obstruction, nasal discharge, facial pain, headache, and loss of smell cause a worsening in the quality of life of patients. The source of the nasal polyps remains unclear, although it seems to be due to a chronic inflammation process in the sinonasal mucosa. Fibroblasts, the main cells in connective tissue, are intimately involved in the inflammation processes of various diseases; to this end, we carried out a systematic review to evaluate their inflammatory role in nasal polyps. Thus, we evaluated the main cytokines produced by nasal polyp-derived fibroblasts (NPDF) to assess their involvement in the production of nasal polyps and their involvement in different inflammatory pathways. The results of the review highlight the inflammatory role of NPDF through the secretion of various cytokines involved in the T1, T2, and T3 inflammatory pathways, as well as the ability of NPDF to be stimulated by a multitude of substances. With these findings, the fibroblast is positioned as a new potential therapeutic target in the treatment of CRSwNP.
Could Young Cerebrospinal Fluid Combat Glaucoma? Comment on Lee et al. Association between Optic Nerve Sheath Diameter and Lamina Cribrosa Morphology in Normal-Tension Glaucoma. J. Clin. Med. 2023, 12, 360
Authors: Wostyn Peter
Published: May 2023

I enjoyed reading the article by Lee et al. [...]
Overview of Spontaneous Intracranial Hypotension and Differential Diagnosis with Chiari I Malformation
Authors: Bin Wan Hassan Wan Muhammad Nazief , Mistretta Francesco , Molinaro Stefano , Russo Riccardo , Bosco Giovanni , Gambino Andrea , Bergui Mauro
Published: May 2023

Spontaneous intracranial hypotension (SIH) occurs due to a leakage of the cerebrospinal fluid (CSF) lowering the pressure of subarachnoid space, mostly caused by a dural breach or discogenic microspur. As a result of less support provided by CSF pressure, intracranial structures are stretched downward, leading to a constellation of more or less typical MRI findings, including venous congestion, subdural effusions, brainstem sagging and low-lying cerebellar tonsils. Clinic examination and an MRI are usually enough to allow for the diagnosis; however, finding the location of the dural tear is challenging. SIH shares some MRI features with Chiari malformation type I (CM1), especially low-lying cerebellar tonsils. Since SIH is likely underdiagnosed, these findings could be interpreted as signs of CM1, leading to a misdiagnosis and an incorrect treatment pathway. Medical treatment, including steroids, bed rest, hydration caffeine, and a blind epidural blood patch, have been used in this condition with variable success rates. For some years, CSF venous fistulas have been described as the cause of SIH, and a specific diagnostic and therapeutic pathway have been proposed. The current literature on SIH with a focus on diagnosis, treatment, and differential diagnosis with CM1, is reviewed and discussed.
The Pain Management of Trauma Patients in the Emergency Department
Authors: Fabbri Andrea , Voza Antonio , Riccardi Alessandro , Serra Sossio , Iaco Fabio
Published: May 2023

The vast majority of injured patients suffer from pain. Systematic assessment of pain on admission to the emergency department (ED) is a cornerstone of translating the best treatment strategies for patient care into practice. Pain must be measured with severity scales that are validated in clinical practice, including for specific populations (such as children and older adults). Although primary care ED of trauma patients focuses on resuscitation, diagnosis and treatment, pain assessment and management remains a critical element as professionals are not prepared to provide effective and early therapy. To date, most EDs have pain assessment and management protocols that take into account the patient’s hemodynamic status and clinical condition and give preference to non-pharmacological approaches where possible. When selecting medications, the focus is on those that are least disruptive to hemodynamic status. Pain relief may still be necessary in hemodynamically unstable patients, but caution should be exercised, especially when using opioids, as absorption may be impaired or shock may be exacerbated. The analgesic dose of ketamine is certainly an attractive option. Fentanyl is clearly superior to other opioids in initial resuscitation and treatment as it has minimal effects on hemodynamic status and does not cause central nervous system depression. Inhaled analgesia techniques and ultrasound-guided nerve blocks are also increasingly effective solutions. A multimodal pain approach, which involves the use of two or more drugs with different mechanisms of action, plays an important role in the relief of trauma pain. All EDs must have policies and promote the adoption of procedures that use multimodal strategies for effective pain management in all injured patients.
Cardiovascular Health in Pregnant Women and Their Off-Spring
Authors: Erbas Gizem Seyda , Nordenstam Felicia , Oberhoffer-Fritz Renate , Sitzberger Christina , Wacker-Gußmann Annette
Published: May 2023

Child development requires complex interactions between the pregnant woman and the growing child [...]
Optic Disc Morphology and Paracentral Scotoma in Patients with Open-Angle Glaucoma and Myopia
Authors: Kim Minha , Hong Euntak , Lee Eun Ji
Published: May 2023

This study’s aim was to investigate the association between optic disc morphology and the occurrence of paracentral scotoma in eyes with open-angle glaucoma (OAG) and myopia. Two-hundred and eleven myopic eyes with OAG were classified into three groups according to the location of visual field (VF) defect (99 paracentral scotoma, 65 peripheral scotoma, and 47 no VF defect). Optic disc morphology was assessed based on the tilt ratio and eccentricity of the central retinal vessel trunk (CRVT). Clinical characteristics of the three groups were compared, and factors affecting the occurrence of paracentral scotoma were determined. Eyes with paracentral scotoma had a higher tilt ratio than the other groups (ps ≤ 0.04). Multiple linear regression showed that a nasal location of CRVT (p < 0.001), longer axial length (p = 0.001), and lower VF mean deviation (p = 0.021) were significantly associated with higher tilt ratio. In logistic regression analysis, tilt ratio was the only factor that was significantly associated with the occurrence of paracentral scotoma (odds ratio = 7.12, p = 0.032). In conclusion, the optic disc tilt ratio increased with nasal shift of CRVT, longer axial length, and lower VF mean deviation. Higher optic disc tilt was significantly associated with the occurrence of paracentral scotoma in eyes with OAG and myopia.
Application and Progress of Artificial Intelligence in Fetal Ultrasound
Authors: Xiao Sushan , Zhang Junmin , Zhu Ye , Zhang Zisang , Cao Haiyan , Xie Mingxing , Zhang Li
Published: May 2023

Prenatal ultrasonography is the most crucial imaging modality during pregnancy. However, problems such as high fetal mobility, excessive maternal abdominal wall thickness, and inter-observer variability limit the development of traditional ultrasound in clinical applications. The combination of artificial intelligence (AI) and obstetric ultrasound may help optimize fetal ultrasound examination by shortening the examination time, reducing the physician’s workload, and improving diagnostic accuracy. AI has been successfully applied to automatic fetal ultrasound standard plane detection, biometric parameter measurement, and disease diagnosis to facilitate conventional imaging approaches. In this review, we attempt to thoroughly review the applications and advantages of AI in prenatal fetal ultrasound and discuss the challenges and promises of this new field.
Cybersecurity for AI Systems: A Survey
Authors: Sangwan Raghvinder S. , Badr Youakim , Srinivasan Satish M.
Published: May 2023

Recent advances in machine learning have created an opportunity to embed artificial intelligence in software-intensive systems. These artificial intelligence systems, however, come with a new set of vulnerabilities making them potential targets for cyberattacks. This research examines the landscape of these cyber attacks and organizes them into a taxonomy. It further explores potential defense mechanisms to counter such attacks and the use of these mechanisms early during the development life cycle to enhance the safety and security of artificial intelligence systems.
Methods for Antifungal Susceptibility Testing of the Cryptococcus neoformans/C. gattii Complex: Strengths and Limitations
Authors: Espinel-Ingroff Ana , Cantón Emilia
Published: May 2023

When method-dependent categorical endpoints are available, namely either BPs or ECVs, MICs could aid in selecting the best treatment agent(s). BPs can categorize an isolate as either susceptible or resistant while the ECVs/ECOFFs can distinguish the wild type (WT, no known resistance mechanisms) from the Non-WT (NWT, harboring resistant mechanisms). Our literature review focused on the Cryptococcus species complex (SC) and the available methods and categorization endpoints. We also covered the incidence of these infections as well as the numerous Cryptococcus neoformans SC and C. gattii SC genotypes. The most important agents to treat cryptococcal infections are fluconazole (widely used), amphotericin B, and flucytosine. We provide data from the collaborative study that defined CLSI fluconazole ECVs for the most common cryptococcal species or genotypes and modes. EUCAST ECVs/ECOFFs are not yet available for fluconazole. We have summarized the incidence of cryptococccal infections (2000–2015) where fluconazole MICs were obtained by reference and commercial antifungal susceptibility tests. This occurrence is documented all over the world and those fluconazole MICs are mostly categorized by available CLSI ECVs/BPs as “resistant” instead of non-susceptible strains, including those by the commercial methods. As expected, the agreement between the CLSI and commercial methods is variable because SYO and Etest data could yield low/variable agreement (<90%) versus the CLSI method. Therefore, since BPs/ECVs are species and method dependent, why not gather sufficient MICs by commercial methods and define the required ECVs for these species?
Home-Based Spirometry in Patients with Interstitial Lung Diseases: A Real-Life Pilot “FACT” Study from Serbia
Authors: Ilić Miroslav , Javorac Jovan , Milenković Ana , Živanović Dejan , Miljković Dejan , Kašiković Lečić Svetlana , Savić Nevena , Vereš Kristina Tot , Kovačević Dragica , Vujičić Emilija , Kopitović Ivan
Published: May 2023

(1) Background: home-based spirometry, as a form of telemedicine in pulmonology, was previously successfully implemented in clinical practice in developed countries. However, experiences from developing countries are lacking. The aim of this study was to assess the reliability and feasibility of home-based spirometry in patients with interstitial lung diseases from Serbia. (2) Methods: 10 patients were given a personal hand-held spirometer with operating instructions and asked to perform daily domiciliary spirometry for the next 24 weeks. The K-BILD questionnaire was used to assess patients’ quality of life, while the questionnaire designed specifically for this study was used to assess their attitudes toward and satisfaction with domiciliary spirometry. (3) Results: there was a significant positive correlation between office- and home-based spirometry at the beginning (r = 0.946; p < 0.001) and end of the study (r = 0.719; p = 0.019). The compliance rate was nearly 70%. The domiciliary spirometry did not affect patients’ overall quality of life or anxiety levels, as measured via different domains of the K-BILD. Patients expressed positive experiences and high satisfaction with the home spirometry program. (4) Conclusions: home-based spirometry may represent a reliable form of spirometry, exploited in routine clinical practice; however, additional research in developing countries with a larger sample size is required.
Reputation as Capital—How Decentralized Autonomous Organizations Address Shortcomings in the Venture Capital Market
Authors: Kaal Wulf
Published: May 2023

Venture capital (VC) models can be optimized with emerging decentralized technology. There are many disadvantages that come with traditional VC fundraising including illiquidity and ownership struggles, as well as timing. This paper will discuss alternative funding mechanisms that may be available and advantageous to emerging businesses. After discussing the shortcomings of the existing VC market and the rise of alternative early round funding mechanisms, the paper highlights the evolution of VC businesses that are operated by a Decentralized Autonomous Organization (DAO). More specifically, models discussed in this article contribute to the much-needed experimentation with venture capital reputation models.
Recent Advancements in Computational Drug Design Algorithms through Machine Learning and Optimization
Authors: Choudhuri Soham , Yendluri Manas , Poddar Sudip , Li Aimin , Mallick Koushik , Mallik Saurav , Ghosh Bhaswar
Published: May 2023

The goal of drug discovery is to uncover new molecules with specific chemical properties that can be used to cure diseases. With the accessibility of machine learning techniques, the approach used in this search has become a significant component in computer science in recent years. To meet the Precision Medicine Initiative’s goals and the additional obstacles that they have created, it is vital to develop strong, consistent, and repeatable computational approaches. Predictive models based on machine learning are becoming increasingly crucial in preclinical investigations. In discovering novel pharmaceuticals, this step substantially reduces expenses and research times. The human kinome contains various kinase enzymes that play vital roles through catalyzing protein phosphorylation. Interestingly, the dysregulation of kinases causes various human diseases, viz., cancer, cardiovascular disease, and several neuro-degenerative disorders. Thus, inhibitors of specific kinases can treat those diseases through blocking their activity as well as restoring normal cellular signaling. This review article discusses recent advancements in computational drug design algorithms through machine learning and deep learning and the computational drug design of kinase enzymes. Analyzing the current state-of-the-art in this sector will offer us a sense of where cheminformatics may evolve in the near future and the limitations and beneficial outcomes it has produced. The approaches utilized to model molecular data, the biological problems addressed, and the machine learning algorithms employed for drug discovery in recent years will be the emphasis of this review.
Study on the Trade-Off Synergy Relationship of “Production-Living-Ecological” Functions in Chinese Counties: A Case Study of Chongqing Municipality
Authors: Cheng Ling , Cui Haiyang , Liang Tian , Huang Dan , Su Yuanxia , Zhang Zhiyong , Wen Chuanhao
Published: May 2023

The trade-off and coordinated development of the “production-living-ecological” functions (PLEFs) of an area is an important basis for the optimization of the spatial pattern of the land, and helps to promote the harmonious symbiotic relationship between human beings and nature. This paper combines ecological niche theory, a coupling coordination model, and a trade-off synergy model to construct an evaluation index system for Chinese county PLEFs. Quantitative methods were used to measure spatiotemporal evolution characteristics, trade-off synergy of PLEFs in 38 counties in Chongqing, China, and the coupling coordination degree between PLEFs. The results showed that the ecological niche width of the “production-ecological” function revealed an overall growth trend. However, there was a mismatch in regional development of the “production-ecological” function, showing dislocation characteristics of “high in the west and low in the east” and “high in the east and low in the west.” The niche width of the life function is similar to the comprehensive niche width of PLEFs, showing the characteristics of fluctuation and partition change. PLEFs and both the aforementioned functions showed distribution characteristics of “high in the west and low in the east,” with the whole moving towards the stage of coordinated coupling, of which the “production-living” function has the highest coupling level. The functional coupling coordination degree of “production-living-ecological” is generally manifested as “high in the west and low in the east,” and changing from the primary stage of imbalance to well-coordinated development. The “production-ecological” and “living-ecological” functions are in low-level imbalance in the primary and moderate coordination stages. Additionally, the evolution trend of the “production-ecological” and the “living-ecological” functions are similar, showing alternating and fluctuating development characteristics. Overall, in the past 20 years, Chongqing’s “living-production” function has changed from a trade-off model to a collaborative development relationship, and the “living-ecological” function is generally based on a collaborative development relationship. The “ecological function” is manifested as a trade-off constraint relationship. Moreover, the coordinated development level of “living-production,” “living-ecological,” and “production-ecological” functions in the central urban area has been greatly improved, while counties have gradually shown different degrees of trade-offs.
Biophysical Interactions Underpin the Emergence of Information in the Genetic Code
Authors: Halpern Aaron , Bartsch Lilly R. , Ibrahim Kaan , Harrison Stuart A. , Ahn Minkoo , Christodoulou John , Lane Nick
Published: May 2023

The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. Yet, research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and 4 RNA mononucleotides in 3 charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the −1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least 1 of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomised assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology.
The Chatbots Are Invading Us: A Map Point on the Evolution, Applications, Opportunities, and Emerging Problems in the Health Domain
Authors: Giansanti Daniele
Published: May 2023

The inclusion of chatbots is potentially disruptive in society, introducing opportunities, but also important implications that need to be addressed on different domains. The aim of this study is to examine chatbots in-depth, by mapping out their technological evolution, current usage, and potential applications, opportunities, and emerging problems within the health domain. The study examined three points of view. The first point of view traces the technological evolution of chatbots. The second point of view reports the fields of application of the chatbots, giving space to the expectations of use and the expected benefits from a cross-domain point of view, also affecting the health domain. The third and main point of view is that of the analysis of the state of use of chatbots in the health domain based on the scientific literature represented by systematic reviews. The overview identified the topics of greatest interest with the opportunities. The analysis revealed the need for initiatives that simultaneously evaluate multiple domains all together in a synergistic way. Concerted efforts to achieve this are recommended. It is also believed to monitor both the process of osmosis between other sectors and the health domain, as well as the chatbots that can create psychological and behavioural problems with an impact on the health domain.
Female “Paradox” in Atrial Fibrillation—Role of Left Truncation Due to Competing Risks
Authors: Nakamizo Tomoki , Misumi Munechika , Takahashi Tetsuya , Kurisu Satoshi , Matsumoto Masayasu , Tsujino Akira
Published: May 2023

Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke—controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. However, the underlying mechanism remains unclear. We conducted simulations to examine the hypothesis that this sex difference is generated non-causally through left truncation due to competing risks (CR) such as coronary artery diseases, which occur more frequently among men than among women and share common unobserved causes with stroke. We modeled the hazards of stroke and CR with correlated heterogeneous risk. We assumed that some people died of CR before AF diagnosis and calculated the hazard ratio of female sex in the left-truncated AF population. In this situation, female sex became a risk factor for stroke in the absence of causal roles. The hazard ratio was attenuated in young populations without left truncation and in populations with low CR and high stroke incidence, which is consistent with real-world observations. This study demonstrated that spurious risk factors can be identified through left truncation due to correlated CR. Female sex in patients with AF may be a paradoxical risk factor for stroke.
Tribological Properties of Attapulgite Nanofiber as Lubricant Additive for Electric-Brush Plated Ni Coating
Authors: Nan Feng , Wang Dong
Published: May 2023

In order to expand the application field of attapulgite in tribology, the tribological properties of attapulgite as a lubricant additive on electric-brush plated Ni coating were investigated using the ball-disc contact mode of a SRV-IV friction and wear tester. The worn surfaces were characterized and analyzed via scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). Results indicated that the friction-reducing and antiwear properties of 150 SN lubricating oil on the Ni coating were remarkably improved by an appropriate amount of attapulgite. Tribofilm mainly composed of Ni, NiO, SiO2, Al2O3, graphite, and organic compounds was formed on the worn surface under the action of attapulgite, which was responsible for the reduction of friction and wear.
Lymphoscintigraphy versus Indocyanine Green Lymphography—Which Should Be the Gold Standard for Lymphedema Imaging?
Authors: Figueroa Brian A. , Lammers Jacob D. , Al-Malak Mazen , Pandey Sonia , Chen Wei F.
Published: May 2023

Early detection and treatment can slow the progression of lymphedema. To diagnose lymphedema in the subclinical phase, a sensitive imaging modality is required. Radioisotope-based lymphoscintigraphy (LSG) has been the “gold standard” for a century. Indocyanine green lymphography (ICGL) is being used at our institute for diagnosing and grading all lymphedema patients. In this study, ICGL disease detection rate was compared to that of LSG. Chart review of all patients who presented for lymphedema consult between February 2020 and April 2022 was conducted. Patients who underwent both LSG and ICG for extremity edema in symptomatic/asymptomatic limbs were included. A total of 50 limbs in 23 patients met the inclusion criteria. Of those, 37 were symptomatic and 13 were asymptomatic. LSG detected lymphatic dysfunction in 26/37(70%) of the symptomatic limbs while ICG detected the same in 37/37(100%) limbs (p < 0.01). In the asymptomatic group, LSG detected the disease in 1/13(8%) limbs while ICG detected lymphatic dysfunction in 8/13 (62%) limbs (p < 0.01). LSG missed symptomatic limbs 30% of the time, whereas ICG did not miss any symptomatic limbs (p < 0.01). LSG missed asymptomatic disease 54% of the time (p < 0.01) compared to ICG. In conclusion, ICG lymphography was determined to have a higher lymphatic dysfunction detection rate compared to LSG.
Hungarian Fine-to-Coarse Aggregate, a Possible Constituent of Near-Vessel Structural Concrete of Nuclear Power Plants
Authors: Gméling Katalin , Szilágyi Veronika , Harsányi Ildikó , Szentmiklósi László
Published: May 2023

Significant gravel mines, representative of four regions of Hungary (northeast, central, northwest, and southwest) were systematically sampled to characterize their sand and pebbles as potential constituents of nuclear-grade concrete. The samples were analysed for their elemental compositions as a function of the mining locality and grain size, using two complementary neutron-based analytical techniques, prompt gamma activation analysis (PGAA) and neutron activation analysis (NAA). The combined analysis resulted in reliable mass fractions for over thirty elements that could be used to assess the radiation shielding and activation properties of the resulting concrete, essential in nuclear applications, by means of computer simulations. The studied aggregates are proven to be appropriate constituents for biological shielding at radiological centres, NPPs, and at nuclear research installations, even in mixed neutron/gamma radiation fields. The elemental compositions also revealed geochemical differences between the sedimentologically different regions.