bluuebunny/crossref_metadata_2025 huggingface dataset:
Distributed Online Multi-Label Learning with Privacy Protection in Internet of Things
Authors: Huang  Fan , Yang Nan , Chen  Huaming , Bao Wei , Yuan Dong
Published: February 2023

With the widespread use of end devices, online multi-label learning has become popular as the data generated by users using the Internet of Things devices have become huge and rapidly updated. However, in many scenarios, the user data are often generated in a geographically distributed manner that is often inefficient and difficult to centralize for training machine learning models. At the same time, current mainstream distributed learning algorithms always require a centralized server to aggregate data from distributed nodes, which inevitably causes risks to the privacy of users. To overcome this issue, we propose a distributed approach for multi-label classification, which trains the models in distributed computing nodes without sharing the source data from each node. In our proposed method, each node trains its model with its local online data while it also learns from the neighbour nodes without transferring the training data. As a result, our proposed method achieved the online distributed approach for multi-label classification without losing performance when taking existing centralized algorithms as a reference. Experiments show that our algorithm outperforms the centralized online multi-label classification algorithm in F1 score, being 0.0776 higher in macro F1 score and 0.1471 higher for micro F1 score on average. However, for the Hamming loss, both algorithms beat each other on some datasets, and our proposed algorithm loses 0.005 compared to the centralized approach on average, which can be neglected. Furthermore, the size of the network and the degree of connectivity are not factors that affect the performance of this distributed online multi-label learning algorithm.
Developing a New Filtered-X Recursive Least Squares Adaptive Algorithm Based on a Robust Objective Function for Impulsive Active Noise Control Systems
Authors: Akhtar Muhammad Tahir
Published: February 2023

It is well-known that performance of the classical algorithms for active noise control (ANC) systems severely degrades when implemented for controlling the impulsive sources. The objective of this paper is to propose a new recursive least squares (RLS) algorithm (and its variant) for being implemented in the framework of ANC systems. The proposed RLS-based adaptive algorithm employs an objective function designed to achieve robustness against the impulse type sources. The derivation of the algorithm is quite straightforward; however, a few modifications have been incorporated to address the application at hand. In order to improve upon the numerical stability issue of RLS-based adaptation, it is suggested to employ smoothing while updating the inverse correlation matrix. Furthermore, it is proposed to introduce a step size in the update equation of the adaptive algorithm. This results in the fixed step-size modified filtered-x (MFx) robust RLS (FSS-MFxRRLS) algorithm. As expected, a fixed value step size results in a trade-off situation for convergence speed and steady-state misalignment. In order to address this issue of a trade-off situation, the idea of a convex combined step size (CCSS) is introduced into the adaptive procedure to develop the CCSS-MFxRRLS algorithm. When the ANC is started, the CCSS strategy (automatically) selects a large-valued step size to achieve a fast initial convergence. As the ANC system converges at the steady-state, the CCSS is automatically tuned to a small value which improves the steady-state performance of the proposed CCSS-MFxRRLS algorithm. Extensive simulations have been designed to mimic many scenarios for practical applications of ANC for impulsive sources. The simulation results demonstrate that the proposed CCSS-MFxRRLS algorithm is very effective in many practical scenarios involving ANC of impulsive sources.
Ensemble of Below-Cloud Scavenging Models for Assessing the Uncertainty Characteristics in Wet Raindrop Deposition Modeling
Authors: Kiselev Alexey , Osadchiy Alexander , Shvedov Anton , Semenov Vladimir
Published: February 2023

This work is devoted to the development of an ensemble of below-cloud scavenging models of pollutant aerosol transport into the atmosphere. Among other factors contributing to the uncertainty of the forecasts of the dispersion and deposition of technogenic gas-aerosol releases in the atmosphere, precipitation scavenging is one of the least studied and, in case of precipitation, can be the dominant mechanism for aerosol deposition. To form the ensemble of below-cloud scavenging models, appropriate experimental data, raindrop-aerosol capture models, raindrop terminal velocity parameterizations, and raindrop size distributions were chosen. The pool of models was prepared and then evaluated to adequately describe the experimental data using statistical analysis. Rank diagrams were used to analyze the adequacy of meteorological ensembles; together with the ensemble distribution construction, they allowed selecting the groups of models with such properties as to produce unbiased estimates and dispersion corresponding to the dispersion of the experimental data. The model calculations of the concentration fraction deposited due to below-cloud scavenging were performed using a log-normal distribution with characteristics corresponding to those observed during the accidents at the Chernobyl NPP and Fukushima-1 NPP. The results were compared with those obtained using the models of the NAME and FLEXPART codes. The results of this work can be used to improve the current approaches applied for modelling the distribution of pollutants in the atmosphere in the case of emergency, enhancing the reliability of forecasts by taking into account uncertainties in the results. The formed multi-model ensemble will be included in the decision support system used in responding to releases of radioactive substances into the atmosphere.
Morphological and Mineralogical Characteristics of Atmospheric Microparticles and Chemical Pollution of Street Dust in the Moscow Region
Authors: Kolesnikova Varvara M. , Salimgareeva Olga A. , Ladonin Dmitry V. , Vertyankina Victoria Y. , Shelegina Anna S.
Published: February 2023

Comprehensive morphological and mineralogical studies of atmospheric microparticles sampled on the roof of the museum complex and near roads in the town of Istra, Moscow region, have been carried out. Morphological research at different hierarchical levels revealed the multicomponent composition of microparticles and made it possible to identify the most characteristic groups of microparticles of natural and anthropogenic origin. The composition of the studied atmospheric microparticles is dominated by mineral grains of quartz and feldspars; biotite and calcite are singly noted, which reflects the ecological and geographical conditions of their formation, namely the Central Russian mineralogical province. A small share of technogenic particles in the composition of aerosol fallout indicates a low level of technogenic load and a favorable environmental situation in the study area, largely due to the protective functions of the forest park zone. The results of determining the material composition and calculating the enrichment factors also indicate a low level of technogenic impact on the natural environment.
The Impact of Atmospheric Synoptic Weather Condition and Long-Range Transportation of Air Mass on Extreme PM10 Concentration Events
Authors: Lai Hsin-Chih , Dai Yu-Tung , Mkasimongwa Simon William , Hsiao Min-Chuan , Lai Li-Wei
Published: February 2023

Atmospheric synoptic weather patterns have a significant impact on the concentration, dispersion, and transportation of air pollution in various regions and times around the world. To assess the impact of atmospheric synoptic weather patterns and long-range air mass transportation, we used weather classification techniques from the BP training model and the HYSPLIT model. Our research uncovered four weather conditions linked to PM10 concentration categories ranging from normal to extreme. Weather conditions 3 and 4 are the most significant conditions supporting the occurrence of extreme concentration events that are heavily influenced by anti-cyclones. Despite weather conditions influencing high concentrations, 60% of long-distance air mass transport to Secunda from Mpumalanga province increased to extreme PM10 concentrations. Furthermore, long-term weather shifts have been observed to positively impact reducing the concentration of PM10 extreme events.
Influence of Particulate Matter on Asthma Control in Adult Asthma
Authors: Liwsrisakun Chalerm , Chaiwong Warawut , Bumroongkit Chaiwat , Deesomchok Athavudh , Theerakittikul Theerakorn , Limsukon Atikun , Trongtrakul Konlawij , Tajarernmuang Pattraporn , Niyatiwatchanchai Nutchanok , Pothirat Chaicharn
Published: February 2023

No clear evidence shows the association between particulate matter (PM) with an aerodynamic diameter < 10 µm (PM10) and asthma control. Therefore, the objective of this study was to determine the association between PM10 and asthma control. A retrospective observational study was conducted at the Airway Clinic, Chiang Mai University Hospital, Chiang Mai, Thailand, between January 2010 and April 2013. Various values of asthma control test (ACT) scores between high and low PM10 periods were analyzed. The association of an increased monthly average PM10 level and ACT score was analyzed using a time series analysis. There were a total of 1180 visits from 236 asthmatic patients. The monthly average ACT score was significantly lower in the high PM10 period compared with the low PM10 period. Every 10 µg/m3 increment of monthly average PM10 resulted in a significantly decreased ACT score at lag zero and one month, with an adjusted coefficient of –0.101 (95% CI; –0.165, –0.037), p-value = 0.002 and –0.079 (95% CI; –0.147, –0.012), p-value = 0.021, respectively. Monthly average PM10 significantly affected asthma control in asthmatic patients. During the air pollution period, the serial assessments of ACT should be measured for early detection of worsening asthma control.
Stability Analysis of Simple Root Seeker for Nonlinear Equation
Authors: Wang Xiaofeng , Li Wenshuo
Published: February 2023

In this paper, the stability of a class of Liu–Wang’s optimal eighth-order single-parameter iterative methods for solving simple roots of nonlinear equations was studied by applying them to arbitrary quadratic polynomials. Under the Riemann sphere and scaling theorem, the complex dynamic behavior of the iterative method was analyzed by fractals. We discuss the stability of all fixed points and the parameter spaces starting from the critical points with the Mathematica software. The dynamical planes of the elements with good and bad dynamical behavior are given, and the optimal parameter element with stable behavior was obtained. Finally, a numerical experiment and practical application were carried out to prove the conclusion.
On a Resolution of Another Isolated Case of a Kummer’s Quadratic Transformation for 2F1
Authors: Atia Mohamed , Al-Mohaimeed Ahmed
Published: February 2023

It is well-known that the Kummer quadratic transformation formula is valid provided that its parameters fulfill some specific conditions (see Gradshteyn, Ryzhik, Tables of Integrals, Series and Products, 9.130, 9.134.1). Very recently, one of us established a new identity when one of these conditions is not fulfilled. In this paper, we aim to discuss another isolated case which completely different from the first. Moreover, in the end, we mention two interesting consequences of these two new results.
K2S Challenge: From Undersampled K-Space to Automatic Segmentation
Authors: Tolpadi Aniket A. , Bharadwaj Upasana , Gao Kenneth T. , Bhattacharjee Rupsa , Gassert Felix G. , Luitjens Johanna , Giesler Paula , Morshuis Jan Nikolas , Fischer Paul , Hein Matthias , Baumgartner Christian F. , Razumov Artem , Dylov Dmitry , Lohuizen Quintin van , Fransen Stefan J. , Zhang Xiaoxia , Tibrewala Radhika , de Moura Hector Lise , Liu Kangning , Zibetti Marcelo V. W. , Regatte Ravinder , Majumdar Sharmila , Pedoia Valentina
Published: February 2023

Magnetic Resonance Imaging (MRI) offers strong soft tissue contrast but suffers from long acquisition times and requires tedious annotation from radiologists. Traditionally, these challenges have been addressed separately with reconstruction and image analysis algorithms. To see if performance could be improved by treating both as end-to-end, we hosted the K2S challenge, in which challenge participants segmented knee bones and cartilage from 8× undersampled k-space. We curated the 300-patient K2S dataset of multicoil raw k-space and radiologist quality-checked segmentations. 87 teams registered for the challenge and there were 12 submissions, varying in methodologies from serial reconstruction and segmentation to end-to-end networks to another that eschewed a reconstruction algorithm altogether. Four teams produced strong submissions, with the winner having a weighted Dice Similarity Coefficient of 0.910 ± 0.021 across knee bones and cartilage. Interestingly, there was no correlation between reconstruction and segmentation metrics. Further analysis showed the top four submissions were suitable for downstream biomarker analysis, largely preserving cartilage thicknesses and key bone shape features with respect to ground truth. K2S thus showed the value in considering reconstruction and image analysis as end-to-end tasks, as this leaves room for optimization while more realistically reflecting the long-term use case of tools being developed by the MR community.
An In Vivo Rat Study of Bioresorbable Mg-2Zn-2Ga Alloy Implants
Authors: Drobyshev Alexey , Gurganchova Zaira , Redko Nikolay , Komissarov Alexander , Bazhenov Viacheslav , Statnik Eugene S. , Sadykova Iuliia A. , Sviridov Eugeny , Salimon Alexey I. , Korsunsky Alexander M. , Zayratyants Oleg , Ushmarov Denis , Yanushevich Oleg
Published: February 2023

In the present study, pins made from the novel Mg-2Zn-2Ga alloy were installed within the femoral bones of six Wistar rats. The level of bioresorption was assessed after 1, 3, and 6 months by radiography, histology, SEM, and EDX. Significant bioresorption was evident after 3 months, and complete dissolution of the pins occurred at 6 months after the installation. No pronounced gas cavities could be found at the pin installation sites throughout the postoperative period. The animals’ blood parameters showed no signs of inflammation or toxication. These findings are sufficiently encouraging to motivate further research to broaden the experimental coverage to increase the number of observed animals and to conduct tests involving other, larger animals.
Two Decades of Coastal Dolphin Population Surveys in Israel, Eastern Mediterranean
Authors: Galili Ori , Goffman Oz , Roditi-Elasar Mia , Mevorach Yaly , Bigal Eyal , Zuriel Yotam , Haitovich Yaron , Hadar Nir , Markovich Meytal , Vardimon Dror , Reininger Dana , Marco Shlomi , Morick Danny , Ratner Eliana , Tchernov Dan , Scheinin Aviad
Published: February 2023

Along the Mediterranean coast of Israel, two near-shore dolphin species are prevalent; Tursiops truncatus (least concern, IUCN) and Delphinus delphis (endangered, IUCN). Ship-board surveys and sporadic sightings over the last two decades have shown that the two differ in distribution—T. truncatus is found along the entire coast and D. delphis only in the south. The environmental and anthropological factors affecting these species’ spatial distribution and determining their habitat preferences in this area are largely unknown. This work is a first attempt at summarizing 20 years of observations and studying habitat preferences for both species, by use of Generalized Additive Models. T. truncatus was found to be present in all areas of the continental shelf where survey effort coverage was sufficient, with a high affinity towards bottom trawlers. Model results showed D. delphis distribution to be associated to (shallow) water depths, though the factors driving their limited latitudinal distribution currently remain unknown. It is evident that T. truncatus and D. delphis are present in segregated areas of the Israeli continental shelf and T. truncatus currently sustains a delicate balance with continuously shifting human activities, while the drivers of D. delphis distribution are more specified, yet still not fully understood.
The Ecological Status and Change in High-Latitude Coral Assemblages at the Xuwen Coral Reef, Northern South China Sea: Insight into the Status and Causes in 2020
Authors: Yang Zhenxiong , Tao Wei , Liu Yue , Yu Wei , Peng Xiaojuan , Lu Chuqian , Jiang Guangjia , Chen Bin , Deng Wei , Lv Yihua
Published: February 2023

Taking the coral communities of the Xuwen coral reef in 2020 as the research object, we analyzed the species composition, diversity, and interspecific Spearman correlation of the scleractinian coral communities, investigated the features and spatial distribution of the scleractinian coral community, and discussed the correlation between the community composition and environmental factors to identify the affecting factors and their sources. These results showed that (1) compared with the survey in 2004, the coverage of corals in 2020 had significantly decreased, while the dominant genera were still Goniopora and Porites. The coral morphology was massive, and the diversity of the coral community (Shannon–Wiener index, H’) was 2.87. The distribution of coral was uneven. The competition among some dominant species of coral was intense. (2) The mass coral bleaching event in the NSCS in August 2020 did not cause severe coral death in the short term on the Xuwen coral reef. (3) The growth of the coral community in 2020 might be greatly affected by high suspended solids and nutrient levels, which were related to the current, mariculture, and coastal erosion. (4) Anthropogenic activities such as coastal aquaculture and fishing were the major factors leading to the reduction in coral coverage on Xuwen coral reef in the past 10 years.
Structural Characterization of Nanobodies during Germline Maturation
Authors: Seidler Clarissa A. , Kokot Janik , Fernández-Quintero Monica L. , Liedl Klaus R.
Published: February 2023

Camelid heavy-chain antibody variable domains (VHH), nanobodies, are the smallest-known functional antibody fragments with high therapeutic potential. In this study, we investigate a VHH binding to hen egg-white lysozyme (HEL). We structurally and dynamically characterized the conformational diversity of four VHH variants to elucidate the antigen-binding process. For two of these antibodies, not only are the dissociation constants known, but also the experimentally determined crystal structures of the VHH in complex with HEL are available. We performed well-tempered metadynamics simulations in combination with molecular dynamics simulations to capture a broad conformational space and to reconstruct the thermodynamics and kinetics of conformational transitions in the antigen-binding site, the paratope. By kinetically characterizing the loop movements of the paratope, we found that, with an increase in affinity, the state populations shift towards the binding competent conformation. The contacts contributing to antigen binding, and those who contribute to the overall stability, show a clear trend towards less variable but more intense contacts. Additionally, these investigated nanobodies clearly follow the conformational selection paradigm, as the binding competent conformation pre-exists within the structural ensembles without the presence of the antigen.
Granzyme B in Autoimmune Skin Disease
Authors: Gleave Anna , Granville David J.
Published: February 2023

Autoimmune diseases often present with cutaneous symptoms that contribute to dysfunction, disfigurement, and in many cases, reduced quality-of-life. Unfortunately, treatment options for many autoimmune skin diseases are limited. Local and systemic corticosteroids remain the current standard-of-care but are associated with significant adverse effects. Hence, there is an unmet need for novel therapies that block molecular drivers of disease in a local and/or targeted manner. Granzyme B (GzmB) is a serine protease with known cytotoxic activity and emerging extracellular functions, including the cleavage of cell–cell junctions, basement membranes, cell receptors, and other structural proteins. While minimal to absent in healthy skin, GzmB is markedly elevated in alopecia areata, interface dermatitis, pemphigoid disease, psoriasis, systemic sclerosis, and vitiligo. This review will discuss the role of GzmB in immunity, blistering, apoptosis, and barrier dysfunction in the context of autoimmune skin disease. GzmB plays a causal role in the development of pemphigoid disease and carries diagnostic and prognostic significance in cutaneous lupus erythematosus, vitiligo, and alopecia areata. Taken together, these data support GzmB as a promising therapeutic target for autoimmune skin diseases impacted by impaired barrier function, inflammation, and/or blistering.
Predictive Value of Collagen Biomarkers in Advanced Chronic Kidney Disease Patients
Authors: Ureche Carina , Dodi Gianina , Șerban Adela Mihaela , Covic Andreea Simona , Voroneanu Luminița , Hogaș Simona , Sascău Radu Andy , Stătescu Cristian , Covic Adrian
Published: February 2023

Patients with chronic kidney disease have an increased risk of all-cause death. The value of collagen biomarkers such as procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III N-terminal peptide (P3NP), in end-stage renal disease (ESRD), has not yet been defined (in the literature and in clinics). The purpose of this study was to determine the potential value of these new biomarkers in the prediction of mortality in this population. Plasma PICP and P3NP levels were determined in 140 patients with ESRD, not yet on dialysis, who were followed up for 36 ± 5.3 months. During follow-up, 58 deaths were recorded (41.4%), with the majority of them being cardiovascular deaths (43, 74.13%). Using the ROC curve, the cut-off value for the prediction of mortality for PICP was 297.31 µg/L, while for P3NP, the cut-off value was 126.67 µg/L. In univariate analysis, a value of PICP above the cut-off point was associated with a fivefold increased risk of mortality (hazard ratio (HR) 5.071, 95% confidence interval 1.935–13.29, p = 0.001) and a value of P3NP above the cut-off point was associated with a twofold increased risk of mortality (HR 2.089, 95% CI 1.044–4.178, p = 0.002). In a multivariable Cox proportional hazards model, PICP values remained independent predictors of mortality (HR 1.22, 95% CI 1.1–1.31, p < 0.0001). Our data suggest that the collagen biomarker PICP is an independent predictor of mortality in ESRD patients who are not yet on dialysis.
High-Intensity Focused Ultrasound Decreases Subcutaneous Fat Tissue Thickness by Increasing Apoptosis and Autophagy
Authors: Byun Kyung-A , Park Hyun Jun , Oh Seyeon , Batsukh Sosorburam , Sun Hye Jin , Kim Taehui , Kim Sunggeun , Kang Donghwan , Son Kuk Hui , Byun Kyunghee
Published: February 2023

High-intensity focused ultrasound (HIFU) leads to decreased subcutaneous adipose tissue (SAT) thickness via heat-induced adipocyte necrosis. Heat can induce adipocyte apoptosis and autophagy, and it is known that nuclear or mitochondrial p53 is involved in apoptosis and autophagy. However, whether HIFU leads to apoptosis or autophagy is unclear. We evaluated whether HIFU decreases SAT thickness via p53-related apoptosis or autophagy in high-fat diet (HFD)-fed animals. The expression of nuclear and mitochondrial p53 was increased by HIFU. HIFU also led to decreased expression of BCL2/BCL-xL (an antiapoptotic signal), increased expression of BAX/BAK (an apoptotic signal), increased levels of cleaved caspase 3/9, and increased numbers of apoptotic cells as evaluated by TUNEL assay. Furthermore, HIFU led to increased levels of ATG5, BECN1, and LC3II/LC3I, and decreased levels of p62, a marker of increased autophagy. The thickness of SAT was decreased by HIFU. In conclusion, HIFU led to nuclear and mitochondrial p53 expression, which led to apoptosis and autophagy, and eventually decreased SAT thickness in HFD-fed animals.
FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility
Authors: Chhor Michael , Chen Hao , Jerotić Djurdja , Tešić Milorad , Nikolić Valentina N. , Pavlović Milan , Vučić Rada M. , Rayner Benjamin , Watson Chris J. , Ledwidge Mark , McDonald Kenneth , Robson Tracy , McGrath Kristine C. , McClements Lana
Published: February 2023

Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated—for the first time—FKBPL’s role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01–0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.
Imaging the Vulnerable Carotid Plaque with CT: Caveats to Consider. Comment on Wang et al. Identification Markers of Carotid Vulnerable Plaques: An Update. Biomolecules 2022, 12, 1192
Authors: Rotzinger David C. , Qanadli Salah D. , Fahrni Guillaume
Published: February 2023

We read with great interest the review by Wang et al. entitled “Identification Markers of Carotid Vulnerable Plaques: An Update”, recently published in Biomolecules [...]
Long-Term Deficits in Muscle Composition, Performance and Quality of Movement after Achilles Tendon Rupture: A Review
Authors: Pečjak Rebeka , Kozinc Žiga
Published: February 2023

The acute rupture of the Achilles tendon is an increasingly common injury due to an active lifestyle and participation in sports, especially in the middle-aged group. We conducted a focused review of the literature and found that the acute rupture of the Achilles tendon leaves long-term changes in the structure of the triceps surae muscle, regardless of whether it was treated surgically or conservatively. Significant elongation of the Achilles tendon and atrophy of the triceps surae can be observed on the injured leg, even 4 years or more after the injury. The injury also has long-lasting consequences on movement patterns of walking, running and jumping. These compensatory strategies place stress on other musculoskeletal structures, which are then at greater risk for injury.
In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors
Authors: Milusheva Miglena , Gledacheva Vera , Stefanova Iliyana , Pencheva Mina , Mihaylova Rositsa , Tumbarski Yulian , Nedialkov Paraskev , Cherneva Emiliya , Todorova Mina , Nikolova Stoyanka
Published: February 2023

Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. Methods: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. Results: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca2+ channel regulation, Ca2+ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Conclusion: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS.
H2S Prodrug, SG-1002, Protects against Myocardial Oxidative Damage and Hypertrophy In Vitro via Induction of Cystathionine β-Synthase and Antioxidant Proteins
Authors: Islam Rahib , Donnelly Erinn , Donnarumma Erminia , Hossain Fokhrul , Gardner Jason , Islam Kazi
Published: February 2023

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), galectin-3, TIMP1, collagen type III, and TGF-β1 in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with H2O2. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H2S levels or H2S producing enzymes, CBS, and antioxidant proteins.
Ocular Behçet Disease—Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset
Authors: Ostrovsky Michael , Rosenblatt Amir , Iriqat Salam , Shteiwi Abdallah , Sharon Yael , Kramer Michal , Vishnevskia-Dai Vicktoria , Sar Shaul , Boulos Yosif , Tomkins-Netzer Oren , Lavee Natalie , Ben-Arie-Weintrob Yael , Pizem Hadas , Hareuveni-Blum Tamar , Schneck Marina , Gepstein Raz , Masarwa Dua , Nakhoul Nakhoul , Bakshi Erez , Shulman Shiri , Goldstein Michaella , Ramon Dan , Anouk Marina , Habot-Wilner Zohar
Published: February 2023

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18–39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.
Uveitis in Children: The Role of Biological Agents in Its Management
Authors: Corredores Jamel , Vofo Brice , Amer Radgonde
Published: February 2023

We aimed to determine medium and long-term effects of TNF-α inhibitors in patients with pediatric uveitis. This was a retrospective review of medical charts. Included were 50 patients (84 eyes). Mean age at diagnosis was 7.22 ± 4.04 years. At baseline (time of initiation of biologic therapy), all patients had active uveitis. Complete control of uveitis was achieved in 84.52% (n = 71) of eyes, after a median of 3 months (IQR 2 months). Mean LogMAR BCVA at baseline was 0.23 ± 0.44; it remained stable at 12 and 24 months. At baseline, 64% of patients were treated with oral corticosteroids, this decreased to 29.5% at 12 months (p = 0.001) and to 21.9% at 24 months (p < 0.001). Mean time to prednisone dose of ≤0.2 mg/kg/day was 8.1 ± 2.02 months after baseline. A total of 40.5% of eyes were treated with topical steroids at baseline and this significantly decreased to 5.8% at 12 months. Multiple linear regression model was calculated to predict moderate and severe visual loss; only presenting visual acuity accounted for a unique variance in the model. In conclusion, TNF-α inhibitors achieved rapid disease control while enabling a remarkable steroid-sparing effect in children suffering from chronic uveitis. Presenting visual acuity was the sole predictor of moderate to severe visual loss.
Acute Acalculous Cholecystitis Associated with Abscesses—An Unknown Dual Pathology
Authors: Gluhovschi Cristina , Gadalean Florica , Velciov Silvia , Petrica Ligia , Duta Ciprian , Botoca Mircea , Cipu Daniela
Published: February 2023

(1) Introduction and Aims: Little is known about the relationship between renal pathology and gallbladder pathology, although the two organs (the gallbladder and the right kidney) are in close proximity to one another. If a renal abscess disseminates, the gallbladder would be one of the secondary organs involved. As the bile provides a favorable environment for the development of pathogenic germs, it allows for the development of acute cholecystitis, even if calculi are absent, thus resulting in the development of acute acalculous cholecystitis. The aim of our study was to analyze the association between acute acalculous cholecystitis (AAC) and renal abscesses. (2) Methods: A department-wide retrospective cohort observational study including 67 patients with renal abscesses, with a mean age of 34.5+/−16.21 years and with five males and 62 females, was conducted. All of the patients were examined by an abdominal ultrasound. The lab tests included CBC with differential liver enzymes and serum bilirubin (in order to assess alterations in the liver function which can be associated with AAC) and serum creatinine (in order to assess the renal function). Blood culture and urine culture tests were also performed. (3) Results: Of the 67 patients with renal abscesses, eight (11.94%) were associated with acute cholecystitis: four cases (5.97%) of acalculous cholecystitis and four cases (5.97%) of calculous cholecystitis, two of which presented biliary sludge (acute micro-calculous cholecystitis). All four cases of acute acalculous cholecystitis presented with sepsis, and there was one case of septic shock at onset. We did not observe an impairment in renal function in the patients presenting with acute acalculous cholecystitis, and hepatic impairment was inconstant and moderate. All of the cases had a favorable outcome after a prompt initiation of intensive antibiotic therapy; both the renal abscess and the acute acalculous cholecystitis receded without further complications. (4) Conclusions: The association of acute acalculous cholecystitis with renal abscesses could be related to the possibility of germ dissemination from the infectious focus. In the case of a renal abscess, careful clinical, lab, and imaging exams of the gallbladder are recommended in order to ensure early therapeutic intervention in the event of an association with acute acalculous cholecystitis.
Oncogenic Long Noncoding RNAs in Prostate Cancer, Osteosarcoma, and Metastasis
Authors: Al-Shehri Aishah , Bakhashab Sherin
Published: February 2023

Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancy cases. Cancer metastasis is a process by which malignant tumor cells detach from the primary tumor site via a cascade of processes and migrate to secondary sites through the blood circulation or lymphatic system to colonize and form secondary tumors. PC has a specific affinity to the bone based on the “seed and soil” theory; once PC reach the bone, it becomes incurable. Several studies have identified long noncoding RNAs (lncRNAs) as potential targets for cancer therapy or as diagnostic and prognostic biomarkers. The dysregulation of various lncRNAs has been found in various cancer types, including PC, OS, and metastasis. However, the mechanisms underlying lncRNA oncogenic activity in tumor progression and metastasis are extremely complex and remain incompletely understood. Therefore, understanding oncogenic lncRNAs and their role in OS, PC, and metastasis and the underlying mechanism may help better manage and treat this malignancy. The aim of this review is to summarize current knowledge of oncogenic lncRNAs and their involvement in PC, OS, and bone metastasis.
Influence of FOSL1 Inhibition on Vascular Calcification and ROS Generation through Ferroptosis via P53-SLC7A11 Axis
Authors: Shao Sisi , Liu Yaoxin , Hong Wanzi , Mo Yuanxi , Shu Fen , Jiang Lei , Tan Ning
Published: February 2023

Background: Vascular calcification during aging is highly prevalent in patients with cardiovascular disease; however, there is still no improvement in clarifying the development of vascular calcification. FOSL1 is a transcription regulator belonging to the AP-1 family, which has a unique function in vascular senescence, but its role in vascular calcification needs to be further explored. Methods: Primary mouse vascular smooth muscle cells were isolated and used to construct a calcification model in vitro. Seven-week-old male C57BL/6 mice were used to build the vitD3-induced calcification model in vivo. qRT-PCR and western blot were used to verify the expression of FOSL1 and other genes expressed in vascular smooth muscle cells and aortas. The level of calcification was determined by Alizarin Red S (ARS) staining and the calcium content assay. The level of cellular GSH was detected by the GSH assay kit. Results: Here, we report that FOSL1 was up-regulated after high-calcium/phosphate treatment in both the in vivo and in vitro vascular calcification models. Functional studies have shown that the reduction of FOSL1 attenuates ferroptosis and calcification in vascular smooth muscle cells, as indicated by ARS staining, calcium content assay, and western blot. The inhibition of FOSL1 downregulated the expression of bone-related molecules including Msh Homeobox 2 (MSX2) and tumor necrosis factor receptor superfamily, member 11b/osteoprotegerin (OPG), suggesting that FOSL1 promoted osteogenic differentiation of vascular smooth muscle cells. Furthermore, we found that the ferroptosis-inducing drug erastin can significantly accelerate calcification in the aortic ring while Ferrostatin-1 (fer-1), a drug to protect cells from ferroptosis, can alleviate calcification. Further experiments have shown that inhibiting FOSL1 can promote the expression of ferroptosis-related genes and attenuate calcification. Functionally, cellular GSH levels were increased after the reduction of FOSL1. Conclusions: In this study, we observed a significant protective effect when we reduced the expression of FOSL1 during vascular calcification, and this effect might regulate ferroptosis to a great extent.
The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol
Authors: Escalante Jenny , Nishimura Brent , Tuttobene Marisel R. , Subils Tomás , Mezcord Vyanka , Actis Luis A. , Tolmasky Marcelo E. , Bonomo Robert A. , Ramirez María Soledad
Published: February 2023

The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with high-affinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell. The removal of HSA from HS or HPF resulted in a reduction in the minimal inhibitory concentration (MIC) of CFDC. Concomitant with these results, an enhancement in the expression of TonB-dependent transporters known to play a crucial role in transporting iron was observed. In addition to inducing modifications in iron-uptake gene expression, the removal of HSA also decreased the expression of β-lactamases genes. Taken together, these observations suggest that environmental HSA has a role in the expression levels of select A. baumannii genes. Furthermore, the removal of iron from HSA had the same effect as the removal of HSA upon the expression of genes associated with iron uptake systems, also suggesting that at least one of the mechanisms by which HSA regulates the expression of certain genes is through acting as an iron source.
Targeted Therapy Development in Acute Myeloid Leukemia
Authors: Totiger Tulasigeri M. , Ghoshal Anirban , Zabroski Jenna , Sondhi Anya , Bucha Saanvi , Jahn Jacob , Feng Yangbo , Taylor Justin
Published: February 2023

Therapeutic developments targeting acute myeloid leukemia (AML) have been in the pipeline for five decades and have recently resulted in the approval of multiple targeted therapies. However, there remains an unmet need for molecular treatments that can deliver long-term remissions and cure for this heterogeneous disease. Previously, a wide range of small molecule drugs were developed to target sub-types of AML, mainly in the relapsed and refractory setting; however, drug resistance has derailed the long-term efficacy of these as monotherapies. Recently, the small molecule venetoclax was introduced in combination with azacitidine, which has improved the response rates and the overall survival in older adults with AML compared to those of chemotherapy. However, this regimen is still limited by cytotoxicity and is not curative. Therefore, there is high demand for therapies that target specific abnormalities in AML while sparing normal cells and eliminating leukemia-initiating cells. Despite this, the urgent need to develop these therapies has been hampered by the complexities of this heterogeneous disease, spurring the development of innovative therapies that target different mechanisms of leukemogenesis. This review comprehensively addresses the development of novel targeted therapies and the translational perspective for acute myeloid leukemia, including the development of selective and non-selective drugs.
Investigation of Biomolecule Interactions: Optical-, Electrochemical-, and Acoustic-Based Biosensors
Authors: Plikusiene Ieva , Ramanaviciene Almira
Published: February 2023

Today, optical, electrochemical, and acoustic affinity biosensors; immunosensors; and immunoanalytical systems play an important role in the detection and characterization of a number of biological substances, including viral antigens, specific antibodies, and clinically important biomarkers [...]
A Review of Detection Methods for Vancomycin-Resistant Enterococci (VRE) Genes: From Conventional Approaches to Potentially Electrochemical DNA Biosensors
Authors: Zakaria Nor Dyana , Hamzah Hairul Hisham , Salih Ibrahim Luqman , Balakrishnan Venugopal , Abdul Razak Khairunisak
Published: February 2023

Vancomycin-resistant Enterococci (VRE) genes are bacteria strains generated from Gram-positive bacteria and resistant to one of the glycopeptides antibiotics, commonly, vancomycin. VRE genes have been identified worldwide and exhibit considerable phenotypic and genotypic variations. There are six identified phenotypes of vancomycin-resistant genes: VanA, VanB, VanC, VanD, VanE, and VanG. The VanA and VanB strains are often found in the clinical laboratory because they are very resistant to vancomycin. VanA bacteria can pose significant issues for hospitalized patients due to their ability to spread to other Gram-positive infections, which changes their genetic material to increase their resistance to the antibiotics used during treatment. This review summarizes the established methods for detecting VRE strains utilizing traditional, immunoassay, and molecular approaches and then focuses on potential electrochemical DNA biosensors to be developed. However, from the literature search, no information was reported on developing electrochemical biosensors for detecting VRE genes; only the electrochemical detection of vancomycin-susceptible bacteria was reported. Thus, strategies to create robust, selective, and miniaturized electrochemical DNA biosensor platforms to detect VRE genes are also discussed.
Multiplex Surface-Enhanced Raman Scattering: An Emerging Tool for Multicomponent Detection of Food Contaminants
Authors: Wei Qingyi , Dong Qirong , Pu Hongbin
Published: February 2023

For survival and quality of human life, the search for better ways to ensure food safety is constant. However, food contaminants still threaten human health throughout the food chain. In particular, food systems are often polluted with multiple contaminants simultaneously, which can cause synergistic effects and greatly increase food toxicity. Therefore, the establishment of multiple food contaminant detection methods is significant in food safety control. The surface-enhanced Raman scattering (SERS) technique has emerged as a potent candidate for the detection of multicomponents simultaneously. The current review focuses on the SERS-based strategies in multicomponent detection, including the combination of chromatography methods, chemometrics, and microfluidic engineering with the SERS technique. Furthermore, recent applications of SERS in the detection of multiple foodborne bacteria, pesticides, veterinary drugs, food adulterants, mycotoxins and polycyclic aromatic hydrocarbons are summarized. Finally, challenges and future prospects for the SERS-based detection of multiple food contaminants are discussed to provide research orientation for further.