The recent Planck Legacy release confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background (CMB) power spectra, which endorses the positive curvature of the early Universe with a confidence level exceeding 99%. In this study, the pre-existing curvature is incorporated to extend the field equations where the derived wave function of the Universe is utilized to model Universe evolution with reference to the scale factor of the early Universe and its radius of curvature upon the emission of the CMB. The wave function reveals both positive and negative solutions, implying that matter and antimatter of early Universe plasma evolve in opposite directions as distinct Universe sides. The wave function indicates that a nascent hyperbolic expansion is followed by a first phase of decelerating expansion away from early plasma during the first 10 Gyr, and then, a second phase of accelerating expansion in reverse directions, whereby both Universe sides free-fall towards each other under gravitational acceleration. Simulations of the predicted conformal curvature evolution demonstrate the fast orbital speed of outer stars owing to the external fields exerted on galaxies as they travel through conformally curved space-time. Finally, the wave function predicts an eventual time-reversal phase comprising rapid spatial contraction that culminates in a Big Crunch, signalling a cyclic Universe. These findings reveal that early plasma could have separated and evolved into distinct sides that collectively and geometrically influencing the Universe evolution, physically explanting the effects attributed to dark matter and energy.

Recent research emphasises the importance of Artificial Intelligence applications as supporting tools for students in higher education. Simultaneously, an intensive exchange of views has started in the public debate in the international educational community. However, for a more proper use of these applications, it is necessary to investigate the factors that explain their intention and actual use in the future. With the Unified Theory of Acceptance and Use of Technology (UTAUT2) model, this work analyses the factors influencing students' use and intention to use artificial intelligence technology. For this purpose, a sample of 199 Greek students at the School of Humanities and Social Sciences from the University of Patras participated in a survey. The findings highlight that expected performance, habit, and enjoyment of these Artificial Intelligence applications are key determinants influencing teachers' intentions to use them. Moreover, behavioural intention, habit, and facilitating conditions explain the usage of these Artificial Intelligence applications. The study did not reveal any moderating effects. The limitations, practical implications, and proposed directions for future research based on these results are discussed.

We are using information from a paper deriving a Lorentz-violating energy-momentum relation entailing an exact mo_mentum cutof as stated by G. Salesi . Salesi in his work allegedly defines Pre Planckian physics, whereas we restrict our given application to GW generation and DE formation in the first 10^-39s to 10^-33s or so seconds in the early universe. This procedure is inacted due to an earlier work whereas referees exhibited puzzlement as to the physical mechanism for release of Gravitons in the very early universe. The calculation is meant to be complementary to work done in the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, and also a calculation for Black hole destruction as outlined by Karen Freeze, et. al. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes but we claim that this destruction is directly linked to a Lorentz violating energy-momentum G. Salesi derived, which we adopt, with a mass m added in the G. Salesi energy momentum results proportional to a tiny graviton mass, times the number of gravitons in the first 10^-43 seconds

Our comprehension of fundamental cosmological principles hinges on a thorough understanding of the early universe. The Lambda Cold Dark Matter (ΛCDM) model has emerged as a valuable framework for elucidating various cosmic phenomena, uniting a cosmological constant (Λ) with cold dark matter (CDM). Nevertheless, recent observations, particularly data from the Planck, WMAP, and DES missions that probe the early universe, alongside local measurements of the Hubble constant, have unveiled significant inconsistencies. These inconsistencies have magnified the perplexing issue known as the Hubble Tension, thereby challenging our current understanding of the universe. To address this conundrum, we adopt a comprehensive approach encompassing a review of cosmological fundamentals, an exploration of the ΛCDM model, an examination of the cosmic microwave background (CMB), power spectrum, and perturbation theory, a thorough review of existing research, and finally, an investigation of real data. By undertaking these early universe processes, we aim to understand more about Hubble constant and its consequence in ΛCDM model.

In a recent paper we had discussed possibility of DM at high redshifts forming primordial planets composed entirely of DM to be one of the reasons for not detecting DM (as the flux of ambient DM particles would be consequently reduced). In this paper we discuss the evolution of these DM objects as the universe expands. As universe expands there will be accretion of DM, Helium and Hydrogen layers (discussed in detail) on these objects. As they accumulate more and more mass, the layers get heated up leading to nuclear reactions which burn H and He when a critical thickness is reached. In the case of heavier masses of these DM objects, matter can be ejected explosively. It is found that the time scale of ejection is smaller than those from other compact objects like neutron stars (that lead to x-ray bursts). These flashes of energy could be a possible observational signature for these dense DM objects.

In this work, the author employs the quantum hydrodynamic formalism to achieve the geometrization of spacetime for describing the gravitational interaction within the framework of quantum theory. This approach allows for the development of an equation of gravity that is mathematically connected to the fermion and boson fields. This achievement is accomplished by incorporating two fundamental principles: covariance of the quantum field equations and the principle of least action. By considering these principles, a theory is established that enables the calculation of gravitational corrections to Quantum Electrodynamics, and potentially, to the standard model of particle physics as well. The theory also provides an explanation for two phenomena: the existence of a cosmological pressure density similar to quintessence, that is compatible with the small value of the observed cosmological constant, and the breaking of matter-antimatter symmetry at high energies offering insights into why there is an imbalance between the two in the early universe. In the cosmological modeling of the theory, there exists a proposal to account for the formation of supermassive black holes that are accompanied by their own surrounding galaxies, without relying on the process of mass accretion. The model, in accordance with recent observations conducted by the James Webb Space Telescope, supports the notion that galactic configurations were established relatively early in the history of the universe, shortly after the occurrence of the Big Bang.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

Here we mathematically model black holes and the early universe following dynamics similar to RLC electrical models, focusing on their similarities at the singularity. We use this mathematically modelling to hypothesize the evolution of an expanding universe as the result of a black hole collapse followed by its evaporation. Or model consists of several steps defined by: (1) the formation of a black hole following general relativity equations; (2) growth of the black hole modelled as a resistance-capacitance-like electrical circuit; (3) expansion of space-time following the disintegration of the black hole, modelled by RLC-like dynamics. In updating this article, version 2, we will expand by presenting three additional examples related to the theory of the generalization Boltzmann's constant in curved space-time and the theory of general and especial relativity. We will calculate the critical mass to produce a black hole in the LHC, the existence of a high temperature Bose-Einstein condensate and finally we will demonstrate the existence of a tangential force to the repulsion force in the disintegration of subatomic particles. In the update of this article, version 3, we will expand to develop two examples. First, we will present the relationship between M-theory, extra dimensions with the theory of the generalization of Boltzmann's constant in curved space-time. Secondly, we will propose the idea of ​​updating the Lambda-CDM model, considering the primordial gravitational waves to correctly describe the evolution of the universe.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

The stage of a super-early scale-invariant Universe is considered on the basis of the Poincaré–Weyl gauge theory of gravity in a Cartan–Weyl space-time. An approximate solution has been found that demonstrates an inflationary behavior of the scale factor and, at the same time, a sharp exponential decrease in the effective cosmological constant from a huge value at the beginning of the Big Bang to an extremely small (but not zero) value in the modern era, which solves the well-known “cosmological constant problem”.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Sweat rate and electrolyte losses have a large inter-individual variability, a personalized approach to hydration can overcome this issue to meet an individual’s needs. This study aimed to investigate the effects of personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with 3-day of familiarization exercise following by two random exercise trials with a either PHS or control (CON). Then, participants crossed-over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, and HYP+CON. The PHS was prescribed according to participants’ fluid and sweat sodium losses. CON drank ad-libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: 1) 45min constant workload; 2) high-intensity intermittent exercise (HIIT) until exhaustion. PHS had a significantly greater fluid intake compared to CON. HYP+CON produced the lowest sweat sodium concentration. HYP+PHS had a lower thirst perception and a longer HIIT compared to HYP+CON. Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor to preventing negative physiological consequences during high-intensity exercise in the heat.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

A case-crossover study examined how PM_2.5 from Asian Dust Storms (ADS) affects the number of emergency room (ER) admissions for cardiovascular diseases (CVDs) and respiratory diseases (RDs). Our data indicated that PM_2.5 concentration from ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR) increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per increase 10 µg/m³ in PM_2.5 levels, for CVDs and RDs, respectively. A 10 µg/m³ increase in PM_2.5 from ADSs was significantly associated with increase in ER visits for CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for females (an increase of 3.09 in OR). In contrast, PM_2.5 levels had a significant impact on RD ER visits among those under 65 years of age (OR=1.77). The risk of ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the day after (lag 0 and lag 1); the corresponding risk increase for RDs only increased on the fifth day after the ADS (lag 5). In Taiwan’s late winter and spring, the severity of ER visits for CVDs and RDs increases. Environmental protection agencies should employ an early warning system for ADS to reduce high-risk groups’ exposure to PM_2.5.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

The Lorentz boost and rapidity for a radially falling frame are derived for the Schwarzschild metric in Kruskal-Szekeres coordinates. It is found through this analysis that the spacetime is radially length contracted toward the metric source in the falling frame as a result of the Lorentz boosting relative to the rest frame (which is shown to be consistent with the rest frame). When the falling frame reaches the event horizon, the Lorentz boost goes to infinity, causing the falling frame to become light-like, but trapped at the horizon. It is shown that in the falling frame at the horizon, the density of the source goes to infinity as a result of the length contraction.

Physics theory has yet to settle on specific descriptions for new elementary particles, for dark matter, and for dark energy forces. Our work extrapolates from the known elementary particles. The work suggests well-specified candidate descriptions for new elementary particles, dark matter, and dark energy forces. This part of the work does not depend on theories of motion. This work embraces symmetries that correlate with motion-centric conservation laws. The candidate descriptions seem to explain data that prior physics theory seems not to explain. Some of that data pertains to elementary particles. Our theory suggests relationships between masses of elementary particles. Our theory suggests a relationship between the strengths of electromagnetism and gravity. Some of that data pertains to astrophysics. Our theory seems to explain ratios of dark matter effects to ordinary matter effects. Our theory seems to explain aspects of galaxy formation. Some of that data pertains to cosmology. Our theory suggests bases for inflation and for changes in the rate of expansion of the universe. Generally, our work proposes extensions to theory in three fields. The fields are elementary particles, astrophysics, and cosmology. Our work suggests new elementary particles and seems to explain otherwise unexplained data.

Kinesiophobia (fear of movement) has been recognized as a significant barrier to recovery and rehabilitation in patients after total knee arthroplasty (TKA). Our goal was to identify predictors of kinesiophobia and examine its correlation with early functional outcomes in TKA recipients. On the first and fifth postoperative days (POD1 and POD5), we evaluated pain using the International Pain Outcomes Questionnaire (IPO-Q) and created multidimensional pain composite scores (PCS). Pain Composite Score-total (PCStotal) assesses the overall impact of pain, taking into account outcomes of pain intensity, pain-related interference with function, and emotions and side effects. Functional status on POD 5 was determined by the Barthel index, 6-minute walking test, and knee range of motion. Kinesiophobia was measured on POD5 using the Tampa Scale for Kinesiophobia (TSK) and multivariable logistic regression was used to assess factors associated with kinesiophobia. Among 75 TKA patients, 27% exhibited kinesiophobia. The final regression model highlighted PCStotal on POD5 (OR=6.2, CI=1.9-19.9), PCStotal (OR=2.1, CI=1.2-3.8) on POD1, and the intensity of chronic pain before surgery (OR=1.4, CI=1.1-2.1) as significant kinesiophobia predictors. On POD5, those with kinesiophobia showed increased dependency, slower gait, and poorer knee extension recovery. This study highlights the importance of identifying and addressing kinesiophobia in TKA patients to optimize functional outcomes and improve recovery. Also, it is important to assess not only pain intensity but also the physical and emotional interference caused by pain, which can contribute to the development of kinesiophobia.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Imaginary dimensions in physics require an imaginary set of base Planck units and some negative parameter $c_n$ corresponding to the speed of light in vacuum $c$. The second, negative fine-structure constant $\alpha_2^{-1} \approx -140.178$ present in Fresnel coefficients for the normal incidence of electromagnetic radiation on monolayer graphene leads to the imaginary Planck units. Furthermore, it sets $c_n \approx -3.06 \times 10^8~\text{[m/s]}$. It follows that electric charges are the same in real and imaginary dimensions. Neutron stars and white dwarfs, objects emitting perfect black-body radiation, need energy exceeding their mass-energy equivalence ratios. Complex energies are defined in terms of real and imaginary Planck units. Their imaginary parts, inaccessible for direct observation, store the excess of these energies. It follows that black holes are fundamentally uncharged, charged micro neutron stars and white dwarfs with masses lower than $5.7275 \times 10^{-10}~[\text{kg}]$ are unphysical, and the radii of white dwarfs' cores are limited to $R_{\text{WD}} < 6.7933~G M_{\text{WD}}/c^2$. It is conjectured that the maximum atomic number $Z=238$. A black-body object is in the equilibrium of complex energies of masses, charges, and wavelengths if its radius $R_\text{eq} \approx 2.7665~G M_{\text{BBO}}/c^2$, which corrects the value of the photon sphere radius $R_{\text{ps}}=3G M/c^2$, taking into account the value(s) of the fine-structure constant(s), which is otherwise neglected in general relativity.

This paper proposes a relativistic model of the Universe in which the geometry describes a 4D version of the 2-sheeted hyperboloid that is isotropic, homogeneous in space at a given time and inhomogeneous in time. The radius of this metric is temporal as opposed to spatial. It predicts both a Universe and Anti-Universe moving in opposite directions of time undergoing an expansion phase, followed by a collapsing phase. Using only the current age of the Universe and transition redshift, it predicts the accelerated expansion and it is shown that its Hubble diagram fits currently available supernova and quasar data as well as predicting a Hubble constant $H_0\approx71.6km/s/Mpc$. The angular term of the metric describes time dilation caused by the relativistic kinematic precession effect known as Thomas Precession which can be interpreted as spin about the time dimension. The model also makes two novel predictions: that the early Universe should have structures older than expected due to an increased amount of proper time relative to coordinate time in that era and that the background Universe should appear brighter than current models predict.

The evolution of life on the planet Earth is happening primarily in the universe and secondary on the Earth. We will examine in this article evolution of life as the cosmic phenomena. In our model multidimensional time-invariant superfluid quantum space that is the fundamental arena of the universe and represents about 95% of the energy in the universe has stable entropy. The increase of entropy happens only by about 5% of the energy in the universe that is in the form of matter. The evolution of life in our model is a process of matter organization into living systems that tends to develop towards the constant entropy of the time-invariant multidimensional quantum space. This process runs in the entire universe. The development of life into intelligent organisms is the universal process running throughout the entire universe.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤32 weeks of gestational age (GA) within 24 hours of birth. Materials and Methods: It is a prospective study conducted from March 15, 2022, to November 15, 2023, in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n=44) and non-surfactant (n=44) subgroups. Results: 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler Score at 24 hours of life (1-RR = 1-0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p=0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p=0.0178) pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p=0.0210) post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p=0.0336). There were no significant changes in ductus arteriosus parameters at 24 hours of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤32 weeks of gestational age at 24 hours of life.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

It is generally believed that the universe emerged from the Big Bang, before which space and time did not exist. However, Penrose proposed his theory of conformal cyclic cosmology, in which an aeon existed preceding this universe. Based on the cosmological principle, the universe is homogeneous and isotropic, expanding without center, but recently more and more deviations have been observed. By studying the fundamental particles and reactions of nature, we initiated a model that the Big Bang is the result of the collapse of a neutrino star within a black hole. We therefore re-analyze the cosmic microwave background (CMB) and find that the Center of the universe where the Big Bang occurred was at 0.66 ^+0.03 _-0.01 times the radius of the surface of last scattering away from the Local Supercluster (LS) and at Galactic coordinates (l, b) = (286^o +/- 10^o, -43^{o +7} _-6). If we look from the LS to the Center, the universe is spinning clockwise. Our findings are supported by Penrose’s conformal cyclic cosmology, low-variance circle sets in the CMB, and many other independent observational evidence of cosmic inhomogeneities, spatial anisotropies, and time variations.

The limited velocity in a geometry of Lorentzian signature, seem to prevent the universe to reach thermodynamic equilibrium as suggested by the cosmic microwave background. Thus it was suggested that the universe which was initially minuscule has reached a more considerable radius in a short duration by a process known as cosmic inflation. However, to drive such a process have led to the suggestion of an ad-hoc scalar field the inflaton, which has no purpose in nature other than driving the cosmic inflation field and then stopping it once the universe reached the right size. In a recent paper it was shown that rapid expansion can occur without postulating an inflation by following Hawking's suggestion and assuming that primordially the metric of the universe had an Euclidean signature, in which case velocity is not limited and thermalization and rapid expansion are derived without the need to assume an ad-hoc field. However, while in the previous work emphasis was put on the dynamics and physical statistics of the particles in a Euclidean space vs. Lorentzian space in which both spaces were given. No mathematical model was given regarding the development of current Lorentzian space-time from the early Euclidean space-time, and how fundamental problems such as the space-time singularity and the homogeneity of the CMB can be solved in the hybrid Euclidean-Lorentzian picture. This lacuna is to be rectified in the current paper.

The sources of dark matter and its spatial distribution is not in the typical standard model. The study thought to induct the physical causalities with empirical evidence on the theory of black hole and white hole juxtapose. The research applied a mixed method of data analysis and observational cosmology. With the cosmological observations on the traces of white holes, the research finds that the accretion phenomenon of black holes is largely contributed by its thermonuclear binding with the white hole. The antimatter saturated plasma of cold fusion and hot fission are key to the phenomenon of black hole and white hole juxtapose. The force between the black hole and the white hole is stronger than the strong force, and sheds new directions on cosmological and gravitation studies. The research concludes that black holes are white hole entropy. The higher order of the universe in matter forms can exist beyond the observed force. The thermal arrow of time is critical to future general relativity dependent instrumentation discoveries.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p&lt;0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was &lt;0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p&lt;0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p&lt;0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was &lt;0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Herein, we examined the effects of weather parameters and individual clinicodemographic risk factors on hemorrhagic stroke (HS) incidence, severity on admission, and disability at discharge in a harsh desert climate. In a retrospective design we studied patients admitted to a stroke unit in Arab Emirates in 2016-2019. With a distributed lag nonlinear model we explored immediate and delayed effects of weather on stroke incidence. Supervised machine learning was used to build models predictive of scores in NIHSS and mRS scales. We assessed model performance by calculating ROC AUC, F1 scores, specificity, and sensitivity. HS risk increased after a significant change in any weather parameter. The risk was reduced below baseline after 1-week adjustment to environmental changes. Climate input from the previous 3 days yielded reliable classification models. Humidex was a better predictor of severity than air temperature, whereas body mass index, age, and time of day at stroke onset were the strongest clinical predictors. Weather parameters before admission were stronger predictors of disease severity than individual clinical factors. We addressed limitations of previous studies by analyzing a full set of climate parameters: ambient temperature, relative humidity, humidex, atmospheric pressure, and wind speed. Predictive models may help to optimize patient management and develop preventative strategies.

Maize is an important staple food crop in sub-Saharan Africa (SSA). However, the average grain yield on farmers’ fields falls considerably short of the demand of the region’s population. In addition, the normal endosperm maize widely consumed in SSA is deficient in vitamin A. Drought, a consequence of climate change, is a major constraint to maize production, resulting in seasonal low grain yield in farmers’ fields. The objectives of this study were to assess the performance of newly developed extra-early maturing provitamin A hybrids under managed drought and well-watered conditions, compare the outcomes of multiple trait base-index and multi-trait genotype-ideotype distance index selection procedures, and identify drought-tolerant hybrids with stable performance across contrasting environments for commercialization in SSA. One hundred and ninety provitamin A hybrids and six checks were evaluated under managed drought and well-watered conditions at Ikenne for two seasons between 2021 and 2023. A 14*14-lattice design was used for the field evaluations under both research conditions. Drought stress was achieved by the complete withdrawal of irrigation water 25 days after planting. Results revealed significant differences among the hybrids under drought and well-watered conditions. Grain yield, ears per plant, and plant aspect under managed drought were correlated to the same traits under well-watered conditions suggesting that the expression of these traits is governed by common genetic factors. Twenty-nine hybrids were identified as top-performing drought-tolerant hybrids by the multiple trait base index and multiple-trait genotype–ideotype distance index. Of the selected outstanding 29 hybrids, 34% were derived from crosses involving the tester TZEEIOR 197, demonstrating the outstanding genetic potential of this inbred line. Further analysis of the 29 selected hybrids revealed TZEEIOR 509 × TZEEIOR 197 as the hybrid that combined the most drought-tolerant adaptive traits. However, the hybrids TZEEIOR 526 × TZEEIOR 97, TZEEIOR 384 × TZEEIOR 30, TZEEIOR 515 × TZEEIOR 249, TZEEIOR 510 × TZEEIOR 197, TZEEIOR 479 × TZEEIOR 197, and TZEEIOR 458 × TZEEIOR 197 were identified as the most stable hybrids across drought and well-watered conditions. These hybrids should be extensively tested in multi-location trials for deployment and commercialization in SSA.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

The model of an oscillating universe proposed by A. Friedmann in 1922 dominated cosmology for a long time. R. Tolman put forward a thermodynamic argument against the cyclic cosmological model, believing that entropy should accumulate from cycle to cycle. J. Bekenstein and S. Hawking discovered a tremendous amount of entropy associated with black holes. This discovery led to the conclusion that the majority of the Universe's entropy is contained in black holes. N. Poplawski considers a Universe that oscillates within a black hole. This paper analyzes the relationship between the entropy of black holes and the oscillating Universe inside a large black hole. It is demonstrated that the entropy of a black hole can only be defined for an external observer. For an observer inside the black hole, its entropy is zero. This opens up the possibility of constructing a cyclic cosmology in which entropy and the size of the visible part of the Universe change strictly periodically. This does not violate the second law of thermodynamics because the continuous accumulation of entropy from cycle to cycle pertains to the surface of the big black hole, which is invisible to the internal observer.

It is shown that the gravitational mass-energy defect could be the main cause of Big Bang energy and triggering inflation in the newborn Universe.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

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

This paper is given to the investigation of warm inflation using Modified Chaplygin gas in the background of locally rotationally symmetric Bianchi Identity type I. We find out the field equations and perturbations parameters such as; scalar power spectrum, scalar spectral index, scalar potential and tensor to scalar ratio under slow roll approximation. We find out these parameters in directional of Hubble parameter during the Logamediate inflationary regime in weak and strong case. These comological parameters shows that the anisotropic model is also compatible WMAP$7$ with recent observational data Planck $2018$.

We present a model of space that considers it to be a quantized dynamical entity which is a component of the universe along with matter and radiation. The theory is used together with thermodynamic data to provide a new view of cosmic evolution and an insight into the nature of dark energy and dark matter. Space is made up of energy quanta. The universe started from an atomic size volume at very high temperature and pressure near the Planck epoch. Upon expansion and cooling, phase transitions occurred resulting in the formation of radiation, fundamental particles, and matter. These nucleate and grow into stars, galaxies, and clusters. From a phase diagram of cosmic composition, we obtained a correlation between dark energy and the energy of space. Using the Friedmann equations, data from WMAP studies of the composition of the universe at 3.0 x 10⁵ (a=5.25 x 10^-2) years and at present (a=1), are well fitted by our model with an equation of state parameter, w= -0.7. The accelerated expansion of the universe, starting at about 7 billion years, determined by BOSS measurements, also correlates well with the dominance of dark energy at 7.25 x 10⁹ years ( a= 0.65). The expansion can be attributed to Quintessence with a space force arising from a quantum space field. From our phase diagram, we also find a correlation suggesting that dark matter is a plasma form of matter similar to that which existed during the photon epoch immediately prior to recombination. Our Quantum Space Model leads to a universe which is homogeneous and isotropic without the need for inflation. The thermodynamics of expansion is consistent with BOSS data that show the process to be adiabatic and the rate of expansion decelerating during the first 6 billion years after the Big Bang. However, it became non-adiabatic and accelerating thereafter. This implies an influx of energy from a source outside the universe; it warrants consideration as a possible factor in the accelerated expansion of the universe.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

We show that Universe inflation occurs when Einstein's gravity couples to nonlinear electromagnetic fields with cosmic stochastic magnetic fields background. Nonlinear electrodynamics with two parameters is used. The strength of magnetic fields to have the Universe inflation is obtained. It is shown that singularities of the energy density and pressure are absent for any scale factors. At large scale factors one arrives at equation of state for ultra-relativistic case. It is demonstrated that the curvature invariants do not have singularities. By computing the deceleration parameter we show that graceful exit takes place with reasonable e-folding number. The duration of Universe inflation as a function of model parameters is obtained. The classical stability and causality are analyzed by calculating the speed of the sound.

Based on four major cosmological and astrophysical coincidences, it seems possible to develop a new model of Hubble-Hawking Universe having light speed expansion. Considering the analysis of 740 super novae data, it is possible to consider a constant rate of cosmic expansion. As there is no physical reasoning for the observed speed of light and all the cosmological observations are completely based on speed of light-by considering ‘light speed expansion’ as a characteristic nature of the universe, big bang, inflation, dark energy, quintessence and lambda term like ideal and unidentified concepts can be reviewed and relinquished at fundamental level and a practical model of expanding universe can be developed with ease and clarity. In this context, we would like to emphasize the point that, traditional definition of cosmic red shift is absolutely wrong. In terms of energy of photon, true cosmic red shift must be defined as - ratio of loss of energy in photon to the energy of photon at galaxy. We encourage the reader to see Figure 1 and Table 1 pertaining to light travel distances prepared with $\left(\frac{z}{1+z}\right)\left(\frac{c}{H_0}\right)\cong z_{new}\left(\frac{c}{H_0}\right)$. For data comparison, readers are encouraged to visit https://cosmocalc.icrar.org/ and http://www.atlasoftheuniverse.com/cosmodis.c. It may be noted that, considering 200 million solar masses as a cut off for ordinary gravity, dark matter can be considered as an effect of power law based super gravity of galactic baryonic mass. It is well believed that, Hawking’s findings about black holes are the most important contributions to physics in recent decades. Hence, we appeal the science community to recommend our Hubble-Hawking model for further research and study.

The standard Cosmological model (LCDM) assumes that the expanding spacetime around us is infinite, which is inconsistent with the observed cosmic acceleration unless we include Dark Energy (DE) or a Cosmological Constant ($\Lambda$). But the observed cosmic expansion can also be explained with a finite mass $M$, inside a uniform expanding sphere, with empty space outside. An object with mass $M$ has a gravitation radius $r_S=2GM$. When $M$ is all contained within $r_S$, this is a Black Hole (BH). Nothing can escape from $r_S$, which becomes a boundary for the inside dynamics. In the limit where there is nothing outside, the inside corresponds to a local isolated Universe. The $r_S$ boundary condition corresponds to an effective force which is mathematically equivalent to $\Lambda=3/r_S^2$. We can therefore interpret cosmic acceleration as a measurement of the gravitational boundary of our Universe, with a mass $M = \frac{c^2}{2G}\sqrt{3/\Lambda} \simeq 6 \times 10^{22} M_{\odot}$. Such BH Universe (BHU) is observationally very similar to the LCDM, except for the very large scale perturbations, which are bounded by $r_S$.

In paper I, we showed that the observed (LCDM) Universe can be modeled as a local Black Hole (BH) Universe (BHU) of fixed mass M, without Dark Energy (DE): cosmic acceleration is caused by the BH event horizon rS=2GM. %The same BHU solution can be used to model the interior of a stellar or galactic BHs. Here, we propose that our BHU could form from the hierarchical free-fall collapse of regular matter. We argue that the singularity could be avoided with a Big Bounce explosion, caused by neutron degeneracy pressure (Pauli exclusion principle). This happens at GeV energies, like in core collapse supernova, well before the collapse reaches Planck energies (1E19 GeV). If our universe formed this way, there is no need for cosmic Inflation or a singular start (The Big Bang). Nucleosynthesis and recombination follow a hot expansion, like in LCDM, but cosmological measurements, which are free parameters in LCDM, could be estimated from first principles. Dark Matter could be made up of a wide mass range of primordial compact objects (BHs and Neutron stars), remnants of the collapse and bounce, which can provide a faster start for galaxy formation. We present a simple prediction to explain the observed value of Lambda and the coincidence problem.

It is shown that the Lambda component in the cosmological Lambda-CDM model can be conceived as vacuum energy, consisting of gravitational particles subject to Heisenberg’s energy-time uncertainty. These particles can be modelled as elementary polarisable Dirac-type dipoles (“darks”) in a fluidal space at thermodynamic equilibrium, with spins that are subject to the Bekenstein-Hawking entropy. Around the baryonic kernels, uniformly distributed in the universe, the spins are polarized, thereby invoking an increase of the effective gravitational strength of the kernels. It explains the dark matter effect to the extent that the numerical value of Milgrom’s acceleration constant can be assessed by theory. Non-polarized vacuum particles beyond the baryonic kernels compose the dark energy. The result is a quantum mechanical interpretation of gravity in terms of quantitatively established shares in baryonic matter, dark matter and dark energy, which correspond with the values of the Lambda-CDM model..

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

In this paper, we investigate an exact Universe which is observational viable and filled with binary mixture of perfect fluid and cosmological constant $\Lambda$. Owning the non-uniform expansion of cosmos, we have considered redshift drift $\dot{z} = -(1+z)H_{0}+H(z)$ and performed statistical test to obtain the best fit value of model parameters of derived Universe with its observed values. Here $H_{0}$ and $z$ denote the present value of Hubble constant and redshift respectively. We estimate the best fit values of Hubble constant and density parameters are $H_{0} = 68.58 \pm 0.84$ km/s/Mpc, $(\Omega_{m})_{0} = 0.26 \pm 0.010$ and $(\Omega_{\Lambda})_{0} = 0.71 \pm 0.025$ by bounding the derived model with latest observational Hubble data (OHD) while with joint Pantheon data and OHD, its values are $H_{0} = 71.93 \pm 0.58$ km/s/Mpc, $(\Omega_{m})_{0} = 0.272 \pm 0.06$ and $(\Omega_{\Lambda})_{0} = 0.74 \pm 0.09$. The analysis of deceleration parameter and jerk parameter show that the Universe in derived model is compatible with $\Lambda$CDM model.

We investigate the matching point between non-inertial frames and local inertial frames. This localization of gravity lead to an emergence of a timeless state of the universe in a mathematically consistent way. We find a geometric interpretation of the speed of light and mass. We find also a relation between every mass measured and the black hole entropy which introduces an information-matter equation from gravity. The experimental evidence of the timeless state of the universe is the quantum entanglement. Since the spin measurement is the manifestation of quantum entanglement measurement. Therefore, the spin of quantum particles can be understood as a relative gravitational red-shift at two different points. Therefore the spin measurements introduce the quantum gravity measurements in local inertial frames. We conjecture that the universe emerges from a black hole that has global symmetry of $SU(3)\times SU(2)\times U(1)$. We introduce a geometric realization of spontaneous symmetry breaking in the timeless state of the universe and emergence of mass.

In this paper, we consider an economy, in which consumers exhibit unrealistic optimism, and show that such an economy is more likely to undergo early recessions and underinvestment rather than experiencing bubbles or overinvestment. In this model, each consumer incorrectly believes that a negative aggregate preference shock will hit all other consumers, but not herself. When consumers have such an unrealistic optimism, the output price must fall prematurely before the aggregate shock occurs. The reason is that if the price does not plummet today, all consumers would postpone making purchases by falsely expecting that an arbitrage opportunity will arise in the future when the aggregate shock hits the economy, in which case, the output market cannot clear. We also show that the government has the potential to improve welfare of the economy by providing subsidies, if the government judiciously selects the right timing for intervention.

In cosmology dark energy and dark matter are included in the ΛCDM model, but they are still completely unknown. Because in black holes Lorentz invariance seems not to be applicable for curved space-time, we introduce a model for a reduced speed of light in black holes due to quantum gravity effects and the Heisenberg uncertainty relation. Then black holes are a source for a scalar field with dark energy characteristics. This model has no information paradox for black holes because particles / radiation entering the black hole are redshifted in their wavelength that far that the wavelength has the size of the Schwarzschild radius and thus they are in some way "frozen" in the black hole. We show that the scalar field also has characteristics of dark matter shortly after Planck time, when we use a Big Bounce model. This model also presents an alternative to cosmological inflation with the possibility to solve the flatness and horizon problem and the problem of density fluctuations.

Within the framework of the previously proposed formulation of the quantum theory of gravity in terms of world histories, it was suggested that the universe has its own mass. This quantity is analogous to the mass of a particle in relativistic mechanics. The mass of the universe is a distribution of non-zero values of gravitational constraints, which arises and changes in time as a consequence of the initial conditions for fundamental dynamic variables. A formulation of the Euclidean quantum theory of gravity is also proposed to determine the initial state, which can be the source of the universe’s own mass. Being unrelated to ordinary matter, the distribution of its own mass affects the geometry of space and forms a dedicated frame of reference. The existence of selected reference systems is taken into account by the corresponding modification of the system of quantum gravitational constraints. A variant of such a modification of the Wheeler-De Witt equation is the operator representation of gravitational constraints, which, together with the state of the universe, determines the parameters of the reference system in the form of a distribution of the spinor field on a spatial section.

Here we deduce the scales of a spherically symmetric, closed system subject to internal repulsive vacuum pressure. Due to periodic boundary conditions of virtual particle loops, it is shown that Ramanujan summation must be physical for the virtual particle case, as to avoid numerical results of either null, very large or infinity. It is thereafter shown that this closed system must be holographic in nature, with mass-energy inversely proportional to the Planck area, up to a yet to be determined geometrical proportionality constant. The validity of this result is strengthened when it is shown that one may obtain the same answer using different methods, either thermodynamic laws or a force balance equation. Implications of this small study is not yet fully understood and is hopefully investigated in subsequent letters.

We propose that the Big Bang does not have a singular start, but that it originates from gravitational collapse of a low density cloud that collapsed 25 Gyrs ago to form a Black Hole (BH) of mass M ≃ 6 × 1022M⊙. The collapse continued inside the BH for 11Gyrs until the density achieves neutron degeneracy and the collapse bounces into expansion like a core collapse supernova. From observations today, this model is very similar to the standard Big Bang cosmology but there is no need for Inflation or Dark Energy (DE). The observed cosmological constant Λ is not a new form of DE, but results from the dynamics of the Big Bang expansion inside the BH event horizon rS = 2GM = √3/Λ. Why our Universe has such a large mass M (or small Λ value)? If τO(≃ 10Gyr) is the astronomical timescale needed for observers like us to exist, we find a simple anthropic prediction, based only on gravitational collapse from Gaussian fluctuations, that the maximum probability for M is MO < M < 3MO where MO = τO/3G. This agrees well with the measured values for τO and M in our Universe.

The anisotropy in the CMBR detected by the COBE satellite has sprouted the research and theories of the void that got created, after being washed away by a parallel universe after its collision. This details of the roadmap to the parallel universe, that are previously been entangled, but now, separated, with the concept of 2-time dimensions as a time curve of containing the closed curves embedded on the surface area, thereby time running backward in orientation in the parallel universe, along with the perspective of eternal inflation and divided subspaces giving birth to twin universes are provided here. This time curve being responsible for creating an exponentiality of time frames, growing in layers, giving us the perception of the confabulations being an indication of the previously connected worlds.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

Strangeness flavor is abundant and in chemical equilibrium in the primordial Quark-Gluon Plasma(QGP) filling the early Universe. Upon hadronization near to T=150 MeV one may think that relatively short lived massive strange hadrons decay rapidly and strangeness disappears. However, we show using detailed balance considerations for inverse decay reactions that the back reaction repopulate strangeness keeping it in chemical equilibrium at least to the time when strange antibaryons annihilate near T≃30-50 MeV. However, our present study is focused on the meson sector of the hadronic Universe. Specifically, we establish here the temperature range in which the expansion of the Universe becomes faster compared to the production processes which balance natural strangeness decay: In the temperature interval 33MeV&lt;T&lt;20MeV: μ±+νμ→K±, π+π→K and l−+l+→ϕ reactions in sequence become slower compared to the characteristic Hubble time.

This article explores the enduring mysteries of consciousness and the afterlife, two enigmatic topics that have fascinated humanity for ages. Despite extensive scientific efforts, the existence of an afterlife remains unproven, and understanding consciousness remains a significant challenge. The research introduces innovative hypotheses through simple thought experiments with empirical evidence and robust theoretical foundations. It delves into the complexities of consciousness, its relationship with the brain, and the need for interdisciplinary approaches encompassing physics, psychology, and philosophy. Boldly contemplating the probability of a continuous consciousness after death, the study argues that existing evidence strongly supports this idea. Beyond theoretical implications, it envisions practical outcomes, suggesting that insights into these mysteries could enhance human well-being and contribute to a more harmonious world. In summary, this article embarks on a quest to shed light on age-old questions about consciousness and the afterlife. Through fresh methodologies, it aims to provide new perspectives that could reshape our understanding of existence and inspire intellectuals to positive individual and societal advancements including psychological well-being and intelligence.

Ontological premises have profound theoretical implications. This analysis posits a single, universal structure composed of two ontic entities: discrete, quantized units of space ("Planck Spheres") and a State of Absolute Nothingness (the "SOAN"). Planck Spheres and the SOAN form a physical, ultra-high (3 x N) dimensional space ("Planck Space") and a discrete 3D space (or "4D spacetime"). Together, Planck Space and 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the "Dual Ontology"). Critically, a one-to-one mapping and identity exists between the Planck Spheres comprising 4D spacetime and Planck Space. The Dual Ontology conjecture supports radically simplified physical explanations for three distinct areas of theoretical physics: First, the conjecture reconciles fundamental issues in Special Relativity and quantum mechanics by explaining why single and N-body quantum states (a) dynamically evolve in 4D spacetime subject to the speed of light and (b) instantaneously collapse in a physical Planck Space that is not subject to Special Relativity. Second, the temporal and physical asymmetry between the dynamic evolution of quantum states in 4D spacetime subject to Special Relativity and the instantaneous collapse of quantum states in a Planck Space where Special Relativity is inapplicable explains quantum path irreversibility and the arrow of time. Third, at or near the heat death of 4D spacetime, the instantaneous collapse of the energy content of Planck Space and the simultaneous transition of 4D spacetime's extremely widely dispersed energy content to a non-singular, generally localized volume at t = 0 explains 4D spacetime's isotropy, homogeneity, extremely high energy, pressure, and temperature, flatness, and low gravitational entropy. It also explains the horizon and fine-tuning problems.

This paper is dedicated to examining dynamic dark energy models in the context of observational constraints and their implications for the universe's future. By integrating theoretical models with various observational data, we aim to provide a comprehensive view of how dynamic dark energy influences cosmic evolution and the universe's fate. This study tests these models against the latest observational evidence, including the Cosmic Microwave Background, supernovae, and large-scale structure surveys, to refine our understanding of the universe's accelerating expansion and the mysterious nature of dark energy.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

We humans are natural-born engineers. As such, we model after machines not only isolated, naturally occurring systems, but also the basic laws of physics, sharing with machines a local-evolution-of-state `grammar'. However, previous work by the author casts doubt upon this mechanistic paradigm, suggesting that it is to blame for the stubbornness of many open problems in physics. Simple experiments are therefore proposed to identify `non-machines'. In one experiment, `non mechanistic correlations' in the spirit of Bell are sought in a pair of separated but previously coupled (macroscopic) chaotic systems. In another it is tested whether chaotic systems could fuzzily `remember their future' in the sense that a future binary perturbation applied to them could be inferred from their present behavior with probability>1/2. Chaotic systems are chosen as candidates because the long-time application of their (deterministic) mechanistic description is conceptually groundless: All scales are significant and mutually coupled in that regime, down to scales governed by QM, yet the quantum-classical transition remains inexplicable---if only due to the measurement problem. Similarly for non-deterministic chaotic systems, modeled as such purely for defying a short-time deterministic mechanistic description. Should a non mechanistic signature be found in such simple systems, the implications for science as a whole and life sciences in particular cannot be overstated.

We measure the accelerated cosmic expansion rate of the late-time Universe and derive constraints on cosmological parameters from the final baryon acoustic oscillation (BAO) uncorrelated measurements of different surveys after two decades of dedicated spectroscopic observation combined with the Pantheon sample of Type Ia supernovae, the Hubble diagram of gamma-ray bursts &amp; quasars data, the Cosmic Chronometers data, and the recent Hubble constant value measurement from the Hubble Space Telescope and the SH0ES Team as an additional prior. In Λ cold dark matter (ΛCDM) scenario, the model fit yields Ωm=0.313±0.034 and ΩΛ=0.672±0.025. Combining BAO with CC+Pantheon+QSR+GRB data sets we get H0=69.21±1.22 km s−1 Mpc−1, rd=133.46±2.49 Mpc. For the a flat wCDM model, we get w=−1.111±0.030. For a dynamical evolution of dark energy in a flat w0waCDM cosmology, we get wa=−0.292±0.167. We apply the Akaike information criteria probe to compare the three models, and see that all models are favored and cannot be discarded from the current data.

Using a joint statistical analysis, we test a four-dimensional FLWR model embedded in a five-dimensional bulk based on the Nash-Greene embedding theorem. Performing a Markov Chain Monte Carlo (MCMC) modelling, we combine observational data sets as those of the recent Pantheon type Ia supernovae, Baryon Acoustic Oscillations (BAO) and the angular acoustic scale of the Cosmic Microwave Background (CMB) to impose restrictions on the model and correlating the model parameters to mimick an equation of state. From statistical classifiers as the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), we use the Jeffreys' scale and find a strong evidence favoring a statistically consistence with a dynamical Dark energy (CPL parameterization) and a relative consistence with both ΛCDM and ωCDM models. Moreover, we find that the transition redshift used as a cosmic discriminator with the best fit z_t=0.634 ± 0.014 at 1-σ C.L. with a range scenario for late time sharp transitions.

The Universe, rather than being homogeneous, displays an almost infinite topological genus, because it is punctured with a countless number of gravitational vortexes, i.e., black holes. Starting from this view, we aim to show that the occurrence of black holes is constrained by geometric random walks taking place during cosmic inflationary expansion. At first, we introduce a visual model, based on the Pascal’s triangle and linear and nonlinear arithmetic octahedrons, which describes three-dimensional cosmic random walks. In case of nonlinear 3D paths, trajectories in an expanding Universe can be depicted as the operation of filling the numbers of the octahedrons in the form of “islands of numbers”: this leads to separate cosmic structures (standing for matter/energy), spaced out by empty areas (constituted by black holes and dark matter). These procedures allow us to describe the topology of an universe of infinite genus, to assess black hole formation in terms of infinite Betti numbers, to highlight how non-linear random walks might provoke gravitational effects also in absence of mass/energy, and to propose a novel interpretation of Beckenstein-Hawking entropy: it is proportional to the surface, rather than the volume, of a black hole, because the latter does not contain information.

We present a thermodynamic approach in modeling the evolution of the universe based on a theory that space consists of energy quanta, the spaceons. From wave-particle duality, they can be treated as an ideal gas. The model is similar to the Big Bang but without Inflation. It provides an insight into the nature of dark energy and dark matter, and an explanation for the accelerated expansion of the universe. The universe started from an atomic size volume of spaceons at very high temperature and pressure. Upon expansion and cooling, phase transitions occurred resulting in the formation of fundamental particles, and matter. These nucleate and grow into stars, galaxies, and clusters due to the action of gravity. From the cooling curve of the universe we constructed a thermodynamic phase diagram of cosmic composition, from which we obtained the correlation between dark energy and the energy of space. Using Friedmann’s equations, our model fits well the WMAP data on cosmic composition with an equation of state parameter, w= -0.7. The dominance of dark energy started at 7.25 x 10⁹ years, in good agreement with BOSS measurements. The expansion of space is attributed to a scalar quantum space field. Dark Matter is identified as a plasma form of matter similar to that which existed during the photon epoch, prior to recombination. The thermodynamics of expansion of the universe was adiabatic and decelerating during the first 7 billion years after the Big Bang; it accelerated thereafter. A negative pressure for Dark Energy is required to sustain the latter. This is consistent with the theory of General Relativity and the law of conservation of energy. We propose a mechanism for the acceleration as due to consolidation of matter forming Dark Energy Stars (DES) and other compact objects. The resulting reduction in gravitational potential energy feeds back energy for the expansion. Space will continue to expand and dark energy will undergo phase transition to a Bose-Einstein condensate, a superfluid form of matter. Self-gravitation can cause a bounce and start a new Big Bang. We show how the interplay of gravitational and space forces leads to a cyclic, maybe eternal, universe.

The Casimir effect can either work over very short distances or at very low temperatures. At the cosmic scale, we naturally deal with long distances, but at the same time, we encounter extraordinarily low temperatures, namely the CMB (Cosmic Microwave Background) tem- perature. Recently, there has been increased interest in the Casimir effect and its implications in cosmology. Here, we briefly demonstrate that the luminosity and radiation pressure of the CMB is mathematical identical to a theoretical Casimir effect within the Hubble sphere, or actually our solution seems to be valid for any Schwarzschild black hole. The Casimir effect forevery Schwarzschild black hole is identical. This also include the Hubble sphere if we treat it as a Schwarzschild black hole that is related to increased interest in black hole cosmology.

The cyclic universe theory is a model of cosmic evolution according to which the universe undergoes endless cycles of expansion and cooling, each beginning with a big bang and ending in a big crunch. In this paper, the researcher finds a unique property of Space-time, this particular and marvelous nature of space shows us that space can shrink, expand, and stretch. This property of space is caused the size of the Universe changing over time: growing or shrinking. The observed accelerated expansion, which relates the stretching of Shrunk space for the new theory, is derived. This model is based on three underlying notions: First, the Big Bang was not the beginning of Space-time, but rather at the very beginning fraction of a second there was an infinite force of infinite Shrunk space in the cosmic singularity, that force gave rise to the big bang and caused the rapidly growing of space-time, and all other forms of energy are transformed into matter and radiation and a new period of expansion and cooling begins. Second, there was a previous phase leading up to it, with multiple cycles of contraction and expansion that repeat indefinitely. Third, the two principal long-range forces are the gravitational force and the repulsive force generated by shrunk space. They are the two most fundamental quantities in the universe that govern cosmic evolution. They may provide the clockwork mechanism that operates our eternal cyclic universe. The space will not continue to expand forever, no need however, for dark energy and dark matter. This model of Space-time and its unique properties enables us to describe a sequence of events from the Big Bang to the Big Crunch.

We discuss the topic of the transparency of the Universe in gamma-rays due to the Extragalactic Background Light, and its cosmological and physical implications. Rather than a review, this is a personal account on the development of 30 years of this branch of physical science. Extensive analysis of the currently available information appears to us as revealing a global coherence among the astrophysical, cosmological, and fundamental physics data, or, at least, no evident need so far of substantial modification of our present understanding. Deeper data from future experiments will verify to what extent and in which directions this conclusion should be modified.

In this paper, we investigate how Rindler observer measures the universe in the ADM formalism. We compute his measurements in each slice of the space-time in terms of gravitational red-shift which is a property of general covariance. In this way, we found special relativity preferred frames to match with the general relativity Rindler frame in ADM formalism. This may resolve the widely known incompatibility between special relativity and general relativity on how each theory sees the red-shift. We found a geometric interpretation of the speed of light and mass.

In the present work, the charged dark matters of B1, B2 and B3 bastons are explained as the right-handed partners of the left-handed neutrinos. The new Higgs mechanism of SU(2)_DM×SU(2)_Weak×SU(2)_Strong including electromagnetic and gravitational forces is applied. And the rest masses of the elementary particles depend on their charge configurations. The left-handed neutrinos have only the lepton charges (LC) and the right-handed dark matters have only the electric charges (EC). This explains the fact that the rest masses of the left-handed neutrinos are so small, and the rest masses of the right-handed dark matters are relatively very large. The proposed rest mass (26.12 eV/c²) of the B1 dark matter is indirectly confirmed from the supernova 1987A data. The missing neutrinos are newly explained by using the dark matters and lepton charge force. The neutrino excess anomaly of the MinibooNE data is explained by the B1 dark matter scattering within the Cherenkov detectors. The quark mixing and neutrino mixing are not required in the present model. It is shown that our matter universe and its partner antimatter universe can be created from the big bang in the point of view of time -, charge -, space -, and quantum state – symmetric universe evolution.

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or programming fetal. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including Celiac Disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age at gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1-3%. It is not known what factors act to modify the risk of disease in genetically at risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD.

This paper gives both a general canonical quantum gravity theory and the general canonical quantum gravity theories of the Universe and general black hole, and discovers the relations reflecting symmetric properties of the standard nonlinear gravitational Lagrangian, which are not relevant to any concrete metric models. This paper concretely shows the general commutation relations of the general gravitational field operators and their zeroth, first, second and third style, respectively, of high order canonical momentum operators for the general nonlinear system of the standard gravitational Lagrangian, and then has finished all the four styles of the canonical quantization of the standard gravity.

We show that the accelerating expansion phase of the universe can emerge from the group field theory formalism, a candidate theory of quantum gravity. The cosmological evolution can be extracted from condensate states using mean field approximation, in a form of modified FLRW equations. By introducing an effective equation of state w, we can reveal the relevant features of the evolution, and show that with proper choice of parameters, w will approach to −1, corresponds to the behaviour of cosmological constant, results in a late time acceleration and leads to de Sitter spacetime asymptotically.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. The model is developed using a constructive approach. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

The wave-particle description of quantum mechanics is briefly reviewed to set an analogy between the quantum mechanics of particles and fields and quantum cosmology. It is shown that quantum cosmology can be seen as a quantum field theory developed in the space of three metrics (the metrics of the spatial sections of the spacetime), where the classical evolution of the universe corresponds to a definite trajectory and the quantum mechanics of matter fields emerges as the first order quantum correction. Like in a quantum field theory developed in an isotropic background, the universes are created in universe-antiuniverse pairs, which might provide us with an explanation for the matter-antimatter asymmetry observed in our universe without going beyond the standard model. Moreover, the states of the matter and the antimatter fields of the pair of universes are entangled and that makes that their initial states are in a non-vacuum state (presumably in a thermal state). That might open the possibility of looking for observable imprints of the creation of universes in pairs is the astronomical data.

Unification point of view, quantum cosmology must be given a priority and one should make a note that, Spin is a basic property of quantum physics and rotation is a very common experience. In this context, we have developed a quantum model of cosmology associated with Machian universe having Planck scale origin, total dark matter, light speed rotation and equality of gravitational self energy density and thermal energy density. We would like to appeal that, observed cosmic radius and age seem to be shortened by 146.3 times their actual magnitudes.

This study delves into hospital mobility, understood as an indicator of perceived service quality, across the Italian regions of Apulia and Emilia Romagna, utilizing logistic regression among machine learning techniques. The focus is on how structural, operational, and clinical variables impact patient perceptions of service quality, influencing their healthcare choices. Through the analysis of mobility trends with machine learning, significant differences between regions were uncovered, highlighting the influence of regional context on perceived quality. The integration of SHAP (SHapley Additive exPlanations) values into our analysis provided deeper insights into the logistic regression model, elucidating the specific contribution of each variable to perceived healthcare quality. This incorporation of SHAP values underscores the study's commitment to employing advanced, explainable AI techniques to enhance the interpretability and fairness of healthcare service evaluations. The choice of logistic regression elucidated the impact of specific variables on quality perception, offering essential insights for optimizing healthcare resource distribution and underscoring the importance of data-driven strategies to foster more equitable, efficient, and patient-centred healthcare systems. Contributing to the understanding of perceived quality dynamics within the healthcare context, the research paves the way for further investigations into enhancing accessibility and service quality, leveraging machine learning as a tool for improving healthcare services efficiency in diverse regional settings.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

A simple line of reasoning, based on the most fundamental concepts of thermodynamics, yields some intriguing results for a better understanding of the processes occurring in the observable Universe. Gravitational mass must be continuously generated within an expanding thermodynamic system for this system to remain closed. The Second Law is a direct consequence of this production of mass. Simple expressions for the entropy and temperature of the Universe were obtained and the results agree well with observable values. Furthermore, it is demonstrated that the conservation laws within the Universe are independent of its energy density. Based on the solution for the quantum state of the Universe, it is conjectured that the Second Law is incomplete and must be complemented to a conservation law, which takes into account the growth of the amount of information within the Universe. Once the Second Law is complemented to a conservation law, the importance of mass generation within the Universe becomes well pronounced – not only gravitational effects play the role of an organising force, but also the amount of mass within the Universe defines both the amount of information within the Universe and the level of the Universe’s complexity.

We present a Quantum Space Model (QSM) of the evolution of the universe based on the theory that space consists of energy quanta from which it began. We used the Friedmann equations to trace its history and show that Dark Energy is the energy of space which caused its accelerating expansion.The universe started from a quanta of space which was triggered by quantum fluctuations that caused the Big Bang. It then expanded and cooled undergoing phase transitions to radiation, fundamental particles, and matter. Matter grew into galaxies, and was consolidated by gravity into Black Holes, ending in a Big Crunch and Deep Freeze inside a Black hole at 1.380 trillion years. Fluctuations caused a new Bang to start another cycle in its life. If the Law of Conservation of Energy is universal, then the cosmos is eternal. Our results support the theoretical predictions of a cyclic universe by Steinhardt and associates, as well as Penrose. Space and energy are equivalent as embodied in the Planck energy equation. They are the two most fundamental quantities that govern cosmic evolution. The two principal long range forces are the gravitational force and the space force,which maybe the fifth force in the universe. They provide the clockwork mechanism operating our cyclic universe.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

The nonlocality of entangled quantum mechanical systems is incompatible with the standard interpretation of special relativity as a single 4D Minkowskian metric spacetime. The difficulty is that the definition of a spacetime interval between any pair of events precludes any form of nonlocal interaction, even the relatively benign non-signaling correlations. By an application of the relativity principle, and the use of the space ←→ time symmetry of the Lorentz boost I propose here a reinterpretation of special relativistic spacetime. This new ontology consists of a set of coexisting 3+1D spaces (‘framespaces’), each containing unique content in the form of a complex density. These spaces are related by the Lorentz boost, and coupled pairwise in a manner dictated by the Lorentz transformation. The inter-space coupling acting on the spacetime content gives rise to a nonlocal wave phenomenon, which is identified as quantum wave mechanics. The interspace coupling strength is then inversely proportional to Planck’s constant. The coexistence of multiple spaces is interpreted as momentum superposition, implying that momentum is the fundamental physical basis of quantum superposition. This new spacetime interpretation of quantum mechanics has many consequences, including explanations of quantum non-locality, the spacetime role of Planck’s constant, quantum measurement as a symmetry-breaking process and the redundancy of description of gauge theory.

A theoretical model to translate the evolution over time, in early stages, of growth and accumulation of biofilm bacterial mass is introduced. The model implies the solution of a system of differential-difference master equations. The application of an algorithm like Miller´s tree term recurrence, already known for Bessel functions of first kind, allows an exact calculation of the solutions of such equations, for a wide range of parameters values and time. For biofilm model a five term recurrence is deduced and applied in a backwards computation. A suitable normalisation condition completes the reach of the solution.

A persistent idea in cosmology is that the universe originated and then continued to evolve as a black hole. While the notion of a black hole universe has generally been framed within the standard cosmological model, the latter has had numerous problems related to dark matter, dark energy and other issues. To avoid such problems an alternative is proposed which omits cosmic expansion, dark matter and dark energy. The observable universe is cast instead as primarily a thin spherical shell of cold (~29 K) baryonic matter situated near the Hubble radius. This shell of plasma holds 95% of the observable universe’s mass, the remaining 5% existing in the interior galaxies and gas clouds. A key premise of the model is that spacetime is fundamentally photonic in nature. This allows photon energy to be transferred to spacetime in the Hubble redshift and to be transferred back to photons in a novel blueshift. These exchanges together drive a cosmic energy cycle for gravity and the cosmological constant, Λ. Photons of the cosmic microwave background originating in the plasma shell lose energy to ‘cooler’ regions of spacetime in interior zones via the Hubble redshift. This gives rise to gravity through the optical gravity approach. The depleted photons moving back towards the shell are then reenergized in ‘hotter’ spacetime regions via the Hubble blueshift. These photons eventually exert outward pressures on the shell which perfectly balance the inward forces of gravity, in this manner functioning as Einstein’s cosmological constant. The observable universe behaves as a closed system in thermodynamic equilibrium with constant energy and entropy and indeterminate age. Black holes are suggested to have analogous plasma shell structures and gravity/Λ cycles.

Following Smolin, we proceed to unification of general relativity and quantum theory by operating solely with events, i.e., without appealing to physical systems and space-time. The universe is modelled as a dendrogram (finite tree) expressing the hierarchic relations between events. This is the observational (epistemic) model; the ontic model is based on p-adic numbers (infinite trees). Hence, we use novel mathematics—not only space-time but even real numbers are not in use. Here, the p-adic space (which is zero dimensional) serves as the base for the holographic image of the universe. In this way our theory relates to p-adic physics; in particular, p-adic string theory and complex disordered systems (p-adic representation of Parisi matrix for spin glasses). Our Dendrogramic-Holographic (DH) theory matches perfectly with the Mach’s principle and Brans-Dicke theory. We found surprising informational interrelation between the fundamental constants, h, c, G, and their DH-analogues, h(D), c(D), G(D). DH-theory is part of Wheeler’s project on the information restructuring of physics. It is also a step towards the Unified Field theory. The universal potential V is nonlocal, but this is relational DH-nonlocality. V can be coupled to the Bohm quantum potential by moving to the real representation. This coupling enhanced the role of the Bohm potential.

We present a Machian model of Quantum Cosmology with full dark matter and light speed expansion and rotation. During galaxy formation and evolution, fraction of dark matter transforms to visual matter with a relation of the form, m_vis = constant * (m_dark)^2/3. Using this relation and replacing MOND’s ‘critical acceleration’ with “current cosmic maximum angular acceleration”, galactic flat rotation speed range of (50 to 500) km/sec can be fitted well. Estimated flat rotation speeds of DD168, Milky Way and UGC12591 are 49.96 km/sec, 199.66 km/sec and 521.75 km/sec respectively. Based on these striking coincidences, it is possible to say that, MOND’s approach is implicitly connected with cosmological estimation of 95% invisible matter. Considering galactic total matter and current cosmic maximum angular acceleration, galactic working radii, angular velocity and visual matter density can be estimated. Even though, this model is free from ‘big bang’, ‘inflation’, ‘dark energy’, ‘flatness’ and ‘red shift’ issues, at 2.722 K, estimated present Hubble parameter is 66.24 km/sec/Mpc, cosmic radius is 146.3 times the Hubble radius, angular velocity is 146.3 times lower than the Hubble parameter and cosmic age is 146.3 times the Hubble age. With future observations and advanced telescopes, it may be possible to see far distant galaxies and very old stars far beyond the current observable cosmic radius.

Although general relativity has been successful in explaining many astronomical phenomena, few problems about the contents and evolution of the universe have remained mysterious since last century. Most important of them is the cosmological constant problem in which conventional calculation of vacuum (or dark) energy density using quantum mechanics leads to a value ~10¹¹⁴ J/m³ which is ~10¹²³ times more than the vacuum energy (5.3×10^-10 J/m³) estimated from astronomical observations of expanding universe. Similarly, cosmic coincidence problem questions why the matter energy density (ordinary plus dark matter) is of the same order as the vacuum energy density at present time. Finally, the mechanism responsible for spatial flatness and expansion of the universe are not clearly understood. In this paper, by taking the vacuum as a finite and closed quantum oscillator, we solve all of the above-mentioned problems. At first, by using purely quantum mechanical approach, we predict that the dark energy density is c⁴/(GR²) = 5.27×10^-10 J/m³ (where R is radius of 3-sphere of universe) and matter energy density is c⁴/(2GR²) = 2.6×10^-10 J/m³ which match well with astronomical observations. We also prove that the dark energy has always been ~66.7% and matter energy has been ~33.3% of total energy and hence, the so called cosmic coincidence problem doesn’t exist. Next, we show how flatness of space could be maintained since the early stage of universe. Finally, using our model, we derive the expression for age and radius of universe which match well with the astronomical data.

With reference to Planck scale, increasing support for large scale cosmic anisotropy and preferred directions and by considering an increasing ratio of Hubble parameter to angular velocity, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity decreases with square of the decreasing cosmic temperature. 3) Increasing ratio of Hubble parameter to angular velocity plays a crucial role in estimating increasing cosmic expansion velocity and decreasing density ratios of dark matter and ordinary matter. 4) There is no need to consider dark energy for understanding cosmic acceleration.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

The Hyper-Torus Universe Model (HTUM) is a novel framework that unifies quantum mechanics, cosmology, and consciousness, proposing that the universe is a higher-dimensional hyper-torus containing all possible states of existence. This paper explores the fundamental concepts and implications of the HTUM, which suggests that the universe is a quantum system in which all possible outcomes are inherently connected, with consciousness playing a crucial role in actualizing reality. The HTUM addresses critical challenges in modern physics, such as the nature of quantum entanglement, the origin of the universe, and the relationship between mind and matter. By introducing concepts like singularity, quantum entanglement at a cosmic scale, and the self-actualization of the universe, the HTUM provides a comprehensive framework for understanding the fundamental nature of reality. This paper discusses the mathematical formulation of the HTUM, its implications for quantum mechanics and cosmology, and its potential to bridge the gap between science and philosophy. The philosophical implications of the HTUM are also examined, including its impact on free will, determinism, and the mind-matter relationship. The HTUM represents a significant shift in our understanding of the universe and our place within it, inviting further research and exploration into the nature of reality and consciousness.

We present a new theory to explain the expansion of the universe that augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension. The theory is tested by accurately modelling against stellar luminosity data that is available for redshifts, z

We will demonstrate that the photon energy density parameter Ωγ of the universe can be derived exactly in Rh = ct cosmology. We find that it must be Ωγ = 1/5760π ≈ 5.52621330180192× 10^(−5). This indicates that there is no uncertainty in the radiation density within at least somesub-classes of Rh = ct cosmology.

A bijective analysis is confirming, the expansion of universal space has never been directly observed, and this assumption is unproven thus far. The measurement of the gravitational redshift, which was confirmed using the Mossbauer experiment, proves only the gravitational redshift and nothing more because there is no causality between the gravitational redshift and hypothetical expansion. Thus, even if the universal space is assumed to expand, the gravitational redshift cannot be assumed to be proof of the expansion. In addition, the Doppler effect was never observed in an expanding space; thus, the claim that the cosmological redshift is partially caused by the Doppler effect, which is caused by the expansion of space, is an unproven assumption. Furthermore, the discovery of cosmic microwave background (CMB) radiation simply proves that the radiation is emitted by the entire universal space, but does not prove the existence of a recombination period. In evidence-based cosmology, every element in the model has a corresponding element in physical reality that is observed and measured. The evidence-based cosmology model is related to the real universe by a bijective function of set theory. Supermassive black holes in the centre of galaxies are rejuvenating systems of the universe. They rotate their local superfluid space which is the physical origin of galactic rotation curves.

Application of the Ramsey graph theory to the analysis of physical systems is reported. Physical interactions may be very generally classified as attractive and repulsive. This classification creates the premises for the application of the Ramsey theory to the analysis of physical systems built of electrical charges, electric and magnetic dipoles. The notions of mathematical logic, such as transitivity and intransitivity relations, become crucial for understanding of the behavior of physical systems. The Ramsey theory explains why nature prefers cubic lattices over hexagonal ones for systems built of electric or magnetic dipoles. The Ramsey approach may be applied to the analysis of mechanical systems when actual and virtual paths between the states in the configurational space are considered. Irreversible mechanical and thermodynamic processes are seen within the reported approach as directed graphs. Chains of irreversible processes appear as transitive tournaments. These tournaments are acyclic; the transitive tournaments necessarily contain the Hamiltonian path. The set of states in the phase space of the physical system, between which irreversible processes are possible, is considered. The Hamiltonian path of the tournament emerging from the graph uniting these states is a relativistic invariant. Applications of the Ramsey theory to the general relativity become possible when the discrete changes in the metric tensor are assumed. Reconsideration of the concept of “simultaneity” within the Ramsey approach is reported.