Present Approach Research Articles

A Computational Investigation on Chitosan Derivatives using Pharmacophore- based Screening, Molecular Docking, and Molecular Dynamics Simulations against Kaposi Sarcoma.

Cancer is one of the most dangerous illnesses to the human body due to its severity and progressive nature. Kaposi's Sarcoma (KS) tumor can appear as painless purple spots on the legs, foot, or face. This cancer develops in the lining of lymph arteries and blood vessels. Along with the enlargement of lymph nodes, the vaginal region and the mouth portion are the additional target areas of KS. DNA-binding proteins known as Sox proteins are found in all mammals and belong to the HMG box superfamily. They controlled a wide range of developmental procedures, such as the formation of the germ layer, the growth of organs, and the selection of the cell type. Human developmental abnormalities and congenital illnesses are frequently caused by the deletion or mutation of the Sox protein. The purpose of this study is to determine the promising Kaposi's sarcoma inhibitors through computational studies. In this present study computational approaches were used to evaluate the anti- carcinogenic efficacy against Kaposi's sarcoma. Ligand-based pharmacophore screening was performed utilising four different chemical libraries (Asinex, Chembridge, Specs, and NCI Natural products (NSC)) depending on the top hypothesis. The top hits were examined using molecular docking, absorption, distribution, metabolism and excretion. Highest occupied molecular orbital and lowest unoccupied molecular orbital were analysed to determine the lead compounds' biological and pharmacological efficacy. The results of the study indicated that the leading candidates were possible SOX protein inhibitors. A pharmacophore model to inhibit the production of SOX protein in Kaposi Sarcoma was generated in this computational experiment using a set of 19 Chitosan compounds. The results revealed that the top hits responded to all of the pharmacological druglikening criteria and had the best interaction residues, fitness scores, and docking scores. The resulting leads might be potential Kaposi's Sarcoma alternative treatments.

Zigzag boron nitride nanotube functionalization as a sensor for the recognition of group IIA (Mg2+, Ca2+) metal ions, quasi-metal (Si2+, Ge2+) ions, and transition metal (Cu2+, Zn2+) ions: a computational study.

Boron nitride nanotubes (BNNTs) provide an exceptional and sophisticated platform for detecting metal ions with high surface area and remarkable chemical stability. Metal cations tend to bind to the surface of BNNTs, which leads to significant changes in the electrical properties of nanotubes. BNNT-based metal ion sensors have shown promising results in various applications, including water quality monitoring, biomedical research, industrial quality control, and environmental monitoring. In the present study, we have explored the electronic sensitivity of the BNNT to metal ions (Si2+, Ge2+, Cu2+, Zn2+, Mg2+, and Ca2+). The interaction between the ions with the pristine BNNT is performed in the solution phase. The results show that ion adsorption on the nanotube surface is exothermic and favorable. The density of states calculation is presented to investigate the electronic properties of the nanotube during the adsorption process. The results display that an increase in the electrical conductivity of the complexes accompanies the reduction in the energy gap. Based on the obtained data, the Si2+ and Ge2+ cations adsorbed on the BNNT with satisfactory Eg changes (%ΔE) can be promising candidates for better sensing ability. All calculations are conducted within the density functional theory (DFT) using the ωB97XD functional and 6-31G(d,p) basis set. The present approach incorporates the utilization of empirical atom-atom dispersion in conjunction with long-range correction. The calculations are performed using the quantum chemistry package GAMESS, and the obtained results are visualized by employing the GaussView 6.0.16 program.

Lipid nanoparticle-based strategies for extrahepatic delivery of nucleic acid therapies – challenges and opportunities

The advent of lipid nanoparticles (LNPs) containing ionizable cationic lipids has enabled the encapsulation, stabilization, and intracellular delivery of nucleic acid payloads, leading to FDA-approved siRNA-based therapy and mRNA-based vaccines. Other nucleic acid-based therapeutic modalities, including protein replacement and CRISPR-mediated gene knockout and editing, are being tested in clinical trials, in many cases, for the treatment of liver-related diseases. However, to fully exploit these therapies beyond the liver, improvements in their delivery to extrahepatic targets are needed. Towards this end, both active targeting strategies based on targeting ligands grafted onto LNPs and passive targeting relying on physicochemical LNP parameters such as surface composition, charge, and size are being evaluated. Often, the latter strategy depends on the interaction of LNPs with blood components, forming what is known as the biomolecular corona. Here, I discuss potential challenges related to current LNP-based targeting strategies and the studies of the biomolecular corona on LNPs. I propose potential solutions to overcome some of these obstacles and present approaches currently being tested in preclinical and clinical studies, which face fewer biological barriers than traditional organ-targeting approaches.

Modeling of Deuteron-Induced Reactions on Molybdenum at Low Energies

The activities of the EUROfusion consortium on the development of high quality nuclear data for fusion applications include evaluations of deuteron induced reactions and related data libraries for needs of the DEMO fusion power plant and IFMIF-DONES neutron-source nuclear analyses. Molybdenum is one of the major constituents of the reference stainless steels used in critical components of these projects. While the TENDL deuteron data library was the current reference used by EUROfusion, need of its further improvement has already been pointed out. The weak binding energy of the deuteron is responsible for the high complexity of its interaction with nuclei, involving also a variety of reactions initiated by the nucleons following the deuteron breakup. Their analysis completed that of the deuteron interactions with Mo and its stable isotopes, from elastic scattering to pre-equilibrium and compound–nucleus reactions, up to 50 MeV. A particular attention has been paid to the breakup, stripping, and pick-up direct interactions which amount to around half of the deuteron total–reaction cross section. The due account of most experimental data has validated the present approach, highlighted some prevalent features, and emphasized weak points and consequently the need for modeling/evaluation upgrade.

Cadence Paradox in Cycling-Part 2: Theory and Simulation of Maximal Lactate Steady State and Carbohydrate Utilization Dependent on Cycling Cadence.

To develop and evaluate a theory on the frequent observation that cyclists prefer cadences (RPMs) higher than those considered most economical at submaximal exercise intensities via modeling and simulation of its mathematical description. The theory combines the parabolic power-to-velocity (v) relationship, where v is defined by crank length, RPM-dependent ankle velocity, and gear ratio, RPM effects on the maximal lactate steady state (MLSS), and lactate-dependent carbohydrate oxidation (CHO). It was tested against recent experimental results of 12 healthy male recreational cyclists determining the v-dependent peak oxygen uptake (VO2PEAKv), MLSS (MLSSv), corresponding power output (PMLSSv), oxygen uptake at PMLSSv (VO2MLSSv), and CHOMLSSv-management at 100 versus 50per minute, respectively. Maximum RPM (RPMMAX) attained at minimized pedal torque was measured. RPM-specific maximum sprint power output (PMAXv) was estimated at RPMs of 100 and 50, respectively. Modeling identified that MLSSv and PMLSSv related to PMAXv (IPMLSSv) promote CHO and that VO2MLSSv related to VO2PEAKv inhibits CHO. It shows that cycling at higher RPM reduces IPMLSSv. It suggests that high cycling RPMs minimize differences in the reliance on CHO at MLSSv between athletes with high versus low RPMMAX. The present theory-guided modeling approach is exclusively based on data routinely measured in high-performance testing. It implies a higher performance reserve above IPMLSSv at higher RPM. Cyclists may prefer high cycling RPMs because they appear to minimize differences in the reliance on CHO at MLSSv between athletes with high versus low RPMMAX.

Biocatalytic Strategy for the Highly Stereoselective Synthesis of Fluorinated Cyclopropanes

Fluorinated cyclopropanes are highly desired pharmacophores in drug discovery owing to the rigidity nature of the cyclopropane ring and the beneficial effects of C–F bonds on the pharmacokinetic properties, cell permeability, and metabolic stability of drug molecules. Herein a biocatalytic strategy for the stereoselective synthesis of mono‐fluorinated and gem‐difluoro cyclopropanes is reported though the use of engineered myoglobin‐based catalysts. In particular, this system allows for a broad range of gem‐difluoro alkenes to be cyclopropanated in the presence of diazoacetonitrile with excellent diastereo and enantiocontrol (up to 200:1 d.r. and 99% e.e.), thereby enabling a transformation not currently accessible with chemocatalytic methods. The synthetic utility of the present approach is further exemplified through the gram‐scale synthesis of a key gem‐difluorinated cyclopropane intermediate useful for the preparation of fluorinated bioactive molecules.

Biocatalytic Strategy for the Highly Stereoselective Synthesis of Fluorinated Cyclopropanes.

Fluorinated cyclopropanes are highly desired pharmacophores in drug discovery owing to the rigidity nature of the cyclopropane ring and the beneficial effects of C-F bonds on the pharmacokinetic properties, cell permeability, and metabolic stability of drug molecules. Herein a biocatalytic strategy for the stereoselective synthesis of mono-fluorinated and gem-difluoro cyclopropanes is reported though the use of engineered myoglobin-based catalysts. In particular, this system allows for a broad range of gem-difluoro alkenes to be cyclopropanated in the presence of diazoacetonitrile with excellent diastereo and enantiocontrol (up to 200:1 d.r. and 99% e.e.), thereby enabling a transformation not currently accessible with chemocatalytic methods. The synthetic utility of the present approach is further exemplified through the gram-scale synthesis of a key gem-difluorinated cyclopropane intermediate useful for the preparation of fluorinated bioactive molecules.

An extended graphical solution for undrained cylindrical cavity expansion in K0‐consolidated Mohr–Coulomb soil

AbstractThis paper develops a general and complete solution for the undrained cylindrical cavity expansion problem in nonassociated Mohr‐Coulomb soil under nonhydrostatic initial stress field (i.e., arbitrary values of the earth pressure coefficient), by expanding a unique and efficient graphical solution procedure recently proposed by Chen and Wang in 2022 for the special in situ stress case with . It is interesting to find that the cavity expansion deviatoric stress path is always composed of a series of piecewise straight lines, for all different case scenarios of K0 being involved. When the cavity is sufficiently expanded, the stress path will eventually end, exclusively, in a major sextant with Lode angle θ in between and or on the specific line of . The salient advantage/feature of the present general graphical approach lies in that it can deduce the cavity expansion responses in full closed form, nevertheless being free of the limitation of the intermediacy assumption for the vertical stress and of the difficulty existing in the traditional zoning method that involves cumbersome, sequential determination of distinct Mohr–Coulomb plastic regions. Some typical results for the desired cavity expansion curves and the limit cavity pressure are presented, to investigate the impacts of soil plasticity parameters and the earth pressure coefficient on the cavity responses. The proposed graphical method/solution will be of great value for the interpretation of pressuremeter tests in cohesive‐frictional soils.

Use of pure recombinant human enzymes to assess the disease-causing potential of missense mutations in urea cycle disorders, applied to N-acetylglutamate synthase deficiency.

N-acetylglutamate synthase (NAGS) makes acetylglutamate, the essential activator of the first, regulatory enzyme of the urea cycle, carbamoyl phosphate synthetase 1 (CPS1). NAGS deficiency (NAGSD) and CPS1 deficiency (CPS1D) present identical phenotypes. However, they must be distinguished, because NAGSD is cured by substitutive therapy with the N-acetyl-L-glutamate analogue N-carbamyl-L-glutamate, while curative therapy of CPS1D requires liver transplantation. Since their differentiation is done genetically, it is important to ascertain the disease-causing potential of CPS1 and NAGS genetic variants. With this goal, we previously carried out site-directed mutagenesis studies with pure recombinant human CPS1. We could not do the same with human NAGS (HuNAGS) because of enzyme instability, leading to our prior utilization of a bacterial NAGS as an imperfect surrogate of HuNAGS. We now use genuine HuNAGS, stabilized as a chimera of its conserved domain (cHuNAGS) with the maltose binding protein (MBP), and produced in Escherichia coli. MBP-cHuNAGS linker cleavage allowed assessment of the enzymatic properties and thermal stability of cHuNAGS, either wild-type or hosting each one of 23 nonsynonymous single-base changes found in NAGSD patients. For all but one change, disease causation was accounted by the enzymatic alterations identified, including, depending on the variant, loss of arginine activation, increased Km Glutamate, active site inactivation, decreased thermal stability, and protein misfolding. Our present approach outperforms experimental in vitro use of bacterial NAGS or in silico utilization of prediction servers (including AlphaMissense), illustrating with HuNAGS the value for UCDs of using recombinant enzymes for assessing disease-causation and molecular pathogenesis, and for therapeutic guidance.

Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration.

Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.

Positive Reframing of Psychosis Risk Is Seen as More Beneficial and Less Harmful Than Negative Framing by Clinicians: An Experimental Videotaped Simulated Feedback Study.

Recent studies show that, despite providing some relief, feedback about being at risk for psychosis often triggers negative emotional reactions. Inspired by Tversky and Kahneman's (1981) work on the framing effect and medical framings that favors positive framing like "life-threatening" over "high-risk for death," this study tested the hypothesis that positive reframing of psychosis risk (PR) could alleviate these concerns. To establish the justifiability and feasibility of testing this hypothesis with patients and their families, the study first sought to test whether mental health professionals (MHPs) view positive framing as superior to present state-of-the-art approaches. The study used an experimental design utilizing a simulated feedback session, recorded with professional actors, featuring a clinician, an adolescent, and his mother. One hundred forty-eight MHPs were randomly assigned to view either negatively or positively framed feedback and were asked about its induced impact on the adolescent and mother. The study results supported our main hypothesis, indicating significant benefits of positive framing over negative in areas like empathy, stress reduction, stigma, help-seeking, and hope. Contrary to our second hypothesis, familiarity with PR did not affect these results. These findings suggest that MHPs view positive reframing of PR as more beneficial and less harmful than present negative framing approaches. This sets the stage for subsequent phases that will assess the perceptions and preferences of individuals at risk and their families. The discussion highlights possible misconceptions of positive framing, such as labeling, positive psychology, and de-medicalization.

Mental health disparities of sexual minority refugees and asylum seekers: Provider perspectives on trauma exposure, symptom presentation, and treatment approach.

Refugees and asylum seekers who identify as sexual minorities and/or who have been persecuted for same-sex acts maneuver through multiple oppressive systems at all stages of migration. Sexual minority refugees and asylum seekers (SM RAS) report experiencing a greater number of persecutory experiences and worse mental health symptoms than refugees and asylum seekers persecuted for reasons other than their sexual orientation (non-SM RAS). SM RAS are growing in numbers, report a need and desire for mental health treatment, and are often referred to therapy during the asylum process. However, little research has been conducted on the treatment needs of SM RAS in therapy or the strategies therapists use to address these needs. This study sought to identify these factors through qualitative interviews with providers at a specialty refugee mental health clinic (N = 11), who had experience treating both SM RAS and non-SM RAS. Interviews were transcribed and coded for themes of similarities and differences between SM RAS and non-SM RAS observed during treatment and factors that could be leveraged to reduce mental health disparities between SM RAS and non-SM RAS. Clinicians reported that compared to the non-SM RAS, SM RAS reported greater childhood trauma exposure, increased isolation, decreased support, identity-related shame, difficulty trusting others, and continued discrimination due to their SM identitiy. Suggested adaptations included reducing isolation, preparing for ongoing identity-based challenges, creating safe spaces to express SM identity, and a slower treatment pace. Providers reported benefits and drawbacks to centering the client's SM identity in treatment and encouraging community involvement for SM RAS, and noted additional training in cultural awareness would be beneficial. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multi‐response optimization of characteristics for graphite reinforced biodegradable PVA‐fumaric acid cross‐linked composite: A gray‐fuzzy logic‐based hybrid approach

AbstractIn the current investigation, enhancement in the mechanical properties, thermal stability, and decrement in the moisture absorption capabilities of polyvinyl alcohol was observed by cross‐linking it with different weight percentages (wt. %) of fumaric acid and reinforcing them along with sulfuric acid‐modified graphite particles. The effects of altering the cross‐linking duration and fumaric acid wt. % were investigated in the resulting composite using the Taguchi L16 experimental design method. As in this contemporary era of rapid industrial expansion and fierce competition, the primary goals of manufacturers revolve around the production of high‐quality goods at optimal costs within a specified timeframe. Therefore, to save both cost and time, the authors have utilized a technique known as “gray‐fuzzy optimization” to balance competing goals between mechanical (toughness, elongation and strength) and physical (water intake capacity) attributes. The present approach aimed to reduce the experimentation expenses and increase the effectiveness of composite manufacturing by considerably reducing the intricacy of practical multi‐response optimization issues. Response graphs and analysis of variance tests were also utilized to calculate the percentage contribution of the input variables and provide model significance.Highlights Polyvinyl alcohol is cross‐linked with different weight percentages (wt. %) of fumaric acid, and reinforced them with sulfuric acid‐modified graphite particles. Enhancement in mechanical properties, thermal stability, and decrease in moisture absorption capabilities were perceived for the fabricated composite. Effects of altering the cross‐linking duration and fumaric acid wt. % were investigated in the resulting composite using the Taguchi L16 experimental design. Gray‐fuzzy optimization technique was utilized to balance competing goals between water intake and mechanical attributes like toughness, elongation and strength. Response graphs and analysis of variance (ANOVA) tests were also utilized to evaluate the percentage contribution of input variables and provide model significance.

Reduced Variance Random Batch Methods for Nonlocal PDEs

Random Batch Methods (RBM) for mean-field interacting particle systems enable the reduction of the quadratic computational cost associated with particle interactions to a near-linear cost. The essence of these algorithms lies in the random partitioning of the particle ensemble into smaller batches at each time step. The interaction of each particle within these batches is then evolved until the subsequent time step. This approach effectively decreases the computational cost by an order of magnitude while increasing the amount of fluctuations due to the random partitioning. In this work, we propose a variance reduction technique for RBM applied to nonlocal PDEs of Fokker-Planck type based on a control variate strategy. The core idea is to construct a surrogate model that can be computed on the full set of particles at a linear cost while maintaining enough correlations with the original particle dynamics. Examples from models of collective behavior in opinion spreading and swarming dynamics demonstrate the great potential of the present approach.

QUANTITATIVE DETERMINATION OF SOME NON-STEROIDAL ANTI-INFLAMMATORY DRUGSAND THEIR ACID DISSOCIATION CONSTANTS BY DIRECT POTENTIOMETRY

Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input. Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH3OH: H2O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C. Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision. Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.

Synthesis of Diverse Allyl Sulfone Derivatives via Sequential Hydroalkoxylation of 1,3-Enynes.

A first metal-free protocol for the synthesis of allylic sulfones featuring aldehyde functionality at the δ-position has been reported. The formation of structurally complex δ,δ-dimethoxy allyl sulfones is enabled by the direct nucleophilic attack of methoxide onto the sulfone-containing 1,3-enynes. The present approach allows facile installation of acetal groups within the allyl sulfone scaffold, providing versatile platforms for further functionalization and drug development.

Strategies to Diversification of the Mechanical Properties of Organic Crystals

AbstractStructurally ordered soft materials that respond to complementary stimuli are susceptible to control over their spatial and temporal morphostructural configurations by intersectional or combined effects such as gating, feedback, shape‐memory, or programming. In the absence of general and robust design and prediction strategies for their mechanical properties, at present, combined chemical and crystal engineering approaches could provide useful guidelines to identify effectors that determine both the magnitude and time of their response. Here, we capitalize on the purported ability of soft intermolecular interactions to instigate mechanical compliance by using halogenation to elicit both mechanical and photochemical activity of organic crystals. Starting from (E)‐1,4‐diphenylbut‐2‐ene‐1,4‐dione, whose crystals are brittle and photoinert, we use double and quadruple halogenation to introduce halogen‐bonded planes that become interfaces for molecular gliding, rendering the material mechanically and photochemically plastic. Fluorination diversifies the mechanical effects further, and crystals of the tetrafluoro derivative are not only elastic but also motile, displaying the rare photosalient effect.

Strategies to Diversification of the Mechanical Properties of Organic Crystals.

Structurally ordered soft materials that respond to complementary stimuli are susceptible to control over their spatial and temporal morphostructural configurations by intersectional or combined effects such as gating, feedback, shape-memory, or programming. In the absence of general and robust design and prediction strategies for their mechanical properties, at present, combined chemical and crystal engineering approaches could provide useful guidelines to identify effectors that determine both the magnitude and time of their response. Here, we capitalize on the purported ability of soft intermolecular interactions to instigate mechanical compliance by using halogenation to elicit both mechanical and photochemical activity of organic crystals. Starting from (E)-1,4-diphenylbut-2-ene-1,4-dione, whose crystals are brittle and photoinert, we use double and quadruple halogenation to introduce halogen-bonded planes that become interfaces for molecular gliding, rendering the material mechanically and photochemically plastic. Fluorination diversifies the mechanical effects further, and crystals of the tetrafluoro derivative are not only elastic but also motile, displaying the rare photosalient effect.

A Rare Consanguineous Case of Alazami Syndrome in a Jordanian Family: Clinical Presentation, Genetic Analysis, and Therapeutic Approaches - A Case Report

Objective: Alazami syndrome (AS) is an infrequent genetic disorder inherited in an autosomal recessive pattern, characterized by the presence of multiple congenital abnormalities. This study explores a case of a 4-year-old girl with AS, examining symptoms, genetic factors, and treatment efficacy. Case report: A 4-year-old girl, born to consanguineous Jordanian parents, displayed dysmorphic features including low birth weight, microcephaly, hyperthyroidism, short stature, blue sclera, triangular-shaped face, deep-set eyes, narrow palpebral fissures, and a prominent forehead. Examination revealed height (92 cm) and weight (7.7 kg) below the 5th and 3rd percentiles respectively. Blood tests and renal ultrasound were normal. Whole exome sequencing (WES) identified a homozygous eight-base pair deletion within exon 5 of the LARP7 gene on chromosome 4q25, confirming the diagnosis of AS, an autosomal recessive disorder. This variant induces frameshift mutations leading to premature stop codons, suggesting a probable mechanism of illness via loss of function. Treatment involving growth monitoring and therapy led to significant improvements in height, weight, and communication skills within three months. Conclusion: We describe a rare autosomal recessive AS case due to consanguinity, with a frameshift mutation in the LARP7 gene found via WES. Our AS treatment program effectively alleviates symptoms and enhances developmental progress.

Immunotherapy for Head and Neck Squamous Cell Carcinoma: Present and Future Approaches and Challenges.

Despite significant progress and improving outcomes in the management of head and neck squamous cell carcinoma (HNSCC), there are few effective treatment options for patients with recurrent or metastatic head and neck squamous cell carcinoma. The advent of immune checkpoint inhibitors has changed the treatment algorithm of head and neck squamous cell carcinoma and are approved in the frontline setting for recurrent and metastatic (R/M) head and neck squamous cell carcinomas. Although promising for some patients, most patients with R/M HNSCC do not derive clinical benefit from currently approved checkpoint inhibitors. Many studies are underway to identify the patient population that would benefit the most from immunotherapy as well as postimmunotherapy treatment failures, including novel combinations of immunomodulatory therapies. In this review, we summarize the clinical development of all major clinical trials of immunotherapy in HNSCC.