Background: This retrospective study evaluates the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. The significant differences of survival between the two groups were only observed in patients with positive EGFR expression. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

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.

Background: This retrospective study evaluate the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. We also demonstrated that EGFR-knockout Caco2 cells are more sensitive to the inhibition effect of fluoropyrimidine than the control those. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression and treatment strategies, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

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.

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)

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.

(1) Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this study is to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. (2) The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. (3) Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. 14% of the sample (23 patients) showed a prolongation of the QTc interval. 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone: in 90% of these patients, a normalization in the QTc length was established. (4) This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of a careful electrocardiographic monitoring in methadone-treated patients.

In the post-PARP inhibitor era, potential changes in tumor biology after maintenance therapy have not been well investigated in recurrent ovarian cancer. We reported a case with alterations in the clinical and histological features of multiple relapsed disease associated with PARP inhibitor maintenance therapy. The patient with high-grade serous carcinoma exhibited BRCA wildtype and homologous recombination proficiency status, and suffered from three recurrences and surgeries accordingly. Olaparib maintenance had been used during the second-line therapy. We compared the differences in clinics and pathology among three recurrences and relapsed lesions. Disease-free survivals were dramatically decreased after the exposure to olaparib. At exploration of quaternary cytoreduction, the relapsed tumor was characterized by a carcinomatosis-like metastasis pattern and an easy tendency of bleeding. Tumor cytopathological changes and alterations were observed in both the tumoral and non-tumoral stroma, among relapsed tumor tissues derived from secondary, tertiary and quaternary cytoreduction. Histopathology indicated hemorrhage, necrosis, atypical tumor cells, massive angiogenesis, and decreased CD8+ tumor-infiltrating lymphocytes, particularly in the third relapsed disease. To our knowledge, this is the first report to show a unique metastatic pattern of angiogenic burst after PARP inhibitor maintenance therapy in ovarian cancer, which seemed to trigger invasive tumor growth and immune suppression. Further prospective studies and translational research focusing cytoreductive surgery after PARP inhibitor could progressively lead to an understanding of the biological behavior and metastatic patterns.

The purpose of this Individually Randomized Group Treatment Trial was to compare an Acceptance and Commitment Therapy-based (ACT) group intervention and a Cog-nitive Behavioral Therapy-based (CBT) group intervention for weight loss maintenance in a sample of adult patients with obesity seeking treatment for weight loss. 155 over-weight adults (BMI: Kg/m2= 43.8[6.8]) attending a multidisciplinary rehabilitation program for weight loss were randomized into two conditions: ACT and CBT. Demo-graphical, physical, and clinical data were assessed at the beginning of the program (t0), at discharge (t1), and at 6-month follow-up (t2). The following measures were ad-ministered: The Acceptance and Action Questionnaire-II (AAQ-II) and the Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM). Generalized linear mixed models were performed to assess differences between groups. Moderation ef-fects for gender and eating disorders (ED) have been considered. From baseline to dis-charge no significant differences between interventions were found, with the only ex-ception of an improvement in the CORE-OM total score and in the CORE-OM subjective well-being subscale for those in the CBT condition. From discharge to follow-up ACT group participants showed significant results in terms of weight loss maintenance, CORE-OM total score, and CORE-OM and AAQ-II’s wellbeing, symptoms, and psy-chological problems subscales. Gender moderated the effects of time and intervention on the CORE-OM’ subscale reporting the risk for self-harm or harm others. The pres-ence of an eating disorder moderated the effect of time and intervention on the CORE-OM total score, on the CORE-Om’ symptoms and psychological problems sub-scales, and on the AAQ-II. Patients who received the ACT intervention were more likely to achieve a ≥5% weight loss from baseline to follow-up and to maintain the weight loss after discharge. The ACT intervention was thus effective in maintaining weight loss over time.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

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.

Patients under immunosuppressive therapy for kidney diseases or on maintenance hemodialysis are more susceptible to infection than the general population since loss of renal function per se was an immunocompromised condition. Of relevance, CT imaging plays a crucial role in the detection and management of pulmonary infectious diseases. We hence presented diverse CT findings of pulmonary infections in the above said patients collected during our arduous work against a wide range of pathogens including klebsiella pneumoniae, staphylococcus aureus, candida parapsilosis, aspergillus, cryptococcus, mucor, pneumocystis carinii, cytomegalovirus, mycobacterium and nocardia. Notably, the pulmonary pathological changes were either primary pneumonia or secondary to the catheter-associated bloodstream infection. For a descriptive purpose, pulmonary manifestations of Wegener’s granuloma, lung cancer and diffuse alveolar hemorrhage/infection in vasculitis were also examined. As such, we retrospectively elaborated most likely CT features of each individual pathogen and briefly covered the differential diagnosis as well. Arguably, combination of pattern recognition with knowledge of the clinical setting could make a presumptive diagnosis and early treatment even more convenient. From the experience of first-line nephrologists, our work could make a substantial contribution to the expeditious and efficacious management of pulmonary infections in the pertinent patient population.

Background: The front-line treatment of advanced NeuroEndocrine Neoplasms (NENs) depends on clinical and pathological factors but there are no standard second-line therapies. Methods: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with second-line metronomic temozolomide, 75 mg/m2 per os “one week on/one week off”. Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. Results: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. Eleven patients presented with PS 1 and 15 with PS 2. The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from temozolomide start was 28.3 months. PS improved in 73% of patients. Conclusions: Metronomic temozolomide is a safe and active treatment for G2 and G3 NENs. Prospective and larger trials are needed to confirm these results.

Background: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. Methods: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate for up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA group. We compared the remission maintenance rates in AZA and ADA groups for up to 5 years after TAC discontinuation. Results: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA group (n=16) exhibited a significantly higher relapse-free rate than the AZA group (n=26) (p<0.05; log-rank test). Conclusion: Switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

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.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

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.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

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.

As a consequence of applying advanced maintenance practices, the theoretical probability of failures is relatively low. However, observation of low market intelligence and maintenance management has been reported. The experimental investigation is supported by findings from a survey targeting asset-intensive companies applying hydraulic power systems. Next, the study incorporates multidimensional data analysis using CA-AHC (Correspondance Analysis with Agglomerative Hierarchical Clustering) approach. The non-parametric machine learning models are used from generated feature subspace to extract features affecting maintenance performance indicators. The results support empirical evidence that equipment age increases the probability of failures. However, the novel findings show that number of maintenance personnel, equipment size measured by nominal working energy consumption, and activities dedicated to maintaining fluid cleanliness impact regression results of companies utilising hydraulic applications.

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&gt;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.

Aggregative multicellularity occurs when dispersed cells join together to form a highly cooperative unit, in contrast to clonal multicellular organisms formed by cells that remain in contact after descent from a single cell. Because aggregative groups may include non-relatives, aggregative multicellular organisms should be particularly vulnerable to the rise of cheater cells that take advantage of social goods without paying the costs, reducing cooperation, and even threatening extinction. We review the key mechanisms by which aggregative multicellular organisms control cheaters with a focus on the best studied aggregative organisms, Myxococcus xanthus and Dictyostelium discoideum. These include various passive and active mechanisms to maintain high relatedness within aggregates, to enforce cooperation on aggregate members, and the costs of cheating on other key functions. Ultimately, aggregative multicellular organisms are not that different from clonal organisms descended from a single cell.

U.S. Navy Surface Ship depot-level maintenance periods of performance were studied to develop a method for predicting maintenance durations. The need for the method has been highlighted by Navy leadership in recent media posts describing unacceptable maintenance delays and this research provides practitioners and decisionmakers with a reliable estimating tool. This study helps by putting forth a method that defines the rate of work accomplishment based on relevant variables. Using ordinary least squares models, this research revealed that the size of the contract obligation and the amount of shipyard work occurring simultaneously in the market are key variables in determining depot maintenance durations. With the knowledge found here, the next logical step is an optimization model for each U.S. Navy surface ship homeport.

Using data-driven models to solve predictive maintenance problems has been prevalent for original equipment manufacturers (OEMs). However, such models fail to solve two tasks that OEMs are interested in: (1) Making the well-built failure prediction models working on existing scenarios (vehicles, working conditions) adaptive to target scenarios. (2) Finding out the failure causes, furthermore, determining whether a model generates failure predictions based on reasonable causes. This paper investigates a comprehensive architecture towards making the predictive maintenance system adaptive and interpretable by proposing (1) an ensemble model dealing with time-series data consisting of a long short-term memory (LSTM) neural network and Gaussian threshold to achieve failure prediction one week in advance and (2) an online transfer learning algorithm and a meta learning algorithm, which render existing models adaptive to new vehicles with limited data volumes. (3) Furthermore, the Local Interpretable Model-agnostic Explanations (LIME) interpretation tool and super-feature methods are applied to interpret individual and general failure causes. Vehicle data from Isuzu Motors, Ltd., are adopted to validate our method, which include time-series data and histogram data. The proposed ensemble model yields predictions with 100% accuracy for our test data on engine stalling problem and is more rapidly adaptive to new vehicles with smaller error following application of either online transfer learning or the meta learning method. The interpretation methods help elucidate the global and individual failure causes, confirming the model credibility.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

In this study, we present case studies to explore the dynamics of implementation and maintenance of health interventions. We analyze how specific interventions are built and eroded, how the building and erosion mechanisms are interconnected, and why we can see significantly different erosion rates across otherwise similar organizations. We use multiple comparative obesity prevention case studies to provide empirical information on the mechanisms of interest, and use qualitative systems modeling to integrate our evolving understanding into an internally consistent and transparent theory of the phenomenon. Our preliminary results identify reinforcing feedback mechanisms, including design of organizational processes, motivation of stakeholders, and communication among stakeholders, which influence implementation and maintenance of intervention components. Over time, these feedback mechanisms may drive a wedge between otherwise similar organizations, leading to distinct configurations of implementation and maintenance processes.

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.

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 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.

As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.

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.

Background and Aim: Tacrolimus is highly effective in intractable ulcerative colitis, but maintenance may be problematic. This study examined 52-week maintenance and adverse events. Methods: This retrospective study of patients who used tacrolimus from April 2009 to December 2021 (N = 136) examined remission induction rates and background factors in the remission (n = 108) and non-remission groups (n = 28); 52-week maintenance; drug-specific maintenance (azathioprine [n = 58] vs tacrolimus [n = 12] and vs biological product [Bio, n = 8]); and adverse events. Results: The mean observation period was 1230175 days. Remission occurred in 72.7%. Significant differences were observed in sex and endoscopic score (before treatment and 2 weeks after tacrolimus trough levels). Maintenance rate at 52 weeks was 61.6%; significant differences were observed in sex, hospitalization duration, and prednisolone during hospitalization (P < 0.05). Drug-specific 52-week maintenance was 67% with azathioprine, 54% with tacrolimus, and 37% with Bio. No tacrolimus-related serious adverse events occurred that led to discontinuation. Discussion: Remission was more common in women with improved endoscopic scores after tacrolimus trough levels and patients with improved endoscopic scores after tacrolimus therapy. Remission maintenance was more common in women with a long hospitalization at remission and high total steroid dose. Results suggest that treatment with adequate prednisolone use during the period with more inflammation may improve subsequent maintenance. Conclusions: In intractable ulcerative colitis, tacrolimus can induce remission even in patients who cannot use azathioprine for maintenance. Remission can be maintained with azathioprine, tacrolimus, or a Bio.

The good management of the building maintenance should be based on the regular maintenance work. Repair works are often not carried out or there are shifts in time, which causes degradation of the building. The article presents a method of planning renovation works of a MUBAR (maintenance Management in an Un-renovated Building with Abandoning Renovation) based on the consequences in case of their lack. No renovation work on individual elements in a building can cause a threat to the stability of the building structure, risking the lives of users, continuing damage to the building by damaging further elements, or even a building disaster. The method can also be applied to historic buildings. Often, due to abandonment of repairs caused most often by lack of the owner, improper manager or irresponsible users, degradation of these objects occurs. The consequences of neglected renovation of buildings lead to irreversible processes of their destruction. The aim of the article is to present the developed method of planning renovation works based on the consequences of lack of renovation works.

Neurodegenerative diseases are universally marked by the accumulation of misfolded protein. Neurons respond to these proteostatic disturbances by sequestering, and thus inactivating, toxic misfolded proteins into a perinuclear organelle called the aggresome. The aggresome can be subsequently degraded in bulk by autophagy, a process termed aggrephagy. The formation of protein aggregates has historically been considered a spontaneous and unregulated process, but emerging research has instead discovered a diverse cohort of regulatory proteins that mediate protein aggregation. Chaperones are the first proteins to respond to misfolded proteins, and do so by recognizing the aberrant exposure of hydrophobic domains. When chaperones are unable to correctly refold proteins, their substrates are transferred to ubiquitin ligating machinery to catalyze polyubiquitination. Although ubiquitin chains typically direct proteins towards proteasomes, severe proteotoxic stress can overwhelm, or even directly inhibit, proteasomes. As an alternative to proteasomal degradation, misfolded proteins are redirected towards the mitotic organizing center (MTOC) and, following retrograde transport by dynein, are packaged and sequestered within an intermediate filament (IF) cage to form the aggresome. The biogenesis of the aggresome is thus a highly regulated event, and a better understanding of the mechanisms facilitating this process will provide critical insight into neurodegenerative disease.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Burnout is common in many countries and is associated with several other problems, such as depression, anxiety, insomnia and memory deficits, and prospectively it predicts long-term sick-leave, cardiovascular disease and death. Clinical burnout or its residual symptoms often last several years and a common assumption is that recovery takes a long time by nature despite full time sick-leave and absence of work stress. Literature suggests models that hypothetically explain the development, but not maintenance, of the syndrome. Based on cognitive and behavioral principles and stress theory this paper describes a theoretical model explaining how clinical burnout can develop and be maintained. While the development of clinical burnout is mainly explained by prolonged stress reactions and disturbed recovery processes due to work related stressors, maintenance of the syndrome is particularly explained by prolonged stress reactions and disturbed recovery processes due to the new context of experiencing burnout and being on sick-leave. Worry about acquired memory deficits, passivity and excessive sleep, shame, fear of stress reactions, and the perception of not being safe are examples of responses that can contribute to the maintenance. The model has important implications for research and how to intervene clinical burnout.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

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.

We present 4 cases of patients diagnosed with multiple myeloma initially treated without monoclonal antibodies. It was decided to provide the benefit of the drug after maintenance with lenalidomide was initiated to consolidate the post-maintenance response followed by monitoring without any kind of treatment. In this series of 4 cases 100% of the patients achieved a strict complete response with undetectable Minimal Residual Disease (MRD) for flow cytometry after post-maintenance consolidation with daratumumab regardless of the scheme used as induction/consolidation, as well as whether they had received HSCT. Until the last follow-up the patients are under surveillance with no evidence of progression. It should be noted that 3 of 4 of these patients debuted with high-risk disease.

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.

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.

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.

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.

Background: Respiratory rehabilitation is a crucial component of cardiac recovery. This study primarily investigates the effectiveness of a novel respiratory rehabilitation technique known as Metronomic Breathing (MB) on cardiac recovery in post-PCI acute myocardial infarction (AMI) patients and compliance with home-based rehabilitation compared to traditional respiratory rehabilitation methods. Methods: From June 2022 to March 2023, 55 AMI patients admitted to the Shanghai Tenth People's Hospital Cardiovascular Department were consecutively enrolled. They were randomly divided into the MB and control groups, which underwent conventional abdominal breathing training. Afterwards, hemodynamic indicators and compliance with home-based rehabilitation were compared between the two groups. Results: After the intervention in the MB group, several cardiac functional parameters (SV, SVI, CO, CI, LCW, LCWI), myocardial contractility parameter (VI), and systemic vascular resistance parameters (SVR, SVRI) were significantly higher compared to the pre-intervention levels, with a significant difference (P < 0.05). Furthermore, post-treatment, the MB group exhibited higher values for SV, SVI, CO, CI, and VI, lower SVR, SVRI, and SBP and a lower readmission rate three months later than the control group. Moreover, the MB group displayed higher compliance with home-based cardiac rehabilitation (P < 0.05). Conclusions: Compared to conventional respiratory rehabilitation training methods, Metronomic respiratory therapy is more effective in the short term for reducing systemic vascular resistance, enhancing left ventricular ejection function, and increasing home-based rehabilitation compliance in patients following AMI with PCI.

Every firm is devoted to polishing and fine-tuning its maintenance strategy. More exactly, when we develop robust and efficient preventive and conditional maintenance approaches, our objective is to combine performance and robustness to increase maintenance decision-making. This, in turn, leads to a reduction in system failures and a subsequent drop in related expenses. This impulse drives the origin of this essay: to provide fresh criteria that allow us to improve and optimize maintenance techniques. Furthermore, our study has been realistically utilized via the deployment of condition-based maintenance (CBM) techniques, which are commonly regarded as a critical lever that allows firms to gain a competitive advantage in the context of the fourth industrial revolution. Combining both perfect and imperfect maintenance actions into CBM strategies appears to be an effective technique to obtain high economic performance and robustness in the maintenance strategies of the companies. Following this idea, we propose and optimize in this paper a set of criteria enabling the combined assessment of the mean economic performance and the resilience of various kinds of maintenance techniques. The advantage of the proposed criterion is that it adapts to different types of maintenance strategies and provides access to a simple and relevant evaluation model. Thanks to this new criterion, we will be able to choose the better maintenance strategies that have more performance and robustness between these strategies for a system with more or less stable behavior. The Monte Carlo Method is incorporated into the comparative assessment of maintenance methods, adding a layer to the evaluation of the performance and robustness of each adaptation in decision-making.

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.

Currently, software development is more associated with families of configurable software rather than the single implementation of a product. Due to the numerous possible combinations in a software product line, testing these families of software product lines (SPLs) is a difficult undertaking (SPL). Moreover, the presence of optional features makes the testing of SPLs impractical. Several features are presented in SPLs, but due to the environment's time and financial constraints, these features are rendered unfeasible. Testing subsets of configured products is thus one approach to solving this issue. In order to reduce testing effort and get better results, alternative methods of testing SPLs are required, such as the combinatorial interaction testing (CIT) technique. Unfortunately CIT method produces unscalable solutions for large size SPLs with excessive constraints. The CIT method costs more because of feature combinations. The optimization of the various conflicting testing objectives, such as reducing the cost and configuration number, have also been considered. In this article, we have proposed a search-based software engineering solution using multi-objective optimization algorithms (MOEAs). In particular, the research is applied to different types of MOEA methods; Indicator-Based Evolutionary Algorithm (IBEA), Multi-objective Evolutionary Algorithm based on Decomposition (MOEA/D), Non-Dominated Sorting Genetic Algorithm II (NSGAII), NSGAIII, and Strength Pareto Evolutionary Algorithm 2 (SPEA2). The results of the algorithms are examined in the context of distinct objectives and two quality indicators. The results revealed how feature model attributes, implementation context and the number of objectives affect the performance of the algorithms.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. Telomere length homeostasis is critical for cancer development then telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere’s dysfunction impinges on intracellular signalling pathways, in particular DNA damage signalling and repair affecting cancer cell survival and proliferation. This review summarizes and discusses about the recent findings in anti-cancer drug development targeting different “telosome” components.

Packaging of the eukaryotic DNA genome with histone and other proteins forms a chromatin structure that regulates the outcome of all DNA mediated processes. The cellular pathways that ensure genomic stability detect and repair DNA damage through mechanisms which are critically dependent upon chromatin structures established by histones and, particularly, transient histone post-translational modifications . Though subject to a range of modifications, histone methylation is especially crucial for DNA damage repair as the methylated histones often form platforms for subsequent repair protein binding at damaged sites. In this review, we highlight and discuss how histone methylation impacts the maintenance of genome integrity through effects related to DNA repair and repair pathway choice.

In the manufacturing industry, orders are typically scheduled and delivered through batches, and the probability of machine failure under high-load operation is high. On this basis, we focus on a single machine batch scheduling problem with a maintenance interval (SMBSP-MI). The studied problem is expressed by three-field representation as 1|B,MI|\sum{F_j+\mu}m, and the optimization objective is to minimize total flow time and delivery costs. Firstly, 1|B,MI|\sum{F_j+\mu}m is proved to be NP-hard by Turing reduction. Secondly, shortest processing time (SPT) order is shown the optimal scheduling of SMBSP-MI, and a dynamic programming algorithm based on SPT (DPA-SPT) with the time complexity of O(n^3T_1) is proposed. A small-scale example is designed to verify the feasibility of DPA-SPT. Finally, DPA-SPT is approximated to a fully-polynomial dynamic programming approximation algorithm based on SPT (FDPAA-SPT) by intervals partitioning technique. The proposed FDPAA-SPT runs in O(\frac{n^5}{\varepsilon^2})\ time with the approximation (1+\varepsilon).

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).

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.

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.

The rapid growth of the aviation industry has progressively heightened the importance of airport maintenance management. There is an increasing need for a comprehensive system that considers the diverse requirements of various stakeholders. Existing research has primarily focused on the technological advancements of optimization models, with limited applicability in practice. In this study, we introduce the Condition Cases Optimization (CCO) to address these limitations while incorporating multi-facility and multi-year network optimization models. We developed condition index, Serviceability Level, integrated assessment indices and performance models for decision-making criteria. We categorize conditions into three classes and propose a practical decision-making strategy that can flexibly adapt to budget constraints. Sensitivity analysis highlights the impact of initial budget, maintenance methods, costs, and thresholds on decision outcomes. Through a case study we validate the effectiveness and practicality of the CCO method as an efficient decision-making tool.

Convolutional Neural Networks combined with autonomous drones are increasingly seen as enablers of partially automating the aircraft maintenance visual inspection process. Such an innovative concept can have a significant impact on aircraft operations. Through supporting aircraft maintenance engineers detect and classify a wide range of defects, the time spent on inspection can significantly be reduced. Examples of defects that can be automatically detected include aircraft dents, paint defects, cracks and holes, and lightning strike damage. Additionally, this concept could also increase the accuracy of damage detection and reduce the number of aircraft inspection incidents related to human factors like fatigue and time pressure. In our previous work, we have applied a recent Convolutional Neural Network architecture known by MASK R-CNN to detect aircraft dents. MASK-RCNN was chosen because it enables the detection of multiple objects in an image while simultaneously generating a segmentation mask for each instance. The previously obtained F1 and F2 scores were 62.67% and 59.35% respectively. This paper extends the previous work by applying different techniques to improve and evaluate prediction performance experimentally. The approaches uses include (1) Balancing the original dataset by adding images without dents; (2) Increasing data homogeneity by focusing on wing images only; (3) Exploring the potential of three augmentation techniques in improving model performance namely flipping, rotating, and blurring; and (4) using a pre-classifier in combination with MASK R-CNN. The results show that a hybrid approache combining MASK R-CNN and augmentation techniques leads to an improved performance with an F1 score of (67.50%) and F2 score of (66.37%)

With the rapid development of global offshore wind power, the demand for offshore wind power operation and maintenance is also increasing. Wisdomization of offshore wind farms is a practical need to improve the operation level and benefit of offshore wind farms. This paper first introduces the current development situation and characteristics of global offshore wind power, and expounds the current situation and main challenges of offshore wind power operation and maintenance market. Therefore, our paper discusses the innovation of offshore wind power operation and maintenance from the aspects of operation and maintenance management of offshore wind power, monitoring and analysis technology of units, far-reaching wind field monitoring and operation and maintenance risks. Then, combined with information technology and lean management concept, a smart operation and maintenance management platform for wind farms in far-reaching sea areas is built to explore centralized and intelligent operation and maintenance management mode, improve operation and maintenance efficiency of wind farms in far-reaching sea areas, and minimize operation and maintenance costs. Finally, through the research on the characteristics of 5G technology, combined with the practical experience of operation and maintenance, and in view of the characteristics of offshore wind farms, we analyze and propose several typical application scenarios of 5G technology in the intelligent operation and maintenance of offshore wind farms, which provides a new solution for the efficient operation and maintenance of offshore wind farms.

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.

Recent technological advancements such as IoT and Big Data have granted industries extensive access to data, opening up new opportunities for integrating Artificial Intelligence (AI) across various applications to enhance production processes. We can cite two critical areas where AI can play a key role in industry such as product quality control and predictive maintenance. This paper presents a survey of AI applications in the domain of Industry 4.0, with a specific focus on product quality control and predictive maintenance. Experiments were conducted using two datasets, incorporating different machine learning and deep learning models from the literature. Furthermore, this paper provides an overview of the AI solution development approach for product quality control and predictive maintenance. This approach includes several key steps, such as data collection, data analysis, model development, model explanation, and model deployment.

This paper proposes a solution for the development of microclimate monitoring for Low Voltage / High Voltage switchgear using the PRTG Internet of Things (IoT) platform. This IoT-based real time monitoring system can enable predictive maintenance to reduce the risk of electrical station malfunctions due to unfavorable environmental conditions. The combination of humidity and dust can lead to unplanned electrical discharges along the isolators inside a low or medium voltage electric table. If no predictive measures are taken, the situation may deteriorate and lead to significant damage inside and outside the switchgear cell. Thus, the mentioned situation can lead to unprogrammed maintenance interventions that can conduct to the change of the entire affected switchgear cell. Using a low-cost and efficient system, the climate conditions inside and outside the switchgear is monitored and transmitted remotely to a monitoring center. From the results obtained using a 365-day time interval, we can conclude that the proposed system is integrated successfully in the switchgear maintaining process, having as result the reducing of maintenance costs.

Predictive maintenance (PM) algorithms are widely applied for detecting operational anomalies on industrial processes to trigger maintenance before a possible breakdown; however, much less focus has been devoted to the use of such PM predictions as feedback in automated process control mechanisms. They usually integrate preventive solutions to protect the machines, usually causing downtimes. The premise of this study is to develop a holistic adaptive process scheduling mechanism that incorporates PM analysis as a safety component to optimize the operation mode of an industrial process toward preventing breakdowns while maintaining its availability and operational state, thereby reducing downtimes. As PM is largely a data-driven approach; hence, relies on the setup, we first compare different PM approaches and identify a one-class support vector machine (OCSVM) as the best performing option for the anomaly detection on our setup. Then, we propose a novel pipeline to integrate maintenance predictions into a real-time adaptive process scheduling mechanism. It schedules for the most suitable operation, i.e., optimizing for machine health and process efficiency, according to the abnormal readings. To demonstrate the pipeline on action, we implement our approach on a small-scale conveyor belt system utilizing our Internet of Things (IoT) framework. The results show that our PM-based adaptive process control provides an efficient process with less or no downtime. We also conclude that a PM approach does not provide sufficient efficiency without its integration into an autonomous planning process.

The Italian Stone Pine (Pinus pinea L.) is one of the most employed ornamental trees in towns with Mediterranean climates. For example, in the city of Rome, Pinus is the most common genus, with more than 51,000 trees. This study investigates technical and economic features of maintenance operations of Stone Pines and evaluates the productivity and costs of the observed yards. Pruning and felling are the most frequent management operations of trees in towns and this study analyzes the features of these operations carried out in 14 work sites. The operations were carried out either with aerial platforms (19 trees) or ascending the crown by tree-climbing (6 trees). The operations were sampled with time studies (12 trees for pruning and 13 for felling). Work time was measured from the beginning of operations to the transport of the residual biomass to the collection and loading point, using centesimal stopwatches and video recording. The total residual biomass was weighed or assessed. Total observation time amounted to 63.1 hours. The evaluation of the costs of each work site considered the fixed and the variable costs and the costs for the labor force. A Multiple Linear Regression model (statistics: determination coefficient R2: 0.74, adjusted R2: 0.67, p-value < 0.001) which utilizes four regressors easily evaluable before the work, was adopted to predict the gross time of the operations. This paper can contribute to optimize trees maintenance methods in urban sites and to assess the potential residual wood biomass attainable from urban forestry maintenance in the city of Rome.

As construction costs continue to rise and adequate amounts of funding continues to be a challenge, the allocation of resources is of critical importance when it comes to the maintenance and rehabilitation (M&R) of highway infrastructure. A Life Cycle Assessment (LCA) methodology is presented here that integrates realistic traffic conditions in the operational phase to compare M&R scenarios over the analysis period of a 26-km stretch of Interstate-495. Pavement International Roughness Index (IRI) were determined using AASHTO’s PavementME System. Meanwhile, vehicle fuel consumption and emission factors were calculated using a combination of Google Maps®, the U.S. EPA’s Motor Vehicle Emission Simulator, the SHRP2 Naturalistic Driving Study, and MassDOT’s Transportation Data Management System. The evaluation of pavement performance with realistic traffic conditions, varying M&R strategies and material characteristics was quantified in terms of Life Cycle Cost (LCC), Global Warming Potential (GWP) and Cumulative Energy Demand (CED) for both agencies and users. The inclusion of realistic traffic conditions into the use phase of the LCA resulted in a 6.4% increase in CED and GWP when compared to baseline conditions simulated for a week long operation duration. Results from this study show that optimization of M&R type, material selection and timing may lead to a 2.72% decrease in operations cost and 47.6% decrease in construction/maintenance costs.

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)’.

The present work provides continuity with studies where currently the industrial market is characterized by a highly variable demand in terms of quantities and flexibility of manufacturing or mass customization, which translates into a more demanding production context in terms of the continuous changes required to the production systems, the effect of which results in an increase in the fatigue subjected to the machines that make up the production systems. On the other hand, current production systems tend to use highly communicative and sensorized cyber-physical systems; these characteristics can be used to integrate them into decision-assisted systems in order to improve the availability of the industrial plant. The assisted system developed focuses on collecting and taking advantage of historical knowledge of industrial plant failures and breakdowns. By ideally integrating the Reliability Centered Maintenance (RCM) methodology and Case-Based Reasoning (CBR) algorithms implemented in a Java application, it is possible to design maintenance plans adjusted to a real and changing operational context of any industrial plant. As a result, faster and more accurate decisions are made, as they are based on data. This article focuses on improving certain aspects of the developed assisted system by adding more value to it by incorporating Fuzzy Logic (FL) techniques. The aim is to improve the way of entering information about risk factors and their relative importance, by incorporating natural language, instead of a numerical score, resulting in increased precision in the calculation of the Risk Priority Number (RPN) of the new cases incorporated into the assisted system.

In the realm of smart manufacturing, equipment plays a pivotal role, impacting the efficiency and quality of production. Ensuring equipment availability and optimal performance is crucial, necessitating effective maintenance strategies. This paper addresses the complexities of smart device maintenance, which often involves collaboration between multiple entities like device owners, manufacturers, suppliers, and external maintenance services. To enhance this cooperative maintenance, we propose a novel maintenance system based on permissioned blockchain technology, offering superior security and reliability compared to conventional cloud-based platforms. Our contributions include developing an integrated maintenance system framework for smart manufacturing, which facilitates interactions among diverse stakeholders. Additionally, we have developed a prototype of this maintenance system, serving as a practical model for real-world application. Our research primarily demonstrates the practicality and advantages of using permissioned blockchain for maintenance systems in the manufacturing sector, paving the way for more secure, efficient, and collaborative maintenance practices.

All kinds of vessels consist of dozens of complex machineries with rotating parts and electric motors that operate continuously in a harsh environment with excess temperature and humidity, vibration, fatigue and load. A breakdown or malfunction in one of these machineries can significantly impact the vessel’s operation and safety and consequently, the safety of the crew and the environment. To maintain operational efficiency and seaworthiness, the shipping industry invests substantial resources in preventive maintenance and repairs. This research presents the economic and technical benefits of predictive maintenance over to traditional preventive maintenance, and repair by replacement approaches in the maritime domain. By leveraging modern technology and Artificial Intelligence, we can analyze real-time operating conditions of machinery, enabling early detection of potential damages and allowing for effective planning of future maintenance and repair activities. In this paper, we propose and develop a Convolutional Neural Network that is fed with raw vibration measurements acquired in a laboratory environment from the ball bearings of a motor. Then, we investigate whether the proposed network can accurately detect the functional state of ball bearings and categorize any possible failures present, contributing to improved maintenance practices in the shipping industry.

Wind power is one of the most important sources of renewable energy available today. A large part of the wind energy cost is due to the cost of maintaining wind power equipment. When a wind turbine component fails to function, it might need to be replaced under the less than ideal circumstances. This is known as corrective maintenance. To minimize unnecessary costs, a more active maintenance policy based on the life expectancy of the key components is preferred. Optimal scheduling of preventive maintenance activities requires advanced mathematical modeling. In this paper, an optimal preventive maintenance algorithm is designed using the renewal-reward theorem. In the multi-component setting, our approach involves a new idea of virtual maintenance which allows us to treat each replacement event as a renewal event even if some components are not replaced by new ones. The proposed optimization algorithm is applied to a four-component model of a wind turbine and the optimal maintenance plans are computed for various initial conditions. The modeling results showed clearly the benefit of PM planning compared to pure CM strategy (about 30% lower maintenance cost).

This study investigated the breakdown trend in an automated production with an aim to recommend the application of Reliability-centered maintenance (RCM) for an improved productivity via a new preventive maintenance (PM) program. Individual Section-forming machine (ISM): a glass blowing machine for making glass bottles was used as the case study of an automated production system. The machine parts and the working mechanisms were analysed with a special focus on methods of processes and procedures that will enable the ISM maintenance department run more effective and achieve its essential goal of ensuring effective machine operation and reducing machine downtime. In this work, information is provided on the steps and procedures to identify critical components of the ISM using Failure Modes and Effect Analysis (FMEA) as a tool to develop an optimal maintenance program based on the reliability data of the equipment’s functional components. A relationship was established between the failure rate of the machine components and the maintenance costs such that using the recommended PM program, an evidence of improvement in the machine’s availability, safety and cost-effectiveness will result into an increase in the company’s profit margin.

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.

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium until 60 days. Explants were evaluated by RT-PCR-16SrRNA, and cytokines gene expression. Viability and infectivity of bacilli recovered from explant (D28 and D60) were evaluated using the Shepard’s model. All explants were RT-PCR-16srRNA positive. Viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice showed an average positivity of 31%, being the highest positivity in the D28 groups (80%). Furthermore, our work showed different pattern in cytokines gene expression (TGF-β, IL-10, IL-8 and TNF-α) in the presence of alive or dead bacilli. Although changes can be made for improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

Artificial Intelligence (AI) models are expected to have a great impact in the manufacturing industry, optimizing time and resource cost by enabling applications such as predictive maintenance (PM) of production machines. A necessary condition for this is the availability of high quality data collected as close as possible to the process in question. With the advent of 5G equipped multi sensor platforms (MSPs), high sampling rate data can be collected and transmitted for processing in real time. This poses a data security challenge, since this data may give valuable insight into confidential business information of companies. Federated learning (FL) enables the training of AI models with data from multiple sources without it leaving the shop floor, by utilizing distributed computing resources available on premise. This paper introduces an architecture of FL based on data collected from 5G MSPs for enabling PM in industrial environments and discusses its potential benefits and challenges.

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.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

This study investigates the application of frequency augmentation techniques to improve condition-based maintenance (CBM+) systems for airborne weapon systems, focusing on the predictive accuracy of velocity and acceleration parameters. Utilizing MIL-STD-1553B MUX data from 138 sorties of fixed-wing aircraft, we explored six augmentation methods, including traditional interpolations (linear, quadratic, cubic spline) and advanced machine learning models (K-Nearest Neighbor, LSTM, and Bi-LSTM). Our findings indicate that while traditional methods like linear interpolation are more effective for velocity parameters, advanced ML techniques, particularly Bi-LSTM, provide better results for acceleration parameters, which exhibit more complex and rapid variability. The study underscores the necessity of tailoring augmentation approaches to specific parameter characteristics and highlights the potential of ML models in capturing intricate patterns within time-series data. These insights are critical for advancing CBM+ systems in military avionics, enhancing reliability and operational efficiency through improved data processing strategies. Future work should explore more performant augmentation techniques, such as by integrating multi-dimensional datasets, and explore ways to develop automated tools for a more powerful predictive maintenance framework.

This study uses a wind turbine case study to showcase an architecture for implementing a distributed digital twin in which all important aspects of a predictive maintenance solution in a DT use a fog computing paradigm, and the typical predictive maintenance DT is improved to offer better asset utilization and management through real time condition monitoring, predictive analytics, and health management of selected components of Wind turbines in a wind farm.. Digital twin (DT) is a technology that sits at the intersection of Internet of Things, Cloud Computing and Software Engineering to provide a suitable tool for replicating physical objects in the digital space. This can facilitate the implementation of asset management in manufacturing systems through predictive maintenance solutions leveraged by Machine Learning (ML). With DTs, a solution architecture can easily use data and software to implement asset management solutions such as Condition Monitoring and Predictive Maintenance using acquired sensor data from physical objects and computing capabilities in the digital space. While DT offers a good solution, it is an emerging technology that could be improved with better standards, architectural framework, and implementation methodologies. Researchers in both academia and industry have showcased DT implementations with different levels of success. However, DTs remain limited in standards and architectures that offer efficient predictive maintenance solutions with real time sensor data, and intelligent DT capabilities. An appropriate feedback mechanism is also needed to improve asset management operations.

Buildings are subject to intrinsic and extrinsic failures at all stages of the construction process, i.e., design to occupancy (i.e., use) as several failure types can affect them. There are three basic steps for researching building failures: listing, cataloging, and solving/deciding whether highlighting the least invasive and lowest cost intervention. Therefore, this research presents some methods used in construction for the intervention prioritization and seeks to illustrate the most suitable methodology for different settings failure x diagnosis x intervention. Therefore, the most traditional tools are shown: BASICO, SWIFT, FEMEA, AAF, and GUT matrix, where a critical assessment of the strengths and weaknesses is carried out. After that, a case study on maintenance services for the moisture on the building facades was performed. Finally, the GUT matrix and the FMEA method are the best results

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96\% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

In the field of industrial process monitoring, more and more interest is being shown in specific process categories. These include time-varying processes, that is, those processes whereby the response one receives as output from the system depends on when the input signal is sent into it. There are many reasons for this process variability and such contexts are not always analyzed with this operational characteristic at their core. At the same time, interest in certain categories of techniques is also becoming more prominent, to meet certain application needs. Among these, clustering and unsupervised techniques in general are gaining ground. This is largely due to the difficulty of finding fault data with which to train, for example, supervised models. On the other hand, the clustering technique, on which this contribution focuses, also makes it possible to compensate for the lack of complete knowledge of the structure of the process itself. With these two considerations in mind, this contribution proposes a literature review on the topic of clustering applied in time-varying contexts, in the maintenance field. The aim is to present an overview of the main fields of study, the role of clustering in this context and the main clustering techniques used.

Timely detection of surface damages on wind turbine blades is imperative for minimising downtime and avoiding possible catastrophic structural failures. With recent advances in drone technology, a large number of high-resolution images of wind turbines are routinely acquired and subsequently analysed by experts to identify imminent damages. Automated analysis of these inspection images with the help of machine learning algorithms can reduce the inspection cost, thereby reducing the overall maintenance cost arising from the manual labour involved. In this work, we develop a deep learning based automated damage suggestion system for subsequent analysis of drone inspection images. Experimental results demonstrate that the proposed approach could achieve almost human level precision in terms of suggested damage location and types on wind turbine blades. We further demonstrate that for relatively small training sets advanced data augmentation during deep learning training can better generalise the trained model providing a significant gain in precision.

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.

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

Grinding processes’ stochastic nature poses a challenge in predicting the quality of the resulting surfaces. Post-production measurements for form, surface roughness, and circumferential waviness are commonly performed due to infeasibility in measuring all quality parameters during the grinding operation. Therefore, it is challenging to diagnose the root cause of quality deviations in real-time resulting from variations in the machine’s operating condition. This paper introduces a novel approach to predicting the overall quality of the individual parts. The grinder is equipped with sensors to implement condition-based maintenance and is induced with five frequently occurring failure conditions for the experimental test runs. The crucial quality parameters are measured for the produced parts. Fuzzy c-means (FCM) and Hotelling’s T-squared (T2) have been evaluated to generate quality labels from the multi-variate quality data. Benchmarked random forest regression models are trained using fault diagnosis feature set and quality labels. Quality labels from the T2 statistic of quality parameters are preferred over FCM approach for their repeatability. The model, trained from T2 labels achieves more than 94% accuracy when compared to the measured ring disposition. The predicted overall quality using the sensors’ feature set is compared against the threshold to reach a trustworthy maintenance decision.

Performing predictive maintenance (PdM) is challenging for many reasons. Dealing with large datasets which may not contain run-to-failure data (R2F) complicates PdM even more. When no R2F data are available, identifying condition indicators (CIs), estimating the health index (HI), and thereafter, calculating a degradation model for predicting the remaining useful lifetime (RUL) are merely impossible using supervised learning. In this paper, a 3 dof delta robot used for pick and place task is studied. In the proposed method, autoencoders (AEs) are used to predict when maintenance is required based on the signal sequence distribution and anomaly detection, which is vital when no R2F data is available. Due to the sequential nature of the data, non-linearity of the system, and correlations between parameter time series, convolutional layers are used for feature extraction. Thereafter, a sigmoid function is used to predict the probability of having an anomaly given CIs acquired from AEs. This function can be manually tuned given the sensitivity of the system or optimized by solving a minimax problem. Moreover, the proposed architecture can be used for fault localization for the specified system. Additionally, the proposed method is capable of calculating RUL using Gaussian process (GP), as a degradation model, given HI values as its input.

The significance of virtual reality (AR/VR/MR) technology stands out because it can be used in various construction fields such as urban design, construction review, maintenance and education, etc. As to prove this, conglomerates such as Facebook, Google, Sony, Microsoft, and Samsung are increasing their investments to preoccupy the virtual reality market and are competing to dominate the contents and platform market. Virtual reality technology has a concept that collectively refers to VR (Virtual Reality), AR (Augmented Reality), and MR (Mixed Reality), but technically, the two technologies are strictly separated. While VR technology is an immersive virtual environment using computer graphic technology, AR technology is a more advanced technology that combines real data and VR data, and MR technology is a technology that combines both AR and VR. In Korea, Republic of, the use of BIM (Building Information Modeling), a 3D information model, becomes mandatory and based on this, the demand for a new market where VR/AR/MR technologies and advanced sensing equipment are combined increases. This study implemented a building maintenance platform using AR based on 5G, and developed matching technology between BIM of the building maintenance platform and AR equipment. Besides this study implemented the technology to enhance the matching rate of the matching technology and carried out the process to enhance the matching rate empirically through continuous tests. As a result, the initial target of 90% matching rate could be improved to 96%. Based on this, it is expected that effective EV (Optimum Life Cycle Cost) could be achieved at a lower cost compared to the previous one by using it for maintenance monitoring after construction and completion of the building, and can be used as an effective solution in the aspect of building maintenance as well.

The aim of this paper is to use deep learning tools to innovate pre-trained object detection models to improve the accuracy of non-destructive testing (NDT) of civil aviation maintenance. First, this thesis classifies object defects for NDT, such as cracks, undercut, etc. Nowadays, thesis surveys innovation deep-learning methods technology is used to improve the defect detection performance inferencing capability, increase the accuracy and efficiency of automatic identification which in enhanced the safety and reliability of aircraft fuselage in future, mark hidden cracks and solve the challenges that cannot be identified by manual inspection. Second, recent mainstream techniques the YOLOv4 neural network to the graphics card GPU core operator to speed up the recognition of defect images is being applied to the non-destructive inspection process of aircraft maintenance on A, C and D-Level, fully validating the deep learning model's powerful defect detection target capability. The attention-based YOLOv4 algorithm is improved by applying a one-stage attention mechanism to the YOLOv4, thereby improving the accuracy of the innovation model. Finally, thesis improved YOLOv4 based on an attention mechanism is proposed for object detection NDT via the deep learning method to effectively improve and shorten the inspection anomaly detection method for automatic detection sensor systems.

Modern engineering faces challenges in ensuring technical standards for service, durability, and sustainability. Political, administrative, and budgetary factors, coupled with climate change, pose tasks to structural integrity, affecting industries and economies. Marine infrastructures represent a strategic asset of the country as it handles a large part of the economic exchanges. This article analyzes five essential factors that play a fundamental role in the performance analysis of coastal structures: Chloride-induced corrosion, degradation models, maintenance strategies, monitoring, and climate change. Starting with reinforcement corrosion, considered as the main cause of distress, particularly in coastal zones for the long-term behavior of structures. Additional pressure from the influences of climate change is becoming evident and extreme, leading to reduction in capacity. To guarantee the lifespan, degradation models contribute by estimating the long-term performance of the asset as a strategic piece to the development of effective maintenance solutions. Additionally, quantifying the condition of the structure from monitoring data, plays a crucial part that provides information on the current situation of the structure. Finally, this review summarizes the challenges associated with the maintenance of aging marine structures considering aspects such as corrosion, monitoring, and the future challenges this area will face due to climate change.

Prediction models in mobility and transportation maintenance systems have been dramatically improved through using machine learning methods. This paper proposes novel machine learning models for an intelligent road inspection. The traditional road inspection systems based on the pavement condition index (PCI) are often associated with the critical safety, energy and cost issues. Alternatively, the proposed models utilize surface deflection data from falling weight deflectometer (FWD) tests to predict the PCI. Machine learning methods are the single multi-layer perceptron (MLP) and radial basis function (RBF) neural networks as well their hybrids, i.e., Levenberg-Marquardt (MLP-LM), scaled conjugate gradient (MLP-SCG), imperialist competitive (RBF-ICA), and genetic algorithms (RBF-GA). Furthermore, the committee machine intelligent systems (CMIS) method was adopted to combine the results and improve the accuracy of the modeling. The results of the analysis have been verified through using four criteria of average percent relative error (APRE), average absolute percent relative error (AAPRE), root mean square error (RMSE), and standard error (SD). The CMIS model outperforms other models with the promising results of APRE=2.3303, AAPRE=11.6768, RMSE=12.0056, and SD=0.0210.

Interpretation of increased gain in the bovine animals is difficult to be validated due to inherent genetic variation to meet their requirement for energy and protein, and those may relate to the bull species, e.g., Thai swamp buffalo. Therein, the study aimed at investigating and predicting protein requirement systems, with providing abundant energy intake 2.20 Mcal/kg DM for maintenance and growth of Thai swamp buffaloes using the comparative prolonged feeding trial for 90 days. Sixteen bull Thai swamp buffaloes at the initial (Age: 18-24 months; BW: 233 ± 25.0 kg) were as-signed into four treatment groups, four buffaloes each, fed 5.42, 6.96, 8.94, and 10.71% DM crude protein (CP). CP intake, BW, and physiological fluid were determined. The net CP requirements for maintenance and growth of Thai swamp buffaloes were 5.41 g CP/kg W0.75 and 0.46 g CP/g average daily gain (ADG), respectively. Our results indicated that CP requirement increases, when BW increases. An increased dietary CP resulted in an increased number at blood urine nitrogen (N), N absorption, total volatile fatty acid, urinary purine derivative, and the microbial N. Notably, the net CP requirement for growth of Thai swamp buffalo was higher than it reported in NRC, but the maintenance was lower.

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.

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.

A comprehensive Energy Audit of a Maintenance facility was performed to assess its energy performance and identify scope for improvement. The facility’s Energy Use Intensity (EUI) for 2022 was 404 kWh/m2 — more than double the Benchmark EUI for Maintenance facilities (151 kWh/m2) recommended by EnergyStar. Furthermore, the Load Factor for 2022 was 0.22, which is lower than the recommended minimum of 0.75 for an efficient building. The audit encompassed an in-depth evaluation of the building's structural and operational characteristics, comprising HVAC systems, lighting, building envelope, and energy-intensive machinery. An energy model of the building was developed to emulate the baseline building energy performance for 2022. Following the energy model's development and validation, an analysis was conducted to identify energy-intensive areas and opportunities for optimization. Energy Efficiency Measures were then formulated, focusing on improving energy efficiency while focusing on energy consumption reduction and GHG emission reduction. Results demonstrated the potential of Energy Audits and Modeling to enable significant reductions in energy consumption and promote sustainable building practices. Among the Energy Efficiency Measures considered, re-sizing and decarbonizing HVAC equipment contributed the most to energy savings, with a 100% decrease in natural gas and 37% decrease in electricity use annually.