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Objectives: Binge eating disorder (BED) is the most prevalent eating disorder associated with multiple adverse health effects, especially mental health issues, including substance use disorders and mood and anxiety disorders. Given these high comorbidities, the objective of our study was to examine whether bingeing behavior would lead to altered perception of reinforcing properties of EtOH and changes in well-being. Methods: We used a sucrose bingeing model based on an intermittent access paradigm with a two-bottle choice, without fasting, in male and female mice. We examined the effect of 2-week sucrose paradigm on ethanol-reinforcing properties using a conditioned place preference test (CPP). Well-being, anxiety- and depressive-like behavioral tests were performed to assess emotional state following 2 and 8-week sucrose bingeing paradigm. Results: Mice with intermittent access to sucrose developed a binge-like behavior assessed by higher sucrose intake and escalation rate during the 1st hour of access, in comparison with mice with a continuous sucrose access. We show for the first time that sucrose bingeing in mice modifies positive reinforcing effect of EtOH in a CPP paradigm without marked alteration of emotional state. Interestingly, prolonging sucrose access for 8 weeks revealed an exacerbated bingeing behavior in female mice, and some signs of emotional state alterations in female with continuous access. Discussion: In sum, our findings broaden the understanding of behavioral alterations associated with bingeing, highlighting the need to investigate addictive-like properties of palatable food both in male and female mice. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells make only a small fraction of immune cells in the human body, however, play a pivotal role in the fight against cancer by the immune system. They are capable of eliminating abnormal cells via several direct or indirect cytotoxicity pathways in a self-regulating manner, which makes them a favorable choice as a cellular therapy against cancer. Additionally, allogeneic NK cells, unlike other lymphocytes, do not or only minimally cause graft-versus-host diseases opening the door for an off-the-shelf therapy. However, to date, the production of NK cells faces several difficulties, especially because the critical process parameters (CPPs) influencing the critical quality attributes (CQAs) are difficult to identify or correlate. There are numerous different cultivation platforms available, all with own characteristics, benefits and disadvantages that add further difficulty to define CPPs and relate them to CQAs. Our goal in this contribution was to summarize the current knowledge about NK cell expansion CPPs and CQAs, therefore we analyzed the available literature of both dynamic and static culture format experiments in a systematic manner. We present a list of the identified CQAs and CPPs and discuss the role of each CPP in the regulation of the CQAs. Furthermore, we could identify potential relationships between certain CPPs and CQAs. The findings based on this systematic literature research can be the foundation for meaningful experiments leading to better process understanding and eventually control. [ABSTRACT FROM AUTHOR]

The American Water Works Association (AWWA) has developed a new standard (ANSI/AWWA C607) for concrete pressure pipe (CPP) installation, expected to be published in early 2025. The standard aims to reduce installation defects and increase the reliability and sustainability of pipelines, covering various CPP materials. Users are responsible for determining if the minimum requirements of the standard are suitable for their specific projects and should provide comprehensive project requirements. The standard also addresses best practices for delivery, handling, trench construction, pipe joint installation, embedment and backfill, corrosion testing, and verification testing to prevent pipeline failures. [Extracted from the article]

The calixarene‐templated synthesis of new cyclo(meta‐ polyphenylenes (CMPs) is described. These compounds are functionalized with added aromatic units, that are suitably oriented for oxidative aromatization to be envisioned. This could pave the way towards the synthesis of elongated segments of zigzag‐type single‐walled carbon nanotubes (SWCNTs). [ABSTRACT FROM AUTHOR]

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage, and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and nonnervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising noninvasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP. [ABSTRACT FROM AUTHOR]

In this paper, we address the biobjective versions of the perfect matching problem (PMP) and the Chinese postman problem (CPP). Both problems are solved by means of integer formulations or separating blossom inequalities, exploiting the PMP relationship with the CPP. In both cases, we first find the set of supported nondominated solutions and then we use them to obtain the nonsupported ones. The set of supported nondominated solutions are obtained solving scalarized integer formulations. To obtain the sets of nonsupported solutions, we resort to solving lexicographic problems based on adding additional linear constraints to the original problems. For this reason, we also characterize the combinatorial structure of the PMP vertices with one or two additional constraints. We also investigate when it is possible to use the PMP to solve CPP in the biobjective case. We report computational experiments comparing the different approaches and formulations based on different types of graphs with up to 700 nodes. [ABSTRACT FROM AUTHOR]

The aim of contemporary education is to shape a competent individual capable of solving life problems based on existing knowledge, skills, and abilities, ready to navigate the information space, receive, use, and create information. Achieving this goal requires dedication from education professionals, primarily pedagogues, psychologists, and teachers who must possess integral quality in their profession, which is competency. The main objective of the research is to examine the opinions of pedagogy students about the potentials of a set of workshops collectively named Creative Pedagogical Practices (CPP) for the development of competencies of school pedagogues. The workshops were implemented in secondary schools as part of courses in the field of school pedagogy. The study employed a descriptive research method, using written structured interviews as the research instrument. Research data indicate that students’ expectations regarding the creation and implementation of CPP workshops are met, as they have recognized the potential for developing professional competencies in the domain of didactic-methodological knowledge, social skills, creativity and general competencies for working in school. Regarding the development of personal competencies, respondents mentioned that the implementation of workshops contributed to developing their responsibility, self-confidence, and creativity, which they consider important qualities for future work in schools. The obtained research results can be relevant when creating study programs for educating educators, especially in light of a greater emphasis on practical activities during studies.

Abstract Background Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.

• CBT effectively improves endometriosis symptoms in adults. • Evidence for CBT is lacking but is needed for adolescents with endometriosis. • We propose a biopsychosocial model using CBT to improve adolescent endometriosis symptoms. Recent advances and interest in nonpharmacological treatment approaches for various chronic pain conditions in adolescent patients have increased. Cognitive behavioral therapy (CBT) is widely regarded as the leading nonpharmacological treatment for chronic pain, encompassing gynecological conditions associated with chronic pelvic pain, such as endometriosis. Adolescents with endometriosis often present with different symptoms than adults and frequently report more comorbid psychiatric disorders than the general public. This review aims to (1) justify the application of CBT interventions in the context of adolescent patients with endometriosis; (2) integrate and analyze existing empirical evidence and reviews; (3) highlight the advantages, constraints, and future research directions in CBT for this demographic; and (4) introduce a novel biopsychosocial conceptual model. This model intricately considers the interplay of thoughts, emotions, behaviors, and physical symptoms specific to adolescents with endometriosis, providing a foundation for targeted CBT interventions. This holistic approach recognizes the multifaceted nature of their experience, paving the way for comprehensive and effective nonpharmacological therapeutic strategies. Given the nuanced and intricate nature of endometriosis in adolescents, there is a pressing need for innovative conceptual models and clinical trials of behavioral interventions explicitly designed for this demographic. [ABSTRACT FROM AUTHOR]

Background/Aim: Cold physical plasma (CPP) has emerged as an effective therapy in oncology by inducing cytotoxic effects in various cancer cells, including chondrosarcoma (CS), Ewing's sarcoma (ES), and osteosarcoma (OS). The current study investigated the impact of CPP on cell motility in CS (CAL-78), ES (A673), and OS (U2-OS) cell lines, focusing on the actin cytoskeleton. Materials and Methods: The CASY Cell Counter and Analyzer was used to study cell proliferation and determine the optimal concentrations of fetal calf serum to maintain viability without stimulation of cell proliferation. CellTiter-BlueCell viability assay was used to determine the effects of CPP on the viability of bone sarcoma cells. The Radius assay was used to determine cell migration. Staining for Deoxyribonuclease I, G-actin, and F-actin was used to assay for the effects on the cytoskeleton. Results: Reductions in cell viability and motility were observed across all cell lines following CPP treatment. CPP induced changes in the actin cytoskeleton, leading to decreased cell motility. Conclusion: CPP effectively reduces the motility of bone sarcoma cells by altering the actin cytoskeleton. These findings underscore CPP's potential as a therapeutic tool for bone sarcomas and highlight the need for further research in this area. [ABSTRACT FROM AUTHOR]

Background: Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results: Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions: The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life. [ABSTRACT FROM AUTHOR]

Software Defined Network (SDN) which is labeled as a new network archetype that decouples the data plane and control plane is capable to solve today's network problems and improve network performance. Yet, among numerous challenges and research openings in software-defined networks, Controller Placement Problem (CPP) is supposed to be the most vital issue which can directly affect the whole network's performance. In this thesis, we deliver a comprehensive review of various metaheuristic CPP-optimized models in SDNs. In this regard, we propose a methodology named Ant Colony Optimization Controller Placement (ACO-CP), to solve the optimal controller location. Ant Colony Optimization is a population-based meta-heuristic algorithm proposed for the optimal location of the controllers, which takes a precise set of the objective function and returns the best potentially location out of the possible set of locations. The objective function is defined by considering, the average and maximum controller-to-controller, switch-to-controller latency, and load balance. By comparing the network performance our proposed algorithm, provides better performance compared with Pareto Simulated Annealing and k-medoid method, Specially on its overall global latency and controller-to-controller latency. [ABSTRACT FROM AUTHOR]

This study evaluated the probable relevance of a non-covalent conjugate of imatinib with TP10 in the context of a neuroprotective effect in Parkinson's disease. Through the inhibition of c-Abl, which is a non-receptor tyrosine kinase and an indicator of oxidative stress, imatinib has shown promise in preclinical animal models of this disease. The poor distribution of imatinib within the brain tissue triggered experiments in which a conjugate was obtained by mixing the drug with TP10, which is known for exhibiting high translocation activity across the cell membrane. The conjugate was tested on the HT-22 cell line with respect to its impact on MPP+-induced oxidative stress, apoptosis, necrosis, cytotoxicity, and mortality. Additionally, it was checked whether the conjugate activated the ABCB1 protein. The experiments indicated that imatinib+PEG4+TP10 reduced the post-MPP+ oxidative stress, apoptosis, and mortality, and these effects were more prominent than those obtained after the exposition of the HT-22 cells to imatinib alone. Its cytotoxicity was similar to that of imatinib itself. In contrast to imatinib, the conjugate did not activate the ABCB1 protein. These favorable qualities of imatinib+PEG4+TP10 make it a potential candidate for further in vivo research, which would confirm its neuroprotective action in PD-affected brains. [ABSTRACT FROM AUTHOR]

Coverage path planning is a central task in agricultural field operations such as tillage, planting, cultivation, and harvesting. In future visions, manual operation will be replaced by fleets of autonomous agricultural vehicles that perform the tasks autonomously. A step towards this transition is to enable simultaneous and safe cooperation of autonomous vehicles on the field. In this article a novel approach is presented for coverage path planning (CPP) for two autonomous tractors that perform sequentially dependent tasks simultaneously on the same area. The approach is based on the idea of computing the coverage solutions for each task by dividing them into short paths that consist of a swath and a turn. The approach ensures collision avoidance by examining that the simultaneous short paths, operated by different tractors, do not collide geometrically, and then schedules them to be operated simultaneously in real-time. The approach was demonstrated successfully in a real-world test environment with two autonomous tractors. The tractor that performed the first task was equipped with a disc cultivator and the second tractor was equipped with a seed drill. A test area of 0.8 ha was used for the demonstration drive, during which the tractors drove 22 swaths simultaneously. Both tractors completed their respective tasks. • We present the problem of sequentially dependent coverage path planning. • Sequentially dependent coverage tasks are performed simultaneously on the same area. • A novel algorithm for solving this problem for two autonomous tractors. • The algorithm solves and schedules non-conflicting paths in real-time online. • Successful collision-free completion of autonomous operation in a field test. [ABSTRACT FROM AUTHOR]

How humans transform sensory information into decisions that steer purposeful behavior is a central question in psychology and neuroscience that is traditionally investigated during the sampling of external environmental signals. The decision-making framework of gradual information sampling toward a decision has also been proposed to apply when sampling internal sensory evidence from working memory. However, neural evidence for this proposal remains scarce. Here we show (using scalp EEG in male and female human volunteers) that sampling internal visual representations from working memory elicits a scalp EEG potential associated with gradual evidence accumulation-the central parietal positivity. Consistent with an evolving decision process, we show how this signal (1) scales with the time participants require to reach a decision about the cued memory content and (2) is amplified when having to decide among multiple contents in working memory. These results bring the electrophysiology of decision-making into the domain of working memory and suggest that variability in memory-guided behavior may be driven (at least in part) by variations in the sampling of our inner mental contents. [ABSTRACT FROM AUTHOR]

Neurophysiological studies in non-human primates characterize perceptual decision-making as a two-stage process: 1) accumulation of sensory evidence and 2) decision boundary leading to response selection. These studies commonly used random dot motion stimuli and demonstrated that firing rates of neurons in the lateral intraparietal area (LIP) increase and behavioral response times decrease as the coherence of motion stimuli increases. Recent EEG studies in humans have revealed the Centro-Parietal Positivity (CPP) potential, which exhibits similar functional properties to LIP neurons and is associated with the process of accumulating sensory evidence. It has been shown that the parameters of the CPP component carry important information about the decisions made. However, previous studies have mainly used simple and low-level stimuli to understand the process in its most basic form. Whether perceptual decision-making processes generalize to more complex and socially meaningful biological motion stimuli, such as human actions, remains unknown. This review article emphasized the significance of investigating the neurophysiological basis of perceptual decision-making processes involved in the recognition of human actions and presented a compilation of studies on perceptual decision-making conducted with simpler stimuli that have guided and shaped these investigations. In the conclusion section, we talked about the implications of research in this field to the diagnosis and treatment of many psychological and neurological disorders and the development of artificial intelligence technologies that would improve the well-being of humans [ABSTRACT FROM AUTHOR]

Background: Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation test, which is expensive and time-consuming. With the widespread application of artificial intelligence in medicine, some studies have utilized clinical, hormonal (laboratory) and imaging data-based machine learning (ML) models to identify CPP. However, the results of these studies varied widely and were challenging to directly compare, mainly due to diverse ML methods. Therefore, the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for CPP remains elusive. The aim of this study was to investigate the diagnostic value of ML models based on clinical, hormonal (laboratory) and imaging data for CPP through a meta-analysis of existing studies. Methods: We conducted a comprehensive search for relevant English articles on clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP, covering the period from the database creation date to December 2023. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP. The I² test was employed to evaluate heterogeneity, and the source of heterogeneity was investigated through meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. Results: Six studies met the eligibility criteria. The pooled sensitivity and specificity were 0.82 (95% confidence interval (CI) 0.62-0.93) and 0.85 (95% CI 0.80-0.90), respectively. The LR+ was 6.00, and the LR- was 0.21, indicating that clinical, hormonal (laboratory) and imaging data-based ML models exhibited an excellent ability to confirm or exclude CPP. Additionally, the SROC curve showed that the AUC of the clinical, hormonal (laboratory) and imaging data-based ML models in the diagnosis of CPP was 0.90 (95% CI 0.87-0.92), demonstrating good diagnostic value for CPP. Conclusion: Based on the outcomes of our meta-analysis, clinical and imaging data-based ML models are excellent diagnostic tools with high sensitivity, specificity, and AUC in the diagnosis of CPP. Despite the geographical limitations of the study findings, future research endeavors will strive to address these issues to enhance their applicability and reliability, providing more precise guidance for the differentiation and treatment of CPP. [ABSTRACT FROM AUTHOR]

Aim: Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) can selectively kill tumor cells but has no significant effect on normal cells. However, the use of TRAIL is limited for resistance by more than 50% of the tumor cell lines. It's very important to develop a more efficient form of TRAIL for cancer treatment. Methods: The N‐terminal in soluble fragments (114–281aa) of TRAIL was redesigned to construct a novel TRAIL mutant‐MuR5S4‐TR. The Cell Counting Kit‐8 method to explore the antitumor effects. The potential mechanisms were also explored. Results: Novel TRAIL mutant with cell‐penetrating peptides (CPP) like and Second mitochondria‐derived activator of caspases (Smac) like structure‐MuR5S4‐TR was successfully constructed. The prokaryotic expression system was successfully built, and the MuR5S4‐TR was purified and reconfirmed by western blot. MuR5S4‐TR could enhance the antitumor effects of TRAIL in most of the cancer cell lines significantly, NCI‐H460 lung cancer cell line, for instance. After MuR5S4‐TR treatment, the expressions of death receptor 4 (DR4), DR5, Caspase‐8, and cleaved Caspase‐3 were remarkably increased, however, there was no significant difference in X‐linked inhibitor of apoptosis expression. Conclusion: We constructed a novel TRAIL mutant with CPP‐like and Smac‐like structure‐MuR5S4‐TR. The MuR5S4‐TR showed significantly stronger antitumor effects than TRAIL in many tumor cell lines. The MuR5S4‐TR showed strong antitumor effects both in vitro and in vivo. This preliminary study implies that MuR5S4‐TR may be a more efficient form of TRAIL for cancer therapy. [ABSTRACT FROM AUTHOR]

The Reln gene encodes for the extracellular glycoprotein Reelin, which regulates several brain functions from development to adulthood, including neuronal migration, dendritic growth and branching and synapse formation and plasticity. Human studies have implicated Reelin signaling in several neurodevelopmental and psychiatric disorders. Mouse studies using the heterozygous Reeler (HR) mice have shown that reduced levels of Reln expression are associated with deficits in learning and memory and increased disinhibition. Although these traits are relevant to substance use disorders, the role of Reelin in cellular and behavioral responses to addictive drugs remains largely unknown. Here, we compared HR mice to wild-type (WT) littermate controls to investigate whether Reelin signaling contributes to the hyperlocomotor and rewarding effects of cocaine. After a single or repeated cocaine injections, HR mice showed enhanced cocaine-induced locomotor activity compared with WT controls. This effect persisted after withdrawal. In contrast, Reelin deficiency did not induce cocaine sensitization, and did not affect the rewarding effects of cocaine measured in the conditioned place preference assay. The elevated cocaine-induced hyperlocomotion in HR mice was associated with increased protein Fos expression in the dorsal medial striatum (DMS) compared with WT. Lastly, we performed an RNA fluorescent in situ hybridization experiment and found that Reln was highly co-expressed with the Drd1 gene, which encodes for the dopamine receptor D1, in the DMS. These findings show that Reelin signaling contributes to the locomotor effects of cocaine and improve our understanding of the neurobiological mechanisms underlying the cellular and behavioral effects of cocaine.

Coverage path planning is an important research direction for unmanned aerial vehicles (UAV), which are primarily used in ground search or mapping scenarios. Although there have been a large number of studies on UAV coverage path planning, there are still some problems in the cooperative work of multi-UAV in complex environments under the constraints of energy consumption and work efficiency requirements of UAV. To solve unnecessary energy loss when multiple UAVs jointly execute complex area coverage tasks and improve the overall work efficiency of the UAV swarm. In this study, we simulated the situation of multiple UAVs performing the mission of area coverage under the constraints of the corresponding energy consumption in a work environment with no-fly zones. We propose the use of multiple UAV base stations to provide takeoff and landing services for UAVs that perform missions. We proposed two algorithms. One is the multi-base station multi-UAV cooperative coverage path planning algorithm with flexible obstacle avoidance ability (MBS-MUCCPPAFOA), which performs coverage route planning from an entire area using multiple base stations to perform multi-UAV area coverage tasks. The other algorithm is a multi-UAV cooperative coverage path planning algorithm with flexible obstacle avoidance capability based on area segmentation (MUAV-CCPPAFOA-AS), which divides the entire work area and performs coverage path planning for each sub-area to perform multi-UAV area coverage tasks. We compared the proposed algorithm with the common scanning coverage path planning algorithm, and proved the robustness of the proposed MBS-MUCCPPAFOA and MUAV-CCPPAFOA-AS algorithms.

Weinan Hu,* Wenting Cai,* Yan Wu, Chengda Ren, Donghui Yu, Tingting Li, Tianyi Shen, Ding Xu, Jing Yu Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding Xu; Jing Yu, Email 15821885240@163.com; dryujing@aliyun.comBackground: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.Methods: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.Results: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.Conclusion: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD. Keywords: age-related macular degeneration, choroidal neovascularization, cell-penetrating peptide, ranibizumab, conbercept, drug delivery

Abstract Background The Norwegian health authorities introduced standardized cancer patient pathways (CPPs) in 2015, aiming to reduce practice variations across hospitals and regions, and improve the continuity, coordination and overall quality of the health care service provided to cancer patients. There has been few studies investigating this change, and that have looked into the organisational and economic benefits of standardized pathways, however the element of care and the patient perspective has been especially neglected. This study explored the care element in cancer patient pathways through an in-depth study of patient experiences. Methods The patients were enrolled approximately three years after the introduction of standardized CPPs in Norway. Through a qualitative design with in-depth interviews, a total of 21 interviews were conducted with seven patients between 2018 and 2020. The first interview took place after the diagnosis was established and before treatment, the second interview during treatment, and the final interview approximately one year after the completion of active treatment. The empirical catchment area was eastern Norway. Data were analysed using a theoretical thematic analysis. Results This study sheds light on the complex challenges patients’ faces, while navigating CPPs, including the need for better transition support, improved coordination and continuity in care, and a more holistic approach that encompasses emotional well-being and family support. Three overarching themes were identified: [1] Navigating CPPs: patient care and transition challenges, [2] Fragmented cancer care: challenges in coordination and continuity [3] Unmet needs and overlooked opportunities in CPPs. Conclusions Patients experience that cancer patient pathways offer good medical treatment, but that the care element deserves more attention. Current CPPs are trapped in a logic of choice, preventing room for the element of care to receive the attention it requires for the patient to truly experience holistic person-centred care and continuous, well-coordinated services. Based in our study we argue there is a need to look into the missed opportunities for using the CPPs as points of departure for more holistic collaborative models for cancer care.

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by the variations in the ATP-binding cassette sub-family D member 1 (ABCD1) gene. This study is the first to report central precocious puberty (CPP) in individuals with X-ALD. A 6-year-old boy exhibited mucocutaneous pigmentation, increased plasma adrenocorticotropic hormone levels, and elevated very long-chain fatty acids (VLCFA). We identified a variant, c.1826A>G (p. Glu609Gly), in exon 8 of the ABCD1 gene in the proband. Additionally, he displayed rapid growth, testicular volume of 5–6 mL, the onset of pubic hair, and pubertal levels of luteinizing hormone (LH), all meeting the diagnostic criteria for CPP. [ABSTRACT FROM AUTHOR]

In patients with traumatic brain injury (TBI), serum biomarkers may have utility in assessing the evolution of secondary brain injury. A panel of nine brain-injury- associated biomarkers was measured in archived serum samples over 10 days post-injury from 100 patients with moderate-severe TBI. Among the biomarkers evaluated, serum glial fibrillary acidic protein (GFAP) had the strongest associations with summary measures of acute pathophysiology, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue pO2 (PbtO2). Group based trajectory (TRAJ) analysis was used to identify three distinct GFAP subgroups. The low TRAJ group (n = 23) had peak levels of 9.4 + 1.2 ng/mL that declined rapidly. The middle TRAJ group (n = 48) had higher peak values (31.5 + 5.0 ng/mL) and a slower decline over time. The high TRAJ group (n = 26) had very high, sustained peak values (59.6 + 12.5 ng/mL) that even rose among some patients over 10 days. Patients in the high TRAJ group had significantly higher mortality rate than patients in low and middle TRAJ groups (26.9% vs. 7.0%, p = 0.028). The frequency of poor neurological outcome (Glasgow Outcome Score Extended [GOS-E] 1–4) was 88.5% in the high TRAJ group, 54.2% in the middle TRAJ group, and 30.4% in the low TRAJ group (p < 0.001). ICP was highest in the high TRAJ group (median 17.6 mm Hg), compared with 14.4 mmHg in the low and 15.9 mm Hg in middle TRAJ groups (p = 0.002). High TRAJ patients spent the longest time with ICP >25 mm Hg, median 23 h, compared with 2 and 6 h in the low and middle TRAJ groups (p = 0.006), and the longest time with ICP >30 mm Hg, median 5 h, compared with 0 and 1 h in the low and middle TRAJ groups, respectively (p = 0.013). High TRAJ group patients more commonly required tier 2 or 3 treatment to control ICP. The high TRAJ group had the longest duration when CPP was <50 mm Hg (p = 0.007), and PbtO2 was <10 mm Hg (p = 0.002). Logistical regression was used to study the relationship between temporal serum GFAP patterns and 6-month GOS-E. Here, the low and middle TRAJ groups were combined to form a low-risk group, and the high TRAJ group was designated the high-risk group. High TRAJ group patients had a greater chance of a poor 6-month GOS-E (p < 0.0001). When adjusting for baseline injury characteristics, GFAP TRAJ group membership remained associated with GOS-E (p = 0.003). When an intensive care unit (ICU) injury burden score, developed to quantify physiological derangements, was added to the model, GFAP TRAJ group membership remained associated with GOS-E (p = 0.014). Mediation analysis suggested that ICU burden scores were in the causal pathway between TRAJ group and 6-month mortality or GOS-E. Our results suggest that GFAP may be useful to monitor serially in moderate-severe TBI patients. Future studies in larger cohorts are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Extant studies have focused on exploring the research output of universities in Nigeria, but the measure of the quality of research output using citations per paper (CPP) from the Web of Science (WoS) and Scopus is scarcely discussed. This paper investigated the quality of papers published by the top 76 universities in Nigeria. Five hypotheses on CPP were tested using Kruskal-Wallis and Mann-Whitney tests. These hypotheses tested whether CPP is the same or different i) across six geo-political regions (GPRs), ii) between the two major regions, iii) across three university funding types, iv) in Scopus and WoS, and v) if these two databases are correlated. Results using these two databases indicated that no significant median differences were detected among universities across the six GPRs, between northern and southern Nigeria, and between the three funding types (federal, state, and private). Moreover, no significant median differences in CPP between Scopus and WoS were detected, and CPP in both databases was highly positively correlated (0.879; p = 0.05). A comparison of the mean CPP of Nigeria (5.90) from Scopus with 57 other African countries ranked it 47th despite being ranked third in terms of volume of published articles. Policy prescriptions are made on the implications of using CPP for practice. [ABSTRACT FROM AUTHOR]

Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chlamydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/ Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treat-ment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP. [ABSTRACT FROM AUTHOR]

Aim: This article aims to analyze the scientific understanding of the role of balneotherapy in the treatment of numerous urological conditions based on the latest research and clinical findings. Materials and Methods: A review of literature from PubMed and Google Scholar databases published between 2000 and 2023 on the use of balneotherapy for urological conditions was performed. The literature data was analyzed to identify the most common urological conditions such as chronic pelvic pain, urinary incontinence, urolithiasis, rehabilitation after prostatectomy and overactive bladder syndrome in which this field of physical medicine is applicable. Publications containing the following keywords were selected for analysis: balneology, urology, cpp, OAB, urolithiasis, post-prostatectomy treatment. Out of 90 papers, 26 sources containing key information related to the topic of the paper were selected. Conclusions: While the potential of balneotherapy in urology appears promising, it is crucial to approach these findings with cautious optimism. Many studies are in their early stages, and larger, multicenter, randomized, controlled trials are essential for a solid understanding of the role of balneotherapy in urology. In addition, it is essential to establish standard protocols to ensure patient safety and treatment efficacy. As our knowledge deepens, balneotherapy, with its rich history, may become a cornerstone of modern urologic care. [ABSTRACT FROM AUTHOR]

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Background: The Norwegian health authorities introduced standardized cancer patient pathways (CPPs) in 2015, aiming to reduce practice variations across hospitals and regions, and improve the continuity, coordination and overall quality of the health care service provided to cancer patients. There has been few studies investigating this change, and that have looked into the organisational and economic benefits of standardized pathways, however the element of care and the patient perspective has been especially neglected. This study explored the care element in cancer patient pathways through an in-depth study of patient experiences. Methods: The patients were enrolled approximately three years after the introduction of standardized CPPs in Norway. Through a qualitative design with in-depth interviews, a total of 21 interviews were conducted with seven patients between 2018 and 2020. The first interview took place after the diagnosis was established and before treatment, the second interview during treatment, and the final interview approximately one year after the completion of active treatment. The empirical catchment area was eastern Norway. Data were analysed using a theoretical thematic analysis. Results: This study sheds light on the complex challenges patients' faces, while navigating CPPs, including the need for better transition support, improved coordination and continuity in care, and a more holistic approach that encompasses emotional well-being and family support. Three overarching themes were identified: [1] Navigating CPPs: patient care and transition challenges, [2] Fragmented cancer care: challenges in coordination and continuity [3] Unmet needs and overlooked opportunities in CPPs. Conclusions: Patients experience that cancer patient pathways offer good medical treatment, but that the care element deserves more attention. Current CPPs are trapped in a logic of choice, preventing room for the element of care to receive the attention it requires for the patient to truly experience holistic person-centred care and continuous, well-coordinated services. Based in our study we argue there is a need to look into the missed opportunities for using the CPPs as points of departure for more holistic collaborative models for cancer care. [ABSTRACT FROM AUTHOR]

This study uses CFD methods to solve the complex flow around a CPP propeller with ducts and aims to investigate the performance differences between ducted and non-ducted propeller designs. In particular, the values for pitch changes and blade spindle torques have been determined at different advance ratios. The study uses STAR-CCM+, a commercial computational fluid dynamics (CFD) code, and has preferred the k-ε model to predict turbulence in the flow. In addition to the thrust coefficient, torque coefficient, and propeller efficiency, the study also examines blade spindle torque, whichprovides movement to the propeller blades. The use of ducts at low advance ratios is found to be beneficial in terms of both improving performance and reducing torque. [ABSTRACT FROM AUTHOR]

Background and aim of the studyWe previously published the increased frequency of new CPP cases during the Covid-19 pandemic in our pediatric endocrinology clinic at Rady Children's Hospital in San Diego, CA, US. We conducted this follow-up study to examine the incidence of new CPP cases requiring treatment with GnRH agonist (GnRHa) in our clinic during 2 years post-pandemic.MethodsWe performed a retrospective comparison of the number of visits of children newly diagnosed with CPP treated with GnRHa during the 2 years following the first year of Covid-19 pandemic (5/2021–7/2023). We evaluated clinical and bone maturation data as well as differences in timing from diagnosis to onset of treatment.ResultsWe previously reported in the pre-Covid year, 28 children (1 boy, 27 girls) treated with GnRHa for CPP out of 2,340 new endocrinology visits (1.2% of patients seen). During Covid-19 year, 64 children (7 boys, 57 girls) were treated out of 2,261 new visits (2.8%). The incidence of new CPP cases requiring GnRHa during the pandemic more than doubled compared to pre-pandemic. In the first year post-year 1 of the pandemic (5/2021–4/2022), 46 children (3 boys, 40 girls) started treatment with GnRHa for CPP out of 2,595 new endocrinology visits (1.6% of patients seen). During the second follow-up year (5/2022–4/2023), 22 children (4 boys, 18 girls) started treatment with GnRHa for CPP out of 2,676 new endocrinology visits (0.8% of patients seen). Age at onset of treatment, degree of bone age (BA) advancement, time from diagnosis to onset of treatment, and changes in BMI during the pandemic were not different from pre-pandemic or post-pandemic.ConclusionsCPP cases requiring GnRHa treatment significantly increased during the first year of the Covid-19 pandemic and then decreased each year post-pandemic. This was not related to BMI, age at diagnosis, degree of bone age advancement, or time from diagnosis to onset of treatment as all these factors have been similar during pre-pandemic, pandemic, and post-pandemic years. It is reasonable that the postulated hypotheses published regarding the increase during the pandemic would resolve post-pandemic.

Abstract Channel plasmonic polariton (CPP) waveguides are a promising technology for integrated photonics. They offer several advantages over other plasmonic waveguides and are well-suited for various applications. In this research, a new design of asymmetric double-trenched CPP waveguide is suggested and examined. This design consists of two silicon trenches etched into a silicon dioxide substrate layer; with a gold layer sandwiched in between. The trenches are asymmetric, with one trench being wider than the other. This asymmetry creates a spatially varying surface plasmon polariton (SPP) field, which can guide light along the waveguide. The polarization characteristics of this proposed design are analyzed over a specific wavelength range (0.7 $$-$$ - 1.7 µm) to evaluate the mode confinement of the light within the structure. The design performance was optimized by changing the gold layer thickness and the dimensions of the lower trench. Different scenarios are examined to observe TE and TM-polarized modes’ behavior within the groove. A 1867.119 dB/µm suppression level at 0.92 µm wavelength is achieved which offers a small-size component for compact photonic logic gates, enabling the development of next-generation photonic devices.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.

This study evaluated the probable relevance of a non-covalent conjugate of imatinib with TP10 in the context of a neuroprotective effect in Parkinson’s disease. Through the inhibition of c-Abl, which is a non-receptor tyrosine kinase and an indicator of oxidative stress, imatinib has shown promise in preclinical animal models of this disease. The poor distribution of imatinib within the brain tissue triggered experiments in which a conjugate was obtained by mixing the drug with TP10, which is known for exhibiting high translocation activity across the cell membrane. The conjugate was tested on the HT-22 cell line with respect to its impact on MPP+-induced oxidative stress, apoptosis, necrosis, cytotoxicity, and mortality. Additionally, it was checked whether the conjugate activated the ABCB1 protein. The experiments indicated that imatinib+PEG4+TP10 reduced the post-MPP+ oxidative stress, apoptosis, and mortality, and these effects were more prominent than those obtained after the exposition of the HT-22 cells to imatinib alone. Its cytotoxicity was similar to that of imatinib itself. In contrast to imatinib, the conjugate did not activate the ABCB1 protein. These favorable qualities of imatinib+PEG4+TP10 make it a potential candidate for further in vivo research, which would confirm its neuroprotective action in PD-affected brains.

The aim of this article is to demonstrate the advantages of the Composition of Probabilistic Preferences method in multicriteria problems with data from Likert scales. Multicriteria decision aids require a database as a decision matrix, in which two or more alternatives are evaluated according to two or more variables selected as decision criteria. Several problems of this nature use measures by Likert scales. Depending on the method, parameters from these data (e.g., means, modes or medians) are required for calculations. This parameterization of data in ordinal scales has fueled controversy for decades between authors who favor mathematical/statistical rigor and argue against the procedure, stating that ordinal scales should not be parameterized, and scientists from other areas who have shown gains from the process that compensates for this relaxation. The Composition of Probabilistic Preferences can allay the protests raised and obtain more accurate results than descriptive statistics or parametric models can bring. The proposed algorithm in R-code involves the use of probabilities with empirical distributions and fitting histograms of data measured by Likert scales. Two case studies with simulated datasets having peculiar characteristics and a real case illustrate the advantages of the Composition of Probabilistic Preferences.

Introduction: Secondary insults due to high intracranial pressure (ICP), low cerebral perfusion pressure (CPP) and impaired cerebral pressure reactivity (PRx) predict outcome after severe traumatic brain injury (TBI). Research question: What is the prevalence, co-occurrence and prognostic importance of secondary insults due to deranged ICP, CPP or PRx after TBI. Material and methods: Severe TBI patients requiring ICP monitoring were included. Secondary insults due to ICP, PRx, and CPP were defined as having at least 1 h with a mean value above (or below for CPP) a respective threshold (ICP 20, CPP 60, and PRx 0.25). Percentage time with isolated or co-occurring insults was calculated (impaired ICP only, CPP only, PRx only, ICP and PRx, ICP and CPP, CPP and PRx, ICP CPP and PRx). Prognostic importance for mortality was assessed using a logistic regression model. Results: 822 patients were included of which 76% had elevated ICP, 92% had disturbed pressure reactivity and 55% had low CPP for at least an hour. Out of the total 115,459 h, 46,111 (40%) were spent with at least one variable within the defined secondary injury range. Odds ratios for mortality were greater for combined (impaired ICP, CPP and PRx OR 1.17 95%CI 1.09 to 1.28) than isolated insults (impaired ICP only OR 1.01 95%CI 1.00–1.02, impaired CPP only 1.00 95%CI 0.95–1.05). Discussion and conclusion: ICP and autoregulation insults are common after TBI and often occur independently. Concurrent ICP, CPP and PRx insults portend worse prognosis than when a single variable is deranged.

Channel plasmonic polariton (CPP) waveguides are a promising technology for integrated photonics. They offer several advantages over other plasmonic waveguides and are well-suited for various applications. In this research, a new design of asymmetric double-trenched CPP waveguide is suggested and examined. This design consists of two silicon trenches etched into a silicon dioxide substrate layer; with a gold layer sandwiched in between. The trenches are asymmetric, with one trench being wider than the other. This asymmetry creates a spatially varying surface plasmon polariton (SPP) field, which can guide light along the waveguide. The polarization characteristics of this proposed design are analyzed over a specific wavelength range (0.7 - 1.7 µm) to evaluate the mode confinement of the light within the structure. The design performance was optimized by changing the gold layer thickness and the dimensions of the lower trench. Different scenarios are examined to observe TE and TM-polarized modes' behavior within the groove. A 1867.119 dB/µm suppression level at 0.92 µm wavelength is achieved which offers a small-size component for compact photonic logic gates, enabling the development of next-generation photonic devices. [ABSTRACT FROM AUTHOR]

The development of machine learning (ML) predictors does not necessarily require the employment of expansive classifiers and complex feature encoding schemes to achieve the highest accuracy scores. It rather requires data pre-processing, feature optimization, and robust evaluation to ensure consistent results and generalizability. Herein, we describe a multi-stage process to develop a reliable ML predictor of cell penetrating peptides (CPPs). We emphasize the challenges of: (i) the generation of representative datasets with all required pre-processing procedures; (ii) comprehensive and exclusive encoding of peptides using their amino acid composition; (iii) obtaining an optimized feature set using a simple classifier (support vector machine, SVM); (iv) ensuring consistent results; and (v) verifying generalizability at the highest achievable accuracy scores. Two peptide sub-spaces were used to generate the negative examples, which are required, along with the known CPPs, to train the classifier. These included: (i) randomly generated peptides with all amino acid types being equally represented and (ii) extracted peptides from receptor proteins. Results indicated that the randomly generated dataset performed perfectly well within its own peptide sub-space, while it poorly generalized to the other sub-space. Conversely, the dataset extracted from receptor proteins, while achieving lower accuracies, showed a perfect generalizability to the other peptide sub-space. We combined the qualities of these two datasets by utilizing the average of their predictions within our ultimate framework. This functional ML predictor, WLVCPP, and associated software and datasets can be downloaded from https://github.com/BahaaIsmail/WLVCPP. Testing machine learning predictors of cell penetrating peptides against new peptide candidates is often disappointing, despite the use of sophisticated classifiers and complex feature encoding schemes. The unrepresentativeness of used datasets, ill-conditioned data, redundant feature sets, and deficient evaluation procedures commonly lead to inconsistent results and ungeneralizable models. Accordingly, we propose a holistic strategy to negate sources of error to obtain a stable, consistent, accurate, and generalizable model. [ABSTRACT FROM AUTHOR]

The aim of this article is to demonstrate the advantages of the Composition of Probabilistic Preferences method in multicriteria problems with data from Likert scales. Multicriteria decision aids require a database as a decision matrix, in which two or more alternatives are evaluated according to two or more variables selected as decision criteria. Several problems of this nature use measures by Likert scales. Depending on the method, parameters from these data (e.g., means, modes or medians) are required for calculations. This parameterization of data in ordinal scales has fueled controversy for decades between authors who favor mathematical/statistical rigor and argue against the procedure, stating that ordinal scales should not be parameterized, and scientists from other areas who have shown gains from the process that compensates for this relaxation. The Composition of Probabilistic Preferences can allay the protests raised and obtain more accurate results than descriptive statistics or parametric models can bring. The proposed algorithm in R-code involves the use of probabilities with empirical distributions and fitting histograms of data measured by Likert scales. Two case studies with simulated datasets having peculiar characteristics and a real case illustrate the advantages of the Composition of Probabilistic Preferences. [ABSTRACT FROM AUTHOR]

Antisense peptide nucleic acids (PNAs) inhibit bacterial growth in several infection models. Since PNAs are not spontaneously taken up by bacteria, they are often conjugated to carriers such as cell-penetrating peptides (CPPs) in order to improve translocation. Hydrophobic counterions such as pyrenebutyrate (PyB) have been shown to facilitate translocation of peptides over natural and artificial membranes. In this study, the capability of PyB to support translocation of CPP-coupled antisense PNAs into bacteria was investigated in Streptococcus pyogenes and Streptococcus pneumoniae. PyB enhanced the antimicrobial activity of CPP-conjugated antisense PNAs in S. pyogenes. The most significant effect of PyB was observed in combination with K8-conjugated anti-gyrA PNAs. In contrast, no significant effect of PyB on the antimicrobial activity of CPP-conjugated PNAs in S. pneumoniae was detected. Uptake of K8-FITC into S. pyogenes, Escherichia coli, and Klebsiella pneumoniae could be improved by pre-incubation with PyB, indicating that PyB supports the antimicrobial effect of CPP-antisense PNAs in S. pyogenes by facilitating the translocation of peptides across the bacterial membrane. [ABSTRACT FROM AUTHOR]