Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. Intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. We aim to evaluate the efficacy and safety of SLN sampling in CAH managed by the da Vinci robotic platform. A total of 113 patients with a preoperative diagnosis of CAH were included in this retrospective cohort study. All underwent a robot assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy with 69 patients undergoing SLN sampling. Statistical analysis calculated the probability of cancer, SLN map rate, and surgical complications. Predictors of cancer were evaluated. Forty-seven percent of the entire cohort were diagnosed with endometrial cancer. Median age was 63 years in the SLN cohort (N = 69) and 61 in the No SLN cohort (N = 44) (p= 0.363).  Median BMI was 34 Kg/m2 in the SLN cohort and 40 in the No SLN cohort (p= 0.004). Bilateral SLN map was 92.8% and unilateral SLN map rate was 7.2%. There were no grade 3-4 complications in the SLN cohort, and 4 grade 3-4 complications in the No SLN group (p=0.021). A preoperative diagnosis of CAH bordering on or cannot rule out cancer was the only predictor of cancer.

Despite the growing capabilities of large language models, concerns exist about the biases they develop. In this paper, we propose a novel, automated mechanism for debiasing through specified dataset augmentation in the lens of bias producers that can be useful in a variety of industries, especially ones that are “restricted” and have limited data. We consider that bias can occur due to intrinsic model architecture and dataset quality. The two aspects are evaluated using two different metrics we created. We show that our dataset augmentation algorithm reduces bias as measured by our metrics.

Sparse training (ST) aims to ameliorate deep learning by replacing fully connected artificial neural networks (ANNs) with sparse or ultra-sparse ones, such as brain networks are, therefore it might benefit to borrow brain-inspired learning paradigms from complex network intelligence theory. Here, we launch the ultra-sparse advantage challenge, whose goal is to offer evidence on the extent to which ultra-sparse (around 1% connection retained) topologies can achieve any leaning advantage against fully connected. Epitopological learning is a field of network science and complex network intelligence that studies how to implement learning on complex networks by changing the shape of their connectivity structure (epitopological plasticity). One way to implement Epitopological (epi- means new) Learning is via link prediction: predicting the likelihood of non-observed links to appear in the network. Cannistraci-Hebb learning theory inspired the CH3-L3 network automata rule for link prediction which is effective for general-purpose link prediction. Here, starting from CH3-L3 we propose Epitopological Sparse Meta-deep Learning (ESML) to apply Epitopological Learning to sparse training. In empirical experiments, we find that ESML learns ANNs with ultra-sparse hyperbolic (epi-)topology in which emerges a community layer organization that is meta-deep (meaning that each layer also has an internal depth due to power-law node hierarchy). Furthermore, we discover that ESML can in many cases automatically sparse the neurons during training (arriving even to 30% neurons left in hidden layers), this process of node dynamic removal is called percolation. Starting from this network science evidence, we design Cannistraci-Hebb training (CHT), a 4-step training methodology that puts ESML at its heart. We conduct experiments on 7 datasets and 5 network structures comparing CHT to dynamic sparse training SOTA algorithms and the fully connected counterparts. The results indicate that, with a mere 1% of links retained during training, CHT surpasses fully connected networks on VGG16, GoogLeNet, ResNet50, and ResNet152. This key finding is an evidence for ultra-sparse advantage and signs a milestone in deep learning. CHT acts akin to a gradient-free oracle that adopts CH3-L3-based epitopological learning to guide the placement of new links in the ultra-sparse network topology to facilitate sparse-weight gradient learning, and this in turn reduces the convergence time of ultra-sparse training. Finally, CHT offers the first examples of parsimony dynamic sparse training because, in many datasets, it can retain network performance by percolating and significantly reducing the node network size. Our code is available at: https://github.com/biomedical-cybernetics/Cannistraci-Hebb-training.

Dynamic sparse training is an effective strategy to alleviate the training and inference demands of artificial neural networks. However, current sparse training methods face a challenge in achieving high levels of sparsity while maintaining performance comparable to that of their fully connected counterparts. The Cannistraci-Hebb training (CHT) method produces an ultra-sparse advantage compared to fully connected training in various tasks by using a gradient-free link regrowth method, which relies solely on the network topology. However, its rigid selection based on link prediction scores may lead to epitopological local minima, especially at the beginning of the training process when the network topology might be noisy and unreliable. In this article, we introduce the Cannistraci-Hebb training soft rule (CHTs), which applies a flexible approach to both the removal and regrowth of links during training, fostering a balance between exploring and exploiting network topology. Additionally, we investigate the network topology initialization using several approaches, including the bipartite scale-free and bipartite small-world network models. Empirical results show that CHTs can surpass the performance of fully connected networks with MLP architecture by using only 1% of the connections (99% sparsity) on the MNIST, EMNIST, and Fashion MNIST datasets and can provide remarkable results with only 0.1% of the links (99.9% sparsity). In some MLPs for image classification tasks, CHTs can reduce the active neuron network size to 20% of the original nodes (neurons), demonstrating a remarkable ability to generalize better than fully connected architectures, reducing the entire model size. This represents a relevant result for dynamic sparse training. Finally, we present evidence from larger network models such as Transformers, with 10% of the connections (90% sparsity), where CHTs outperform other prevalent dynamic sparse training methods in machine translation tasks.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

RNA sequencing techniques, like bulk RNA-seq and Single Cell (sc) RNA-seq, are critical tools for the biologist looking to analyze the genetic activity/transcriptome of a tissue or cell during an experimental procedure. Platforms like Illumina's next-generation sequencing (NGS) are used to produce the raw data for this experimental procedure. This raw FASTQ data must then be prepared via a complex series of data manipulations by bioinformaticians. This process currently takes place on an unwieldy textual user interface like a terminal/command line that requires the user to install and import multiple program packages, preventing the untrained biologist from initiating data analysis. Open-source platforms like Galaxy have produced a more user-friendly pipeline, yet the visual interface remains cluttered and highly technical, remaining uninviting for the natural scientist. To address this, SeqMate is a user-friendly tool that allows for one-click analytics by utilizing the power of a large language model (LLM) to automate both data preparation and analysis (differential expression, trajectory analysis, etc). Furthermore, by utilizing the power of generative AI, SeqMate is also capable of analyzing such findings and producing written reports of upregulated/downregulated/user-prompted genes with sources cited from known repositories like PubMed, PDB, and Uniprot.

We generalize the point information gain (PIG) and derived quantities, i.e., point information gain entropy (PIE) and point information gain entropy density (PIED), for the case of the Rényi entropy and simulate the behavior of PIG for typical distributions. We also use these methods for the analysis of multidimensional datasets. We demonstrate the main properties of PIE/PIED spectra for the real data on the example of several images, and discuss further possible utilizations in other fields of data processing.

Backround: FNH is a common benign liver lesion, mostly solitary, and with no evidence of malignant transformation over time. The diagnosis can usually be made by imaging modalities with distinct features in MRI- and CT-scans. Case series: We present a case series of three patients with solitary liver tumors which were highly suspicious to be large FNH, based on radiological features. The patients were sent to our center for second opinion and probable treatment. Indication for resection was given because of nonconclusive radiologic imaging in the first, substantial growth progression in the second and elevated AFP in the third case. Histology revealed well to poor differentiated HCCs. Discussion: FNH tends to show a distinct pattern in imaging modalities, but HCC can mimic FNH. The MRI-scan using hepatotropic contrast agent is the most sensitive imaging modality to diagnose FNH. AFP is usually not elevated in FNH. Asymptomatic FNH does not require surgery but a reliable diagnosis is crucial. In case of an uncertain diagnosis surgery should be offered to patients. Conclusion: In cases with a progression in size, an elevated level of AFP should be suspicious. A second opinion at a center for hepato-biliary surgery with HCC/FNH-experienced radiologists and surgeons is reasonable. Generally, an over-therapy via surgery should be avoided and follow-ups of a newly diagnosed FNH including measurement of AFP are advisable to detect alterations.

The aim of the study was to examine the long-term prognostic value of changes in cardio-ankle vascular index (CAVI) within a year after coronary artery bypass grafting (CABG). Methods. Patients with coronary artery disease (n = 251) in whom cardio-ankle vascular index (CAVI) was assessed using the VaSera VS-1000 device before and in a year after CABG. Groups with improved CAVI (CAVI decreased from pathological value to normal or the index remained within normal values) or worsened CAVI (persistent pathological index value or an increase in CAVI to pathological values or an increase of 1 unit or more) were identified. The groups were compared for the following events at 10-year follow-up: death from all causes, myocardial infarction, stroke/transient ischemic attack, and the combined endpoint. Results. A year after CABG surgery, 45% of patients showed positive dynamics or stable normal CAVI values. Death from all causes was significantly more common in the group with CAVI progression - 32 (27.6%) than in the group with CAVI improvement - 14 (14.8%; p = 0.029). Patients with CAVI progression were more likely to have MACE (death, MI, stroke/TIA) in 49 (42.2%) cases, compared with patients with CAVI improvement - in 23 (24.5%; p=0.008). Negative dynamics of CAVI (p = 0.024), number of shunts (p = 0.006), and the presence of carotid stenosis more than 30% (p = 0.051) were independent predictors of death from all causes at 10-year follow-up after CABG. The presence of carotid stenosis more than 30% (p = 0.002) and the group with negative dynamics of CAVI after a year (p = 0.008) were independent predictors of the development of the combined endpoint during long-term follow-up. Conclusions. Patients with negative dynamics of CAVI one year after CABG were more likely to experience death from all causes and combined endpoint in the long-term follow-up than patients with normal CAVI. In further studies, it is advisable to evaluate the dynamics of CAVI and, based on this, identify the most effective interventions to improve the prognosis of patients after CABG.

With the rapid growth of large language models (LLMs), there is increasing demand for memory and computation in LLMs. Recent efforts on post-training pruning of LLMs aim to reduce the model size and computation requirements, yet the performance is still sub-optimal. In this paper, we present a plug-and-play solution for post-training pruning of LLMs. The proposed solution has two innovative components: 1) Relative Importance and Activations (RIA), a new pruning metric that jointly considers the weight and activations efficiently on LLMs; and 2) Channel Permutation, a new approach to maximally preserve important weights under N:M sparsity. The two proposed components can be readily combined to further enhance the N:M semi-structured pruning of LLMs. Our empirical experiments show that RIA alone can already surpass all existing post-training pruning methods on prevalent LLMs, e.g., LLaMA ranging from 7B to 65B. Furthermore, N:M semi-structured pruning with channel permutation can even outperform the original LLaMA2-70B on zero-shot tasks, together with practical speed-up on specific hardware. Our code is available at: https://github.com/biomedical-cybernetics/Relative-importance-and-activation-pruning

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

Graves' disease (GD) is an autoimmune disorder in which Thyrotropin Receptor Antibodies (TRAb) continuously stimulate thyroid receptors, leading to excessive production of thyroid hormones. TRAb also affect the orbital tissues, causing Graves' ophthalmopathy. Treatment to control Graves' disease consists of antithyroid drugs, radioiodine and thyroidectomy, and through such treatments, TRAb is reduced and the disease is alleviated. The mechanism by which TRAb, which play a critical role in the pathogenesis of Graves’ disease, decreases after GD treatment is still unknown. This paper presents a theoretical mechanism of how GD patients maintain a vicious cycle and how GD treatment can reduce the TRAb levels and breaks the cycle using stress-based ideas.

Complexity science studies physical phenomena that cannot be explained by the mere analysis of the single units of a system but requires to account for their interactions. A feature of complexity in connected systems is the emergence of mesoscale patterns in a geometric space, such as groupings in bird flocks. These patterns are formed by groups of points that tend to separate from each other, creating mesoscale structures. When multidimensional data or complex networks are embedded in a geometric space, some mesoscale patterns can appear respectively as clusters or communities, and their geometric separability is a feature according to which the performance of an algorithm for network embedding can be evaluated. Here, we introduce a framework for the definition and measure of the geometric separability (linear and nonlinear) of mesoscale patterns by solving the travelling salesman problem (TSP), and we offer experimental evidence on embedding and visualization of multidimensional data or complex networks, which are generated artificially or are derived from real complex systems. For the first time in literature the TSP’s solution is used to define a criterion of nonlinear separability of points in a geometric space, hence redefining the separability problem in terms of the travelling salesman problem is an innovation which impacts both computer science and complexity theory.

Background: Pediatric mallet finger injuries lack specific treatment guidelines, necessitating an exploration of effective techniques. Our aim was to evaluate the outcomes of the extension block technique in adolescent mallet finger management. Methods: A comprehensive retrospective analysis was conducted involving 36 adolescents who underwent surgery between 2014 and 2022. Ishiguro’s extension block pinning technique was the primary method employed. Treatment outcomes were evaluated using Crawford's criteria, and complications were also assessed. Results: Bone union was achieved in all cases with a mean union time of 42 days (range: 30-92 days). According to Crawford's criteria, 27 cases (75%) were classified as excellent, 5 cases (14%) as good, and 4 cases (11%) as fair. Minimal complications were observed, including three cases (8%) of superficial infections, one case (3%) of dermal necrosis, and another rare instance (3%) of osteomyelitis. No cases of poor outcomes or significant long-term complications were noted. The average follow-up period was 8.6 months (range: 2-42 months). Conclusions: Ishiguro’s extension block technique is a promising surgical option for adolescent mallet fingers. Its adoption could enhance pediatric orthopedic care, offering a valuable child-friendly treatment alternative.

Microwave technology has a potential application in the extraction of zinc from sulphide ores, knowledge of the dielectric properties of these ores plays a major role in the microwave design and simulation for any process. The dielectric properties of zinc sulfide concentrate for two different apparent densities—1.54 and 1.63 g/cm³—have been measured by using the resonance cavity perturbation technique at 915 and 2450 MHz during the roasting process for the temperature ranging from room temperature to 850 °C. The variations of dielectric constant, the dielectric loss factor, the dielectric loss tangent and the penetration depth with the temperature, frequency and apparent density have been investigated numerically. The results indicate that the dielectric constant increases as the temperature increases and temperature has a pivotal effect on the dielectric constant, while the dielectric loss factor has a complicated change and all of the temperature, frequency and apparent density have a significant impact to dielectric loss factor. Zinc sulfide concentrate is high loss material from 450 to 800 °C on the basis of theoretical analyses of dielectric loss tangent and penetration depth, its ability of absorbing microwave energy would be enhanced by increasing the apparent density as well. The experimental results also have proved that zinc sulfide concentrate is easy to be heated by microwave energy from 450 to 800 °C. In addition, the experimental date of dielectric constant and loss factor can be fitted perfectly by Boltzmann model and Gauss model, respectively.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Objective To assess the quality and readability of online information on holmium laser enucleation of the prostate in management of benign prostate hyperplasia using the most used search engine worldwide, google. Methods The google search term “Holmium laser surgery” and “enlarged prostate” was used and the initial 150 webpages were reviewed. Webpages that were paywall, scientific literature, and/or promoted advertisements were excluded. Quality assessment tools - DISCERN, QUEST, and JAMA criteria were used, while readability tools like FKG, GFI, SMOG, and FRE score were used. Two authors independently reviewed the included sites for further analysis; for any discrepancy, a third author would be involved. Results 107 webpages were included in the data analysis. The median DISCERN score was 42 out of 80 (IQR 35-49). The median JAMA score was 0 out of 4 (IQR 0-1). The median QUEST score was 9 out of 28 (IQR 9-12). Using the non-parametric ANOVA and post-hoc test, significant differences were identified between rankings of webpages. Sponsorship had no influence on quality of webpages. Overall readability level required a minimum reading level of grade 11. Linear regression analysis showed a higher rank webpage is a positive predictor for all three quality assessment tools. Conclusion The overall quality of online information regarding HoLEP is poor. We identify that top ranked google searches have a higher DISCERN score and is a positive predictor for DISCERN/QUEST/JAMA. Quality online information can be used to benefit patients but should be used in conjunction with consultation from a medical professional.

While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, joint), mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides, and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical pictures is attributed to complex interplay of host characteristics (hygiene, aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance, species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions.

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL with the coexistence of CD19, CD20, CD5, and CD23 and the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Atypical CLL cells are defined as prolymphocytes; morphologically, these present as deeply-clefted lymphocytes which are larger than those in typical CLL, with condensed chromatin and without prominent nucleoli. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression compared with classic CLL. However, no standard or commonly-accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic and genetic abnormalities of aCLL.

The real systems are often complex, nonlinear, and noisy in various areas including mathematics, natural science, and social science. We present the symplectic entropy (SymEn) measure as well as an analysis method based on SymEn to estimate the nonlinearity of the complex system by analyzing the given time series. The SymEn estimation is a kind of entropy based on symplectic principal component analysis (SPCA) which represent organized but unpredictable behaviors of systems. The key to SPCA is to preserve the global submanifold geometrical properties of the systems through symplectic transform in the phase space, which is a kind of the measure-preserving transforms. The capability of preserving the global geometrical characteristics makes the SymEn a test statistic to detect the nonlinear characteristics in several typical chaotic time series and the stochastic characteristic in the Gaussian white noise. The results are in agreement with findings in the approximate entropy (ApEn), the sample entropy (SampEn) and the fuzzy entropy (FuzzyEn). Moreover, the SymEn method is also used to analyze the nonlinearities of the real signals (including the EEG signals for ASD and healthy subjects, and the sound and vibration signals for the mechanical systems). The results indicate that the SymEn estimation can be taken as a measure for describing the nonlinear characteristics in the data collected from the natural complex systems.

Almost two decades ago, Ernesto P. Borges and Bruce M. Boghosian embarked on the intricate task of composing a manuscript to honor the profound contributions of Constantino Tsallis to the realm of statistical physics, coupled with a concise exploration of q-Statistics. Fast forward to Constantino Tsallis’ illustrious 80th birthday celebration in 2023, where Deniz Eroglu and Ugur Tirnakli delved into Constantino’s collaborative network, injecting renewed vitality into the project. With hearts brimming with appreciation for Tsallis’ enduring inspiration, Eroglu, Boghosian, Borges and Tirnakli proudly present this meticulously crafted manuscript as a token of their gratitude.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

An information-theoretic data mining method is employed to analyze categorical spatiotemporal Geographic Information System land use data. Reconstructability Analysis (RA) is a maximum-entropy-based data modeling methodology that works exclusively with discrete data such as those in the National Land Cover Database (NLCD). The NLCD are organized into a spatial (raster) grid, and are available in consistent format for every five years from 2001 to 2021. An NLCD tool reports how much change occurred for each category of land use; for the study area examined the most dynamic class is Evergreen Forest (EFO), so the presence or absence of EFO in 2021 was chosen as the dependent variable that our data modeling attempts to predict. RA predicts the outcome with approximately 80% accuracy using a sparse set of cells from a spacetime data cube consisting of neighboring lagged-time cells. When the predicting cells are all Shrubs & Grasses there is a high probability for a 2021 state of EFO, while when the predicting cells are all EFO, there is a high probability that the 2021 state will be not-EFO. These findings are interpreted as detecting forest clear-cut cycles that show up in the data, and explain why this class is so dynamic. This study introduces a new approach to analyzing GIS categorical data and expands the range of applications that this entropy-based methodology can successfully model.

Presenting a case report about an occurrence of duodeno-duodenal intussusception in a 17-year-old female patient. Intussusception is typically observed in children. The patient has a history of recurrent pain and vomiting for four days. During the examination tenderness in the epigastric area worsened when the legs were elevated. An initial X-ray of the abdomen was done and the findings were normal. Subsequent ultrasound and abdominal CECT scans of the abdomen revealed intussusception involving the 2^nd, 3^rd, and 4^th part of the duodenum ampulla of Vater and pancreas without any identifiable cause for this condition. There was no abnormal thickening of the wall. This case shows how using radiological imaging and surgical management helps to prevent severe complications in cases like duodeno-duodenal intussusception in adults.

Atypical Anorexia Nervosa (AAN) had been found to have significant physical and psychological complications at presentation but has not been described in a multi-ethnic Asian population. This retrospective cohort analysis aimed to characterize the baseline presentation of adolescents with Anorexia nervosa (AN) (N=317) and AAN (N=141) in an Asian cohort that presented to a specialist paediatric eating disorder program between January 2010 to October 2020 for assessment. In patients with AAN, there were increased proportions of males (16% vs 7%) and of Malay ethnicity (11% vs 4%) compared to AN. Adolescents with AAN had lower admission rates (61% vs 81%) as well as lower rates of bradycardia (45% vs 75%) and hypotension (7% vs 21%) but higher rate of syncope (13% vs 7%) compared to adolescents with AN. However, adolescents with AAN had higher frequency of psychological complications including self-harm and drug overdose (14% vs 1.5%) requiring admission as well as higher rates of purging (45.1% vs 14.8%) and for Eating Disorder Questionnaire score in the shape domain was more severe. Asian adolescents with AAN manifest with physical complications of malnutrition and had worse eating disorder psychopathology with higher frequency of other psychological co-morbidities underlining the severity of the illness.

Macrophage Migration Inhibitory Factors (MIF) are pivotal cytokines/chemokines for vertebrate immune systems. MIFs are typically soluble single-domain proteins that are conserved across plant, fungal, protist, and metazoan kingdoms but their functions have not been determined in most phylogenetic groups. Here we describe an atypical multidomain MIF protein. The marine dinoflagellate Lingulodinium polyedra produces a transmembrane protein with an extra-cytoplasmic MIF domain, which localizes to cell wall-associated membranes and vesicular bodies. This protein is also present in the membranes of extracellular vesicles accumulating at the secretory pores of the cells. Upon exposure to biotic stress, L. polyedra exhibits reduced expression of the MIF gene and reduced abundance of the surface-associated protein. These findings indicate that the transmembrane MIF may contribute to intercellular communication and/or interactions between free-living organisms in multispecies planktonic communities and raise the question of possible analogies in MIF functions between cells of metazoan organisms and protist communities.

In addition to their importance in statistical thermodynamics, probabilistic entropy measurements are crucial for understanding and analyzing complex systems, with diverse applications in time series and one-dimensional profiles. However, extending these methods to two- and three-dimensional data still requires further development. In this study, we present a new method to classify spatiotemporal processes based on entropy measurements. To test and validate the method, we selected four classes of similar processes related to the evolution of random patterns: dynamic colored noises ((i)~white and (ii)~red); (iii)~weak turbulence from reaction-diffusion; (iv)~hydrodynamic fully developed turbulence, and (v)~plasma turbulence from MHD. Considering seven possible ways to measure entropy from a matrix, we present the method as a parameter space composed of the two best separating measures of the five selected classes. The results highlight better combined performance of Shannon Permutation Entropy ($S^p_H$) and a new approach based on Tsallis Spectral Permutation Entropy ($S^s_q$). Notably, our observations reveal the segregation of reaction terms in this $S^p_H \times S^s_q$ space, a result that identifies specific sectors for each class of dynamic process, and can be used to train machine learning models for automatic classification of complex spatiotemporal patterns.

This paper describes the first results of an Image Recognition Based Location (IRBL) for mobile application focusing on the procedure to generate a Database of range images (RGB-D). In an indoor environment, to estimate the camera position and orientation, a prior spatial knowledge of the surrounding is needed. In order to achieve this objective a complete 3D survey of two different environment (Bangbae metro station of Seoul and E.T.R.I. building in Daejeon – Republic of Korea) was performed using LiDAR (Light Detection And Ranging) instrument and the obtained scans were processed in order to obtain a spatial model of the environments. From this, two databases of reference images were generated using a specific software realized by the Geomatics group of Politecnico di Torino (ScanToRGBDImage). This tool allow to generate synthetically different RGB-D images) centered in the each scan position in the environment. Later, the external parameters (X, Y, Z, ω, φ, κ) and the range information extracted from the DB images retrieved, are used as reference information for pose estimation of a set of acquired mobile pictures in the IRBL procedure. In this paper the survey operations, the approach for generating the RGB-D images and the IRB strategy are reported. Finally the analysis of the results and the validation test are described.

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

We describe a family of paraxial and quasi-monochromatic optical wave packets with finite energy and smoothly shaped amplitude in space and time that develops a singularity in the intensity when spatiotemporally focused by imparting a converging spherical wave front and a negative temporal chirp. This singular behavior upon ideal focusing is manifested in actual focusing with finite apertures and in media with high-order dispersion in an "exploding" behavior featuring indefinitely increasing concentration of the energy when opening the aperture radius, thus exercising a continuous control on the focal intensity and spatial and temporal resolution. These wave packets offer a new way of focusing that outperforms what can be achieved with standard Gaussian wave packets in terms of focal intensity and resolution, and new possibilities in applications where energy concentration and its control are crucial.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

S. aureus is an alarming human pathogen since it triggers numerous diseases, including impetigo and pneumonia. The S. aureus' ability to colonise the upper respiratory tract and other tissues, such as the skin, throat and gut, operate as reservoirs for infection. Indeed, being a carrier of S. aureus in the gut represents a risk factor for developing infection in distinct sites, including an unusual gastrointestinal tract disease. Here, we present an atypical clinical course of staphylococcal enterocolitis (SEC) in a man in his early seventies. After an unforeseen identification of methicillin-resistant Staphylococcus aureus (MRSA), the oral administration of vancomycin was critical in the outcome of the case. Although infrequent, SEC is an underestimated disease and requires a chapter in the treatment recommendations for antibiotic-related diarrhoea. Awareness of the risk factors and diagnostic tests, along with including SEC in algorithms for handling antibiotic-associated diarrhoea, is a step towards new epidemiological information.

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

Super-high (x400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received an x20 (D20) and x400 (D400) magnification dermoscopic examination of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20 atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p<0.001). At D400 melanoma showed more frequently than benign lesions melanocytes with an irregular arrangement and irregular in shape and size (p<0.001). Network with edged papillae was more frequent in benign lesions than melanomas (p<0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement and irregular in shape and size in melanomas, adding information to the conventional D20 examination.

In this paper, a complete tool for real-time detection of atypical energy behaviors of airplanes is presented. The methodology extends in real time an existing offline process using Dubins trajectories as a predictor of the remaining distance to the runway threshold. Two major contributions are presented in this paper. First, a real-time measure of the aircraft energy behaviour is defined, indicating whether the aircraft is in good condition to intercept the extended runway centreline from its current position. Secondly, a 2D trajectory suggestion is given, allowing safe management of the approach path according to atypical criteria of historical data. Finally, this document proposes a comprehensive tool for air traffic controllers, which is a major step forward in understanding, becoming aware of and resolving critical situations that could lead to accidents.

Atypical antipsychotic drugs were introduced in the early 1990th. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics show effectiveness against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic, but also in affective disorders, by their own or as adjuncts to antidepressant drugs. While typical antipsychotics act, almost exclusively, via dopamine-2 (D2) receptors, atypical target serotonin-1A/1B/2A/2C (5-HT1A/1B/2A/2C), α1/2-adrenergic, and/or histamine-1 (H1) receptors as well. Blocking of 5-HT1A/1B autoreceptors, inducing their early desensitization, and/or activation of α1-adrenoceptors, allow some atypical drugs to enhance 5-HT transmission. Blocking of 5-HT2A/2C and/or α2-adrenoceptors enable some atypical antipsychotics to stimulate catecholamine transmission and/or diminish the inhibition of catecholamine neurons induced by some antidepressants. It is possible, that the activation of H1 and/or blocking of H3 boost monoamine transmission as well, via a mechanism involving stimulation of firing activity of dopamine neurons. The experimental drugs with antipsychotic potential, acting on adenosine and trace amino associated (TAAR) receptors, might be effective in mood disorders as well, because of the ability to modulate the excitability of monoamine-secreting neurons and to potentiate extracellular concentrations of monoamines in the limbic areas of the brain.

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential for sustenance of life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context, to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were tested and implemented for mostly cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more complex systems (for instance, multi-protein complexes, oligomeric assemblies, membrane proteins and post-translationally modified proteins), the initial axioms defined by Michaelis-Menten (MM) kinetics are rendered inadequate and the development of a new kind of kinetic analysis to study these systems is required. The current review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug-discovery for such systems, to enable effective screening and characterisation of small-molecule inhibitors with desirable physiological outcomes.

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

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system caused by myelin-specific autoreactive T cells. We previously demonstrated intestinal barrier disruption and signs of inflammation in experimental autoimmune encephalomyelitis (EAE), a model of MS. Fecal calprotectin is a disease activity biomarker in inflammatory bowel diseases, released by neutrophils in response to inflammation. We aimed to further investigate EAE manifestations in the gastrointestinal tract, and to determine whether calprotectin is a useful biomarker of intestinal inflammation in EAE. Calprotectin was analyzed in feces, cecal contents, and plasma of EAE mice. Infiltrating neutrophils and goblet cells were investigated in different parts of the gastrointestinal tract, before onset of neurological symptoms and during established disease. We found increased calprotectin levels in feces, cecal content and plasma, preceding EAE onset that further escalated during disease progression. Increased neutrophil infiltration in the intestinal tissue concomitant with IL-17 expression and myeloperoxidase activity was found correlating well with clinical activity. Increased goblet cells in intestine similar to irritable bowel syndrome (IBS) were also observed. The results suggest calprotectin as a good biomarker of gastrointestinal inflammation in EAE, also the potential of this model as a useful animal model for IBS.

We evaluated diagnostically differential radiological findings between focal nodular hyperplasia (FNH)-like lesions and hepatocellular carcinoma (HCC). We studied pathologically confirmed FNH-like lesions in 13 alcoholic-cirrhosis patients who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography (CT) and magnetic resonance imaging (MRI), including superparamagnetic iron oxide (SPIO) and/or gadoxetic acid-enhanced MRI. Seven patients underwent angiography-assisted CT. Evaluated lesion features included arterial enhancement pattern, washout appearance (low density compared to surrounding liver parenchyma), signal intensity on T1-weighted image (T1WI) and T2-weighted image (T2WI), central scar presence, chemical shift on in- and out-of-phase images, and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and on SPIO-enhanced MRI. Eleven patients had multiple small lesions (<1.5 cm). Radiological features of FNH-like lesions included hypervascularity despite small lesion, lack of “corona-like” enhancement in the late phase on CT during hepatic angiography (CTHA), high-intensity on T1WI, slightly high- or iso-intensity on T2WI, no signal decrease in out-of-phase images, and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid. Pathologically, like HCC, FNH-like lesions showed many unpaired arteries and sinusoidal capillarization. In summary, FNH-like lesions have unique radiological findings useful for differential diagnosis. Specifically, SPIO- and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent outbreak in several countries around the world. A 39-year-old male with HIV-HBV coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox infection, presented to our hospital with disseminated dermatosis (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for Mpox. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. After 65 days of Mpox PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox infection because it could be related to higher mortality.

Based on the dynamic strength variation mechanism of concrete under complex loading conditions, two approaches were devised: numerical testing and CT scanning, guided by the principle of minimizing energy dissipation. A methodology for calculating concrete's failure area and measuring its strength was developed. The analysis delves into the mechanisms behind failure patterns and variations in concrete specimen strength, focusing on crack initiation, development, and the resultant failure surface formed by crack propagation, along with the stress distribution in concrete specimens subjected to diverse loading conditions. Through evaluating the strength and computed failure area of concrete specimens, it is evident that the loading method influences both the strength and failure area of concrete specimens. In general, a larger failure area correlates with a higher measured strength.

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.

Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.

The Marun-Keu complex plays a significant role in understanding the geological evolution of the Ural orogen; however, it remains poorly understood. This study aims to provide insights into the complex's age, protolith composition, rock formation conditions, and its position in the region's history. The zircons from the host granitic gneisses are characterized by magmatic cores with an age of 470 Ma and metamorphic rims with an age of approximately 370 Ma. We suggest that the metamorphic rims were formed during eclogite metamorphism and that the metagranitoids hosting the eclogites experienced eclogite metamorphism simultaneously with the basic and ultrabasic rocks that are common in this area. Heterogeneous zircons were also isolated from the selvage of a pegmatite vein, in which four domains are distinguished, two to three of which can be identified within single grains, as follows: 1) igneous cores with an age of approximately 470 Ma and the geochemical characteristics of zircon crystallized in basic rocks; 2) zircons recrystallized during eclogite metamorphism with geochemical characteristics intermediate between those of the magmatic cores and true eclogitic zircon; 3) pegmatitic zircon, exhibiting the most sharply differentiated REE spectra of all four domains, characterized by a prominent positive Ce anomaly and a weakly expressed negative Eu anomaly; and 4) eclogitic zircon, observed in the form of veins and rims, superimposed in relation to the other three domains. The age of the latter three domains is within the error range and is estimated to be approximately 370 Ma. This indicates that the processes of eclogite metamorphism and the formation of pegmatites occurred at approximately the same time in the studied area.

In the current era of emerging technologies and cutting-edge inventions, it is equally important to consider the ethical aspects of research and innovations to have an ethical space for the sustainable progress and safety of humanity. The field of nanotechnology research and innovation often faces criticism due to its potential adverse impacts on health, the environment, limited accessibility, high costs, and concerns about data privacy. Therefore, it is crucial to address and resolve these ethical issues systematically. In this regard, we present our findings and methods for exploring the application of the ethics technology assessment method by considering its relevance at different stages of innovation development. Specifically, the present work provides a conceptual framework for ethics technology assessment focused on evaluating a significant innovation in nanotechnology within the domain of food safety with specific reference to mycotoxin remediation. By leveraging the value-sensitive design approach, we described various strategies for analyzing the ethical implications of nanotechnology-based innovations in mycotoxin remediation. Through comprehensive ethics technology assessment, nanotechnology-based innovations can be guided toward becoming more value-oriented, thereby making substantial contributions to social progress.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

This study addresses the critical need for standardizing Building Information Modeling (BIM) Execution Plans (BEPs) in the Architecture, Engineering, Construction, and Operations (AECO) sector. By analyzing 36 BEP documents from international organizations, we identify key elements and propose a comprehensive framework aimed at enhancing digital transformation and collaboration in complex construction projects. This research employs scientometric analysis to map the evolution of BEP standards and integrates empirical data from industry surveys to validate the proposed framework. Our findings highlight the benefits of standardized BEPs in reducing inefficiencies and improving project outcomes, thereby providing a significant contribution to the field of BIM implementation.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Watching the international COVID-19 epidemics unfold during February and early March 2020, we began to highlight how outbreaks in care homes were inevitable, given the vulnerable patients in close proximity, and pressures on social care to help relieve pressure on the NHS. We suggested public health measures would significantly impact on care homes. Specifically we felt all homes would have multiple individuals isolated within days of introduction of guidance requiring isolation of new cough (or fever), and that a clear definition of an outbreak would be needed that differentiated COVID19 from influenza. We share the experiences of a GP practice looking after 900 nursing or dual registration care homes in the London Borough of Ealing in the early stages of the COVID19 Pandemic 2020. We believe that the altered presentation of cases of COVID19 in care homes contributed to the size of outbreaks, and that keeping COVID19 out of homes is the only way to manage this disease, with early isolation and complete segregation of positive and negative cases. We have seen over 300 suspected cases resulting in four fold (n=175) average monthly death rates, three fold usual issue of anticipatory medications, and approximately 32% mortality rate (up to 43% in over 90’s). Discharge pathways from hospital and admissions to care homes must be clear and robust. COVID19 naïve patients should not be admitted to units with outbreaks and COVID19 positive patients should not be admitted to anything other than a designated “hot” home until risk of contagion is passed. Some patients are testing positive at over 30 days since initial mild symptoms.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

Background: The psychomotor agitation of the behavioural and psychological symptoms of dementia (BPSD) is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferred choice of treatment, but which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from Randomised Control Trials (RCTs) and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who have taken agitation treatments. Assessing the efficacy of selective serotonin reuptake inhibitors (SSRI) and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This review includes RCT that compared one or more active ingredient medications with another medication or with a placebo, along with systematic reviews comparing citalopram (SSRI) with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies were extracted by searching and accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Conclusion: There is still limited studies of SSRIs for the treatment of agitation in BPSD. SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. Future studies are required to assess the long-term safety and efficacy of SSRI treatments for agitation in BPSD.

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

A hybrid material, consisting of commercially available nitrocellulose (NC) membrane non-covalently modified with amino-polyethylene glycol functionalized reduced graphene oxide (NH2-PEG-rGO) nanoparticles, was successfully synthesized for oligonucleotide extraction. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the modification of the NC membrane, revealing characteristic peaks of both compounds NC and NH2-PEG-rGO. Scanning Electron Microscopy (SEM) exhibited morphological changes in the NC/NH2-PEG-rGO hybrid membrane, marked by the introduction of NH2-PEG-rGO particles, resulting in a distinctly smothered surface compared to the porous surface of the NC control membrane. Wettability assays revealed hydrophobic behavior for the NC/NH2-PEG-rGO hybrid membrane, with a water contact angle exceeding 90°, contrasting with the hydrophilic behavior characterized by a 16.7° contact angle in the NC membrane. The performance of the NC/NH2-PEG-rGO hybrid membrane was evaluated for the extraction of ssDNA with fewer than 50 nucleotides from solutions containing various ionic species (MnCl2, MgCl2, and MnCl2/MgCl2). The NC/NH2-PEG-rGO hybrid membrane exhibited optimal performance when incubated in MgCl2, presenting the highest fluorescence emission at 525 relative fluorescence units (r.f.u.). This corresponds to the extraction of approximately 610 pg (≈13%) of the total oligo-DNA, underscoring the efficacy of the pristine material, which extracts 286 pg (≈6%) of oligo-DNA in complex solutions.

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.

Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target-ligand complexes. Large, linear peptides like the tail regions of histones are challenging ligands for docking due to their large conformational flexibility, extensive hydration, and weak interactions with the shallow binding pockets of their reader proteins. Thus, fast docking methods often fail to produce complex structures of such peptide ligands at a level appropriate for drug design. To answer this challenge, and improve the structural quality of the docked complexes, post-docking refinement has been applied using various molecular dynamics (MD) approaches. However, a final consensus has not been reached on the desired MD refinement protocol. In the present study, MD refinement strategies were systematically explored on a set of problematic complexes of histone peptide ligands with relatively large errors in their docked geometries. Six protocols were compared that differ in their MD simulation parameters. In all cases, pre-MD hydration of the complex interface regions was applied to avoid the unwanted presence of empty cavities. The best-performing protocol achieved a median of 32 % improvement over the docked structures in terms of the change of root mean squared deviations from the experimental references. The influence of structural factors and explicit hydration on the performance of post-docking MD refinements was also discussed to help their implementation in future methods and applications.

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.

The Great Reset has been presented by the World Economic Forum (WEF) in response to the COVID-19 pandemic in 2022 as a model through which a “stakeholder economy” would achieve “resilient, equitable and sustainable” economic, social and environmental goals. A more equitable distribution of resources, better working conditions, and ecological transitions are included in a social, economic and environmental reform agenda. This article raises the question of whether the Great Reset project should be interpreted as a “realistic utopia” and what is its reform potential. In an attempt to answer the question of whether the Great Reset as a realist utopia is consistent with the current state of science and philosophy, the article re-examines the idea of utopia in the light of recent philosophical and scientific approaches, such as critical realism in philosophy, so-cial systems theory in sociology and complexity theory in science. A comparative conceptual analysis is carried out and discussed introducing the idea of a realist utopia in Rawls' theory of justice as fairness. In the final discussion, some doubts are raised about the logical coherence, rigor of scientific theorizing, policy prescriptions, and predictive potential of the Great Reset emerging paradigm. It is concluded that utopian projects of radical reform can become realistic when they offer explanations of the deep structural changes that underlie social and economic evolution, drawing from these explanations the policy implications and prescription that can support struc-tural changes, rather than from assumed long-term effects of exogenous shocks or “black swan” events such as the COVID-19 pandemic.

Atypical Polypoid Adenomyoma (APA) is a benign uterine lesion that occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Our work consists of a systematic review of the literature, including the description and analysis of a case study, and assesses the main immunohistochemical and molecular markers that contribute to making a differential diagnosis against endometrial adenocarcinoma. This allows offering patients conservative treatment compared to the radical management required for endometrial cancer, due to the significant physical and psychological consequences that one procedure or another can have on women's health. The goal of this research is to carry out an adequate diagnosis of APA by providing the necessary information to guide clinical management, establish patient prognosis, and minimize the emotional impact associated with the disease, all in combination with clinical and histopathological findings and complementary imaging tests. In conclusion, an appropriate immunohistochemical and molecular approach, along with the presumptive histological diagnosis, determine the correct classification of the lesion as APA and not as other malignant pathologies, which allows establishing a treatment protocol adjusted to the biological reality of this pathology.

Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from 2 independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant Prx3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.

GABAA receptors are channel proteins crucial to mediating neuronal balance in the CNS. The structure of GABAA receptors allows for multiple binding sites and is key to drug development. Yet, the formation mechanism of the receptor’s distinctive pentameric structure is still unknown. This study aims to investigate the role of three predominant subunits of the human GABAA receptor in the formation of protein pentamers. Through purifying and refolding the protein fragments of the GABAA receptor α1, β2, and γ2 subunits, homopentamers were visualised with negative staining and Cryo-EM. To aid the analysis, AlphaFold2 was used to compare the structures. Results show that α1 and β2 subunit fragments successfully formed homo-oligomers, particularly homopentameric structures, while the predominant heteropentameric GABAA receptor was also replicated through the combination of the three subunits. However, it is still unclear whether γ2 subunits can form homopentamers or their main purpose is to bring together the α1 and β2 subunits to form GABAA receptors. Nevertheless, this study will lead to a deeper understanding of the atomic structure of GABAA receptors, especially in the formation mechanism of complex protein structures, and hopefully pave the way to the development of novel therapeutics for neuropsychiatric diseases.

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under under investigation. The dentate gyrus, a structure highly susceptible to injury, and has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by non-biased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-seq was performed to determine differential gene expression in PTE+ vs. PTE- that may comport with the epileptogenic process. Results: CCI injury resulted in 37% PTE+-incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

Redox mediators comprising I–, Co3+, and Ti3C2Tx MXene were applied to dye-sensitized solar cells (DSCs). In the as-prepared DSCs (I-DSCs), wherein hole conduction occurred via the redox reaction of I−/I3− ions, the power conversion efficiency (PCE) was not altered by the addition of Ti3C2Tx MXene. The I-DSCs were exposed to light to produce Co2+/Co3+-based cells (Co-DSCs), wherein the holes were transferred via the redox reaction of Co2+/Co3+ ions. A PCE of 9.01% was achieved in a Co-DSC with Ti3C2Tx MXene (Ti3C2Tx-Co-DSC), which indicated an improvement from the PCE of a bare Co-DSC without Ti3C2Tx MXene (7.27%). It was also found that the presence of Ti3C2Tx MXene in the redox mediator increased the hole collection, dye regeneration, and electron injection efficiencies of the Ti3C2Tx-Co-DSC, leading to an improvement in both the short-circuit current and the PCE when compared with those of the bare Co-DSC without MXene.

Species identification and phylogenetic relationships clarification are fundamental goals in species delimitation. Yet these tasks pose challenges when based on morphologies, geographic distribution, and genomic data. Previously, two new species of fern genus Bolbitis, B. × multipinna and B. longiaurita, were described based on morphological traits, are phylogenetically intertwined with B. sinensis and fail to form monophyletic groups. To address the unclear phylogenetic relationships within the B. sinensis species complex, RAD sequencing was performed on 65 individuals from five populations. Our integrated analysis of phylogenetic tree, neighbor net, and genetic structure, indicate that the B. sinensis species complex should not be considered as separate species. Moreover, our findings reveal differences in the degree of genetic differentiation among five populations, ranged from low to moderate, which might be influenced by geographical distance and gene flow. The Fst values also confirmed that genetic differentiation intensifies with increasing geographic distance. Collectively, this study clarifies the complex phylogenetic relationships within the B. sinensis species complex, elucidates the genetic diversity and differentiation across the studied populations, and offers valuable genetic insights that contribute to the broader study of evolutionary relationships and population genetics within the Bolbitis species.

This study presents a detailed computational investigation aimed at identifying and evaluating potential small organic molecular scaffolds as inhibitors targeting the Pks13 protein, a critical enzyme in tuberculosis (TB) drug discovery. Our approach integrates multiple computational techniques, including quantitative structure-activity relationship (QSAR) modelling, compound library generation, molecular docking, biological activity prediction, re-evaluation of screened compounds, molecular dynamics (MD) analysis, and binding free energy estimation using the MM-GBSA approach. We developed a robust QSAR model using multiple linear regression (MLR) techniques, specifically tailored to predict the minimum inhibitory concentration (MIC) values of potential anti-TB agents. This model demonstrated excellent predictive performance, validated through rigorous internal and external validation procedures. Through molecular docking simulations, we identified five promising inhibitors Ethyl (R,Z)-2-(2-((2-chlorobenzyl) oxy)benzylidene)-5-(4-chlorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo [3,2-a] pyrimidine-6-carboxylate (PKD1), (7R,9aR)-7-(2-hydroxyphenyl)-4-(2-methoxyphenyl)-3-methyl-7,8,9,9a-tetrahydroisoxazolo[5,4-b]quinolin-5(6H)-one (PKD2), (7-(4-methoxy phenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-yl)(4-(3-(trifluoromethyl)phenyl) piperazin-1-yl)methanone (PKD3), (8S,10S)-10-(((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl tetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetra-hydrotetracene-5,12-dione (PKD4), 3-(3,4-dimethylphenyl)-5-((2-(4-fluorophenyl)-2-oxoethyl) thio)-6-phenyl-2-thioxo-2,3,5,7a-tetrahydrothiazolo[4,5-d]pyrimidin-7(6H)-one (PKD5)with high binding affinities, prioritizing them based on their binding energies. These selected compounds were further assessed for their biological activity predictions, guiding the selection of candidates for experimental validation. Subsequent re-evaluation using absolute binding free energy estimation and MD simulations provided insights into the stability and dynamics of the protein-ligand complexes over time. Our findings highlighted the potential of identified compounds as stable binders within the Pks13-TE domain binding pocket, underscoring their viability as drug candidates. Additionally, binding free energy analysis using MM-GBSA reaffirmed the strong affinity of the proposed compounds towards Pks13. Our integrated computational approach offers a systematic and detailed framework for the identification and characterization of potential Pks13 inhibitors with specific relevance to TB drug discovery.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered

Aiming at the limitations of single-functionality, limited applicability, and complex designs prevalent in current metasurfaces, we propose a terahertz multifunctional and multiband tunable metasurface utilizing a VO2-metal hybrid structure. This metasurface structure comprises a top VO2-metal resonance layer, a middle polyimide dielectric layer, and a gold film reflective layer at the bottom. This metasurface exhibits multifunctionality, operating independently of polarization and incident angle. The varying conductivity states of the VO2 layers, enable the metasurface to achieve various terahertz functionalities, including single-band absorption, broadband THz absorption, and multiband perfect polarization conversion for linear (LP) and circularly polarized (CP) incident waves. Finally, we believe that the functional adaptability of the proposed metasurface expands the repertoire of options available for future terahertz device designs.

This paper considers the solution of the equations for ruin probabilities in infinite continuous time. Using the Fourier Transform and certain results from the theory of complex functions, these solutions are obtained as com- plex integrals in a form which may be evaluated numerically by means of the inverse Fourier Transform. In addition the relationship between the re- sults obtained for the continuous time cases, and those in the literature, are compared. Closed form ruin probabilities for the heavy tailed distributions: mixed exponential; Gamma (including Erlang); Lognormal; Weillbull; and Pareto, are derived as a result (or computed to any degree of accuracy, and without the use of simulations).

This work is a top-level summary of several contributions published in the last three decades. It makes the case that complex dynamics of nonlinear systems lies at the heart of foundational physics.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p<0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

Background: Asthma is a widespread chronic respiratory disease that poses a significant public health challenge. The current study investigated the associations between air pollution and asthma severity among individuals residing near the Sohar industrial port (SIP) in Oman. Despite the presence of multiple major industrial complexes in Oman, limited knowledge regarding their impact on respiratory health is accredited. Hence, the primary objective of this study is to offer valuable insights into the respiratory health consequences of industrial air pollution in Al Batinah North. Methods: The state health clinics' records for patient visits related to asthma were collected for the timeframe spanning 2014 to 2022. Exposure was defined as the distance from SIP, Majan Industerial Area (MIA) and Sohar Industerial Zone (SIZ) to determine high, intermediate, and low exposure zones (12 km, respectively). Exposure effect modifications by age, gender, and smoking status were also examined. Results: The conducted cross-sectional study of 410 patients (46.1% males and 53.9% females) living in over 17 areas around SIP revealed that 73.2% of asthmatics were under 50 years old, with severity significantly associated with closeness to the port. Risk ratios were estimated to be (RR:2.42; CI95%: 1.01–5.78), (RR:1.91; CI95%: 1.01–3.6), and (RR:1.68; CI95%: 0.92–3.09) for SIP, MIP and SIZ areas, respectively, compared to the control area. Falaj Al Qabail (6.4 km) and Majees (6 km) had the highest number of asthma patients (N. 69 and N. 72), and highest percentages of severe asthma cases among these patients (28% and 24%) with significant risk ratios (RR:2.97; CI95%: 1.19–7.45 and RR:2.55; CI95%: 1.00–6.48), correspondingly. Moreover, severe asthma prevalence peaked in the 25-50 age group (RR:2.05; CI95%: 1.26–3.33), and this linkage between asthma and age was much more pronounced in males than females. Smoking and exposure to certain contaminant (dust and smoke) increased also the risk of severe asthma symptoms, but their effects were less important in the high risk zone, suggesting much more important risk factor. A neural network model accurately predicted asthma risk (94.8% accuracy), with proximity to Sohar Industrial Port as the most influential predictor. Conclusion: The study highlights the High asthma burden near Sohar Industrial Port, linked to port proximity and smoking and wind direction as major risk factors. These findings inform vital public health policies to reduce air pollution and improve respiratory health in the region, prompting national policy review.

The effect of doublet state metalloradical complex in a solar cell inside the common active layer poly(3-hexylthiophene)/ [6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PC60BM) is explored. In this work is demonstrated that the role of the Bis-[1,3-Bis-(2,6-diisopropylphenyl)-4,5-dichloroimidazol-2-ylidene]palladium(I) hexafluoridophosphate dopant, [Pd(IPrCl)2][PF6], is crucial because, by having a stable unpaired electron in the molecule, it significantly improves the optoelectronic performance of the devices. We found the optimal concentration of this molecule in the active layer, and we demonstrated that the presence of this additive in the active layer helps to significantly improve the morphology of the device. The improvements in optoelectronic and morphological parameters are associated with a remarkable increase of photocurrent generation due to more favourable mechanisms of charge separation at the donor/acceptor (D/A) interfaces of the active layer and reduced recombinations. Moreover, the presence of this additive improves the stability of the unencapsulated solar cell against photochemical degradation produced by sunlight.

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organised by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organisation and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organisation, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibres, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organisation and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

Controlling injection parameters is paramount when it comes to producing high-quality green parts using powder injection molding. This work combines experimental and numerical approaches to study the impact of injection parameters on mold in-cavity pressure and on the overall quality of green parts produced by low-pressure powder injection molding. The properties of two low-viscosity feedstocks (formulated from a water-atomized stainless-steel powder and wax-based binder system) were measured and implemented in an Autodesk Moldflow numerical model to quantify the molding pressures, which were finally validated using experimental real-scale injections. The results confirmed that an increase in mold temperature, an increase in feedstock temperature, and a decrease in solid loading decrease the mold in-cavity pressure, which was correlated with the feedstock viscosity. As a key result, real-scale injections confirmed that a minimum flow rate was required to avoid atypical high in-cavity pressure leading in several visual defects such as weld lines, flow marks, cracks, sinks, and incomplete filling. Due to differences in its thermal transfer properties, this flow rate threshold value decreases as the feedstock solid loading increases. For injection speeds higher than this value, the injection pressure measured experimentally was linearly correlated with the injection flow rate.

An acrobot is a planar robot with a passive actuator in its first joint. The control problem of the acrobot tries to make it rise from the rest position to the inverted pendulum position. This control problem can be divided in the swing-up problem, when the robot has to rise itself through swinging up as a human acrobat does, and the balancing problem, when the robot has to maintain itself on the inverted pendulum position. We have developed three controllers for the swing-up problem applied to two types of motors: small and big. For small motors, we used the SARSA controller and the PD with a trajectory generator. For big motors, we propose a new controller to control the acrobot, a PWM controller. All controllers except SARSA are tuned using a Genetic Algorithm.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive pediatric central nervous system neoplasm. However, a universal clinical consensus or reliable prognostic evaluation system for this malignancy is lacking. Our study aimed to develop a risk model based on comprehensive clinical data to assist in clinical decision-making. Methods: We conducted a retrospective study by examining data from the Surveillance, Epidemiology, and End Results (SEER) repository, spanning 2000 to 2019. The external validation cohort was sourced from the Children's Hospital Affiliated to Chongqing Medical University, China. To discern independent factors affecting overall survival (OS) and cancer-specific survival (CSS), we applied Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) regression analyses. Based on these factors, we structured nomogram survival predictions and initiated a dynamic online risk-evaluation system. To contrast survival outcomes among diverse treatments, we used propensity score matching (PSM) methodology. Molecular data with the most common mutations in AT/RT were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The annual incidence of AT/RT showed an increasing trend (APC, 2.86%; 95% CI:0.75-5.01). Our prognostic study included 316 SEER database participants and 27 external validation patients. The entire group had a median OS of 18 months (range 11.5 to 24 months) and median CSS of 21 months (range 11.7 to 29.2). Evaluations involving C-statistics, DCA, and ROC analysis underscored the distinctive capabilities of our prediction model. An analysis via PSM highlighted that individuals undergoing triple therapy (integrating surgery, radiotherapy, and chemotherapy) had discernibly enhanced OS and CSS. The most common mutations of AT/RT identified in the COSMIC database were SMARCB1, BRAF, SMARCA4, NF2, and NRAS. Conclusions: In this study, we devised a predictive model that effectively gauges the prognosis of AT/RT and briefly analyzed its genomic features, which might offer a valuable tool to address existing clinical challenges.

An ongoing monkeypox outbreak in non-endemic countries has resulted in the declaration of a Public Health Emergency of International Concern by the World Health Organization (WHO). Though monkeypox has long been endemic in regions of Sub-Saharan Africa, relatively little is known about its ecology, epidemiology, and transmission. Here, we consider the relevant research on both monkeypox and smallpox, a close relative, to make inferences about the current outbreak. Undetected circulation, combined with atypical transmission and case presentation, including mild and asymptomatic disease, have led to the spread of monkeypox in non-endemic regions. Broader availability of diagnostics, enhanced surveillance, and targeted education, combined with a better understanding of the routes of transmission, are critical to identify at-risk populations and design science-based countermeasures to control the current outbreak.

The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

This paper seeks to fill in the gaps of modern relativistic Cosmology by utilizing the total symmetry between space and time dimensions and re-interpreting the scale factor of the Universe as a gravitational potential generated by the mass/energy of the entire Universe as a whole. The gradient of this potential is along the cosmological time dimension through which the Universe is falling. This gradient gives us an arrow of time, we find explanations for why the Universe began expanding and why the expansion is accelerating without the need for a Cosmological Constant. In a finite time, the gradient will point in the opposite direction of time turning the expanding Universe into a collapsing one where it is shown that when placing the Schwarzschild metric in the dynamic Cosmological background, gravity becomes repulsive and things like would-be Black Holes become White Holes. The model naturally describes a Universe and an anti-Universe (consisting of antimatter) moving in opposite directions of time that collide at the end of collapse, annihilating and subsequently pair producing two new Universes as the cycle begins again. It is shown that the model's Hubble diagram fits the currently available supernova and quasar data. It is found that Dark Matter can perhaps be understood as ordinary matter that is not connected to us with null geodesics.

Real and complex analytic functions are largely studied in the field of complex analysis and are seen as very useful tools in solving problems in mathematics, physics and engineering. Real and complex numbers are a subset of semi-structured complex numbers (a new number set created to algebraically solve division by zero). Nevertheless, the properties of analytic functions made up of semi-structured complex variables (called semi-structured complex analytic functions) is yet to be explored. This limits the range of possible problems that can be resolved using analytic functions). In this regard, the aim of this paper was to expound upon the properties of semi-structured complex analytic functions and show their application in solving engineering problems. The results of this paper included (1) developing a full set of Cauchy–Riemann Equations for the semi-structured complex -space; (2) define sufficient and necessary conditions for a semi-structured complex function to be analytic; (3) determine the relationship between semi-structured complex analytic functions, Laplace’s Equations and Poisson’s Equations; and (5) provide an example of the use of these functions.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Alterations in the composition and diversity, metabolism, and products of the microbiome, and of the gut microbiome (GM), have been shown to be closely associated with the onset and progression of many human diseases, including cancer (i.e. hematological neoplasms). Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Affected cases present typical alterations of GM, followed by inflammation, which contribute to its progression, response to therapy, as well as possible relapses. Recent evidence also reports that GM influences the development and functions of the newborn's hematopoietic system through the process of developmental programming during fetal life, as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Furthermore, in children with ALL, GM has been found to vary in composition, variety, and functions during the clinical stages of ALL, and such variation may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplant. Here, we suggest some therapeutic strategies, which can be applied at two levels of intervention to recover the microbiome, and consequently prevent/delay ALL or arrest its progression.

Twelve wild North American Porcupines (Erethizon dorsatum) were diagnosed with dermatopathies while being cared for at two wildlife rehabilitation clinics. Biopsy and necropsy were performed on 7 and 5 animals respectively. Atypical dermatophytosis was diagnosed in all cases. Lesions consisted of diffuse severe epidermal hyperkeratosis and mild hyperplasia, with mild lymphoplasmacytic dermatitis, and no folliculitis. Dermatophytes were noted histologically as hyphae and spores in hair shafts, and follicular and epidermal keratin. Trichophyton sp. was grown in 5/6 animals where culture was performed, with molecular diagnosis of Arthroderma benhamiae / Trichophyton mentagrophytes in these 5 cases. Metagenomic analysis of formalin-fixed paraffin-embedded tissue samples from 3 cases identified fungi from 17 orders in phyla Basidiomycota and Ascomycota. Alteration of therapy from ketaconazole, which was unsuccessful in 4 of 5 early cases, to terbinafine or nitraconazole lead to resolution of disease and recovery to release in four subsequent animals. In all, 6 animals were euthanized or died due to dermatopathy, no cases resolved spontaneously, and 6 cases resolved with therapy. The work we present demonstrates an atypical lesion and anatomical distribution due to dermatophytosis in a series of free-ranging wild porcupines and successful development of novel techniques for extraction and sequencing nucleic acids from fungus in archival formalin-fixed paraffin-embedded animal tissue.

Burkholderia are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. B. pseudomallei and B. mallei, the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the B. pseudomallei complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic Burkholderia species exists known as the Burkholderia cepacia complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan-Burkholderia vaccine capable of protecting against both disease-causing groups.

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long-term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyse the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in germination rate and RNA integrity number (RIN) after long-term storage, or CDT. The RIN value was obtained by electrophoresis of total RNA extracted from seed embryos. Seeds of ‘Vandaran (Indica)’, ‘Tupa 729 (Japonica)’, and ‘Badari Dhan (Indica)’ consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions, regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between germination rates and RIN values of the seeds after long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials, including both Japonica and Indica cultivars, for improving rice seed longevity.

In this paper, the time-resolved model of photoacoustic signal for samples with a complex inner structure is derived including local non-equilibrium of structural elements with multiple degrees of freedom, i.e. structural entropy of the system. The local non-equilibrium is taken into account through the fractional operator. By analyzing the model for two types of time-dependent excitation, a very short pulse and a very long pulse, it is shown that the rates of non-equilibrium relaxations in complex samples can be measured by applying the derived model and time-domain measurements. Limitations of the model and further directions of its development are discussed.

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

The dynamics of surface and sub-surface water events can lead to slope instability resulting in anomalies such as slough slides on earthen levees. Early detection of these anomalies by a remote sensing approach could save time versus direct assessment. We have implemented a supervised Mahalanobis distance classification algorithm for the detection of slough slides on levees using complex polarimetric Synthetic Aperture Radar (polSAR) data. The classifier output was followed by a spatial majority filter post-processing step which improved the accuracy. The effectiveness of the algorithm is demonstrated using fully quad-polarimetric L-band Synthetic Aperture Radar (SAR) imagery from the NASA Jet Propulsion Laboratory’s (JPL’s) Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR). The study area is a section of the lower Mississippi River valley in the southern USA. Slide detection accuracy of up to 98 percent was achieved, although the number of available slides examples was small.

Many of the wide-ranging symptoms of COVID-19 have not been associated previously with a respiratory illness. A similarity between these atypical symptoms and the symptoms of malnutrition was observed. To investigate, a comparison of COVID-19 symptomatology with recognised states of malnutrition showed a significant relationship that was further explored in a review of the literature. This hypothesis links the atypical symptoms to the effects of increasing protein malnutrition. The rapid appearance of malnutrition symptoms at the beginning of the COVID-19 infection is concurrent with the rapid cell proliferation of the immune system. Although previous work has, in general, assumed that the body is capable of providing for the needs of the immune system during infection, heightened immune activity from the commencement of COVID-19 could require an early increase in energy yielding sources. Should insufficient availability of protein resources occur, this could quickly lead to malnutrition. Any continuing insufficiency, during the active phase of the virus, might result in widespread depletions in the tissues and the consequential malfunctioning of many organs. A new appraisal of the immune system requirements needed to counteract the impact of the novel virus, COVID-19, could show the potential benefit for earlier protein intervention in the disease process. This hypothesis could also have relevance for other life situations where a rapid cell proliferation might occur.

Recent technological advancements in conservation genetics and genomics have resulted in diverse tools for aiding conservation of species. The precision and resolution of high throughput sequencing technologies provide valuable insights to aid conservation decisions, but these technologies are often financially unfeasible or unavailable in resource constrained countries. Inter-Simple Sequence Repeat (ISSR) markers, when combined with sensitive automated detection systems, provide a simple, cheap means to investigate genetic diversity and discriminate closely related species. Here we apply this technology to assess genetic diversity and taxonomic delimitation in the Encephalartos eugene-maraisii species complex, a highly threatened, taxonomically dubious group of cycads in South Africa. Our analyses support taxonomic singularity of E. dyerianus, E. dolomiticus and E. eugene-maraisii. Relationships between E. nubimontanus and E. cupidus remain uncertain. E. middelburgensis samples showed no clustering but had poor amplification success. This study demonstrates the suitability of automated ISSR fingerprinting as a method for plant conservation studies, especially in resource-constrained countries, and we make recommendations as to how this methodology can be effectively implemented.

This work aims to shed light on the differential diagnosis of Complex Post-Traumatic Stress Disorder (cPTSD), Post-Traumatic Stress Disorder (PTSD), and Borderline Personality Disorder (BPD) within the context of Intimate Partner Violence (IPV), which represents an extremely inno-vative field of clinical research. To this end, a critical review of the literature was conducted to identify and compare the clinical patterns and symptomatic overlaps among cPTSD, PTSD, and BPD, with an emphasis on their manifestation in both victims and offenders. The results show that despite some symptomatic similarities, cPTSD, PTSD and BPD have distinct clinical patterns in IPV. Disturbances in Self-Organization (DSO), are more commonly in offenders, while the di-agnosis of cPTSD is more aligned with the victims. In addition, cPTSD and characteristics of BPD, such as fear of rejection and instability of identity, constitute risk factors for IPV victimiza-tion. cPTSD is a predisposing factor not only for victims but also for offenders, while PTSD emerges as a consequential factor. The specific pathways linking PTSD, cPTSD, and BPD with IPV have significant implications for clinical practice. Further research is needed to understand these profiles and the mechanisms linking trauma-related features to IPV, which is crucial for imple-menting effective violence prevention programs.