(1) Background: Double-strand breaks (DSBs) in a single nucleus are usually measured using the sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test, and comet assay (CA). We developed mono-dimensional single-cell pulsed-field gel electrophoresis (1D-SCPFGE) and angle-modulated two-dimensional single-cell pulsed-field gel electrophoresis (2D-SCPFGE) to observe DNA fragmentation in separated motile sperm. (2) Methods: We set up comparative standards, calibration curves, the required sensitivity, and eligibility criteria for test sperm to validate their measurement principles. (3) Results: We revealed that the conventional methods overlooked the interference of nucleoproteins in their measurements. In-gel proteolysis improves the measurement accuracies of 1D- and 2D-SCPFGE. We recommend using naked DNA for comparative standards and test specimens. Moreover, we have observed several dysfunctions that may induce DNA damage in the separated motile sperm. Overall, our discussion highlights the need to revisit the conventional univariable analyses based on the SCSA, SCD test, and CA. (4) Conclusions: Human infertility is a complex syndrome, and the aim of quality control in intracytoplasmic sperm injection is to identify the underlying dysfunctions remaining in the separated motile sperm that render them ineligible for injection. Well-designed, multivariable analyses with special consideration to confounding factors are necessary in future cohort studies.

Improper sitting positions are known as the primary reason for back pain and the emergence of musculoskeletal disorders (MSD) among individuals who spend prolonged time working with computer screens, keyboards, and mice. At the same time, it is well understood that automated technological tools can play an important role in the process of unhealthy habit alteration, so plenty of research efforts are focused on research and technology development (RTD) activities that aim to provide support to the prevention of back pain or the development of MSD. Here, we report on creating a new resource in support of RTD activities aiming at the automated detection of improper sitting positions. It consists of multimodal multisensory recordings of 100 persons made with a video recorder, camera, and wrist-attached sensors that capture physiological signals (PPG, EDA, Skin temperature), as well as motion sensors (three-axis accelerometer). Our multimodal multisensory dataset (MMD-MSD) opens new opportunities for modeling the body stance (sitting posture and movements), physiological state (stress level, attention, emotional arousal, valence), and performance (success rate on the Stroop test) of people working with a computer. Finally, we demonstrate two use cases: improper neck posture detection from pictures and cognitive load detection from physiological signals.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

This study aimed to explore the feasibility of using airborne acoustic emission in laser beam butt welding for the development of an automated classification system based on neural networks. The focus was on monitoring the formation of joint gaps during the welding process. To simulate various sizes of butt joint gaps, controlled welding experiments were conducted, and the emitted acoustic signals were captured using audible to ultrasonic microphones. To implement an automated monitoring system, a method based on short-time Fourier transformation was developed to extract audio features, and a convolutional neural network architecture with data augmentation was utilized. The results demonstrated that this non-destructive and non-invasive approach was highly effective in detecting joint gap formations, achieving an accuracy of 98%. Furthermore, the system exhibited promising potential for low latency monitoring of the welding process. The classification accuracy for various gap sizes reached up to 90%, providing valuable insights for characterizing and categorizing joint gaps accurately. Additionally, increasing the quantity of training data with quality annotations could potentially improve the classifier model's performance further. This suggests that there is room for future enhancements in the study.

Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in AD’s brain. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, expressed Iba1 and showed reduced viability, consistent with a neurotoxic effect of HPU. Rats received daily i.p. HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Thr205, Ser199 and Ser396 sites was seen in hippocampal homogenates of treated rats, with no alterations in total tau or GSK-3b levels. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.

Rainfall variability has resulted in extreme events like devastating floods and droughts which is the main cause of human vulnerability to precipitation in West Africa. Attempts have been made by previous studies to understand rainfall variability over Ghana but these have mostly focused on the major rainy season of April-July, leaving a gap in our understanding of the variability in the September-November season which is a very important aspect of the Ghanaian climate system. The current study seeks to close this knowledge gap by employing statistical tools to quantify variabilities in rainfall amounts, rain days, and extreme precipitation indices in the minor rainfall season over Ghana. We find extremely high variability in rainfall with a Coefficient of variation (CV) between 25.3% and 70.8%, and moderate to high variability in rain days (CV=14.0% - 48.8%). Rainfall amount was found to be higher over the middle sector (262.7 mm – 400.2 mm) but lowest over the east coast (125.2 mm – 181.8 mm). Analysis of the second rainfall season using the Mankandell Test presents a non-significant trend of rainfall amount and extreme indices (R10, R20, R99p, and R99p) for many places in southern Ghana. Rainfall Anomaly Indices show that the middle sector recorded above normal precipitation which is the opposite for areas in the transition zone. The result of this work provides a good understanding of rainfall in the minor rainfall season and may be used for planning purposes.

Autonomous unmanned aerial vehicles (UAVs) require highly reliable navigation information. Generally, navigation systems with the inertial navigation system (INS) and global navigation satellite system (GNSS) have been widely used. However, the GNSS is vulnerable to jamming and spoofing. The terrain referenced navigation (TRN) technique can be used to solve this problem. In this study, to obtain reliable navigation information even if a GNSS is not available or the degree of terrain roughness is not determined, we propose a federated filter based INS/GNSS/TRN integrated navigation system. we also introduce a TRN system that combines batch processing and an auxiliary particle filter to ensure stable flight of UAVs even in a long-term GNSS-denied environment. As an altimeter sensor for the TRN system, we use an interferometric radar altimeter (IRA) to obtain reliable navigation accuracy in high altitude flight. In addition, a parallel computing technique with general-purpose computing on graphics processing units (GPGPU) is applied to process a high resolution terrain database and a nonlinear filter in real time on board. Finally, we verify the performance of the proposed system through software-in-the-loop (SIL) tests and captive flight tests in a GNSS unavailable environment.

Abstract: Discussed is an expansion of SRT to fourth-order of space-time including any velocities and possible negative kinetic energies by real rest mass in analogy of the model amplitude of enforced damped oscillation. This paper serves an introduction to developed SRT including superluminar translating velocities without tachyons or imaginary restmass. Focused is on those parts, which develop the elaborated lorentz-transformations. Discussed are the problems of this theory.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

Investigations reporting positive effects of Extracorporeal Shock Wave Therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7-mm segment of the right median nerve was reconstructed either with an ANG or MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. Animals were observed for 12 weeks and nerve regeneration was assessed via computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.

Nowadays, according to spectacular improvement in health care and biomedical level, a tremendous amount of data is recorded by hospitals. In addition, the most effective approach to reduce disease mortality is to diagnose it as soon as possible. As a result, data mining by applying machine learning in the field of diseases provides good opportunities to examine the hidden patterns of this collection. An exact forecast of the mortality after heart surgery will cause Successful medical treatment and fewer costs. This research wants to recommend a new stacking predictive model after utilizing the random forest feature importance method to foresee the mortality after heart surgery on a highly unbalanced dataset by using the most practical features. To solve the unbalanced data problem, a combination of the SVM-SMOTE over-sampling algorithm and the Edited-Nearest-Neighbor under-sampling algorithm is used. This research compares the introduced model with some other machine learning classifiers to ensure efficiency through shuffle hold-out and 10-fold cross-validation strategies. In order to validate the performance of the implemented machine learning methods in this research, both shuffle hold-out, and 10-fold cross-validation results indicated that our model had the highest efficiency compared to the other models. Furthermore, the Friedman statistical test is applied to survey the differences between models. The result demonstrates that the introduced stacking model reached the most accurate predicting performance after Logistic Regression.

The growing market penetration of heat pumps indicates the need for a performance test method which better reflects the dynamic behavior of heat pumps. In this contribution, we developed and implemented a dynamic test method for the evaluation of the seasonal performance of heat pumps by means of laboratory testing. Current standards force the heat pump control inactive by fixing the compressor speed. In contrast, during dynamic testing, the compressor runs unfixed while the heat pump is subjected to a temperature profile. The profile consists of the different outdoor temperatures of a typical heating season based on the average European climate and also includes temperature changes to reflect the dynamic behavior of the heat pump. The seasonal performance can be directly obtained from the measured heating energy and electricity consumption making subsequent data interpolation and recalculation with correction factors obsolete. The method delivers results with high precision and high reproducibility and could be an appropriate method for a fair rating of heat pumps.

Forest recreation can be successfully conducted for the purpose of psychological relaxation, as has been proven in previous scientific studies. During the winter in many countries, when snow cover occurs frequently, forest recreation (walking, relaxation, photography, etc.) is common. Nevertheless, whether forest therapy conducted in a forest environment with a snow cover will also have a positive effect on psychological indicators remains unknown. Furthermore, male subjects frequently participate in forest therapy experiments, whereas females are rarely involved. Thus, in this study, the effectuality of forest recreation during winter and with snow cover was tested on 32 young females. For these reasons, the experiment involved 15-minute periods of relaxation in a forest environment or in an urban environment, in addition to a pre-test under indoor conditions. Four psychological questionnaires (POMS, PANAS, ROS, SVS) were administered to participants before and after interventions. Results showed that participants’ levels of negative mood, as measured by different aspects of the POMS questionnaire (tension-anxiety, anger-hostility, depression-dejection, confusion, fatigue), decreased after exposure to the forest environment. In contrast, both tension-anxiety and anger-hostility increased in the urban environment. The indicator of negative affect from the PANAS questionnaire also increased after exposure to the urban environment, whereas the indicator of positive affect based on PANAS was higher in the forest environment than in the urban environment. Restorativeness and subjective vitality exhibited higher values after exposure to the forest environment in comparison to those from the control and pre-test. The changes in these indicators demonstrates that forest recreation in the snow during winter can significantly increase psychological relaxation in young females, as well as showing that recreation can be successfully conducted under these winter conditions.

This research paper explores the framework of Extended Classical Mechanics, with a focus on the Equivalence Principle, Mass, and Gravitational Dynamics. Volume 1 of this study re-examines the classical equivalence principle, which maintains the equivalence of inertial mass and gravitational mass (also referred to as gravitating mass) and extends this concept to incorporate new findings related to both illuminating (baryonic) matter and dark matter. The paper provides a comprehensive analysis of Matter Mass (Mᴍ) and Gravitating Mass (Mɢ) and their roles within the extended framework. It introduces the concept of Apparent Mass (Mᵃᵖᵖ), a negative mass component that influences Effective Mass (Mᵉᶠᶠ), in alignment with the research by A.D. Chernin et al. on dark energy and the structure of the Coma Cluster of Galaxies. Additionally, the paper reinterprets Newton's Law of Universal Gravitation by integrating Apparent Mass, leading to a revised understanding of gravitational potential. The study demonstrates how the interaction between Matter Mass and Negative Apparent Mass contributes to a redefined concept of Gravitating Mass. These extensions enhance classical mechanics by incorporating modern scientific insights, including the gravitational effects of dark matter and the alignment of Apparent Mass with the negative effective mass of dark energy.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Obesity in adolescents combined with the increased exposure time to electronic devices, enhances a sedentary lifestyle and is linked to the risk of developing musculoskeletal injuries. The aim of this study was to identify possible correlations between anthropometric characteristics, body composition, exposure time to electronic devices or screen time (ST) and physical activity (PA) level along with muscle power and dynamic knee valgus (DKV) in young athletes to avoid future injuries. A total of 125 adolescent basketball athletes (66.4% boys), 12 to 17 years old (13.94±1.58 years) participated. Anthropometric and demographic characteristics were recorded. PA level was assessed through IPAQ and ST through a single question from the HELENA study. The Counter Movement Jump test was used for the evaluation of the lower limb muscle power, while the Single Leg Drop Jump test was used for the evaluation of the dynamic knee valgus via two-dimensional (2D) kinematic analysis. The Pearson index showed a statistically significant positive correlation between muscle power and height (r=0.788, p<0.001), while the Spearman index showed a smaller but equally statistically significant positive correlation with BMI (rs =0.651, p<0.001) and age (rs=0.579, p<0.001). The ST (rs= -0.194, p=0.03) showed a weak negative correlation with DKV, while PA (r=0.85, p<0.001) showed a high, statistically significant, positive correlation. The anthropometric characteristics of adolescent athletes can determine their ability to produce muscle power. A high level of physical activity could play a key role in compensating and thus reducing the negative effects of high exposure to screen time on the dynamic knee valgus

Rodents are known to be reservoirs of Toxoplasma gondii and keep the parasite circulation in the environment. We conducted biomonitoring to assess the role of sylvatic rodents in maintaining T. gondii and to analyse the prevalence and seroprevalence of the parasite in seven wild rodent species. Rodents were collected in our study sites (woodland and open grasslands) located in northeastern Poland and dissected. We collected brain, spleen, blood and serum samples. We applied both molecular (PCR assay, nested-PCR assay) and serological (ELISA and agglutination tests) methods to indicate the best approach for application in the biomonitoring of T. gondii in small mammals. We screened samples from 95 individuals sing PCR assays and found no T. gondii DNA. The agglutination test showed no signal. We found antibodies against T. gondii in 6 sera samples out of 74 analysed (seroprevalence = 8.11% [4.0-17.1]). Our results confirm that rodents participate in the life cycle of T. gondii as reservoirs of this parasite in the sylvatic environment. However, biomonitoring should be performed with the ELISA tests to search for T. gondii antigens, rather than a molecular approach only.

Minerals are the chief constituents of rocks and they have varied properties such as surface area, surface charge, site densities etc. Hence, numerous interactions are bound to occur in the reservoir during rock-fluids (i.e., rock, crude oil and brine) interactions. This study seeks to assess the role of mineralogical composition on the wettability of Sandstone Rocks (SR) and Mineral Mixture (MM) using both Surface Complexation Modelling (SCM) and flotation test. From the considered sandstone rocks, both the experimental results and its simulated counterpart revealed that, the SR were preferentially hydrophilic. For the MM, when the mass fraction of the hydrophobic mineral was increased, the affinity of the MM became slightly hydrophobic and vice-versa. For the dominant sandstone reservoir rock minerals with predominantly negatively charged surfaces, negligible oil adsorption took place due the interfacial repulsive forces at the oil-brine and mineral-brine interfaces. For the MM with low calcite content, the wetting preference was influenced by the mineral with prominent surface area. Our developed model portrayed that the main mechanism for oil adhesion onto sandstone minerals was divalent cations bridging. Nonetheless, adhesion of carboxylate (&gt;COO-) onto the illite, montmorillonite and calcite sites also took place with the latter being more pronounced.

Pavement friction plays a crucial role in ensuring the safety of road networks. Accurately assessing friction levels is vital for effective pavement maintenance and management strategies employed by state highway agencies. Traditionally, friction evaluations have been conducted on a case-by-case basis, focusing on specific road sections. However, this approach fails to provide a comprehensive assessment of friction conditions across the entire road network. This paper introduces a hybrid clustering algorithm, namely the combination of density-based spatial clustering of applications with noise (DBSCAN) and Gaussian mixture model (GMM), to perform pavement friction performance rating across a statewide road network. A large, safety-oriented dataset is first generated by integrating network friction and vehicle crash data based on the attributes contributing possibly to friction related crashes. One-, two-, and multi-dimensional clustering analyses, respectively, are then performed to rate pavement friction. The Chi-square test is further employed to validate and identify the practical ratings. It is shown that by effectively capturing the hidden, intricate patterns within the integrated, complex dataset and prioritizing friction-related safety attributes, the hybrid clustering algorithm can produce pavement friction ratings that align effectively with the current practices of the Indiana Department of Transportation (INDOT) in friction management.

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants and antibodies that are escaped by these variants have important implications in the development of therapeutic and diagnostic solutions as well as in improving understanding of the humoral response to SARS-CoV-2 infection. We characterized seven anti-RBD monoclonal antibodies for their binding activity, pairing capability and neutralization activity to SARS-CoV-2 and three variant RBDs (UK, SA and BR P.1) via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the SA and BR P.1 RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. Further, we demonstrated that the lateral flow immunoassay can be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. From these studies, the potential contributions of the mutations (N501Y, E484K and K417N/T) contained in these variants’ RBDs on antibody pairing capability, neutralization activity and therapeutic antibody targeting strategy are discussed.

Finding out how cells with the same genome change fates in differentiation commitment is a challenge of biology. We used MCF-7 breast cancer cells treated with the ErbB2 ligand heregulin (HRG), which induces differentiation, to address if and how the constitutive pericentromere-associated domains (PADs) may be involved in this process. PAD-specific repressive heterochromatin (H3K9me3) and active euchromatin (H3K4me3) marking, centromere (CENPA) labelling, qPCR, acridine-orange-DNA structural test, and microscopic image analysis were applied. We found a two-step DNA unfolding, at 15-20 min and 60 min after HRG treatment, coinciding with bi-phasic activation of the early response genes (c-FOS family) and two steps of critical phase transition which were revealed in transcriptome studies. In control, the distribution of PAD number and size displays a power-law scaling with a boundary at the nucleolus. PADs’ clustering correlates with centromere numbers. 15 min after HRG treatment, the unravelling of PADs occurs, coinciding with the first step of euchromatin unfolding. The second step is associated with transcription of long-non-coding-RNA from satellite III DNA. We hypothesize that splitting of the PAD clusters under the critical size threshold of the silencing domain abrupts position effect variegation. It allows the first genome transcription avalanche to occur, starting differentiation commitment.

Hidradenitis suppurativa and Langerhans cell histiocytosis are rare disorders that can reveal similar clinical manifestations, making differential diagnosis difficult. A definitive diagnosis requires biopsy and histological confirmation in suspicious cases. The complex pathophysiology of these diseases has still not been understood, therefore the treatment is still a challenge for physicians. It is seen with predilection in the intertriginous areas of the body, predominantly in the axillary region, rarely requiring a surgical procedure. However perineal, perianal, and gluteal HS usually necessitates some form of surgical treatment. Langerhans cell histiocytosis (histiocytosis X) is a very rare systemic disease manifested by clonal cell proliferation of histiocytic-dendritic nature, with pseudonodular manifestation that deeply infiltrates the hypodermis and ulcerates the epidermis on the surface. Langerhans cells are dendritic, antigen-presenting cells localized in the suprabasal regions of the squamous epithelium of the skin and mucous membranes, which help regulate the immune system. In this report, we present our experience with extensive gluteal, perineal, and perianal hidradenitis suppurativa and Langerhans cell histiocytosis cases, including our treatment methods and outcomes.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Background: The Covid-19 pandemic was in reality a syndemic there the balance between a multitude of biological (Nature-made) and socio-political (men-made) factors determined individually the outcome of every single infection, on a scale of nothing-to-fatal. Blaming the virus for everything bad that happened to us after January 2020 is incorrect. Now, in ~ 2 years distance from the syndemic, it may be timely and possible to uncover the human contribution to this historical event and learn of it. Objective: To identify and use some qualitative approach to estimate the objective, statistical / epidemiological ‘value’ of the virus-selected individuals (in age-normalized groups) for the rest of the society. This non-political, non-religious approach may be the only way to understand the benefit / cost ratio of actions and emergency orders we had to survive in addition to the virus itself. Methods: Statistical data were obtained from publicly available official databases, including the relevant actuarial tables and evaluated by widely used statistical methods. The estimation of statistical/epidemiological ‘value of life’ was based, strictly and exclusively, on the real age and the statistically calculated Residual Life Expectancy (RLE, i.e. remaining years alive at a given age). The American healthcare expenses were compared to the corresponding healthcare costs/capita in other similarly well-developed west-European countries. This was the only available method to get some ideas about the magnitude of the well-established (rational) healthcare spending and compare it to the American standards. Results 1) Life expectancy uninterruptedly increased in USA since 1933, due to continuous reduction of Mortality Rate of the youngest and oldest citizens. COVID didn’t stop the population growth (+8.2 M /2020-2023). 2) The total count of Excess COVID associated Deaths (XCD) is ~ 2-times as much as the official statistic was able to explain by virus infection. It is speculated that these Complementary Covid Deaths (CCD) are probably the unexpected side-effects of the pandemic related emergency orders. 3) The worldwide ‘longevity’ trend exponentially increased the healthcare expenses, especially the care of elderly. However the USA is unique in this aspect and the healthcare costs are irrationally much higher than in any other country. 4) We can see a large economic incentive in the development of excesses under COVID syndemic. Conclusions The harm of the COVID virus - as well as the benefits of the mandatory, emergency actions during the pandemic - were grossly over-estimated. Professional, unbiased (non-religious, non-political) and independent reviews are strongly recommended.

The aim of this report is to evaluate the segmental rib index (RI) from T1-T12 spinal level in mild and moderate idiopathic scoliosis (IS) curves of thoracic, thoracolumbar and lumbar type by gender. The relationship of segmental RI to the frontal plane radiological deformity presented as the Cobb angle and to the posterior truncal surface deformity presented as the scoliometric readings of Angle of Trunk Rotation (ATR) in these patients is also assessed. Any statistical significant rela-tionship of these parameters would be very important for biomechanical relations of the rib cage (RC) deformity presented as the rib hump deformity (RHD) and the deformity in the spine and it would thus provide valuable information about scoliogeny. The segmental rib index (RI) is presented in 83 boys and girls with mild and moderate IS. The measurements include the scoliometric readings for truncal asymmetry (TA), the Cobb angle assessment and the segmental RI from T1-T12. The statistical package SPSS 23 was used for statistical analysis. The TA is documented and the Cobb angle is presented by gender and curve type. The segmental RI of thoracic, thoracolumbar and lumbar curves are presented for the first time. The correlations of the segmental RI to surface deformity presented as the rib hump deformity (RHD) in all IS patients and particularly in thoracic curves, to Cobb angle by gender and age and the comparison of the segmental RI index of asymmetric but not scoliotic children to the scoliotic peers by curve (in thoracic, thoracolumbar, lumbar curves) in boys and girls are presented. The findings emphasize the significant protagonistic role of the thoracic asymmetry in relation to the spinal deformity mainly in girls for the thoracic and in boys for the thoracolumbar curves. The cut-off point of age of the examined scoliotics is 14 years, that is when the RI shows stronger correlation with the spinal deformity, namely when the thoracic deformity is decisively effective to the developing thoracic spinal deformity, in terms of Cobb angle. In summary, the results of this study provide aetiological implications for IS, as far as the role of thorax is con-cerned.

Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN ar-chitecture for the detection of abnormal cervical cells in cytology images from cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cer-vical image dataset of “Digital Human Body" Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using tra-ditional computer-vision techniques, 6-9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear.

Matiyasevich's theorem states that there is no algorithm to decide whether or not a given Diophantine equation has a solution in non-negative integers. Smorynski's theorem states that the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable. We prove: (1) Smorynski's theorem easily follows from Matiyasevich's theorem, (2 ) Hilbert's Tenth Problem for Q has a negative solution if and only if the set of all Diophantine equations with a finite number of rational solutions is not recursively enumerable.

Assuming a two component, positive and negative mass, superfluid/supersolid for space (the Winterberg model), we model the Higgs field as a condensate made up of a positive and a negative mass, planckion pair. The connection is shown to be consistent (compatible) with the underlying field equations for each field, and the continuity equation is satisfied for both species of planckions, as well as for the Higgs field. An inherent length scale for space (the vacuum) emerges, which we estimate from previous work to be of the order of,

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

This paper offers a comprehensive examination of the process involved in developing and automating supervised end-to-end machine learning workflows for forecasting and classification purposes. It offers a complete overview of the components (i.e. feature engineering, model selection, etc), principles (i.e. bias-variance decomposition, model complexity, overfitting, model sensitivity to feature assumptions and scaling, output interpretability, etc), models (i.e. neural networks, regression models, etc), methods (i.e. Cross-Validation, data augmentation, etc), metrics (i.e. Mean Squared Error, F1-score, etc) and tools that rule most supervised learning applications with numerical and categorical data, as well as their integration, automation, and deployment. The end goal and contribution of this paper is the education and guidance of the non-AI expert academic community over complete and rigorous machine learning pipelines and data science practices, from problem scoping to design and state-of-the-art automation tools, including basic principles and reasoning in the choice of methods. The paper delves into the critical stages of supervised machine learning workflow development, many of which are often omitted by researchers due to brevity, and covers foundational concepts essential for understanding and optimizing a functional machine learning workflow, thereby offering a holistic view of task-specific application development for applied researchers who are not AI experts.

We present a new interpretation of the Higgs field as a composite particle made up of a positive, with, a negative mass Planck particle. According to the Winterberg hypothesis, space, i.e., the vacuum, consists of both positive and negative physical massive particles, which he called planckions, interacting through strong superfluid forces. In our composite model for the Higgs boson, there is an intrinsic length scale associated with the vacuum, different from the one introduced by Winterberg, where, when the vacuum is in a perfectly balanced state, the number density of positive Planck particles equals the number density of negative Planck particles. Due to the mass compensating effect, the vacuum thus appears massless, charge-less, without pressure, energy density, or entropy. However, a situation can arise where there is an effective mass density imbalance due to the two species of Planck particle not matching in terms of populations, within their respective excited energy states. This does not require the physical addition or removal of either positive or negative Planck particles, within a given region of space, as originally thought. Ordinary matter, dark matter, and dark energy can thus be given a new interpretation as residual vacuum energies within the context of a greater vacuum, where the populations of the positive and negative energy states exactly balance. In the present epoch, it is estimated that the dark energy number density imbalance amounts to, , per cubic meter, when cosmic distance scales in excess of, , are considered. Compared to a strictly balanced vacuum, where we estimate that the positive, and the negative Planck number density, is of the order, particles per cubic meter, the above is a very small perturbation. This slight imbalance, we argue, would dramatically alleviate, if not altogether eliminate, the long standing cosmological constant problem.

We prove: (1) the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable, (2) the set of all Diophantine equations which have at most finitely many solutions in positive integers is not recursively enumerable, (3) the set of all Diophantine equations which have at most finitely many integer solutions is not recursively enumerable, (4) analogous theorems hold for Diophantine equations D(x₁, …, x_p) = 0, where p ∈ N\{0} and for every i ∈ {1, …, p} the polynomial D(x₁, …, x_p) involves a monomial M with a non-zero coefficient such that x_i divides M, (5) the set of all Diophantine equations which have at most k variables (where k ≥ 9) and at most finitely many solutions in non-negative integers is not recursively enumerable.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

The Mediterranean basin is a hot spot of climate change where the Posidonia oceanica (L.) Delile (PO) and other seagrass are under stress due to its effect on marine habitats and the rising influence of anthropogenic activities (tourism, fishery). The PO and seabed ecosystems, in the coastal environments of Pantelleria and Lampedusa, suffer additional growing impacts from tourism in synergy with specific stress factors due to increasing vessel traffic for supplying potable water, fossil fuels for electrical power generation. Earth Observation (EO) data, provided by high resolution (HR) multi/hyperspectral operative satellite sensors of the last generation (i.e. Sentinel 2 MSI and PRISMA) have been successfully tested, using innovative calibration and sea truth collecting methods, for monitoring and mapping of PO meadows under stress, in the coastal waters of these islands, located in the Sicily Channel, to better support the sustainable management of these vulnerable ecosystems. The area of interest in Pantelleria was where the first prototype of the Italian Inertial Sea Wave Energy Converter (ISWEC) for renewable energy production was installed in 2015, and sea truth campaigns on the PO meadows were conducted. The PO of Lampedusa coastal areas, impacted by ship traffic linked to the previous factors and tropicalization effects of Italy southernmost climate change transitional zone, was mapped through a multi/hyper spectral EO-based approach, using training/testing data provided by side scan sonar data, previously acquired. Some advanced machine learning algorithms (MLA) were successfully evaluated with different supervised regression/classification models to map seabed and PO meadow classes and related Leaf Area Index (LAI) distributions in the areas of interest, using multi/hyperspectral data atmospherically corrected via different advanced approaches.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.