Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

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.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

In the paper we show that the general relativity in recent Einstein-Palatini formulation is equivalent to a gauge field. We begin with a bit of information of the Einstein-Palatini formulation and derive Einstein field equations from it. In the next section, we consider general relativity with a positive cosmological constant in terms of the corrected curvature. We show that in terms of the corrected curvature general relativity takes the form typical for a gauge field. Finally, we give a geometrical interpretation of the corrected curvature.

Using coherent optical detection and digital signal processing, laser phase noise and equalization enhanced phase noise can be effectively mitigated using the feed-forward and feed-back carrier phase recovery approaches. In this paper, theoretical analyses of feed-back and feed-forward carrier phase recovery methods have been carried out in the long-haul high-speed n-level phase shift keying (n-PSK) optical fiber communication systems, involving a one-tap normalized least-mean-square (LMS) algorithm, a block-wise average algorithm, and a Viterbi-Viterbi algorithm. The analytical expressions for evaluating the estimated carrier phase and for predicting the bit-error-rate (BER) performance (such as the BER floors) have been presented and discussed in the n-PSK coherent optical transmission systems by considering both the laser phase noise and the equalization enhanced phase noise. The results indicate that the Viterbi-Viterbi carrier phase recovery algorithm outperforms the one-tap normalized LMS and the block-wise average algorithms for small phase noise variance (or effective phase noise variance), while the one-tap normalized LMS algorithm shows a better performance than the other two algorithms for large phase noise variance (or effective phase noise variance). In addition, the one-tap normalized LMS algorithm is more sensitive to the level of modulation formats.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

With reference to Planck scale Hubble parameter, super luminal expansion speeds, super luminal rotation speeds, Mach’s principle and Holographic principle, we review the current cosmological observations with eight simple assumptions. By understanding Yuri N. Obukhov and V.A. Korotky proposed cosmic rotational effects of polarization of radiation due to massive bodies, to some extent cosmic rotation can be deep-rooted in an observational approach and the ratio of current angular velocity and Hubble parameter can be estimated. It is possible to show that, at H₀ =70 km/sec/Mpc, current cosmic temperature, age, radius, mass, mass density are 2.721 K, 4.41x10¹⁷ sec, 90 billion light years, 1.14654x10⁵⁴ kg, 0.0482 times the current critical density respectively. Clearly speaking, current universe seems to constitute 267 Hubble spheres. Important point to be noted is that, current rotational kinetic energy is 0.6667 times the current critical energy. Based on the estimated current mass density and current rotational kinetic energy, current cosmic dark matter density can be shown to be 0.2851 times the current critical density. These numerical coincidences cast serious doubt on the on the real existence of currently believed ‘dark energy’. Initial and current expansion speeds are 3x10⁸ m/sec and 3.56x10⁹ m/sec respectively. With increasing cosmic age and increasing cosmic expansion speed, current universe is expanding with a speed of 11.885c. By knowing the time to time future cosmic temperatures, future Hubble parameters and corresponding future cosmic expansion speeds can be estimated and thus future expansion speed can be understood. Starting from ‘speed of light’, our model assumes a continuous increase in expansion speed and attains a current radius of 90 billion light years (without inflationary concepts) and casts a serious doubt on the actuality of currently believed ‘inflation’.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a “Failed SCS Syndrome” in the back pain component. Fourteen patients were included in this study and randomized into 2 groups (“SCS + PNfS” group/n=6 vs “SCS only” group/n=8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the ”SCS+PNfS” group (80.2% ± 21.3%) compared to the “SCS only” group (13.2% ± 94.8%) (p=0.012), highlighting the clinical interest of SCS+PNfS, in cases where SCS fails to address back pain.