bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Methylation Signatures of Response to Conventional Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis
Authors: Wang Susan Siyu , Lewis Myles J. , Pitzalis Costantino
Published: July 2023

Rheumatoid arthritis (RA) is a complex condition that displays heterogeneity in disease severity and response to standard treatments between patients. Failure rates for conventional, target synthetic, and biologic disease-modifying rheumatic drugs (DMARDs) are significant. Although there are models for predicting patient response, they have limited accuracy, require replication/validation, or for samples to be obtained through a synovial biopsy. Thus, currently, there are no prediction methods approved for routine clinical use. Previous research has shown that genetics and environmental factors alone cannot explain the differences in response between patients. Recent studies have demonstrated that deoxyribonucleic acid (DNA) methylation plays an important role in the pathogenesis and disease progression of RA. Importantly, specific DNA methylation profiles associated with response to conventional, target synthetic, and biologic DMARDs have been found in the blood of RA patients and could potentially function as predictive biomarkers. This review will summarize and evaluate the evidence for DNA methylation signatures in treatment response mainly in blood but also learn from the progress made in the diseased tissue in cancer in comparison to RA and autoimmune diseases. We will discuss the benefits and challenges of using DNA methylation signatures as predictive markers and the potential for future progress in this area.
Building Predictive Models for Schizophrenia Diagnosis with Peripheral Inflammatory Biomarkers
Authors: Kozyrev Evgeny A. , Ermakov Evgeny A. , Boiko Anastasiia S. , Mednova Irina A. , Kornetova Elena G. , Bokhan Nikolay A. , Ivanova Svetlana A.
Published: July 2023

Machine learning and artificial intelligence technologies are known to be a convenient tool for analyzing multi-domain data in precision psychiatry. In the case of schizophrenia, the most commonly used data sources for such purposes are neuroimaging, voice and language patterns, and mobile phone data. Data on peripheral markers can also be useful for building predictive models. Here, we have developed five predictive models for the binary classification of schizophrenia patients and healthy individuals. Data on serum concentrations of cytokines, chemokines, growth factors, and age were among 38 parameters used to build these models. The sample consisted of 217 schizophrenia patients and 90 healthy individuals. The models architecture was involved logistic regression, deep neural networks, decision trees, support vector machine, and k-nearest neighbors algorithms. It was shown that the algorithm based on a deep neural network (consisting of five layers) showed a slightly higher sensitivity (0.87 ± 0.04) and specificity (0.52 ± 0.06) than other algorithms. Combining all variables into a single classifier showed a cumulative effect that exceeded the effectiveness of individual variables, indicating the need to use multiple biomarkers to diagnose schizophrenia. Thus, the data obtained showed the promise of using data on peripheral biomarkers and machine learning methods for diagnosing schizophrenia.
Neuropsychological Assessment in Patients with Traumatic Brain Injury: A Comprehensive Review with Clinical Recommendations
Authors: Torregrossa William , Torrisi Michele , De Luca Rosaria , Casella Carmela , Rifici Carmela , Bonanno Mirjam , Calabrò Rocco Salvatore
Published: July 2023

Traumatic brain injury is damage to the brain occurring after birth, often resulting in the deterioration of cognitive, behavioural, and emotional functions. Neuropsychological evaluation can assist clinicians to better assess the patient’s clinical condition, reach differential diagnoses, and develop interventional strategies. However, considering the multiple rating scales available, it is not easy to establish which tool is most suitable for the different brain injury conditions. The aim of this review is to investigate and describe the most used neurocognitive assessment tools in patients with traumatic brain injury to provide clinicians with clear indications on their use in clinical practice. Indeed, during the acute phase, after the head trauma, alertness and wakefulness of the patients affected by a disorder of consciousness can be assessed using different scales, such as the Coma Recovery Scale-Revised. In both postacute and chronic phases after traumatic brain injury, general cognitive assessment tools (such as the Mini Mental State Examination) or more specific cognitive tests (e.g., Wisconsin Card Sorting Test and Trail Making Test) could be administered according to the patient’s functional status. In this way, clinicians may be aware of the patient’s neuropsychological and cognitive level, so they can guarantee a personalized and tailored rehabilitation approach in this frail patient population.
Involvement of the Opioid Peptide Family in Cancer Progression
Authors: Sánchez Manuel Lisardo , Rodríguez Francisco D. , Coveñas Rafael
Published: July 2023

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.
Binary Sand Cat Swarm Optimization Algorithm for Wrapper Feature Selection on Biological Data
Authors: Seyyedabbasi Amir
Published: July 2023

In large datasets, irrelevant, redundant, and noisy attributes are often present. These attributes can have a negative impact on the classification model accuracy. Therefore, feature selection is an effective pre-processing step intended to enhance the classification performance by choosing a small number of relevant or significant features. It is important to note that due to the NP-hard characteristics of feature selection, the search agent can become trapped in the local optima, which is extremely costly in terms of time and complexity. To solve these problems, an efficient and effective global search method is needed. Sand cat swarm optimization (SCSO) is a newly introduced metaheuristic algorithm that solves global optimization algorithms. Nevertheless, the SCSO algorithm is recommended for continuous problems. bSCSO is a binary version of the SCSO algorithm proposed here for the analysis and solution of discrete problems such as wrapper feature selection in biological data. It was evaluated on ten well-known biological datasets to determine the effectiveness of the bSCSO algorithm. Moreover, the proposed algorithm was compared to four recent binary optimization algorithms to determine which algorithm had better efficiency. A number of findings demonstrated the superiority of the proposed approach both in terms of high prediction accuracy and small feature sizes.
A Comparative and Collaborative Study of the Hydrodynamics of Two Swimming Modes Applicable to Dolphins
Authors: Xia Dan , Li Zhihan , Lei Ming , Yan Han , Zhou Zilong
Published: July 2023

This paper presents a hydrodynamics study that examines the comparison and collaboration of two swimming modes relevant to the universality of dolphins. This study utilizes a three-dimensional virtual swimmer model resembling a dolphin, which comprises a body and/or caudal fin (BCF) module, as well as a medium and/or paired fin (MPF) module, each equipped with predetermined kinematics. The manipulation of the dolphin to simulate various swimming modes is achieved through the application of overlapping grids in conjunction with the parallel hole cutting technique. The findings demonstrate that the swimming velocity and thrust attained through the single BCF mode consistently surpass those achieved through the single MPF mode and collaborative mode. Interestingly, the involvement of the MPF mode does not necessarily contribute to performance enhancement. Nevertheless, it is encouraging to note that adjusting the phase difference between the two modes can partially mitigate the limitations associated with the MPF mode. To further investigate the potential advantages of dual-mode collaboration, we conducted experiments by increasing the MPF frequency while keeping the BCF frequency constant, thus introducing the concept of frequency ratio (β). In comparison to the single BCF mode, the collaborative mode with a high β exhibits superior swimming velocity and thrust. Although its efficiency experiences a slight decrease, it tends to stabilize. The corresponding flow structure indirectly verifies the favorable impact of collaboration.
Biosensing by Polymer-Coated Etched Long-Period Fiber Gratings Working near Mode Transition and Turn-around Point
Authors: Dey Tanoy Kumar , Trono Cosimo , Biswas Palas , Giannetti Ambra , Basumallick Nandini , Baldini Francesco , Bandyopadhyay Somnath , Tombelli Sara
Published: July 2023

A methodology to enhance the sensitivity of long-period fiber gratings (LPFGs) based on the combination of three different enhancement approaches is presented; the methods here adopted are the working near mode transition (MT) of a cladding mode (CM), working near the turn-around point of a CM and the enhancement of the evanescent field of CMs by reducing the cladding diameter or by increasing the order number of CMs. In order to combine these enhancement methodologies, an electrostatic self-assembly (ESA) process was used to deposit a polymeric overlay, with a chosen thickness, onto the etched fiber. The add-layer sensitivity of the sensor was theoretically calculated, and the demonstration of the real applicability of the developed LPFG as a biosensor was performed by means of an IgG/anti-IgG immunoassay in human serum in a thermostated microfluidic system. The limits of detection (LODs) calculated by following different procedures (three times the standard deviation of the blank and the mean value of the residuals) were 6.9 × 10−8 µg/mL and 4.5 × 10−6 µg/mL, respectively. The calculated LODs demonstrate the effectiveness of the applied methodology for sensitivity enhancement.
Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use
Authors: Harmelech Tal , Hanlon Colleen A. , Tendler Aron
Published: July 2023

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, drug-free, neural-circuit-based therapeutic tool that was recently cleared by the United States Food and Drug Associate for the treatment of smoking cessation. TMS has been investigated as a tool to reduce consumption and craving for many other substance use disorders (SUDs). This review starts with a discussion of neural networks involved in the addiction process. It then provides a framework for the therapeutic efficacy of TMS describing the role of executive control circuits, default mode, and salience circuits as putative targets for neuromodulation (via targeting the DLPFC, MPFC, cingulate, and insula bilaterally). A series of the largest studies of TMS in SUDs are listed and discussed in the context of this framework. Our review concludes with an assessment of the current state of knowledge regarding the use of rTMS as a therapeutic tool in reducing drug, alcohol, and nicotine use and identifies gaps in the literature that need to be addressed in future studies. Namely, while the presumed mechanism through which TMS exerts its effects is by modulating the functional connectivity circuits involved in executive control and salience of drug-related cues, it is also possible that TMS has direct effects on subcortical dopamine, a hypothesis that could be explored in greater detail with PET imaging.
Sports Value Consciousness Moderates the Effect of Exercise Behavior on Sport Activity Loyalty: A Moderated Mediation Model with Sports YouTube Engagement
Authors: Oh Youngtaek
Published: July 2023

This study aims to address a lack of research on sports value consciousness among Korean university students by examining the moderated mediating effect of sports value consciousness on the relationship between university students’ sports YouTube engagement and their sport activity loyalty. A total of 231 Korean university students were recruited for this study. The analytical model was validated using the SPSS PROCESS Macro (Model no. 8). Exercise behavior was found to have a significant positive effect on both sports YouTube engagement and sport activity loyalty, while sports YouTube engagement had a significant positive effect on sport activity loyalty. Furthermore, the interaction between exercise behavior and sports value consciousness had a significant positive effect on sport activity loyalty at a low to moderate level. Results suggest that, for Korean university students, sports value consciousness is more important at a low to moderate level of sport activity loyalty than at a high level. The importance of sports value consciousness is highlighted in the context of the development of sports media and the sociological aspects of sports engagement among university students.
Intramedullary Nailing with and without the Use of Bone Cement for Impending and Pathologic Fractures of the Humerus in Multiple Myeloma and Metastatic Disease
Authors: Kobryn Andriy , Nian Patrick , Baidya Joydeep , Li Tai L. , Maheshwari Aditya V.
Published: July 2023

Although intramedullary nailing (IMN) is considered the standard of care for the surgical management of most femur metastatic diseases, the optimal treatment of metastatic humeral impending and/or pathologic fractures is still debatable. Moreover, the use of cemented humeral nails has not been thoroughly studied, and only a few small series have compared their results with uncemented nails. The purpose of this study was to compare the (1) survivorship, (2) functional outcomes, and (3) perioperative complications in patients receiving cemented versus uncemented humerus IMN for impending or complete pathologic fractures resulting from metastatic disease or multiple myeloma. We retrospectively reviewed 100 IMNs in 82 patients, of which 53 were cemented and 47 were uncemented. With a mean survival of 10 months (Cemented: 8.3 months vs. Uncemented: 11.6 months, p = 0.34), the mean Musculoskeletal Tumor Society (MSTS) scores increased from 42.4% preoperatively (Cemented: 40.2% vs. Uncemented: 66.7%, p = 0.01) to 89.2% at 3 months postoperatively (Cemented: 89.8% vs. Uncemented: 90.9%, p = 0.72) for the overall group (p < 0.001). Both cohorts yielded comparable complication rates (overall [22.6% vs. 19.1%)], surgical ([11.3% vs. 4.3%], and medical [13.2% vs. 14.9%], all p > 0.05), but estimated blood loss was significantly higher in the cemented group (203 mL vs. 126 mL, p = 0.003). Thus, intramedullary nailing, with and without cement augmentation in select patients, is a relatively safe and effective therapeutic modality for metastatic humeral disease with similar clinical outcomes and acceptable complication rates. While controlling for possible selection bias, larger-scale, higher-level studies are warranted to validate our results.
Trends in Systemic Inflammatory Reaction (SIR) during Paclitaxel and Carboplatin Chemotherapy in Women Suffering from Epithelial Ovarian Cancer
Authors: Mleko Michal , Pluta Elzbieta , Pitynski Kazimierz , Bodzek Maciej , Kałamacki Andrzej , Kiprian Dorota , Banas Tomasz
Published: July 2023

Background: Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy treated with cytoreductive surgery followed by adjuvant taxane-platinum-based chemotherapy. It has been shown that the pretreatment systemic inflammatory reaction (SIR) in women with OC can be evaluated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII), depending on the stage of disease, and has prognostic value for overall survival. The aim of this study was to evaluate the changes in NLR, LMR, PLR and SII during chemotherapy. Methods: A total of 107 women with EOC (23 with type I and 84 with type II tumours) were included in a retrospective single-centre analysis. The Kologomorov−Smirnoff, Kruskal-Wallis or Friedman analysis of variance tests were used for data analysis, and a p value of 0.05 was considered statistically significant. Results: A significant decrease in NLR, PLR and SII but not LMR was observed during adjuvant treatment. Pretreatment NLR, PLR and SII were dependent on disease stage and tumour grade; however, this association was lost during therapy. Additionally, strong and positive mutual correlations between NLR, LMR, PLR and SII were sustained during the whole course of chemotherapy. Conclusions: During first-line adjuvant chemotherapy in women with EOC, a decrease in SIR is confirmed.
Liver Transplantation for Incidental Cholangiocarcinoma or Combined Hepatocellular Carcinoma/Cholangiocarcinoma—Own Experiences and Review of the Literature
Authors: Schwenk Laura , Rohland Oliver , Ali-Deeb Aladdin , Dondorf Felix , Settmacher Utz , Rauchfuß Falk
Published: July 2023

Background: Data about liver transplantation for mixed tumors from hepatocellular carcinoma to cholangiocarcinoma are limited. Furthermore, the diagnosis of intrahepatic cholangiocarcinoma or combined tumors in a cirrhotic liver is considered a contraindication for transplantation. Our aim was to evaluate the long-term outcomes of patients with incidental cholangiocarcinoma or combined tumors after liver transplantation. Methods: In our descriptive analysis, data were evaluated from all patients since 2010 who received a liver transplant due to an assumed hepatocellular carcinoma at Jena University Hospital. Survival rates were determined using the Kaplan–Meier method. Results: Between January 2010 and December 2022, an incidental intrahepatic cholangiocarcinoma was found in eight patients post-transplant. Four combined hepatocellular and cholangiocarcinoma and four sole intrahepatic cholangiocarcinomas were found. A recurrence through distant metastases from combined hepatocellular- and cholangiocarcinoma was found in one patient at one year after transplantation. Another patient developed a pulmonary primary tumor independently one year post-transplant. The recurrence rate was at 14.3%. While two patients died, the 1- and 5-year overall survival rates post-transplant were 87.5% and 75%, respectively. Conclusion: Patients with intrahepatic cholangiocarcinoma or combined hepatocellular- and cholangiocarcinoma could profit from liver transplantation.
Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation
Authors: Barone Cristiana , Orsenigo Roberto , Cazzola Anna , D’Errico Elisabetta , Patelli Arianna , Quattrini Giulia , Vergani Barbara , Bombelli Silvia , De Marco Sofia , D’Orlando Cristina , Bianchi Cristina , Leone Biagio Eugenio , Meneveri Raffaella , Biondi Andrea , Cazzaniga Giovanni , Rabbitts Terence Howard , Brunelli Silvia , Azzoni Emanuele
Published: July 2023

Infant acute myeloid leukemia (AML) is a heterogeneous disease, genetically distinct from its adult counterpart. Chromosomal translocations involving the KMT2A gene (MLL) are especially common in affected infants of less than 1 year of age, and are associated with a dismal prognosis. While these rearrangements are likely to arise in utero, the cell of origin has not been conclusively identified. This knowledge could lead to a better understanding of the biology of the disease and support the identification of new therapeutic vulnerabilities. Over the last few years, important progress in understanding the dynamics of fetal hematopoiesis has been made. Several reports have highlighted how hematopoietic stem cells (HSC) provide little contribution to fetal hematopoiesis, which is instead largely sustained by HSC-independent progenitors. Here, we used conditional Cre-Lox transgenic mouse models to engineer the Mll-Af9 translocation in defined subsets of embryonic hematopoietic progenitors. We show that embryonic hematopoiesis is generally permissive for Mll-Af9-induced leukemic transformation. Surprisingly, the selective introduction of Mll-Af9 in HSC-independent progenitors generated a transplantable myeloid leukemia, whereas it did not when introduced in embryonic HSC-derived cells. Ex vivo engineering of the Mll-Af9 rearrangement in HSC-independent progenitors using a CRISPR/Cas9-based approach resulted in the activation of an aberrant myeloid-biased self-renewal program. Overall, our results demonstrate that HSC-independent hematopoietic progenitors represent a permissive environment for Mll-Af9-induced leukemic transformation, and can likely act as cells of origin of infant AML.
Ropinirole Cotreatment Prevents Perivascular Glial Recruitment in a Rat Model of L-DOPA-Induced Dyskinesia
Authors: Elabi Osama F. , Espa Elena , Skovgård Katrine , Fanni Silvia , Cenci Maria Angela
Published: July 2023

Dopamine replacement therapy for Parkinson’s disease is achieved using L-DOPA or dopamine D2/3 agonists, such as ropinirole. Here, we compare the effects of L-DOPA and ropinirole, alone or in combination, on patterns of glial and microvascular reactivity in the striatum. Rats with unilateral 6-hydroxydopamine lesions were treated with therapeutic-like doses of L-DOPA (6 mg/kg), an equipotent L-DOPA-ropinirole combination (L-DOPA 3 mg/kg plus ropinirole 0.5 mg/kg), or ropinirole alone. Immunohistochemistry was used to examine the reactivity of microglia (ionized calcium-binding adapter molecule 1, IBA-1) and astroglia (glial fibrillary acidic protein, GFAP), as well as blood vessel density (rat endothelial cell antigen 1, RECA-1) and albumin extravasation. L-DOPA monotreatment and L-DOPA–ropinirole cotreatment induced moderate-severe dyskinesia, whereas ropinirole alone had negligible dyskinetic effects. Despite similar dyskinesia severity, striking differences in perivascular microglia and astroglial reactivity were found between animals treated with L-DOPA vs. L-DOPA–ropinirole. The former exhibited a marked upregulation of perivascular IBA-1 cells (in part CD68-positive) and IBA-1–RECA-1 contact points, along with an increased microvessel density and strong perivascular GFAP expression. None of these markers were significantly upregulated in animals treated with L-DOPA–ropinirole or ropinirole alone. In summary, although ropinirole cotreatment does not prevent L-DOPA-induced dyskinesia, it protects from maladaptive gliovascular changes otherwise associated with this disorder, with potential long-term benefits to striatal tissue homeostasis.
Bismuth-Germanate Glasses: Synthesis, Structure, Luminescence, and Crystallization
Authors: Serkina Ksenia , Stepanova Irina , Pynenkov Aleksandr , Uslamina Maria , Nishchev Konstantin , Boldyrev Kirill , Avetisov Roman , Avetissov Igor
Published: July 2023

Bismuth-germanate glasses, which are well known as a promising active medium for broadband near-infrared spectral range fiber lasers and as an initial matrix for nonlinear optical glass ceramics, have been synthesized in a 5–50 mol% Bi2O3 wide concentration range. Their structural and physical characteristics were studied by Raman and FT-IR spectroscopy, differential scanning calorimetry, X-ray diffraction, optical, and luminescence methods. It has been found that the main structural units of glasses are [BiO6] and [GeO4]. The growth in bismuth oxide content resulted in an increase in density and refractive index. The spectral and luminescent properties of glasses strongly depended on the amount of bismuth active centers. The maximum intensity of IR luminescence has been achieved for the 5Bi2O3-95GeO2 sample. The heat treatment of glasses resulted in the formation of several crystalline phases, the structure and amount of which depended on the initial glass composition. The main phases were non-linear Bi2GeO5 and scintillating Bi4Ge3O12. Comparing with the previous papers dealing with bismuth and germanium oxide-based glasses, we enlarge the range of Bi2O3 concentration up to 50 mol% and decrease the synthesis temperature from 1300 to 1100 °C.
Legal Conditions for Refugees’ Mental Health: Implications of Legislative Changes in Programs for Newly Arrived Refugees in Sweden
Authors: Gunnarsson David , Larsson Sofia , Vikdahl Linda
Published: July 2023

As the number of refugees in the world is increasing and it is known that social inequality negatively impacts mental health, it is important to study integration policies, such as labour market measures. In this article, the strategic interventions of the Swedish Public Employment Service are analysed to determine how the agency’s management handled and implemented the legal changes in the new support document for its case workers. The focus is on the effects of the changes in the legal text that transferred the responsibility for establishment initiatives for newly arrived migrants to the agency and, as a result, changed the conditions for newly arrived refugees’ mental health in the new establishment programme. Eight people representing different management functions at the agency were interviewed. The results show that the intention in the new programme to view newly arrived refugees in the same way as all other unemployed people, rather than as a special category, has meant that less attention is paid to the refugees’ mental health, and the opportunities for the agency’s street-level bureaucrats to help clients have decreased. In the face of predicted growing numbers of people having to abandon their homes due to conflicts and climate changes, governmental strategies such as these needs to be revisited in order for societies worldwide to be better prepared for that challenge.
Microplasma-Enabled Sustainable Synthesis of Nitrogen-Doped Graphene Quantum Dots for Sensitive Detection of 4-Nitrophenol
Authors: Rahardja Michael Ryan , Kurniawan Darwin , Chiang Wei-Hung
Published: July 2023

4-nitrophenol (4-NP) is one of the organic pollutants that can come up from pesticides, explosives, dyes, and pharmaceutical industries. Since it can be extremely harmful to humans and other living organisms, it is crucial to have a system that can effectively detect the presence of 4-NP. Here, we report the microplasma synthesis of nitrogen-doped graphene quantum dots (N-GQDs) for fluorescence-based detection of 4-NP. Through Förster resonance energy transfer (FRET) between donor N-GQDs to the acceptor 4-NP, synthesized N-GQDs can be employed for the detection of 4-NP starting from 0.5 to 100 µM with a limit of detection as low as 95.14 nM. 4-NP detection also demonstrates remarkable stability over all pH values and wide temperatures (10–60 °C), indicating the high possibility for robust organic pollution monitoring. Our work provides insight into a simple, fast, and environmentally friendly method for synthesizing N-GQDs at ambient conditions usable for environmental nanosensors.
Current Status and Prospect of Diabetes Diagnosis and Treatment Based on Biosensing Technology
Authors: Xu Xinyi , Wang Xuemei , Jiang Hui
Published: July 2023

Diabetes mellitus has increasingly become a threat to health all over the world. This review focuses on the promoting effect of biosensing technology on the diagnosis and treatment of diabetes mellitus. Types of diabetes and their corresponding pathogeneses are first introduced, followed by the diabetes prevalence and research progress at home and abroad. To emphasize the importance of diabetes diagnosis and treatment, we secondly summarize the breakthrough technology in this field based on biosensing technology at the present stage. In terms of diagnosis, diversified ways of blood glucose detection and multiple combinations of diabetes biomarkers are discussed, while a variety of insulin administration routes and non-drug treatment means are presented in the aspect of treatment. In conclusion, the prospect of the future development of diabetes diagnosis and treatment is put forward at the end of the review.
SPR-Enhanced Au@Fe3O4 Nanozyme for the Detection of Hydroquinone
Authors: Zhang Bin , Wang Xiaoming , Hu Wei , Liao Yiquan , He Yichang , Dong Bohua , Zhao Minggang , Ma Ye
Published: July 2023

Artificial nanozymes that are based on ferric oxides have drawn enormous attention due to their high stability, high efficiency, and low cost as compared with natural enzymes. Due to the unique optical plasmonic properties, gold nanoparticles (Au NPs) have been widely utilized in the fields of colorimetric, Raman, and fluorescence sensing. In this work, a photo-responsive Au@Fe3O4 nanozyme is prepared with outstanding peroxidase-like activity. The hot electrons of Au NPs that are excited by a surface plasmon resonance (SPR) effect of NPs improve the catalytic activity of Au@Fe3O4 in oxidizing 3,3′,5,5′-tetramethylbenzidine (TMB) and the detection of hydroquinone (HQ). The magnetic separation and reusability of the nanozyme further lower its costs. The detection linear range of the sensor is 0–30 μM and the lowest detection limit is 0.29 μM. Especially in the detection of real water samples, a good recovery rate is obtained, which provides promising references for the development of the HQ detection technology in seawater.
Development of Chemiluminescent ELISA for Detection of Diisobutyl Phthalate in Water, Lettuce and Aquatic Organisms
Authors: Berlina Anna N. , Ragozina Maria Y. , Gusev Daniil I. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: July 2023

The use of plasticizers to improve the quality of plastics widely used for household purposes inevitably leads to an increase in their pollution of food and environmental objects. Diisobutyl phthalate (DiBP) is one of the ortho-substituted phthalic acid esters that negatively affect human health and ecosystems. This work is directed to the development of a chemiluminescent enzyme immunoassay (CL-ELISA) for the determination of diisobutyl phthalate in water and food. Luminol, which is oxidized with hydrogen peroxide in the presence of p-iodophenol as an enhancer, was chosen as the substrate for horseradish peroxidase used as a label in the analysis. For this development, rabbit anti-DiBP polyclonal antibodies were generated and tested with the synthesized hapten–protein conjugate. The developed chemiluminescent ELISA has a detection limit of 1.8 ng/mL; the operating range was 5.0–170.8 ng/mL at a content of 10% methanol in the assay medium. The assay was successfully applied to detect diisobutyl phthalate in lettuce leaves, seafood, and water. When using extraction with methanol and hexane, the recovery of DiBP in samples varies in the range of 76.9–134.2%; for assays in natural waters, the recovery rates are from 79.5 to 113.4%.
Biochar for Water Pollution Control: From Sensing to Decontamination
Authors: Krajčovičová Timea Ema , Hatala Michal , Gemeiner Pavol , Híveš Ján , Mackuľak Tomáš , Nemčeková Katarína , Svitková Veronika
Published: July 2023

Biochar, a biologically originated carbon-rich material derived from the oxygen-limited pyrolysis of biomass, is usually added to the soil for its enrichment, increasing its water-holding capacity and pH. This revolutionary material thus contributes to a reduction in the overall environmental impact and mitigation of climate change. Due to the beneficial properties of this material, especially for electrochemical applications (large active surface area, conductivity, etc.), biochar demonstrates an extremely high capacity for the adsorption and detection of micropollutants simultaneously. However, finding the optimal conditions for the adsorptive and electrochemical properties of prepared biochar-based sensors is crucial. The adsorption efficiency should be sufficient to remove pollutants, even from complex matrices; on the other hand, the electrochemical properties, such as conductivity and charge transfer resistance, are key factors concerning the sensing ability. Therefore, the balanced design of biochar can ensure both the usability and the effectiveness of sensing. To enhance levels of electroactivity that are already high, the pre- or post-modification of biochar can be performed. Such recycled carbon-based materials could be promising candidates among other electrochemical sensing platforms. In this study, different biochar modifications are presented. Utilizing important biochar properties, it should be possible to create a bifunctional platform for removing micropollutants from water systems and simultaneously confirming purification levels via their detection. We reviewed the use of biochar-based materials for the effective removal of micropollutants and the methods for their detection in water matrices.
Pyrogallol Detection Based on the Cobalt Metal–Organic Framework of Nanomaterial-Enhanced Chemiluminescence
Authors: Wang Yanran , Wang Zhiqiang , Liu Yincheng , Liu Zixuan , Gao Zhan , Li Kuangjun , Zhao Dajun , Wu Jing , Liu Xuanhe
Published: July 2023

The cobalt metal–organic framework (Co-MOF) is a kind of crystalline porous material within a periodic network structure, which is formed via the self-assembly of a Co metal center and a bridged organic ligand. In this paper, a Co-MOF was facilely synthesized via an ultrasonic method and applied to enhance the chemiluminescence (CL) emission of the NaIO4-H2O2 system. The synthesized Co-MOF was nanosheet-like in nature and stacked in 2–3-micrometer flower shapes. Compared to the NaIO4-H2O2 system without a Co-MOF, the CL intensity of the Co-MOF-NaIO4-H2O2 system was enhanced about 70 times. This CL mechanism was determined to be a result of the synergistic effects of chemiluminescence resonance energy transfer (CRET) and electron–hole annihilation (EHA). The Co-MOF not only acted as a catalyst to accelerate the generation of reactive oxygen species in the CL reaction, but also worked as an emitter to further enhance the CL. Based on the Co-MOF-NaIO4-H2O2 system, a highly sensitive CL analysis method was established for pyrogallol (PG) detection. Addition of PG into the CL system generated 1O2*, which could transfer energy to the Co-MOF and further enhance the CL response. The enhanced CL was linear with the PG concentration. The CL analysis method exhibited a linear range of 1 × 10−4 M to 1 × 10−7 M, as well as having a linear correlation coefficient of 0.9995 and a limit of detection of (S/N = 3) of 34 nM.
Management of the Pediatric Patient with Suspected Diagnosis of Obstructive Sleep Apnea Syndrome
Authors: Savin Sorina , Mezzofranco Luca , Gracco Antonio , Bruno Giovanni , De Stefani Alberto
Published: July 2023

Aim: The aim of this paper is to describe the multidisciplinary management pathway for pediatric patients with suspected obstructive sleep apnea syndrome (OSAS) conducted by the Pediatric and Orthodontic Department of the Dental Clinic of Padua. Materials and methods: All pediatric subjects undergo a comprehensive medical history, including the completion of the Pediatric Sleep Questionnaire (PSQ), and a physical examination. Patients with suspected OSAS are placed on a waiting list for home respiratory polygraphy testing. The respiratory polygraphy examination is conducted over two consecutive nights and interpreted by a neurologist. Additionally, patients diagnosed with OSAS undergo a case study involving intraoral and extraoral photography, as well as radiographic evaluation. Results: Between September 2021 and May 2023, a total of 134 subjects (including 76 males), with an average age of 9.2 years, were identified as diagnostic suspects. Among these, 38 patients (28.3%) tested positive based on respiratory polygraphic results. Depending on the severity and etiopathogenetic characteristics of the disease, the positive cases were referred to various specialists. Conclusion: In the daily clinical practice of dentistry, particularly in orthodontics and pedodontics, the establishment of a defined management pathway for pediatric patients with OSAS is crucial. The collaboration of a multidisciplinary team with a shared objective of achieving accurate diagnosis and implementing targeted treatment in a timely manner is essential. Regular re-evaluation of patients through clinical and instrumental examinations is recommended.
A Metagenome from a Steam Vent in Los Azufres Geothermal Field Shows an Abundance of Thermoplasmatales archaea and Bacteria from the Phyla Actinomycetota and Pseudomonadota
Authors: Marín-Paredes Roberto , Bolívar-Torres Hermes H. , Coronel-Gaytán Alberto , Martínez-Romero Esperanza , Servín-Garcidueñas Luis E.
Published: July 2023

Los Azufres National Park is a geothermal field that has a wide number of thermal manifestations; nevertheless, the microbial communities in many of these environments remain unknown. In this study, a metagenome from a sediment sample from Los Azufres National Park was sequenced. In this metagenome, we found that the microbial diversity corresponds to bacteria (Actinomycetota, Pseudomonadota), archaea (Thermoplasmatales and Candidatus Micrarchaeota and Candidatus Parvarchaeota), eukarya (Cyanidiaceae), and viruses (Fussellovirus and Caudoviricetes). The functional annotation showed genes related to the carbon fixation pathway, sulfur metabolism, genes involved in heat and cold shock, and heavy-metal resistance. From the sediment, it was possible to recover two metagenome-assembled genomes from Ferrimicrobium and Cuniculiplasma. Our results showed that there are a large number of microorganisms in Los Azufres that deserve to be studied.
Targeting RAF Isoforms and Tumor Microenvironments in RAS or BRAF Mutant Colorectal Cancers with SJ-C1044 for Anti-Tumor Activity
Authors: Hong Sungpyo , Jeon Myeongjin , Kwon Jeonghee , Park Hanbyeol , Lee Goeun , Kim Kilwon , Ahn Soonkil
Published: July 2023

Colorectal cancer (CRC) is a significant global health issue characterized by a high prevalence of KRAS gene mutations. The RAS/MAPK pathway, involving KRAS, plays a crucial role in CRC progression. Although some RAS inhibitors have been approved, their efficacy in CRC is limited. To overcome these limitations, pan-RAF inhibitors targeting A-Raf, B-Raf, and C-Raf have emerged as promising therapeutic strategies. However, resistance to RAF inhibition and the presence of an immunosuppressive tumor microenvironment (TME) pose additional obstacles to effective therapy. Here, we evaluated the potential of a novel pan-RAF inhibitor, SJ-C1044, for targeting mutant KRAS-mediated signaling and inhibiting CRC cell proliferation. Notably, SJ-C1044 also exhibited inhibitory effects on immunokinases, specifically, CSF1R, VEGFR2, and TIE2, which play crucial roles in immune suppression. SJ-C1044 demonstrated potent antitumor activity in xenograft models of CRC harboring KRAS or BRAF mutations. Importantly, treatment with SJ-C1044 resulted in increased infiltration of T cells and reduced presence of tumor-associated macrophages and regulatory T cells within the TME. Thus, SJ-C1044 shows immunomodulatory potential and the ability to enhance antitumor responses. The study underscores the therapeutic potential of SJ-C1044 as a novel pan-RAF inhibitor capable of targeting oncogenic signaling pathways and overcoming immune suppression in CRC.
Genome-Wide Mining of Selaginella moellendorffii for Hevein-like Lectins and Their Potential Molecular Mimicry with SARS-CoV-2 Spike Glycoprotein
Authors: Alsolami Ahmed , Dirar Amina I. , Konozy Emadeldin Hassan E. , Osman Makarim El-Fadil M. , Ibrahim Mohanad A. , Alshammari Khalid Farhan , Alshammari Fawwaz , Alazmi Meshari , Said Kamaleldin B.
Published: July 2023

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0’s genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein’s receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of −17.5, −13.0, and −26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein–protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus’s virulence and infection.
Statistical Descriptive Analysis of Portuguese Public Procurement Data from 2015 to 2022
Authors: Jacques de Sousa Luís , Simões Maria Lurdes , Poças Martins João , Sanhudo Luís , Moreira da Costa Jorge
Published: July 2023

During the tender phase of public construction projects in Portugal, documents that describe the project are mandatorily submitted to open data repositories. However, in their current state, most of these repositories do not allow for benchmarking analysis due to a lack of data treatment and cohesion. This paper seeks to diagnose the main trends during the public construction project’s tender phase by performing a descriptive statistical analysis on the Portuguese Public Procurement Database (PPPData), a database that compiles 5172 public procurement contracts in Portugal from 2015 to 2022, to respond to the research gap in construction procurement benchmarking. The results of this statistical analysis draw out the main trends, uncover which tender variables can influence budget compliance, and diagnose Portugal’s public procurement in terms of its geographical, temporal, financial, and performance dispersion. This paper concludes that the award criteria are not correlated with final project performance and that multifactor assessment criteria do not necessarily lead to better performance. High-value projects awarded solely with the price award criterion tend to perform worse than those awarded with the multifactor assessment. The study also identified frequent errors and omissions in construction reporting; thus, there is a need for error mitigation tools.
Extreme Recreational Conditions in the Black Sea Resorts Associated with the North Atlantic Climate
Authors: Stefanovich Anna A. , Voskresenskaya Elena N. , Maslova Veronika N.
Published: July 2023

The tourist and recreational conditions of the Mediterranean-Black Sea resorts are closely related to hydrometeorological anomalies, which in turn are largely associated with the North Atlantic climate. The aim of this paper was to study the change and variability of the bioclimatic indices and their extremes at the Black Sea resorts (on the example of Yalta, Southern coast of Crimea, and Sochi, Caucasian coast) associated with the North Atlantic Oscillation (NAO) and East Atlantic Oscillation (EAO). Using daily NCEP/NCAR (2.5° × 2.5°) and E-OBS (0.25° × 0.25°) reanalysis datasets, bioclimatic indices (wind cooling index, weight oxygen content, and equivalent-effective temperature) were calculated for January and July in 1950–2013/2018. The extreme index values were obtained using the 5th and 95th percentile relative thresholds. The results suggest that bioclimatic indices in Yalta are more sensitive to the global warming effect than those in Sochi, likely due to the geographical features. As a result, Yalta is becoming a year-round resort. It was shown for both resorts that negative EAO phase is significantly manifested in the increase of windy days in July versus the increase of windless days in the positive phase, and in the more frequent fresh and cold days in July (versus the opposite conditions in the positive phase only in Yalta). The NAO manifestations are mostly less pronounced than those of the EAO and are more significant in Sochi (mostly in January and in the negative NAO phase). Thus, it was shown that extreme values of bioclimatic indices occur at both resorts on the interannual scale depending on the NAO and EAO phases, but the conditions remain in the comfort range for now, even with the significant linear trends. The study can be expanded to other Mediterranean–Black Sea resorts for their sustainable development in a changing climate.
A Review of Evidence for the Involvement of the Circadian Clock Genes into Malignant Transformation of Thyroid Tissue
Authors: Putilov Arcady A. , Budkevich Elena V. , Budkevich Roman O.
Published: July 2023

(1) Background: In 2013, the results of a pioneer study on abnormalities in the levels and circadian rhythmicity of expression of circadian clock genes in cancerous thyroid nodules was published. In the following years, new findings suggesting the involvement of circadian clockwork dysfunction into malignant transformation of thyroid tissue were gradually accumulating. This systematic review provides an update on existing evidence regarding the association of these genes with thyroid tumorigenesis. (2) Methods: Two bibliographic databases (Scopus and PubMed) were searched for articles from inception to 20 March 2023. The reference lists of previously published (nonsystematic) reviews were also hand-searched for additional relevant studies. (3) Results: Nine studies published between 2013 and 2022 were selected. In total, 9 of 12 tested genes were found to be either up- or downregulated. The list of such genes includes all families of core circadian clock genes that are the key components of three transcriptional–translational feedback loops of the circadian clock mechanism (BMAL1, CLOCK, NPAS2, RORα, REV-ERBα, PERs, CRYs, and DECs). (4) Conclusions: Examination of abnormalities in the levels and circadian rhythmicity of expression of circadian clock genes in thyroid tissue can help to reduce the rate of inadequate differential preoperative diagnosis for thyroid carcinoma.