Search

Joshua T Myers, Jacques Van Dam, Mir Imran, Mir Hashim, Arvinder K Dhalla Rani Therapeutics, San Jose, CA, USACorrespondence: Joshua T Myers, Rani Therapeutics, 2051 Ringwood Ave, San Jose, CA, 95131, USA, Tel +1 408-457-3700, Email joshua.myers@ranitherapeutics.comBackground: Rani Therapeutics is developing a robotic pill (RP), an oral drug delivery platform called RaniPill™ that can deliver a number of biotherapeutics with high bioavailability; eliminating the need for injections. While patients in general prefer oral to injectable therapies, preference for a more frequent oral regimen compared to a less frequent injectable regimen is unknown. Two marketing surveys were conducted to gather data on preference for oral versus injectable therapies. A clinical study gathered data on participant preference for oral pills vs injections before and after swallowing a Mock-RP capsule.Methods: A total of 1689 adults taking injections (mean duration 3– 7 years) to treat endocrine or inflammatory conditions were anonymously surveyed online for their preference to administer/prescribe medications orally via the RP. In the clinical study, 150 participants currently taking injections for chronic conditions evaluated the swallowability of a Mock-RP and completed a questionnaire regarding their preferences.Results: Majority of respondents surveyed stated they would be willing to convert to an oral alternative over their current parenteral therapy regardless of drug or disease. In the clinical study, all participants were able to swallow the Mock-RP and 91% indicated their preference for the oral route versus their current parenteral route of drug administration. Survey respondents and those in the clinical study using frequent injections were more willing to select a once-daily capsule compared to those injecting infrequently. Even study participants who inject infrequently (≥monthly: 80%) would prefer a once-daily pill over their injection regimen.Conclusion: Patients taking injections and prescribing physicians strongly prefer oral dosing to parenteral administration of biologics even if dosing frequency with the oral option, such as the RP, is increased.Keywords: oral drug delivery, biotherapeutic, robotic pill, once-daily pill, swallowability

During COVID-19 pandemic, disinfection is a commonly used practice to control and prevent spreading the infection. Overexposure to these chemicals has led to negative health consequences. This study aimed to evaluate the level of knowledge and effects of the overuse of disinfectants during the COVID-19 outbreak in Baghdad, Iraq. One hundred employees working in medical field (Ibn Al-Bitar Research Center/ Corporation of research and Industrial Development, Ministry of Industry and Minerals – Iraq) were participated in a cross-sectional questionnaire survey conducted between January and March 2022. The study found that 68% of participants were confirmed to be infected with the virus, while 32% were not. The participants showed a significant age and gender distribution. According to data, 86% of the participant committed to wearing masks, 58% committed to wearing gloves while 35% committed to wearing both gloves and masks. People pick news as their main information source over social media. Furthermore, 70% of participants used ethanol for hand sterilization, while 36% used gel hand sanitizers from different manufactures. According to health consequences that appeared with different symptoms and documented during overuse of disinfectant, the regular hand sanitizer use could cause irritation and skin damage for 33% of the participants, while 67% did not show any reaction. Employers with health symptoms suggested to be related to sterilizer overuse were found to be 33% and 35% affected in skin and breathing, respectively. To summarize, this survey provides a scientific vision on the negative side effect of the excessive use of disinfectant on health which should increase the public awareness worldwide.

This study proposes a novel thermoelastic model that incorporates Hall current effects, acoustic pressure, and ramp-type heating within the framework of the two-temperature (2T) linear theory. Essentially, this model aims to advance the overarching theory of thermoelasticity enabling both thermal-acoustic and mechanical analyses of elastic plate material under a strong external magnetic field to produce a Hall current. Normal mode (harmonic wave) approximation solved specific boundary value problems within the applied theory of magneto-thermal acoustic systems. Constitutive equations were formulated, yielding two distinct temperatures: conductive and thermodynamics, acoustic pressure displacements, and mechanical stress distribution. The study examines the thermoacoustic interactions and resulting stresses within the material under both external mechanical loads and magnetic fields subjected to ramp-type heating. Notably, the study delves into the effects of Hall current, relaxation times, and ramp-type heating parameters, elucidating their significance within the given context. The wave propagation of physical quantities is represented graphically and discussed and analyzed theoretically.

The goal of this work is to provide a novel mathematical model that explains how certain physical variables propagate (acoustic-thermal-mechanical diffusive) as waves in a photoexcited non-Gaussian laser pulse semiconductor medium. Under the impact of acoustic pressure, the isotropic and homogeneous semiconductor medium is discussed concerning the fundamental equations according to charge carrier recombination processes with optoelectronic properties. Given the impact that relaxation times have on the governing equations. Laplace transforms were utilized in a one-dimensional (1D) context to examine essential non-dimensional properties such as displacement, stress components, carrier density, temperature, and acoustic pressure in order to mathematically answer the required problem. By imposing specific initial and boundary conditions, inverse Laplace transformations were employed to generate precise solutions for the numerical modeling of different physical quantities depicted graphically. The graphical representation of wave propagation data was followed by a theoretical analysis and interpretation, emphasizing the influence of other factors (such as heat rise time, relaxation times, and laser pulse effects) on the observed occurrences.

This work explores the complex interactions of magnetic fields, photothermal effects, thermoelasticity theory, and acoustic pressure in a nonlocal semiconductor medium. These numerous physical phenomena are integrated into a complete theoretical mathematical framework used to understand the dynamic behavior of wave propagation within semiconductors. Considering the spatial distribution of carriers and their interactions, the non-local character of the semiconductor material is taken into account. The physical fields as temperature, mechanical stress, displacement, carrier density, and acoustic pressure can be analytically represented mathematically using the harmonic wave approach. Numerical simulations and theoretical discussions are performed to understand the complex interactions between these fundamental physical processes. The stability analysis of the interaction between the mechanical thermal and acoustic properties of the nonlocality medium under the impact of magnetic field by add it to the physical quantities is investigation. The theoretical results are examined and graphically shown according to the nonlocal semiconductor with magnetic field.

Abstract Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results in differential of binding to RNA targets causing alternative RNA splicing, which contributes to neurodegeneration in MS and its models. Using RNAseq of MS brains, we discovered differential expression and aberrant splicing of hnRNP A1 target RNAs involved in neuronal function and RNA homeostasis. We confirmed this in vivo in experimental autoimmune encephalomyelitis employing CLIPseq specific for hnRNP A1, where hnRNP A1 differentially binds and regulates RNA, including aberrantly spliced targets identified in human samples. Additionally, dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical changes in splicing, corroborating hnRNP A1 dysfunction as a cause of neurodegeneration. Collectively, these data indicate hnRNP A1 dysfunction causes altered neuronal RNA splicing, resulting in neurodegeneration in MS.

This study explores the behavior of laser-exposed photo-excited carriers, investigating the propagation of photoacoustic waves in the thermoelastic domain. It also delves into the theoretical generation of surface acoustic waves in semiconductors through photo-thermoelastic processes. The research considers the interaction between thermomechanical and acoustic waves in a nonlocal medium with temperature-dependent thermal conductivity. Unlike relying on electron–phonon or electron-hole thermalization processes, photoacoustic waves here result from thermoelastic stress induced by the laser-induced temperature increase. The investigation accounts for the optical, mechanical, and thermoelastic properties of nanoscale semiconductor materials. Predictions of photoacoustic signals are derived by solving a combined thermal diffusion issue and a thermoelastic problem, using Laplace and Fourier transforms in the mathematical model. Numerical solutions encompass various physical fields within the time domain using the inversion technique of Laplace and Fourier transforms, such as thermal, acoustic, mechanical, and carrier density diffusion. The study evaluates and compares the influences of thermal memory and thermal conductivity presenting visual representations.

Abstract Sparse and short-lived excited RNA conformational states are essential players in cell physiology, disease, and therapeutic development, yet determining their 3D structures remains challenging. Combining mutagenesis, NMR spectroscopy, and computational modeling, we determined the 3D structural ensemble formed by a short-lived (lifetime ~2.1 ms) lowly-populated (~0.4%) conformational state in HIV-1 TAR RNA. Through a strand register shift, the excited conformational state completely remodels the 3D structure of the ground state (RMSD from the ground state = 7.2 ± 0.9 Å), forming a surprisingly more ordered conformational ensemble rich in non-canonical mismatches. The structure impedes the formation of the motifs recognized by Tat and the super elongation complex, explaining why this alternative TAR conformation cannot activate HIV-1 transcription. The ability to determine the 3D structures of fleeting RNA states using the presented methodology holds great promise for our understanding of RNA biology, disease mechanisms, and the development of RNA-targeting therapeutics.

AbstractNonlinear partial differential equations (NLPDEs) are widely utilized in engineering and physical research to represent many physical processes of naturalistic occurrences. In this paper, we investigate two well-known NLPDEs, namely, the (2 + 1)-dimensional first integro-differential KP hierarchy equation and the (2 + 1)-dimensional second integro-differential KP hierarchy equation, through a well-stable algorithm known as the [Formula: see text]-expansion approach for the first time. This algorithm is generally based on the expansion of function method and has the advantage of easy implementation and can provide a reliable solution to any NLPDEs. Employing the algorithm, we have been able to perceive the closed form solitons of the two chosen NLPDEs that physically represent the solitary wave solutions like, singular, singular periodic, bell, and anti-bell-shaped types of solitons. Furthermore, we explore the graphical manifestations of the obtained solutions, which are of the mentioned soliton types. From the findings of our in-depth study, we can state that the acquired solutions for the selected two equations may greatly aid to extracting the associated natural phenomena in mathematical physics such as fluid dynamics and ocean engineering.

SignificanceUnderstanding and treating neurological disorders are global priorities. Some of these diseases are engendered by mutations that cause defects in the cellular synthesis of transfer RNAs (tRNAs), which function as adapter molecules that translate messenger RNAs into proteins. During tRNA biogenesis, ribonuclease P catalyzes removal of the transcribed sequence upstream of the mature tRNA. Here, we focus on a cytoplasmic tRNAArgUCU that is expressed specifically in neurons and, when harboring a particular point mutation, contributes to neurodegeneration in mice. Our results suggest that this mutation favors stable alternative structures that are not cleaved by mouse ribonuclease P and motivate a paradigm that may help to understand the molecular basis for disease-associated mutations in other tRNAs.

Screening mammography is considered to be the most effective means for the early detection of breast cancer. However, epidemiological studies suggest that longitudinal exposure to screening mammography may raise breast cancer radiation-induced risk, which begs the need for optimization and internal auditing. The present work aims to establish a comprehensive well-structured Diagnostic Reference Level (DRL) system that can be confidently used to highlight healthcare centers in need of urgent action, as well as cases exceeding the dose notification level. Screening mammographies from a total of 2048 women who underwent screening mammography at seven different healthcare centers were collected and retrospectively analyzed. The typical DRL for each healthcare center was established and defined as per (A) bilateral image view (left craniocaudal (LCC), right craniocaudal (RCC), left mediolateral oblique (LMLO), and right mediolateral oblique (RMLO)) and (B) structured compressed breast thickness (CBT) criteria. Following this, the local DRL value was established per the bilateral image views for each CBT group. Screening mammography data from a total of 8877 images were used to build this comprehensive DRL system (LCC: 2163, RCC: 2206, LMLO: 2288, and RMLO: 2220). CBTs were classified into eight groups of

This investigation aims to study the behavior of a Jeffery fluid on a stretching surface while considering thermophoresis and Brownian motion effects through Buongiorno's model. The governing equations include thermal and mass transport effects, heat source-sink interactions and chemical reaction rates. Similarity transformations are utilized to solve partial differential equations, transforming them into ordinary differential equations. The bvp5c built-in program in MATLAB is then used to obtain a numerical solution for the ODEs. The study generates graphs to examine how different physical flow parameters affect fluid flow, temperature, and concentration distributions. The graphical analysis shows that mass diffusion decreases as the Brownian parameter and Schmidt number increase, while an increase in thermophoresis and heat source-sink improves thermal transport. The study also explores the influence of various emerging variables on velocity, thermal, and solutal distributions, providing valuable insights into the complex interplay of these factors and contributing to advancing our understanding of fluid dynamics.

Numerous biological processes and mechanisms depend on details of base pairing and hydrogen bonding in DNA. Hydrogen bonds are challenging to quantify by X-ray crystallography and cryo-EM due to difficulty of visualizing hydrogen atom locations but can be probed with site specificity by NMR spectroscopy in solution and the solid state with the latter particularly suited to large, slowly tumbling DNA complexes. Recently, we showed that low-temperature dynamic nuclear polarization (DNP) enhanced solid-state NMR is a valuable tool for distinguishing Hoogsteen base pairs (bps) from canonical Watson-Crick bps in various DNA systems under native-like conditions. Here, using a model 12-mer DNA duplex containing two central adenine-thymine (A-T) bps in either Watson-Crick or Hoogsteen confirmation, we demonstrate DNP solid-state NMR measurements of thymine N3-H3 bond lengths, which are sensitive to details of N-H···N hydrogen bonding and permit hydrogen bonds for the two bp conformers to be systematically compared within the same DNA sequence context. For this DNA duplex, effectively identical TN3-H3 bond lengths of 1.055 ± 0.011 Å and 1.060 ± 0.011 Å were found for Watson-Crick A-T and Hoogsteen A (syn)-T base pairs, respectively, relative to a reference amide bond length of 1.015 ± 0.010 Å determined for N-acetyl-valine under comparable experimental conditions. Considering that prior quantum chemical calculations which account for zero-point motions predict a somewhat longer effective peptide N-H bond length of 1.041 Å, in agreement with solution and solid-state NMR studies of peptides and proteins at ambient temperature, to facilitate direct comparisons with these earlier studies TN3-H3 bond lengths for the DNA samples can be readily scaled appropriately to yield 1.083 Å and 1.087 Å for Watson-Crick A-T and Hoogsteen A (syn)-T bps, respectively, relative to the 1.041 Å reference peptide N-H bond length. Remarkably, in the context of the model DNA duplex, these results indicate that there are no significant differences in N-H···N A-T hydrogen bonds between Watson-Crick and Hoogsteen bp conformers. More generally, high precision measurements of N-H bond lengths by low-temperature DNP solid-state NMR based methods are expected to facilitate detailed comparative analysis of hydrogen bonding for a range of DNA complexes and base pairing environments.

In the present investigation, we employed the Jacobi elliptic function (JEF) method to invoke the perturbed nonlinear Schrödinger equation with self-steepening (SS), self-phase modulation (SPM), and group velocity dispersion (GVD), which govern the propagation of solitonic pulses in optical fibres. The proposed algorithm proves the existence of the family of solitons in optical fibers. Consequently, chirped and chirp free W-shaped bright, dark soliton solutions are obtained from dn(ξ), cn(ξ) and sn(ξ) functions. The final results are displayed in three-dimensional plots with specific physical values of GVD, SPM and SS for an optical fiber.

Objective: Varicocele, the dilation of the pampiniform plexus of the spermatic cord. It is discovered incidentally in most patients. Symptoms vary, but its impact is especially experienced in the field of fertility and reflected in semen parameters. Varicocelectomy is a surgical approach to correct the varicocele, however, reports are conflicting regarding its success. Our aim was to evaluate the efficacy of varicocelectomy on semen parameters and conception rates in patients who underwent surgery and its association with comorbidities such as diabetes, hypertension, and obesity. Materials and Methods: This cross-sectional study included the complete medical records of 86 patients. Data collection form included the patient's age, body mass index (BMI), chronic diseases, smoking, surgical history, medication usage, and the reason for performing surgery. Presurgical and postsurgical semen parameters were evaluated 3 months before surgery and an average of 6 months postoperatively. Data were analyzed with SPSS, Chi-square test, and independent and paired t-test. Results: No significant difference was found between primary and secondary infertility regarding semen analysis, postoperative semen analysis indicated an improvement in semen motility at 180 min with no effect on other parameters. Using spontaneous intercourse or in vitro fertilization (IVF) after varicocelectomy was significantly associated with increasing conception rates irrespective of the type of infertility. Diabetes, hypertension, BMI, and smoking did not appear to affect semen parameters. Conclusion: Patients who underwent varicocelectomy had improved sperm motility at 180 min and subsequently had a higher chance of successful conception either through spontaneous intercourse or IVF. Further studies are needed to understand the relationship between conception and sperm motility. Semen parameters were not affected if the patient had comorbidities such as diabetes and hypertension. Furthermore, smoking and BMI did not appear to affect the conception rate.

This paper studies the formulation of dark and singular stationary optical solitons that stem from quadratic-cubic and generalized quadratic-cubic forms of nonlinear refractive index coupled with nonlinear chromatic dispersion. The temporal evolution is taken to be of both kinds, namely linear and generalized. The enhanced Kudryashov’s approach enables this retrieval possible.

This paper secures solitary waves, shock waves and singular solitary waves for the Boussinesq equation, which is studied with the inclusion of surface tension. The method of undetermined coefficients has yielded such waves. The Lie symmetry analysis has introduced a fresh perspective to the model. Conserved densities and corresponding conserved quantities are computed using the multiplier approach.