bluuebunny/crossref_metadata_2025 huggingface dataset:
Insect Predation Estimate Using Binary Leaf Models and Image-Matching Shapes
Authors: Vieira Gabriel S. , Fonseca Afonso U. , Rocha Bruno M. , Sousa Naiane M. , Ferreira Julio C. , Felix Juliana P. , Lima Junio C. , Soares Fabrizzio
Published: November 2022

Estimating foliar damage is essential in agricultural processes to provide proper crop management, such as monitoring the defoliation level to take preventive actions. Furthermore, it is helpful to avoid the reduction of plant energy production, nutrition decrement, and consequently, the reduction of the final production of the crop and economic losses. In this sense, numerous proposals support the defoliation estimate task, ranging from traditional methodologies to computational solutions. However, subjectivity characteristics, reproducibility limitations, and imprecise results persist. Then, these circumstances justify the search for new solutions, especially in defoliation assessments. The main goal of this paper consists of developing an automatic method to estimate the percentage of damaged leaf areas consumed by insects. As a novelty, our method provides high precision in calculating defoliation severity caused by insect predation on the leaves of various plant species and works effectively to estimate leaf loss in leaves with border damage. We describe our method and evaluate its performance concerning 12 different plant species. Our experimental results demonstrate high accuracy in the determination of leaf area loss with a correlation coefficient superior to 0.84 for apple, blueberry, cherry, corn, grape, bell pepper, potato, raspberry, soybean, and strawberry leaves, and mean absolute error (MAE) less than 4% in defoliation levels up to 54% in soybean, strawberry, potato, and corn leaves. In addition, the method maintains a mean error of less than 50%, even for severe defoliation levels up to 99%.
Qualitative Characterization and Antifungal Activity of Romanian Honey and Propolis
Authors: Vică Mihaela Laura , Glevitzky Mirel , Dumitrel Gabriela-Alina , Bostan Roxana , Matei Horea Vladi , Kartalska Yordanka , Popa Maria
Published: November 2022

The purpose of this study was to review the physicochemical characterization of Romanian honey and propolis and their antifungal effect on different strains. As an indicator of environmental pollution, lead exceeded the allowed limits in two study areas. The relationship between the acidity and electrical conductivity of polyfloral honey and the antioxidant activity with the total content of phenolics and flavonoids was investigated. The antifungal activity of 13 polyfloral honey and propolis samples from North-West and Central Romania and 12 samples from Alba County was investigated against six fungal strains: Aspergillus niger, Aspergillus flavus, Candida albicans, Penicillium chrysogenum, Rhizopus stolonifer, Fusarium oxysporum. All honey and propolis samples exhibited an antifungal effect. The most sensitive strains were P. chrysogenum and R. stolonifer for honey and P. chrysogenum and F. oxisporumn for propolis. A two-way analysis of variance was used to evaluate the correlations between the diameter of the inhibition zones for the strains and the propolis extracts. Statistical analysis demonstrated that the diameter of the inhibition zone was influenced by the strain type and the geographical origin of honey and propolis. Pearson’s correlation coefficient shows a significant positive linear relationship between the diameter of the inhibition zone and the flavonoid and phenol concentration of honey and propolis, respectively.
Look-Back and Look-Forward Durations and the Apparent Appropriateness of Ambulatory Antibiotic Prescribing
Authors: Guzman Adriana , Brown Tiffany , Lee Ji Young , Fischer Michael A. , Friedberg Mark W. , Chua Kao-Ping , Linder Jeffrey A.
Published: November 2022

Ambulatory antibiotic stewards, researchers, and performance measurement programs choose different durations to associate diagnoses with antibiotic prescriptions. We assessed how the apparent appropriateness of antibiotic prescribing changes when using different look-back and look-forward periods. Examining durations of 0 days (same-day), −3 days, −7 days, −30 days, ±3 days, ±7 days, and ±30 days, we classified all ambulatory antibiotic prescriptions in the electronic health record of an integrated health care system from 2016 to 2019 (714,057 prescriptions to 348,739 patients by 2391 clinicians) as chronic, appropriate, potentially appropriate, inappropriate, or not associated with any diagnosis. Overall, 16% percent of all prescriptions were classified as chronic infection related. Using only same-day diagnoses, appropriate, potentially appropriate, inappropriate, and not-associated antibiotics, accounted for 14%, 36%, 22%, and 11% of prescriptions, respectively. As the duration of association increased, the proportion of appropriate antibiotics stayed the same (range, 14% to 18%), potentially appropriate antibiotics increased (e.g., 43% for −30 days), inappropriate stayed the same (range, 22% to 24%), and not-associated antibiotics decreased (e.g., 2% for −30 days). Using the longest look-back-and-forward duration (±30 days), appropriate, potentially appropriate, inappropriate, and not-associated antibiotics, accounted for 18%, 44%, 20%, and 2% of prescriptions, respectively. Ambulatory programs and studies focused on appropriate or inappropriate antibiotic prescribing can reasonably use a short duration of association between an antibiotic prescription and diagnosis codes. Programs and studies focused on potentially appropriate antibiotic prescribing might consider examining longer durations.
Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits
Authors: Ali Alaa M. , Hill Harriet J. , Elkhouly Gehad E. , Bakkar Marwa Reda , Raya Nermeen R. , Stamataki Zania , Abo-zeid Yasmin
Published: November 2022

Hand hygiene is considered to be the key factor in controlling and preventing infection, either in hospital care settings or in the community. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against bacteria and viruses. However, their frequent administration during COVID-19 pandemic was associated with serious hazards, such as skin toxicity, including irritation, skin dermatitis, skin dryness or cracking, along with peeling redness or itching, with the higher possibility of getting infections. Thus, there is a need to find alternative and novel approaches for hand sanitation. In our previous publications, we reported that rhamnolipids nano-micelles had a comparable antibacterial activity to alcohol-based hand sanitizer and a lower cytotoxicity against human dermal fibroblast cells. In the current study, we investigated the antiviral activity of rhamnolipids nano-micelles against SARS-CoV-2. There was no cytotoxic effect on Vero cells noted at the tested concentrations of rhamnolipids nano-micelles. The rhamnolipids nano-micelles solution at 20, 78, and 312 µg/mL all demonstrated a significant (p < 0.05) decrease of virus infectivity compared to the virus only and the blank vehicle sample. In addition, an acute irritation test was performed on rabbits to further ascertain the biosafety of rhamnolipids nano-micelles. In the eye and skin irritation tests, no degree of irritation was recorded after topical application of rhamnolipids nano-micelles. In addition, histopathological, biomarker, and hematological analyses from animals treated with rhamnolipids nano-micelles were identical to those recorded for untreated animal. From the above, we can conclude that rhamnolipids nano-micelles are a good candidate to be used as a hand sanitizer instead of alcohol-based hand sanitizers. However, they must still be tested in the future among healthcare workers (HCW) in a health care setting to ascertain their antimicrobial efficacy and safety compared to alcohol-based hand sanitizers.
Physician-Targeted Interventions in Antibiotic Prescribing for Urinary Tract Infections in General Practice: A Systematic Review
Authors: Cox Stefan , Lo-A-Foe Kelly , van Hoof Minke , Dinant Geert-Jan , Oudhuis Guy , Savelkoul Paul , Cals Jochen , de Bont Eefje
Published: November 2022

Urinary tract infections (UTIs) are the most common reason for women to consult a general practitioner (GP). While UTIs are self-limiting in half of cases, most women are prescribed antibiotics, often in discordance with established guidelines. Researchers have employed different interventions to improve GPs’ prescribing behavior, especially for respiratory infections, but it is uncertain whether these are effective for UTI care. Therefore, we performed a systematic review, including (cluster) randomized clinical trials investigating the effect of interventions targeted at GPs to improve antibiotic prescriptions for UTI. From September to December 2021 we searched the Medline, Web of Science, and CENTRAL databases, ultimately including ten studies describing eleven trials. We determined the effect of the interventions on the decision to prescribe and on the choice of antibiotic. Results showed that most studies employed multifaceted interventions, most frequently including audit & feedback and/or educational meetings. Seven out of nine trials that recorded first-choice prescriptions saw an increased proportion of first-choice antibiotics in the intervention groups compared to control groups. The employed interventions also caused a decreased proportion of at least one broad-spectrum antibiotic in five out of six studies that measured broad-spectrum antibiotic prescriptions. However, the total number of antibiotic prescriptions for UTIs increased in four out of eight studies. Therefore, while effective at influencing GPs’ prescribing behavior, future interventions should also focus on improving the decision to prescribe at all.
Genomic Study of Chromosomally and Plasmid-Mediated Multidrug Resistance and Virulence Determinants in Klebsiella Pneumoniae Isolates Obtained from a Tertiary Hospital in Al-Kharj, KSA
Authors: Moglad Ehssan , Alanazi Nuor , Altayb Hisham N.
Published: November 2022

Klebsiella pneumoniae is an emergent pathogen causing respiratory tract, bloodstream, and urinary tract infections in humans. This study defines the genomic sequence data, genotypic and phenotypic characterization of K. pneumoniae clinically isolated from Al-Kharj, KSA. Whole-genome analysis of four K. pneumoniae strains was performed, including de novo assembly, functional annotation, whole-genome-phylogenetic analysis, antibiotic-resistant gene identification, prophage regions, virulent factor, and pan-genome analysis. The results showed that K6 and K7 strains were MDR and ESBL producers, K16 was an ESBL producer, and K8 was sensitive to all tested drugs except ampicillin. K6 and K7 were identified with sequence type (ST) 23, while K16 and K8 were identified with STs 353 and 592, respectively. K6 and K7 were identified with the K1 (wzi1 genotype) capsule and O1 serotype, while K8 was identified with the K57 (wzi206 genotype) capsule and O3b. K6 isolates harbored 10 antimicrobial resistance genes (ARGs) associated with four different plasmids; the chloramphenicol acetyltransferase (catB3), blaOXA-1 and aac(6′)-Ib-cr genes were detected in plasmid pB-8922_OXA-48. K6 and K7 also carried a similar gene cassette in plasmid pC1K6P0122-2; the gene cassettes were the trimethoprim-resistant gene (dfrA14), integron integrase (IntI1), insertion sequence (IS1), transposase protein, and replication initiation protein (RepE). Two hypervirulent plasmids were reported in isolates K6 and K7 that carried synthesis genes (iucA, iucB, iucC, iucD, and iutA) and iron siderophore genes (iroB, iroC, iroD, and iroN). The presence of these plasmids in high-risk clones suggests their dissemination in our region, which represents a serious health problem.
Microbiological Assessment of Titanium Plates Coated with PLGA, Chitosan, and/or Meropenem: An In Vitro Study
Authors: Al-Qubaisey Mohammad , Khounganian Rita , Al-Badah Abdulhakim
Published: November 2022

This investigation was conducted to evaluate the efficacy of coated titanium plates against gram-positive Staphylococcus aureus (SA) and gram-negative Pseudomonas aeruginosa (PA) using various methods. The Colony-forming unit “CFU” was higher in chitosan (CH) in relation to PA than in poly lactic-co-glycolic acid (PLGA) in relation to SA, followed by meropenem-chitosan “MC” coated plates in relation to PA and SA. A significant difference in the zone of inhibition (ZOI) of SA was determined in MP, MC, and meropenem (MEM). PA was significantly inhibited by MP, MEM, then MC, and the largest ZOI among SA and PA groups were MP coating. Using an MTT assay, MP had the lowest bacterial viability in the SA group, followed by MC and MEM, with no statistically significant difference between the PLGA or CH alone nor the polymers augmented with MEM. Using confocal microscopy, MP-coated plates were seen to have the highest bacterial inhibition, followed by MC, MEM, PLGA, and CH. In the PA group, MP had the highest bacterial inhibition, followed by MEM, MC, CH, and PLGA. The uncoated group presented the lowest inhibition in relation to both SA and PA. Conclusively, coating titanium plates with PLGA or CH with MEM appeared to enhance the antibacterial efficacy as opposed to MEM without polymers through bacterial adhesion inhibition, hindering biofilm formation and preventing bacterial proliferation.
Phage Cocktail in Combination with Kasugamycin as a Potential Treatment for Fire Blight Caused by Erwinia amylovora
Authors: Kim Sang-Guen , Lee Sung-Bin , Jo Su-Jin , Cho Kevin , Park Jung-Kum , Kwon Jun , Giri Sib Sankar , Kim Sang-Wha , Kang Jeong-Woo , Jung Won-Joon , Lee Young-Min , Roh Eunjung , Park Se-Chang
Published: November 2022

Recently, there has been an increasing number of blight disease reports associated with Erwinia amylovora and Erwinia pyrifoliae in South Korea. Current management protocols that have been conducted with antibiotics have faced resistance problems and the outbreak has not decreased. Because of this concern, the present study aimed to provide an alternative method to control the invasive fire blight outbreak in the nation using bacteriophages (phages) in combination with an antibiotic agent (kasugamycin). Among 54 phage isolates, we selected five phages, pEa_SNUABM_27, 31, 32, 47, and 48, based on their bacteriolytic efficacy. Although only phage pEa_SNUABM_27 showed host specificity for E. amylovora, all five phages presented complementary lytic potential that improved the host infectivity coverage of each phage All the phages in the cocktail solution could lyse phage-resistant strains. These strains had a decreased tolerance to the antibiotic kasugamycin, and a synergistic effect of phages and antibiotics was demonstrated both in vitro and on immature wound-infected apples. It is noteworthy that the antibacterial effect of the phage cocktail or phage cocktail-sub-minimal inhibitory concentration (MIC) of kasugamycin was significantly higher than the kasugamycin at the MIC. The selected phages were experimentally stable under environmental factors such as thermal or pH stress. Genomic analysis revealed these are novel Erwinia-infecting phages, and did not encode antibiotic-, virulence-, or lysogenic phage-related genes. In conclusion, we suggest the potential of the phage cocktail and kasugamycin combination as an effective strategy that would minimize the use of antibiotics, which are being excessively used in order to control fire blight pathogens.
Model Predictive Control of Running Biped Robot
Authors: Cho Jaeuk , Park Jong Hyeon
Published: November 2022

With the feet of a biped robot attached insecurely to a terrain, its stability is strongly affected by the characteristics of the terrain on which it runs. Therefore, for stable bipedal running, online motion control based on the states of the robot and the environment is needed. This paper proposes a method for online motion control of a running biped robot on an uneven terrain based on a dual linear inverted pendulum model (D-LIPM) and hierarchical control which consists of linear model predictive control (MPC) and quadratic-problem (QP) based momentum control. The D-LIPM, which splits the nonlinear dynamics model of the running biped robot into two linear models under some assumptions, is proposed to generate the running motion through linear MPC. The D-LIPM is applied to the proposed hierarchical control for stable bipedal running. In the first stage of hierarchy, linear MPC is employed to generate the trajectory of the center of mass (COM) based on the dynamics of D-LIPM to overcome terrain uncertainties such as elevation levels and surface conditions at foot-landing sites. In the second stage, momentum control based on a QP solver is used to generate the angular motions of the robot while following the COM trajectory. Computer simulations with uncertainties on the running terrain were carried out to measure the performance of the proposed method.
Research on the Processing of Microstructures on Silicon Carbide Surfaces Using a Blowing-Assisted Nanosecond Laser
Authors: Zhang Suorong , Li Jian , He Bin , Yuan Jian , Chen Guoyan
Published: November 2022

The properties of high strength, wear resistance, and high brittleness, make silicon carbide (SiC) materials difficult to process by traditional processing methods. The non-traditional processing method of laser processing has emerged as a viable means of processing silicon carbide materials, as it is very suitable for processing hard and brittle materials, and has the additional advantages of no tool wear, no cutting force, and high processing efficiency. However, in conventional laser processing of silicon carbide, oxidation products occur in the processing area, which can hinder the further removal of the material. To avoid the accumulation of oxidation products and improve the laser processing of the groove structure on the silicon carbide surface, a blowing-assisted laser processing method is proposed by this paper. Comparison experiments between conventional and blowing-assisted laser processing were conducted, in which groove structures of different depths and widths were processed. Two models were established based on the experimental results to explain the material removal process. Finally, the array microgroove structures were successfully processed by blowing-assisted laser processing, verifying the feasibility of improving the laser processing capability of microstructures on silicon carbide surfaces with the assistance of blowing.
Smart Battery Management Technology in Electric Vehicle Applications: Analytical and Technical Assessment toward Emerging Future Directions
Authors: Hossain Lipu Molla Shahadat , Miah Md. Sazal , Ansari Shaheer , Wali Safat B. , Jamal Taskin , Elavarasan Rajvikram Madurai , Kumar Sachin , Naushad Ali M. M. , Sarker Mahidur R. , Aljanad A. , Tan Nadia M. L.
Published: November 2022

Electric vehicles (EVs) have received widespread attention in the automotive industry as the most promising solution for lowering CO2 emissions and mitigating worldwide environmental concerns. However, the effectiveness of EVs can be affected due to battery health degradation and performance deterioration with lifespan. Therefore, an advanced and smart battery management technology is essential for accurate state estimation, charge balancing, thermal management, and fault diagnosis in enhancing safety and reliability as well as optimizing an EV’s performance effectively. This paper presents an analytical and technical evaluation of the smart battery management system (BMS) in EVs. The analytical study is based on 110 highly influential articles using the Scopus database from the year 2010 to 2020. The analytical analysis evaluates vital indicators, including current research trends, keyword assessment, publishers, research categorization, country analysis, authorship, and collaboration. The technical assessment examines the key components and functions of BMS technology as well as state-of-the-art methods, algorithms, optimization, and control surgeries used in EVs. Furthermore, various key issues and challenges along with several essential guidelines and suggestions are delivered for future improvement. The analytical analysis can guide future researchers in enhancing the technologies of battery energy storage and management for EV applications toward achieving sustainable development goals.
Importance of Continuous and Simultaneous Monitoring of Both Electrode Voltages during Discharge/Charge Battery Tests: Application to Zn-Based Batteries
Authors: Lorca Sebastián , Santos Florencio , Padilla Javier , López Cascales J. J. , Fernández Romero Antonio J.
Published: November 2022

Two different Zn-based batteries are tested, simultaneously recording the voltage of the negative and positive electrodes during the discharge/charge processes to evidence the advantages of using a three-electrode cell, including a pseudo-reference electrode, with respect to the normally applied two electrodes system. The three-electrode cell allows us to identify in each moment which electrode reveals unexpected events during a battery test and thus to act on it accordingly. In this work, alkaline Zn/Bi2O3 and Zn/air batteries, including a pseudo-reference electrode, are subjected to different galvanostatic discharge/charge tests, highlighting several unforeseen changes and failures in both negative and positive electrodes. Thus, the usefulness of using a three-electrodes system in Zn-based batteries is revealed because it allows us to explain what the cause of the battery failure was and, if necessary, to act immediately. Finally, Spectroscopic Impedance measurements are also applied to a specific case of the Zn/Bi2O3 battery using the same three-electrode cell.
Mesenchymal Stromal Cell on Liver Decellularised Extracellular Matrix for Tissue Engineering
Authors: Croce Stefania , Cobianchi Lorenzo , Zoro Tamara , Dal Mas Francesca , Icaro Cornaglia Antonia , Lenta Elisa , Acquafredda Gloria , De Silvestri Annalisa , Avanzini Maria Antonietta , Visai Livia , Brambilla Szandra , Bruni Giovanna , Gravina Giulia Di , Pietrabissa Andrea , Ansaloni Luca , Peloso Andrea
Published: November 2022

Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation.
Antiviral Innate Immune Responses in Autoimmunity: Receptors, Pathways, and Therapeutic Targeting
Authors: Stergioti Eirini Maria , Manolakou Theodora , Boumpas Dimitrios T. , Banos Aggelos
Published: November 2022

Innate immune receptors sense nucleic acids derived from viral pathogens or self-constituents and initiate an immune response, which involves, among other things, the secretion of cytokines including interferon (IFN) and the activation of IFN-stimulated genes (ISGs). This robust and well-coordinated immune response is mediated by the innate immune cells and is critical to preserving and restoring homeostasis. Like an antiviral response, during an autoimmune disease, aberrations of immune tolerance promote inflammatory responses to self-components, such as nucleic acids and immune complexes (ICs), leading to the secretion of cytokines, inflammation, and tissue damage. The aberrant immune response within the inflammatory milieu of the autoimmune diseases may lead to defective viral responses, predispose to autoimmunity, or precipitate a flare of an existing autoimmune disease. Herein, we review the literature on the crosstalk between innate antiviral immune responses and autoimmune responses and discuss the pitfalls and challenges regarding the therapeutic targeting of the mechanisms involved.
Critical Role of Inflammation and Specialized Pro-Resolving Mediators in the Pathogenesis of Atherosclerosis
Authors: Rangarajan Subhapradha , Orujyan Davit , Rangchaikul Patrida , Radwan Mohamed M.
Published: November 2022

Recent research on how the body resolves this inflammation is gaining traction and has shed light on new avenues for future management of cardiovascular diseases. In this narrative review, we discuss the pathophysiological mechanisms of atherosclerosis, the recent development in the understanding of a new class of molecules called Specialized Pro-resolving Mediators (SPMs), and the impact of such findings in the realm of cardiovascular treatment options. We searched the MEDLINE database restricting ourselves to original research articles as much as possible on the complex pathophysiology of atherosclerosis and the role of SPMs. We expect to see further research in translating these findings to bedside clinical trials in treating conditions with a pathophysiological basis of inflammation, such as coronary artery disease, asthma, and periodontal disease.
“Descriptive Risk-Averse Bayesian Decision-Making,” a Model for Complex Biological Motion Perception in the Human Dorsal Pathway
Authors: Misaghian Khashayar , Lugo Jesus Eduardo , Faubert Jocelyn
Published: November 2022

Biological motion perception is integral not only to survival but also to the social life of human beings. Identifying the underlying mechanisms and their associated neurobiological substrates has been a matter of investigation and debate for some time. Although, in general, it is believed that the integration of local motion and dynamic form cues in the brain empowers the visual system to perceive/recognize biological motion stimuli, some recent studies have indicated the importance of dynamic form cues in such a process. Inspired by the previous neurophysiologically plausible biological motion perception models, a new descriptive risk-averse Bayesian simulation model, capable of discerning a ball’s direction from a set of complex biological motion soccer kick stimuli, is proposed. The model represents only the dorsal pathway as a motion information processing section of the visual system according to the two-stream theory. The stimuli used have been obtained from a previous psychophysical study on athletes in our lab. Furthermore, the acquired psychophysical data from that study have been used to re-enact human behavior using our simulation model. By adjusting the model parameters, the psychometric function of athlete subjects has been mimicked. A correlation analysis between human and simulation data shows a significant and robust correlation between angular thresholds and slopes of the psychometric functions of both groups. Although it is established that the visual system optimally integrates all available information in the decision-making process, the results conform to the speculations favoring motion cue importance over dynamic form by testing the limits in which biological motion perception only depends on motion information processing.
Impaired Inter-Hemispheric Functional Connectivity during Resting State in Female Patients with Migraine
Authors: Zhang Yanan , Liu Ni , Wang Zhenjia , Liu Junlian , Ren Mengmeng , Hong Yueying , Luo Xuanzhi , Liu Huilin , Huo Jianwei , Wang Zhenchang
Published: November 2022

The application of voxel-mirrored homotopic connectivity (VMHC) analysis to study the central mechanism of migraine has been limited. Furthermore, little is known about inter-hemispheric functional connectivity (FC) alterations during resting state in female patients with migraine. This study aimed to investigate potential interictal VMHC impairments in migraine without aura (MwoA) patients and the relationship between connectivity alterations and clinical parameters. Resting-state functional magnetic resonance imaging data and clinical information were acquired from 43 female MwoA patients and 43 matched healthy controls. VMHC analysis was used to compare differences between these two groups, and brain regions showing significant differences were chosen as a mask to perform a seed-based FC group comparison. Subsequent correlation analysis was conducted to explore the relationship between abnormal inter-hemispheric FC and clinical data. Compared with healthy controls, female MwoA patients revealed significantly decreased VMHC in the bilateral cerebellum; cuneus; and lingual, middle occipital, precentral and postcentral gyri. Seed-based FC analysis indicated disrupted intrinsic connectivity in the cerebellum, and default mode, visual and sensorimotor network. These VMHC and FC abnormalities were negatively correlated with clinical indexes including duration of disease, migraine days and visual analogue scale. These inter-hemispheric FC impairments and correlations between abnormal VMHC and FC and clinical scores may improve our understanding of the central mechanism of female-specific migraine.
Water-Soluble Truncated Fatty Acid–Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma
Authors: Bonsall Sam , Hubbard Simeon , Jithin Uthaman , Anslow Joseph , Todd Dylan , Rowding Callum , Filarowski Tom , Duly Greg , Wilson Ryan , Porter Jack , Turega Simon , Haywood-Small Sarah
Published: November 2022

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU). Our photosensitizers exhibited excellent water solubility and high PDT efficiency in mesothelioma. As expected, absorption spectroscopy confirmed an increased aggregation as a consequence of extending the fatty acid chain length. In vitro PDT activity was studied using human mesothelioma cell lines (biphasic MSTO-211H cells and epithelioid NCI-H28 cells) alongside a non-malignant mesothelial cell line (MET-5A). The PDT effect of these photosensitizers was initially assessed using the colorimetric WST-8 cell viability assay and the mode of cell death was determined via flow cytometry of Annexin V-FITC/PI-stained cells. Photosensitizers appeared to selectively localize within the non-nuclear compartments of cells before exhibiting high phototoxicity. Both apoptosis and necrosis were induced at 24 and 48 h. As our pentanoic acid-derivatized porphyrin (C5SHU) induced the largest anti-tumor effect in this study, we put this forward as an anti-tumor drug candidate in PDT and photo-imaging diagnosis in mesothelioma.
Testicular Neoplasms: Primary Tumour Size Is Closely Interrelated with Histology, Clinical Staging, and Tumour Marker Expression Rates—A Comprehensive Statistical Analysis
Authors: Dieckmann Klaus-Peter , Isbarn Hendrik , Grobelny Francesca , Dumlupinar Cansu , Utschig Julia , Wülfing Christian , Pichlmeier Uwe , Belge Gazanfer
Published: November 2022

The role of primary tumour size (TS) in the clinical course of testicular tumours is incompletely understood. We retrospectively evaluated 641 consecutive patients with testicular neoplasms with regard to TS, histology, clinical stage (CS), serum tumour marker (STM) expression and patient age using descriptive statistical methods. TS ≤ 10 mm was encountered in 13.6% of cases. Median TS of 10 mm, 30 mm, 35 mm, and 53 mm were found in benign tumours, seminomas, nonseminomas, and other malignant tumours, respectively. In cases with TS ≤ 10 mm, 50.6% had benign tumours. Upon receiver operating characteristics analysis, TS of > 16 mm revealed 81.5% sensitivity and 81.0% specificity for detecting malignancy. In subcentimeter germ cell tumours (GCTs), 97.7% of cases had CS1, and CS1 frequency dropped with increasing TS. Expression rates of all STMs significantly increased with TS. MicroRNA-371a-3p (M371) serum levels had higher expression rates than classical STMs, with a rate of 44.1% in subcentimeter GCTs. In all, TS is a biologically relevant factor owing to its significant associations with CS, STM expression rates and histology. Importantly, 50% of subcentimeter testicular neoplasms are of benign nature, and M371 outperforms the classical markers even in subcentimeter tumours.
Prostate Cancer Stem Cells: The Role of CD133
Authors: Yang Jianhui , Aljitawi Omar , Van Veldhuizen Peter
Published: November 2022

Prostate cancer stem cells (PCSCs), possessing self-renewal properties and resistance to anticancer treatment, are possibly the leading cause of distant metastasis and treatment failure in prostate cancer (PC). CD133 is one of the most well-known and valuable cell surface markers of cancer stem cells (CSCs) in many cancers, including PC. In this article, we focus on reviewing the role of CD133 in PCSC. Any other main stem cell biomarkers in PCSC reported from key publications, as well as about vital research progress of CD133 in CSCs of different cancers, will be selectively reviewed to help us inform the main topic.
Role of lncRNA Has2os in Skeletal Muscle Differentiation and Regeneration
Authors: Chen Wanxin , Chen Weicai , Liu Peng , Qian Shiyu , Tao Shuang , Huang Mengchun , Xu Wanyi , Li Cuiping , Chen Xiaoyan , Lin Huizhu , Qin Zhenshu , Lu Jianxi , Xie Shujuan
Published: November 2022

Long non-coding RNAs (lncRNAs) regulate a series of physiological processes and play an important role in development, metabolism and disease. Our previous studies showed that lncRNAs involved in skeletal muscle differentiation. Here, we demonstrated that lncRNA Has2os is highly expressed in skeletal muscle and significantly elevated during skeletal cell differentiation. The knockdown of Has2os inhibited myocyte fusion and impeded the expression of the myogenic factors MyHC and Mef2C. Mechanically, Has2os regulates skeletal muscle differentiation by inhibiting the JNK/MAPK signaling pathway. Furthermore, we also revealed that Has2os is involved in the early stage of regeneration after muscle injury, and the JNK/MAPK signaling pathway is activated at both protein and mRNA levels during early repair. Our results demonstrate the new function of lncRNA Has2os, which plays crucial roles during skeletal muscle differentiation and muscle regeneration, providing a basis for the therapy of lncRNA-related muscle diseases.
Multiplexed Imaging Reveals the Spatial Relationship of the Extracellular Acidity-Targeting pHLIP with Necrosis, Hypoxia, and the Integrin-Targeting cRGD Peptide
Authors: Jin Zhao-Hui , Tsuji Atsushi B. , Degardin Mélissa , Dumy Pascal , Boturyn Didier , Higashi Tatsuya
Published: November 2022

pH (low) insertion peptides (pHLIPs) have been developed for cancer imaging and therapy targeting the acidic extracellular microenvironment. However, the characteristics of intratumoral distribution (ITD) of pHLIPs are not yet fully understood. This study aimed to reveal the details of the ITD of pHLIPs and their spatial relationship with other tumor features of concern. The fluorescent dye-labeled pHLIPs were intravenously administered to subcutaneous xenograft mouse models of U87MG and IGR-OV1 expressing αVβ3 integrins (using large necrotic tumors). The αVβ3 integrin-targeting Cy5.5-RAFT-c(-RGDfK-)4 was used as a reference. In vivo and ex vivo fluorescence imaging, whole-tumor section imaging, fluorescence microscopy, and multiplexed fluorescence colocalization analysis were performed. The ITD of fluorescent dye-labeled pHLIPs was heterogeneous, having a high degree of colocalization with necrosis. A direct one-to-one comparison of highly magnified images revealed the cellular localization of pHLIP in pyknotic, karyorrhexis, and karyolytic necrotic cells. pHLIP and hypoxia were spatially contiguous but not overlapping cellularly. The hypoxic region was found between the ITDs of pHLIP and the cRGD peptide and the Ki-67 proliferative activity remained detectable in the pHLIP-accumulated regions. The results provide a better understanding of the characteristics of ITD of pHLIPs, leading to new insights into the theranostic applications of pHLIPs.
The HSF1-CPT1a Pathway Is Differentially Regulated in NAFLD Progression
Authors: Breternitz Wiebke , Sandkühler Friedrich , Grohmann Frauke , Hampe Jochen , Brosch Mario , Herrmann Alexander , Schafmayer Clemens , Meinhardt Christian , Schreiber Stefan , Arlt Alexander , Geismann Claudia
Published: November 2022

Obesity and obesity-associated diseases represent one of the key health challenges of our time. In this context, aberrant hepatic lipid accumulation is a central pathological aspect of non-alcoholic fatty liver disease (NAFLD). By comparing methylation signatures of liver biopsies before and after bariatric surgery, we recently demonstrated the strong enrichment of differentially methylated heat shock factor 1 (HSF1) binding sites (>400-fold) in the process of liver remodeling, indicating a crucial role of HSF1 in modulating central aspects of NAFLD pathogenesis. Using cellular models of NAFLD, we were able to show that HSF1 is activated during fat accumulation in hepatocytes, mimicking conditions in patients before bariatric surgery. This induction was abolished by starving the cells, mimicking the situation after bariatric surgery. Regarding this connection, carnitine palmitoyltransferase 1 isoform A (CTP1a), a central regulator of lipid beta-oxidation, was identified as a HSF1 target gene by promoter analysis and HSF1 knockdown experiments. Finally, pharmacological activation of HSF1 through celastrol reduced fat accumulation in the cells in a HSF1-dependent manner. In conclusion, we were able to confirm the relevance of HSF1 activity and described a functional HSF1-CPT1a pathway in NAFLD pathogenesis.
Current Status and Prospects of Targeted Therapy for Osteosarcoma
Authors: Hu Zunguo , Wen Shuang , Huo Zijun , Wang Qing , Zhao Jiantao , Wang Zihao , Chen Yanchun , Zhang Lingyun , Zhou Fenghua , Guo Zhangyu , Liu Huancai , Zhou Shuanhu
Published: November 2022

Osteosarcoma (OS) is a highly malignant tumor occurring in bone tissue with a high propensity to metastasize, and its underlying mechanisms remain largely elusive. The OS prognosis is poor, and improving the survival of OS patients remains a challenge. Current treatment methods such as surgical approaches, chemotherapeutic drugs, and immunotherapeutic drugs remain ineffective. As research progresses, targeted therapy is gradually becoming irreplaceable. In this review, several treatment modalities for osteosarcoma, such as surgery, chemotherapy, and immunotherapy, are briefly described, followed by a discussion of targeted therapy, the important targets, and new technologies for osteosarcoma treatment.
Targeting Ferroptosis Holds Potential for Intervertebral Disc Degeneration Therapy
Authors: Chen Jiaxing , Yang Xinyu , Feng Yi , Li Qiaochu , Ma Jingjin , Wang Linbang , Quan Zhengxue
Published: November 2022

Intervertebral disc degeneration (IVDD) is a common pathological condition responsible for lower back pain, which can significantly increase economic and social burdens. Although considerable efforts have been made to identify potential mechanisms of disc degeneration, the treatment of IVDD is not satisfactory. Ferroptosis, a recently reported form of regulated cell death (RCD), is characterized by iron-dependent lipid peroxidation and has been demonstrated to be responsible for a variety of degenerative diseases. Accumulating evidence suggests that ferroptosis is implicated in IVDD by decreasing viability and increasing extracellular matrix degradation of nucleus pulposus cells, annulus fibrosus cells, or endplate chondrocytes. In this review, we summarize the literature regarding ferroptosis of intervertebral disc cells and discuss its molecular pathways and biomarkers for treating IVDD. Importantly, ferroptosis is verified as a promising therapeutic target for IVDD.
The Potential for Placental Activation of PPARγ to Improve the Angiogenic Profile in Preeclampsia
Authors: Grimaldi Brooke , Kohan-Ghadr Hamid-Reza , Drewlo Sascha
Published: November 2022

Preeclampsia (PE) is one of the most common causes of maternal-fetal morbidity and mortality world-wide. While the underlying causes of PE remain elusive, aberrant trophoblast differentiation and function are thought to cause an imbalance of secreted angiogenic proteins resulting in systemic endothelial dysfunction and organ damage in the mother. The placental dysfunction is also characterized by a reduction of the transcription factor, peroxisome proliferator activated receptor γ (PPARγ) which normally promotes trophoblast differentiation and healthy placental function. This study aimed to understand how placental activation of PPARγ effects the secretion of angiogenic proteins and subsequently endothelial function. To study this, healthy and PE placental tissues were cultured with or without the PPARγ agonist, Rosiglitazone, and a Luminex assay was performed to measure secreted proteins from the placenta. To assess the angiogenic effects of placental activation of PPARγ, human umbilical vein endothelial cells (HUVECs) were cultured with the placental conditioned media and the net angiogenic potential of these cells was measured by a tube formation assay. This is the first study to show PPARγ’s beneficial effect on the angiogenic profile in the human preeclamptic placenta through the reduction of anti-angiogenic angiopoietin-2 and soluble endoglin and the upregulation of pro-angiogenic placental growth factor, fibroblast growth factor-2, heparin-binding epidermal growth factor, and follistatin. The changes in the angiogenic profile were supported by the increased angiogenic potential observed in the HUVECs when cultured with conditioned media from rosiglitazone-treated preeclamptic placentas. The restoration of these disrupted pathways by activation of PPARγ in the preeclamptic placenta offers potential to improve placental and endothelial function in PE.
Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology
Authors: Cvekl Aleš , Camerino Michael John
Published: November 2022

In vitro differentiation of human pluripotent stem cells (hPSCs) into specialized tissues and organs represents a powerful approach to gain insight into those cellular and molecular mechanisms regulating human development. Although normal embryonic eye development is a complex process, generation of ocular organoids and specific ocular tissues from pluripotent stem cells has provided invaluable insights into the formation of lineage-committed progenitor cell populations, signal transduction pathways, and self-organization principles. This review provides a comprehensive summary of recent advances in generation of adenohypophyseal, olfactory, and lens placodes, lens progenitor cells and three-dimensional (3D) primitive lenses, “lentoid bodies”, and “micro-lenses”. These cells are produced alone or “community-grown” with other ocular tissues. Lentoid bodies/micro-lenses generated from human patients carrying mutations in crystallin genes demonstrate proof-of-principle that these cells are suitable for mechanistic studies of cataractogenesis. Taken together, current and emerging advanced in vitro differentiation methods pave the road to understand molecular mechanisms of cataract formation caused by the entire spectrum of mutations in DNA-binding regulatory genes, such as PAX6, SOX2, FOXE3, MAF, PITX3, and HSF4, individual crystallins, and other genes such as BFSP1, BFSP2, EPHA2, GJA3, GJA8, LIM2, MIP, and TDRD7 represented in human cataract patients.
Electroanalytical Detection of Indigo Carmine in Presence of Tartrazine Using a Poly(dl-phenylalanine) Modified Carbon Nanotube Paste Electrode
Authors: Bhimaraya Kanthappa , Manjunatha Jamballi G. , Nagarajappa Hareesha , Tighezza Ammar M. , Albaqami Munirah D. , Sillanpää Mika
Published: November 2022

Certain dyes are deleterious to the biological system, including animals and plants living in the water sources, soil sources, and so on. Thus, the analysis of these dyes requires a potent, quick, and cost-effective approach to the environmental samples. The present research work shows a modest, low-cost, and eco-friendly electrochemical device based on poly(dl-phenylalanine)-layered carbon nanotube paste electrode (P(PAN)LCNTPE) material for indigo carmine (ICN) detection in the presence of tartrazine. The cyclic voltammetric, field emission scanning electron microscopy, and electrochemical impedance spectroscopic methods were operated for the detection of the redox nature of ICN and electrode material surface activities, respectively. In better operational circumstances, P(PAN)LCNTPE provided better catalytic activity for the redox action of ICN than the bare carbon nanotube paste electrode. The P(PAN)LCNTPE showed good electrochemical activity during the variation of ICN concentrations ranging from 0.2 µM to 10.0 µM with improved peak current, and the limit of detection was about 0.0216 µM. Moreover, the P(PAN)LCNTPE material was performed as a sensor of ICN in a tap water sample and shows adequate stability, repeatability, and reproducibility.
Clinical Trial Data: Both Parents Having Psychiatric Symptoms as Risk Factor for Children’s Mental Illness
Authors: Suess Hannah , Wiegand-Grefe Silke , Adema Bonnie , Daubmann Anne , Kilian Reinhold , Zapf Antonia , Winter Sibylle M. , Lambert Martin , Wegscheider Karl , Busmann Mareike
Published: November 2022

Children of mentally ill parents represent a particularly vulnerable risk group for the development of mental illness. This study examines whether there is a predictive association between children’s psychiatric symptomatology and (1) the clinical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) of their mentally ill parent as well as (2) to families both parents showing psychiatric symptoms. The study is part of the multicenter controlled trial project “Children of Mentally Ill Parents” (CHIMPS). For this purpose, the psychiatric symptomatology of the mentally ill parent (N = 196) and his or her partner (N = 134) as well as the psychiatric symptomatology of their children aged 4 to 18 years (N = 290) was measured using clinical rated ICD-10-diagnosis, self-rated Brief Symptom Inventory (BSI), and Child Behavior Checklist (CBCL). Using multilevel analyses, the severity of the parental psychiatric symptomatology (BSI) was identified as a significant predictor of children’s psychiatric symptomatology (CBCL). Children of parents with a personality disorder (ICD-10) were not more affected than children of parents with another ICD-10-diagnosis. However, children with two parents showing psychiatric symptoms (CBCL) were significantly more affected than children with one mentally ill parent. The results of this study support the well-known view that parental mental illness is a risk factor for children’s psychiatric symptoms. Therefore, increased support, especially in high-risk families, both parents having psychiatric symptoms, is highly necessary and should be implemented in the future psychotherapeutic family care.