Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P<0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P<0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

The necessity for precise and current data concerning the dynamics of land cover change in Indonesia is crucial for efforts to reduce natural vegetation cover due to agricultural expansion. The functionality of monitoring systems that incorporate Terra-MODIS is currently compromised by the limited availability of data for the immediate future. This study seeks to assess the potential of VIIRS satellite imagery in developing an early warning system for monitoring vegetation cover change in Indonesia. The Normalized Differential Open Area Index (NDOAI) computed from the 8-day’ VIIRS data was employed to detect changes in vegetation cover based on pixel-by-pixel subtraction in the NDOAI data time series. Evaluating the pixel-level accuracy of change detection is complicated due to the fact that we evaluate a change map at a coarser resolution than the Landsat-based reference map. The results revealed that increasing the threshold percentage is associated with improved accuracy. In change detection, there is often a trade-off between accuracy and sensitivity. A threshold that is too low may result in false positives, while a threshold that is too high may lead to missed changes. This study demonstrates that when a threshold value of less than 20% is applied, Landsat can identify vegetation cover changes at an earlier stage. Conversely, when a threshold value greater than 20% is employed, VIIRS will detect the change 4.5 days earlier than Landsat. Additionally, VIIRS is capable of detecting changes 25.4 days and 54.8 days faster than Landsat, respectively, when using thresholds of 40% and 75%.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p < 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

The process of blood coagulation, wherein circulating blood transforms into a clot in response to internal or external injury, is a critical physiological mechanism. Monitoring this coagulation process is vital to ensure that blood clotting occurs neither too rapidly nor too slowly. Anticoagulants, a category of medications designed to prevent and treat blood clots, require meticulous monitoring to optimise dosage, enhance clinical outcomes, and minimise adverse effects. This review article delves into the various stages of blood coagulation, explores commonly used anticoagulants and their targets within the coagulation enzyme system, and emphasises the electrochemical methods employed in anticoagulant testing. Electrochemical sensors for anticoagulant monitoring are categorised into two types. The first type focuses on assays measuring thrombin activity via electrochemical techniques. The second type involves modified electrode surfaces that either directly measure the redox behaviour of anticoagulants or monitor the response of standard redox probes in the presence of these drugs. The review provides a comprehensive list of different electrode compositions and their detection and quantification limits. Additionally, it discusses the potential of employing a universal calibration plot to replace individual drug-specific calibrations. The insights presented are anticipated to significantly contribute to the sensor community's efforts in this field.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

One of the tools for optimal crop production is regular monitoring and assessment of crops. During the growing season of fruit trees, the bloom period has increased photosynthetic rates that correlate with the fruiting process. This paper presents the development of an image processing algorithm to detect peach blossoms on trees. Images of an experimental peach orchard were acquired from the Parma Research and Extension Center of the University of Idaho using an off-the-shelf unmanned aerial system (UAS), equipped with a multispectral camera (Near-infrared, Green, Blue). The orchard has different stone fruit varieties and different plant training system. Individual tree images (high-resolution) and arrays of trees images (low-resolution) were acquired to evaluate the detection capability. The image processing algorithm was based on different vegetation indices. Initial results showed that the image processing algorithm could detect peach blossoms and demonstrate good potential as a monitoring tool for orchard management.

Background: The aim of the study is to present the process of monitoring the changes in the effi-ciency of equilibrium reactions in the children with postural disorders, in the course of the thera-peutic process. Methods: The shape of spine and the efficiency of equilibrium reactions in standing posture and during gait were assessed in all the subjects. The subjects were put in 2 groups: with the shape of spine disorder and without one. The recommended set of therapeutic activities in home conditions lasted about 20 minutes and was performed by the child with parent’s supervision. The therapeutic program was based on elements of the PNF and Vojta methods. The following parameters were measured: maximum movement of the center of presure (CoP) in the frontal plane during gate, maximum movement of the CoP in the sagittal plane, movement of the CoP in the frontal plane in static conditions, movement of the CoP in the sagittal plane in static conditions. Results: Six statistically significant differences were recorded, all of them were related to measurement I. The Friedman test result was statistically significant for all the indexes. Post-hoc analyzes were performed using the Dunn-Bonferroni test. Conclusions: 1. The children with shape of spine disorders are featured by lower efficiency of equivalent reactions in relation to the children without disorders. 2. The therapy with the application of neurophysiological methods in the treatment of shape of spine disorders improves equilibrium reactions in these patients. 3. Long-lasting and thorough observations of the therapeutic process in the children with shape of spine disorders should include the monitoring of the efficiency of equilibrium reactions

Dolichandrone spathacea is a rare and endangered semi-mangrove plant species with an extremely small population, naturally distributed only in Zhanjiang City and the east coast of Hainan Island, China. Regrettably, the present situation of the D. spathacea population in China has not yet been carefully investigated. In this study, we aim to evaluate the current resource status and population dynamic characteristics of D. spathacea on Hainan Island, China, in order to propose sustainable conservation and management strategies for future ecological restoration of its natural population. Our results show that D. spathacea on Hainan Island can be divided into four populations. All the D. spathacea populations present a state of overall dispersion, local concentration, and occasionally sporadic existence, and they exist in geographical isolation. The young, middle, and old D. spathacea plants account for 20.42%, 66.20%, and 13.38%, respectively, indicating that the overall age class of the D. spathacea population on Hainan Island belongs to a declining type. Furthermore, instead of temporal structure, we chose diameter at breast height (DBH) to establish a static life table, draw a population survival curve, and quantify the future development trend through population dynamic analysis and time-series prediction. These results directly point out that the D. spathacea population on Hainan Island is sensitive to external disturbances and possesses two main increases in mortality rate—namely, in its juvenile and mature stages—due to weak vitality, competition, and anthropogenic interferences, which are the most important reasons for its endangered status. Depending on the current conditions of the D. spathacea population, we should conserve and expand mature trees in situ, preserve their germplasm resources, rehabilitate their habitats to promote provenance restoration, and conduct artificial cultivation and spreading planting in order to realize the sustainable conservation and management of D. spathacea.

In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.

Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production, or oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of turning these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and /or response to anticancer treatments. Additionally, the iron addiction of cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we selected relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides, we discuss some co-existing discrepant findings. We will also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anti-cancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy will also be reported.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

This paper investigates an Energy Neutral System using Micro Energy Harvesters for a Health Monitoring Wireless Sensor Node (HM-WSN). We have implemented HM-WSN consisting of a solar cell energy harvester, a Power Management Unit (PMU) and the ucontroller, sensor and transmitter acting as load. A battery extender and a switching logic circuit for sensor node is designed to evaluate the efficiency of the proposed system. The HM-WSN senses body temperature with improvement in lifetime of coincell. The HM-WSN is built using commercially available off the shelf (COTS components and consumes 47.2uW for data being updated every 134s. It can be operated for approximately 1.32 years only on a coincell. Furthermore, the HM-WSN can be operated with solar energy at 200lux, achieving 96.36 years with a combination of a coincell with an additional capacitor of 2.2mF. It attains 4.07 years to 16.87 years lifetime with the load capacitor varying from 1mF to 1.5mF at 350lux lighting condition. With the same ambient condition and a 2mF load capacitor, HM-WSN attains complete energy autonomy.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

This review delves into the growing field of flexible and stretchable strain sensors utilized in human gait analysis, focusing on determining knee bending angle and muscle activities when a human subject walks. Recent advancements have enabled these sensors to accurately capture biomechanical parameters while accommodating the body's natural movements. We examine the principles underlying these sensors' design and fabrication techniques, emphasizing their flexibility, stretchability, and biocompatibility for seamless integration into wearable systems. Through critical evaluation of existing methodologies, we assess the reliability and validity of these sensors in quantifying gait parameters. Furthermore, we discuss this technology's clinical and research implications, highlighting its potential in personalized rehabilitation and sports performance optimization. We provide an overview of flexible strain sensors and their application for analyzing human walking gait, especially for observing walking gait in rehabilitation programs. First, we present the basic working principles of various flexible strain sensors. Second, by the application of flexible strain sensors as walking gait monitoring. Finally, current challenges and future opportunities in this research area are discussed. By synthesizing current knowledge and outlining future directions, this review aims to provide insights for researchers and practitioners seeking to leverage flexible and stretchable strain sensors for comprehensive human gait analysis.

Floods are a common natural disaster whose severity in terms of duration, water resource volume, peak and accumulated rainfall-based damage are likely to differ significantly for different geographical regions. In this paper, we first propose a novel hourly flood index (SWRI24−hr−S), derived from normalising the existing 24-hourly water resources index (WRI24−hr−S) in literature, to monitor flash flood risks on an hourly scale. The proposed SWRI24−hr−S is adopted to identify a flood situation and derive its characteristics, such as the duration (D), volume (V) and peak (Q). The comprehensive result analysis establishes the practical utility of SWRI24−hr−S in identifying flood situations at seven study sites in Fiji between 2014 and 2018 and deriving their characteristics (i.e., D, V, and Q). Secondly, this study develops a vine copula-probabilistic risk analysis system that models the joint distribution of flood characteristics (i.e., D, V, and Q) to extract their joint exceedance probability for the seven study sites in Fiji, enabling probabilistic flood risk assessment. The vine copula approach, particularly suited to Fiji’s study sites, introduces a novel probabilistic framework for flood risk assessment. The results show moderate differences in the spatial patterns of joint exceedance probability of flood characteristics in different combination scenarios generated by the proposed vine copula approach. In the worst-case scenario, the probability of any flood event occurring where the flood volume, peak and duration are likely to exceed the 95th-quantile value (representing an extreme flood event) is found to be less than 5% for all study sites. The proposed hourly flood index and the vine copula approach can be feasible and cost-effective tools for flood risk monitoring and assessment. The methodologies proposed in this study can be applied to other data-scarce regions where only rainfall data is available, offering crucial information for flood risk monitoring, assessment, and the development of effective mitigation strategies.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

In recent decades, as eutrophication in inland and coastal waters (ICWs) has increased due to anthropogenic activities and global warming, so has the need for timely monitoring. Compared with traditional sampling and laboratory analysis methods, satellite remote sensing technology can provide macro-scale, low-cost, and near real-time water quality monitoring services. The Geostationary Ocean Color Imager (GOCI), integrated onboard the Communication Ocean and Meteorological Satellite (COMS) from the Republic of Korea, was the first geostationary ocean color observation satellite and was operational from April 1, 2011 to March 31, 2021. Over ten years, GOCI has observed oceans, coastal waters, and inland waters within its 2,500 km×2,500 km target area centered on the Korean Peninsula. The most attractive feature of GOCI, compared with other commonly used watercolor sensors, was its high temporal resolution (1h, eight times daily from 0 UTC to 7 UTC), providing the opportunity to monitor the quality of ICWs, where optical properties can change rapidly throughout the day. This systematic review aims to comprehensively review GOCI features and applications in ICWs, analyzing progress in atmospheric correction algorithms and water quality monitoring. Analyzing 123 articles from the Web of Science and China National Knowledge Infrastructure (CNKI) through a bibliometric quantitative approach, we examined GOCI’s strength and performance with different processing methods. These articles reveal that GOCI played an essential role in monitoring the ecological health of ICWs in its observation area in East Asia. GOCI has led the way to a new era of geostationary ocean satellites, providing new technical means for monitoring water quality in oceans, coastal zones, and inland lakes. We also discuss the challenges encountered by geostationary satellites in monitoring water quality and provide suggestions for improvements.

Air pollution has created a lot of problems in the developed and developing countries. To avoid or reduce these problems, constant monitoring of the air should be ensured. The conventional techniques is costly because it requires a lot of money and time consuming. Biomonitoring has been the alternative method. Moss, lichens and plants are biomonitors available to entrap air pollutants. The aim of this paper is to discuss one of the ways of monitoring air pollution – Moss bag technique. To do this, types, choice, preparation, handling of bags after preparation of moss were discussed. From the literatures consulted, it was discovered that there were differences in the techniques used by the researchers. In all, the use of mosses with emphasis on the employment of moss bag have proved to be a powerful tool in airborne particulate and toxic elements. To conclude, developing countries should focus more on this technique because it will reduce cost of air monitoring.

To make wind power more competitive, it is necessary to reduce turbine downtime and reduce costs associated with wind turbine Operation and Maintenance (O&amp;M). Incorporating machine learning in developing condition-based predictive maintenance methodologies for wind turbines can enhance their efficiency and reliability. This paper presents a monitoring method that utilizes Base Density for the Support Vector Machine (BDSVM) and the evolutionary Fourier spectra of vibrations. This method allows smart monitoring of the function evolution of the turbine. A complex optimal function (FO) for 5-degree order has been developed that will be the boundary function of the BDSVM to timely determine the magnitude, frequency, and place of the failure occurring in wind turbine drive.

Notwithstanding the fact that there is some improvement for an earlier detection of patients with lung cancer, the majority of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently used factors affecting the prognosis of lung cancer patients (stage, performance and age) the recent application of biomarkers obtained by liquid profiling gained more acceptance. In our study we aimed to answer these questions: i) is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA an useful method for the therapy monitoring and is this also possible for patients treated with different therapy regimens?, and ii) is this approach possible when blood drawing tubes are used which allow for a delayed processing of blood samples? Baseline values for mPTGER4 and mSHOX2 do not allow for a clear discrimination between different response groups. In contrast the combination of the methylation values for both genes show a clear difference between responders vs non-responders at the time of re-staging. Additionally, blood drawing into tubes stabilizing the sample give researchers more flexibility.

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.

Agro-meteorology is the relationship between agriculture and weather. All farm activities are affected by weather. Therefore it is always necessary to monitor the weather as a forecast. The aim of the research was to monitor the weather and rainwater samples obtained at Federal College of Agriculture, Akure, Ondo State, Nigeria. For the eight months periods, results were obtained. The mean results for the physicochemical parameters were: TDS (12.25 mg/L), temp (28.13 ^oC), pH (6.63), EC (24.25µS/cm), Free CO₂ (24.38mg/L), nitrate (0.16mg/L), phosphate (0.17mg/L), sulphate (0.18mg/L). The rainwater was colorless and had no odor. The mean meteorological data: The prevailing wind directions were from SE, mostly in May, June, July and November and NE. The dry and wet temperatures were 22-29 ^oC and 20-26 ^oC respectively. The maximum value was observed in the month of July. The correlation matrix showed that there were many strong correlations in the physicochemical properties. The months of May, June and July had the highest wind speed. In these months there would be a need to use a windbreaker around the crops planted to avoid soil erosion and damaging of plants.

The Food and Drug Administration’s 2011 Process Validation Guidance and International Council for Harmonization Quality Guidelines recommend continued process verification (CPV) as a mandatory requirement for pharmaceutical, biopharmaceutical, and other regulated industries. As a part of product life cycle management, after process characterization in stage 1 and process qualification and validation in stage-2, CPV is performed as stage-3 validation during commercial manufacturing. CPV ensures that the process continues to remain within a validated state. CPV requires the collection and analysis of data related to critical quality attributes, critical material attributes, and critical process parameters on a minimum basis. Data is then used to elucidate process control regarding the capability to meet predefined specifications and stability via statistical process control tools. In statistical process control, control charts and Nelson rules are commonly used throughout the industry to monitor and trend data to ensure that a process remains in control. In the control chart, the mean value is taken as the center line, and 3σ limits are placed on either side of the center line. In CPV, manufactured lots are summarized, trended, and discussed at a cross-functional level at pre-defined intervals (either weekly, bi-weekly, or even monthly) based on the batch run rate. A cross-functional team assesses details regarding 1) violation frequency, 2) statistical strength of the signal, 3) violation magnitude and its impact on process or quality, and 4) any potential root causes for out-of-expectation or out-of-trend signals. The cross-functional team must analyze whether any signal identified by the control chart is reliable and must determine whether corrective action should be taken and justify the decision in the CPV meeting minutes based on statistical strength and reliability of the signal. However, basic control charts are susceptible to false alarms and nuisance alarms. Therefore, it is imperative to understand the assumptions behind control charts and the inherent false alarm rates for different Nelson rules. In this article, the authors have detailed the assumptions behind the usage of control charts, the rate of false alarms for different Nelson rules, the impact of skewness and kurtosis of a data distribution on the false alarm rate, and methods for optimizing control chart design by reducing false alarm rates and nuisance signals.

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

The real long-term influences of in utero drug exposure in pregnant women on childhood development have yet to be fully determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining therapeutic drug levels in maternal blood. Most antibody therapies used in patients with Inflammatory Bowel Disease (IBD) are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here we propose an up to date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the blood cord, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the second and third trimesters, leading to increasing maternal IFX concentrations. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance regarding the safety profile of anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable but very low and therefore it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. It is currently not recommended in patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact for making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the blood cord, the infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data currently available.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

The increasing regulatory pressure to monitor and reduce GHG emissions and air pollutants requires cost-effective methods for their surveillance. The most common technique used for scientific investigations on gas concentration monitoring in barns are accurate but expensive and with a complex maintenance. This research study analysed the potential use of a low-cost portable measurement devices for the measurement of ammonia (NH3) and carbon dioxide (CO2) concentrations in an open dairy barn. A comparison between gas concentrations acquired at different heights from the floor by using portable devices and those acquired by a photoacoustic infrared multigas spectroscope (i.e., reference measurement) in the same sampling locations was carried out to determine the precision of the low-cost portable devices. The performance of low-cost portable devices was statistically analysed by the application of the one-way analysis of variance, correlation analysis and regression analysis. The results showed a significant difference between gas concentration values at various heights from the floor for both NH3 and CO2. The correlations between concentrations acquired by the low-cost portable device and the INNOVA were statistically significant (r=0.83; P&lt;0.001) for gas concentrations monitored at 0.4 m from the floor. Compared with the reference measurement device, the low-cost devices were effective in the monitoring of NH3 concentrations at 0.40 m from the floor though it underestimated them in the barn at increasing of the height from the floor, whereas the device was not adequate for CO2 concentrations. In detail, the relative measurement error of the low-cost devices compared to INNOVA was reduced close to the floor during NH3 concentration measurements. Within these limitations, this device could be useful for monitoring NH3 concentration in the barn and to assess variation in NH3 concentrations mainly related to the animal occupied zone. Further efforts are needed in this field of research to identify low-cost device that could simplify emission estimation from open dairy barns.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Background and Objectives: Cancer as the second leading cause of death in the United States poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care regarding access to an important monoclonal antibody, ramucirumab. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us Database were collected for this study. The Chi-square test of proportions was employed to determine the significance of patient cohort characteristics and ramucirumab usage between Purchased and Medicaid insurance groups. The independent t-test was utilized to assess the influences of other determinants on insurance types. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. Analysis of survey questions demonstrated the relationship between income and education level with insurance type as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower cost medications. In addition, those with Medicaid insurance were identified to have poorer access to expensive therapeutics like ramucirumab compared to those with Purchased insurance.  Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and therapeutics are highly varied and dependent on insurance types. Socioeconomic status determines insurance type, which unfortunately generates a significant impact on cancer treatment and disease outcome.

Shared public buildings have become centers of innovation, integrating advanced technologies to meet evolving societal needs. With a heightened emphasis on occupants’ health and well-being, these buildings serve as hubs for technological convergence, facilitating seamless connectivity and intelligent data analysis and management. Within this context, environmental monitoring emerges as a foundational element, pivotal to all aspects of building management. This article provides findings from the nationally funded RE-START project, which focuses on shared public buildings, with special regard to educational and medical facilities. The project explores enhanced indoor air quality monitoring, focusing in particular on CO2 concentration that is directly correlated with occupancy, as a fundamental element for developing health and safety protocols, energy efficiency strategies, integration of smart building technologies, and data-driven energy management. The intersection of environmental monitoring, energy efficiency, security, and IoT technologies in in indoor spaces are relevant. The outcomes of the study reveal the delicate nature of all the involved components, that need to be carefully developed in an integrated manner.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

Solid tumors universally possess the ability to evade contact inhibition of proliferation (CIP), a mechanism halting cell proliferation when cell-cell contacts occur. Merlin, an ERM-like protein, crucially regulates CIP and is frequently deactivated in various cancers, indicating its signifi-cance as a tumor suppressor in cancer biology. Despite extensive investigations into Merlin's role in cancer, its lack of intrinsic catalytic activity and frequent conformation changes has made it notoriously challenging to study. To address this challenge, we harnessed innovative luciferase technologies to create and validate a split-luciferase biosensor system. This system enables precise quantification of Merlin's conformation and activity both in vitro and within living cells. This biosensor significantly enhances the study of Merlin's molecular functions, serving as a potent tool to explore its contributions to CIP and tumorigenesis.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Persistent land subsidence or uplift can cause serious latent hazards to urban infrastructure. To thoroughly investigate the causes and impacts of land surface deformation, this study examines the case of Wuxi City, focusing on the land fluctuation patterns in the region following the enforcement of the groundwater abstraction prohibition policy in 2005. This research utilizes the PS-InSAR technique to quantify land surface deformations in the Wuxi region from November 2015 to June 2023 and analyzes 100 SAR images to obtain comprehensive spatiotemporal evolution data of the land surface. Furthermore, this study conducts an in-depth analysis of the effects of various factors, including groundwater, precipitation, and soil geology, on the characteristics of land surface deformation. It pioneers the application of the GARCH (Generalized Autoregressive Conditional Heteroskedasticity) model to analyze the time-series displacement in the study area and innovatively introduces the "amplitude factor" index to assess land surface fluctuations. This study investigates the recent land surface deformation patterns and mechanisms in Wuxi City. By integrating the "amplitude factor", it provides a scientific foundation for future urban development and disaster mitigation strategies in Wuxi City, offering valuable insights for related research.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

The European Union Water Framework Directive (2000/60/EC; WFD) aims to achieve a good ecological and chemical status of all bodies of surface water by 2027. The development of an integrated guidance on surface water chemical monitoring (e.g. WFD Guidance Document No. 7/19) has been transferred into national German law (Ordinance for the Protection of Surface Waters, OGewV). For the majority of compounds, this act requires a monthly sampling frequency to assess the chemical water quality status of a surface water body. To evaluate the representativeness of the sampling strategy under the OGewV, high-frequency online monitoring data is investigated under different sampling scenarios and compared with current, monthly grab sampling strategy. About 23 million data points were analyzed for this study, three chemical parameters (dissolved oxygen, nitrate-nitrogen, chloride concentration) and discharge data were selected from four catchment of different sizes ranging from 51391 km² to 84 km² (Elbe, Vereinigte Mulde, Neiße and two stations at Lockwitzbach). In this paper we proposed short-term online-monitoring (STOM) as a sampling alternative. STOM considers the placement of online sensors over a limited duration and return interval. In general we: (I) compare the results of conventional grab sampling with STOM, (II) investigate the different performance of STOM and grab sampling using discharge data as proxy for analyzing event-mobilized pollutants and (III) investigate the related uncertainties and costs of both sampling methods. Results show, that STOM outperforms grab sampling for parameters where minimum/maximum concentrations are required by law as the probability to catch a single extreme value is higher with STOM. Furthermore, parameters showing a pronounced diurnal pattern, like dissolved oxygen, are also captured considerably better. The performance of STOM showed no substantial improvements for parameters with small concentration variability, as nitrogen-nitrate The analysis of discharge events as a proxy parameter for event-mobilized pollutants proved that the probability of capturing samples during events is significantly increased by STOM.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p&lt;0.001), with a shorter time between transplant and CMV (&lt;61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratifcation of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies and thereby the treatment will be more personalized and efficient. Phase I clinical evaluation of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, demonstrated that their injections are safe, well-tolerated and cause low level of absorbed and equivalent doses. The goal of this preclinical study was to select the best probe for patients’ stratification and for response monitoring. Biodis-tribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 ex-pression and MDA-MB-468 xenografts with very low expression. Changes in accumulation of both probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable to sense the decrease of HER2 expression on re-sponse to trastuzumab therapy only 24 h after injection of loading dose. This indicates that this tracer would be better for monitoring early response to such treatment. Results of this study should be considered in planning of further clinical development of HER2 imaging probes.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Spodoptera frugiperda (J.E. Smith) is a global agricultural pest that poses a threat to crop production, characterized by its refractory polyphagous nature that makes it difficult to control and may lead to damage to woody plants. However, research on its adaptability to woody plants remains limited. This study compares the feeding adaptations (survival rate, pupation time, pupation rate, weight, length, and feeding volume), protective enzyme activities, and feeding preferences of S. frugiperda on leaves of six economically significant tree species (Areca catechu, Aquilaria sinensis, Cocos nucifera, Camellia oleifera, Dalbergia odorifera and Hevea brasiliensis) and maize as a control treatment. The results indicate that A. sinensis as the most vulnerable trees in high risk, H. brasiliensis and C. nucifera presented varying degrees of susceptibility, A. catechu, C. oleifera, and D. odorifera were unsuitability for S. frugiperda. In conclusion, this report extensively explores the feeding effects of S. frugiperda on six economically important tree species, and provides insights into the feeding preferences on these plants, thereby informing the potential threat posed by S. frugiperda to economically vital trees.

In order to investigate the size distributions and seasonal variations of carbonaceous aerosols (OC and EC), the carbonaceous species were collected and then analyzed by using a 9-stage Anderson-type aerosol sampler and DRI Model 2001A Thermal/Optical Carbon Analyzer on the typical industrial city Nanjing in Yangtze River Delta, China in the summer, autumn and winter of 2013 and spring of 2014. OC, EC, SOC and POC exhibited obvious seasonal variations, with the highest level in winter (39.1±14.0, 5.7±2.1, 23.6±11.7 and 14.1±5.7 μg•m^-3) and the lowest level in summer (20.6±6.7, 3.3±2.0, 12.2±3.8 and 8.4±4.1 μg•m^-3), and were mainly centralized in PM_1.1 in four seasons. The concentrations of OC in PM_1.1 varied in the order of winter > autumn > spring > summer, while EC ranked in the order of autumn > winter > summer > spring. In the PM_1.1-2.1 and PM_2.1-10, the concentrations of OC and EC decreased in the sequence of winter > spring > autumn > summer. The size spectra of OC, EC and SOC had bimodal distributions in four seasons, except for EC with four peaks in summer. The size spectra of POC varied greatly with seasons, exhibiting bimodal distribution in winter, trimodal distribution in spring and summer, and four peaks in autumn. The OC/EC ratios were 7.0, 6.3, 7.6 and 6.9 in spring, summer, autumn and winter, respectively, which demonstrated the abundance of secondary organic aerosols in Nanjing. The sources of carbonaceous aerosol varied significantly with seasons, and were dominated by vehicle exhaust, coal and biomass burning in PM_2.1, and dominant by dust, coal and biomass burning in PM_2.1-10.

This paper presents a study about the integration of Piezoelectric Energy Harvesting Systems (PE-EHS) in building envelopes for powering Fiber Bragg Grating (FBG) sensors, enabling efficient and low-consumption monitoring with the objective to leverage Structural Health Monitoring (SHM). The research includes preliminary tests conducted in a real environment to validate the PE-EHS when fully integrated into the façade, capturing mechanical vibrations generated mainly by wind loads. Based on these activities, the final configuration of PE-EHS is defined to provide a complete system for façade monitoring. This integrated system includes the Piezoelectric Generator (PEG), Supercapacitor (SC), Power Conditioner Circuit (PCC), Fibre Optic Sensing (FOS) Interrogator, and the IoT Gateway trans-mitting measurement data within an Internet of Things (IoT) monitoring platform. This configuration is tailored to address the challenges related to the structural integrity of building envelopes. Results demonstrate a potential for a stand-alone solution in the façade sector, but, raising issues for certain limitations, requiring further investigation. In particular, the study emphasizes constraints related to the energy production of PE-EHS for façade integration. It highlights the necessity to carefully consider these limitations within the broader context of their applicability, providing insights for the informed deployment of Piezoelectric Energy Harvesting technology in building envelope monitoring.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stay and amputation. We suggest a remote-monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, wound characteristics, and clinical parameters, such as cognitive function, were integrated, contributing to a comprehensive risk factor profile. We evaluated the feasibility of this platform with 124 DFU patients over 12 weeks; 39% experienced unfavorable outcomes such as dropout, adverse events, or non-healing. Digital biomarkers were benchmarked (0-10), categorized into low, medium, and high risk for unfavorable outcomes, and visually represented using color-coded radar plots. The initial results of case reports illustrate the value of this holistic visualization to pinpoint the underlying risk factors for unfavorable outcomes, including a high number of steps, poor adherence, and cognitive impairment. Although future studies are needed to validate the effectiveness of this visualization in personalizing care and improving wound outcomes, early results in identifying risk factors for unfavorable outcomes are promising.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Direct and indirect effects after mine operations cease must ideally be subject to perpetual monitoring routines in order to detect possible risks or avoid adverse effects on the surrounding ecosystems at an early stage. In this contribution, mining subsidence lakes created inside the nature reserve Kirchheller Heide and Hilsfeld Forest are subjected to analysis for a long-term monitoring scheme. For this purpose, we employ high-resolution unmanned aerial system (UAS)-based multispectral and thermal mapping tools to provide a fast, non-invasive and multitemporal environmental monitoring method. Specifically, we propose to monitor vegetation evolution through multispectral analysis, biotypes identification using machine learning algorithms, and water surface extent detection, together with their thermal behavior. The aim of this contribution is to present the proposed workflow and first results to establish a baseline for future analyses and subsequent surveys for longterm multi-temporal monitoring

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which ranges from 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. Improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p&lt;0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Malawi has developed an excellent, nation-wide system for monitoring people infected with HIV and keeping track of key epidemic markers. Their success lies in two things: the focus on simplicity and the use of data collection not only to track the epidemic and identify problems but also to give regular feedback and support to every clinic in the country. This achievement is the more remarkable given that Malawi is one of the poorest countries in the world, ranking 190 out of 194 countries by GDP, but has one of the most severe epidemics of HIV in the world, ranking 9th out of 168 countries by HIV prevalence. We first discuss the current state and likely future epidemic trends in Malawi: unless we know where we are and where we are going we cannot decide what to do or how to do it to in order to achieve a better outcome. We then discuss the history and development of Malawi’s patient monitoring system, as reported in their Integrated HIV Program Reports,ix which have been published quarterly since the beginning of 2004. We consider the current state of patient monitoring and support as reflected in the most recent report for the third quarter (Q3) of 2016 and comment on some of the questions that this raises. Finally, we consider ways in which the current system could be improved by strengthening Malawi’s analytical capacity and making better use of this unique data set. The focus here is on HIV in adultsv because if ART is initiated early in all adults living with HIV this should include testing all pregnant women for HIV and starting them on treatment immediately. However, PMTCT is especially important and care must be given to reducing MTCT and identifying the long-term child survivors of mother-to-child transmission and this demands a complementary assessment. There is an ongoing debate about the relative merits of treatment and prevention in reducing transmission and it should be made clear that the primary reason for starting people on treatment early is that it is in the best interest of the individual patient to start treatment as soon as possible after becoming infected. Allowing a person’s immune system to deteriorate to any degree is not consistent with the clinician’s commitment to ‘first do no harm’ and even those with the highest CD4⁺ cell count are at a substantially increased risk of death. What matters, therefore, is to get as many people as possible onto ART, ensure that they remain virally suppressed, and consider prevention in this context.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

Alzheimer’s Disease (AD) is a neurodegenerative condition that currently has no known cure. The principles of the expanding field of network medicine (NM) have recently been applied to AD research. The main principle of NM proposes that diseases are much more complicated than one mutation in one gene, and incorporate different genes, connections between genes, and pathways that may include multiple diseases to create full scale disease networks. AD research findings as a result of the application of NM principles have suggested that functional network connectivity, myelination, myeloid cells, and genes and pathways may play an integral role in AD progression, and may be integral to the search for a cure. Different aspects of the AD pathology could be potential targets for drug therapy to slow down or stop the disease from advancing, but more research is needed to reach definitive conclusions. Additionally, the holistic approaches of network pharmacology in traditional Chinese medicine (TCM) research may be viable options for the AD treatment, and may lead to an effective cure for AD in the future.

The availability of current land cover and land use (LCLU) information for monitoring the status of land resources has considerable value in ensuring sustainable land use planning. Similarly, the need to provide updated information on the extent of LCLU change in West Africa has become apparent, given the increasing demand for land resources driven by the rapid population growth in the sub-region. SERVIR West Africa, a regional consortium jointly supported by USAID and NASA to foster the use of geospatial and earth observation data and science for decision-making on critical environmental and food security challenges, in collaboration with the Food and Agriculture Organization of the United Nations (FAO), is building technical capacity in the sub-region to develop and implement harmonized regional land cover classification system for LULC change monitoring in West Africa, based on the Land Cover Meta Language (LCML-ISO 19144-2). This article focuses on the process, potential opportunities, outputs of this collaboration, exemplary use cases, and recommendations for the next steps.

Fetuses of pregnant women affected by anti-Ro/anti La antibodies are at risk to develop complete atrioventricular heart block (CAVB) and other potentially life-threatening cardiac affections. CAVB can develop in less than 24 hours. Treatment with anti-inflammatory drugs and immuno-globulins (IVIG) can restore normal rhythm if applied in the transition period. Routine weekly echocardiography as often recommended will seldomly detect emergent AVB. Surveillance of these pregnancies is controversial. To obtain an overview of the current practice in Germany we have developed a web-based survey sent by the DEGUM (German Society of Ultrasound in Med-icine) to ultrasound specialists. Home-monitoring by hand-held Doppler is a promising new approach. With the intention to evaluate practicability, we instructed pregnant women at risk to use hand-held Doppler in the vulnerable period between 18-26 weeks at our university center.

For the treatment of cancer and other diseases, therapeutic targeting of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) is an attractive approach. RNA-based therapeutics have been extensively researched over the past decade, with antisense oligonucleotides and small interfering RNAs being the most commonly used. Some of these have even gained FDA approval. However, the results of trials have been mixed, with some studies reporting strong effects while others have shown limited effectiveness or toxicity. Alternative treatments, such as antimiRNAs, are currently in clinical trials. There is growing interest in the use of lncRNA-based therapies. This Perspective discusses the main challenges of ncRNA therapeutics, including specificity, delivery and tolerability. It also highlights emerging approaches that aim to improve their success.

Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.

Human populations and natural ecosystems are bound to be exposed to ionizing radiation1from the deposition of artificial radionuclides resulting from nuclear accidents, nuclear devices2or radiological dispersive devices ("dirty bombs"). On the other hand, NORM industries such as3phosphate production or uranium mining, contribute to the on site storage of residuals with enhanced4concentrations of natural radionuclides. Therefore, in the context of the European agreements5concerning nuclear energy, namely the EURATOM (European Atomic Energy Community) Treaty,6monitoring is an essential feature of the environmental radiological surveillance. In this work, we7obtain 3D maps from outdoor scenarios, and complete such maps with measured radiation levels8and with its radionuclide signature. In such scenarios, we face challenges such as unknown and9rough terrain, limited number of sampled locations and the need for different sensors and therefore10different tasks. We propose a radiological solution for scouting, monitoring and inspecting an area of11interest, using a fleet of drones and a controlling ground station. First, we scout an area with a LiDAR12onboard a drone to accurately 3D-map the area. Then, we monitor that area with a Geiger-Muller13sensor at a low-vertical distance from the ground to produce a radiological (heat)map that is overlaid14on the 3D map of the scenario. Next, we identify the hotspots of radiation, and inspect them in detail15using a drone by landing on them, to reveal its radionuclide signature using a CZT sensor. We present16the algorithms used to implement such tasks both at the ground station and on the drones. The three17mission phases were validated using actual experiments in three different outdoor scenarios. We18conclude that drones can not only perform the mission efficiently, but in general they are faster and19as reliable as personnel on the ground

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These include renal cancer, prostate and bladder cancers, acute leukemias, hepatocellular carcinoma, breast cancer and melanoma. The antigen plays an espe-cially significant role in renal cell carcinoma. Its high expression serves as a good prognostic marker for patients and high hopes are related to its use in the immunotherapy of the tumor. The biological role of CD15 is the interaction with E-, L- and P-selectins (adhesion molecules) and al-lowing for the adhesion with the endothelial cells. In this way, cancer cells start to interact with the endothelium of blood vessels and consequently move out from the blood flow to the sur-rounding tissues. The blockage of antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibod-ies-based therapies. CD15s is a sialyl derivative of CD15, that possess its own unique characteris-tics. Unlike high expression of CD15, which is a prognostic factor in Hodgkin lymphoma, CD15s relate to poor prognosis for the patients. Due to the high abundance in cancer cells, CD15 is con-sidered as a marker of Cancer Stem Cells. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews the clinical appli-cations of the anti-CD15 therapy.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

Without the use of medicine drones, users are responsible for transporting goods at a high cost. The goal of this patient monitoring system is to identify people's health and, if necessary, administer medicine. The transportation drone is capable of finding healthcare information in a 360-degree rotation within the transportation infrastructure. IoT: Drone doctors are critical for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines in the critical conditions of a heart patient, in the event of failure of traffic location infrastructure, highway roads, or hospitals due to intense climate or site visitor congestion, and for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines. When transmission is difficult, the self-maintaining drone is the format for quickly transporting drug treatments to the appropriate locations. The shipping drone equipped with an Ardupilot can drive in autopilot mode, which guides the drone to its destination. It has a 7-minute flying period and can deliver up to 2 kg of medicine. When the detected heartbeat is 94bpm and the fever range is 101 degrees, a method has been presented in which an IoT Drone Doctor (IDD) System distributes the first AID box to vulnerable patients and heart patients.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

The latest scientific literature outlines a resilient interconnection between cancer modulation and dietary polyphenols by sphingolipid-mediated mechanisms, usually correlated with a modification of their metabolism. We aim to extensively survey this relation to show how it could be advantageous in cancer treatment or prevention by nutrients. Polyphenols, chemically characterized by polyhydroxylated phenolic structure, are well known for their pervasive pharmacological properties: anti-inflammatory, antibiotic, antiseptic, antitumor, antiallergic, cardioprotective and others. Pervasive is also their distribution in food products especially in plant foods as vegetables, cereals, legumes, fruits, nuts and beverages as wine, cider, beer, tea, cocoa. Recently, sphingolipids have been correlated with cancer by a dysregulation of their rheostat emerging as mediator of cell proliferation in cancer and modulator of chemotherapeutics.

In this study, we evaluated the physicochemical and microbial qualities of source and stored household waters in some communities in Southwestern Nigeria using standard methods. Compared parameters include physicochemical constituents; Temperature (T), pH, Total Dissolved Solids (TDS), Total Hardness (TH), Biological Oxygen Demand (BOD), Magnesium ion (Mg²⁺) and Calcium ion (Ca²⁺) and microbiological parameters included Total Coliform Counts (TC), Faecal Coliform Counts (FC), Fungal Counts (Fung C), Heterotrophic Plate Counts (HPC). Comparing Stored and Source samples, the mean values of some physicochemical parameters of most of the stored water samples significantly (P<0.05) exceeded that of Sources and ranged in the following order: T (15.3±0.3^oC - 28.3±0.5^oC), pH (6.4±0.1 - 7.6±0.1), TDS (192.1±11.1 ppm - 473.7±27.9 ppm), TH (10.6±1.7 mg/L - 248.6±18.6 mg/L), BOD (0.5±0.0 mg/L - 3.2±0.3 mg/L), Mg²⁺ (6.5±2.4 mg/L - 29.1±3.2 mg/L) and Ca²⁺ (6.5±2.4 mg/L - 51.6±4.4 mg/L). The mean microbial counts obtained from microbial comparison of different points (Stored and Source) of collection showed that most of the stored water had counts significantly exceeding (P<0.05) those of the source water samples (cfu/100 mL) which ranged as follows: TC (3.1±1.5 - 156.8±42.9), FC (0.0±0.0 - 64.3±14.2) and HPC (47.8±12.1 - 266.1±12.2) across all sampled communities. Also, the predominant isolates recovered from the samples were identified as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterobacter aerogenes, Aspergillus spp, Mucor spp, Rhizopus spp and Candida spp. The presence of these pathogenic and potentially pathogenic organisms in the waters and the high counts of the indicator organisms suggest the waters to be a threat to public health.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

Wetlands are recognized as one of the world’s most valuable natural resources. With the increasing world population, human demands on wetland resources for agricultural expansion and urban development continue to increase. In addition, global climate change has pronounced impacts on wetland ecosystems through alterations in hydrological regimes. To better manage and conserve wetland resources, we need to know the distribution and extent of wetlands and monitor their dynamic changes. Wetland maps and inventories can provide crucial information for wetland conservation, restoration, and management. Geographic Information System (GIS) and remote sensing technologies have proven to be useful for mapping and monitoring wetland resources. Recent advances in geospatial technologies have greatly increased the availability of remotely sensed imagery with better and finer spatial, temporal, and spectral resolution. This chapter presents an introduction to the uses of GIS and remote sensing technologies for wetland mapping and monitoring. A case study is presented to demonstrate the use of high-resolution light detection and ranging (LiDAR) data and aerial photographs for mapping prairie potholes and surface hydrologic flow pathways.

There is a growing body of evidence supporting the significant role of bacterial biofilms in the pathogenesis of various human diseases including cancer. Biofilms are polymicrobial communities enclosed within an extracellular matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This complex matrix provides protection against antibiotics and host immune responses, enabling the microorganisms to establish persistent infections. Moreover, biofilms induce anti-inflammatory responses and metabolic changes in the host, further facilitating their survival. Many of these changes are comparable to those observed in cancer cells. This review will cover recent research on the role of bacterial biofilms in carcinogenesis, especially in colorectal (CRC) and gastric cancers, emphasizing the shared physical and chemical characteristics of biofilms and cancer. This review will also discuss the interactions between bacteria and the tumor microenvironment, which can facilitate oncogene expression and cancer progression. This information will provide insight into developing new therapies to identify and treat biofilm-associated cancers, such as utilizing bacteria as delivery vectors, using bacteria to upregulate immune function, or more selectively targeting biofilms and cancer for their shared traits.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particular vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a hard outcome to be targeted, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD however, the optimal intensity of such therapy is still topic of debate, particularly in the post-acute and long-term setting. Recent well powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and patients selection is a key issue. The aim of this review is therefore to discuss and summarize the most updated available evidences for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both type of atherosclerotic disease and comparing a higher versus a lower intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improving precision medicine.

Purpose: To report the early clinical outcomes of combining intensity‐modulated radiation therapy (IMRT) and intensity‐modulated proton therapy (IMPT) in comparison with IMRT alone in treating the oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients were retrospectively reviewed, who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity‐score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow‐up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, IMRT/IMPT combination group experienced grade ≥3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p<0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p=0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p=0.021); and AQA in 47.4% and 21.1% (p=0.016), respectively. In multivariate logistic regression, grade ≥3 mucositis was significantly less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.027 and 0.024, respectively). AQA score ≥3 was also less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.