The RNA-binding protein ZC3H11A interacts with the nuclear poly(A)-binding protein PABPN1 and alters polyadenylation of viral transcripts.

Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multiprotein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, NF-κB signaling, and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and viral mRNA. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein may act as a novel regulator of polyadenylation of nuclear mRNA.

Optimization and characterization of laccase (LccH) produced by Hexagonia hirta MSF2 in solid-state fermentation using coir pith wastes (CPW).

The accumulation of coir pith waste, a byproduct of coconut husk processing, poses environmental and logistical challenges. An innovative and sustainable solution involves using coir pith as a substrate for solid-state fermentation (SSF). In SSF, coir pith can be converted into valuable products, such as enzymes, organic acids, and bioactive compounds. The present study aimed to evaluate laccase production by Hexagonia hirta MSF2 through SSF using the coir pith waste as substrate. Physico-chemical parameters like moisture, pH, temperature, C source, N source, and CuSO4 concentrations were pre-optimized, and optimized through RSM. Laccase activity of 1585.24 U g-1 of dry substrate was recorded by H. hirta MSF2 on coir pith containing 1 % C source, 0.5 % N source, 0.25 mM of CuSO4 concentration, moisture content of 75 % at pH 4.6 and temperature 28 °C. Subsequently, the enzyme extraction parameters including, extraction buffer, mode of extraction, and temperature were optimized. The molecular weight of laccase was 66 kDa as observed by SDS-PAGE and native-PAGE. The optimum activity of partially purified laccase was achieved at 40 °C, and pH 4.0. Increasing salt concentration and use of different inhibitors affected the laccase activity. Organic solvents like dimethyl sulphoxide (DMSO) and methanol, and metal ions like BaCl2, CaCl2, CuSO4, and MnCl2 stimulated the laccase activity. Hence, coir pith used in SSF offers a dual benefit of waste management and enzyme synthesis through an eco-friendly and cost-effective approach.

How predominant cell and stroma types harmonize to predict head and neck adenoid cystic carcinoma outcomes?

Adenoid cystic carcinoma (ACC) is an uncommon tumor that usually appears in the major salivary glands of the head and neck region, including the minor glands in the oral cavity, sinonasal tract, and other sites. ACC of the head and neck may have a low-grade histological appearance. This malignant tumor has unusual clinical characteristics such as occasional regional lymph node metastases and a prolonged yet continuously advancing clinical course. Additionally, it is an invasive tumor with perineural invasion, difficult-to-clear margins, metastasis, and localized recurrence. The cribriform and tubular proliferation of basaloid cells, which mostly display a myoepithelial cellular phenotype, are ACC's distinct histologic characteristics. The degree of genetic alterations and aneuploidy observed in tumor genomes are linked to the severity of histologic grade, which correlates with clinical prognosis. The three predominant cell types (PCTs) i.e., conventional ACC (C-ACC), myoepithelial-predominant ACC (M-ACC), and epithelial-predominant ACC (E-ACC)-and their respective applications will be reviewed. The function of extracellular matrix (ECM) components such as laminin, type IV collagen, fibronectin, and tenascin are also emphasized. An attempt has been made to explore the recent molecular diversity, regulatory pathways prevalent in PCT, ECM with its genetic changes, and translational utility with targeted therapies for ACC.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome.

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

A review on various aspects of organic synthesis using Comins' reagent.

Recently, researchers have shown great interest in compounds such as triflate and enotriflate that are synthesized by Comins reagent. For the above-mentioned reason, we planned to review the works related to organic synthesis using Comins reagent. So this review includes a whole new investigation of the Comins reagent which is used for stereoselective conversion of α-keto ester, enolate to enol triflate of lactone and vinyl triflate to methyl ketone. Comins reagent plays an important role in regioselectivity such as transformations of ketone or dienolates into vinyl triflates and it has a major application in highly selective oxidation in an easy and environmentally friendly manner.

Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a commonly occurring malignancy with complex genetic alterations contributing to its development. The H-Ras, a proto-oncogene, becomes an oncogene when mutated and has been implicated in various cancers. This systematic review aims to research to what extent H-Ras expression and mutation contribute to the development and progression of OSCC, and how does this molecular alteration impacts the clinical characteristics and prognosis in patients with OSCC. METHODS: A thorough electronic scientific literature search was carried out in PUBMED, SCOPUS, and GOOGLE SCHOLAR databases from 2007 to 2021. The search strategy yielded 120 articles. Following aggregation and filtering all results through our inclusion and exclusion criteria total 9 articles were included in our literature review. It has also been registered with PROSPERO (CRD42023485202). RESULTS: It was found that mutations in the Ras gene commonly reported in hotspots at codons 12, 13, and 61 resulting in the activation of downstream signaling pathways causing abnormal and uncontrolled cell growth. This systematic review has shown an increased prevalence of H-Ras mutation in well-differentiated OSCC and also the prevalence of H-Ras mutation in individuals engaging in multiple risk behaviors, particularly chewing tobacco, demonstrated a significant association with a higher prevalence of H-Ras positivity. CONCLUSION: This review sheds light on the prevalence of H-Ras mutations, their association with clinical characteristics, and their potential implications for OSCC prognosis. It also enhances our comprehension of the molecular mechanisms that underlie OSCC and paves the way for further research into targeted treatments based on H-Ras alterations.

Segmentation of Thoracic Organs through Distributed Extraction of Visual Feature Patterns Utilizing Resio-Inception U-Net and Deep Cluster Recognition Techniques.

BACKGROUND: Segmentation of medical images plays a key role in the correct identification and management of different diseases. In this study, we present a new segmentation method that meets the difficulties posed by sophisticated organ shapes in computed tomography (CT) images, particularly targeting lung, breast, and gastric cancers. METHODS: Our suggested methods, Resio-Inception U-Net and Deep Cluster Recognition (RIUDCR), use a Residual Inception Architecture, which combines the power of residual connections and inception blocks to achieve cutting-edge segmentation performance while reducing the risk of overfitting. RESULTS: We present mathematical equations and functions that describe the design, including the encoding and decoding steps within the UC-Net system. Furthermore, we provide strong testing results that show the effectiveness of our method. Through thorough testing on varied datasets, our method regularly beats current techniques, achieving amazing precision and stability in organ task segmentation. These results show the promise of our residual inception architecture in better medical picture analysis. CONCLUSION: In summary, our research not only shows a state-of-the-art segment methodology but also reinforces its usefulness through thorough testing. The inclusion of residual inception architecture in medical picture segmentation offers good possibilities for improving the identification and management of disease planning.

A Data-Driven Approach to Defining Risk-Adjusted Coding Specificity Metrics for a Large U.S. Dementia Patient Cohort.

Medical coding impacts patient care quality, payor reimbursement, and system reliability through the precision of patient information documentation. Inadequate coding specificity can have significant consequences at administrative and patient levels. Models to identify and/or enhance coding specificity practices are needed. Clinical records are not always available, complete, or homogeneous, and clinically driven metrics to assess medical practices are not logistically feasible at the population level, particularly in non-centralized healthcare delivery systems and/or for those who only have access to claims data. Data-driven approaches that incorporate all available information are needed to explore coding specificity practices. Using N = 487,775 hospitalization records of individuals diagnosed with dementia and discharged in 2022 from a large all-payor administrative claims dataset, we fitted logistic regression models using patient and facility characteristics to explain the coding specificity of principal and secondary diagnoses of dementia. A two-step approach was produced to allow for the flexible clustering of patient-level outcomes. Model outcomes were then used within a Poisson binomial model to identify facilities that over- or under-specify dementia diagnoses against healthcare industry standards across hospitalizations. The results indicate that multiple factors are significantly associated with dementia coding specificity, especially for principal diagnoses of dementia (AUC = 0.727). The practical use of this novel risk-adjusted metric is demonstrated for a sample of facilities and geospatially via a U.S. map. This study's findings provide healthcare facilities with a benchmark for assessing coding specificity practices and developing quality enhancements to align with healthcare industry standards, ultimately contributing to better patient care and healthcare system reliability.

Role of HIF-1α in Ameloblastoma: A Systematic Review.

Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with unfavorable prognosis. Contemporary studies have proved its vital role in ameloblastoma by correlating its expression with the aggressiveness of the tumor. Therefore, an attempt was made to explore its significance in the malignant transformation and prognosis of ameloblastoma. The present systematic review aimed to understand the impact of HIF-1α in AMB which might lead to favorable outcomes in the treatment. An electronic search was carried out using PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles from all languages involving HIF-1α in AMB were scrutinized by two independent authors. Data were compiled and tabulated in Microsoft Excel and the Risk of bias was analyzed using the JBI tool. Twelve eligible articles were included for the quantitative analysis comprising 305 cases of AMB in which HIF-1α expression was studied for various characteristics like pattern, intensity, and site of immunoexpression which were found to be increased with an increase in the aggressiveness of AMB. It was concluded that HIF-1α is proven to have a crucial role in the progression and aggressiveness of AMB. Extended research regarding the crucial role of HIF-1α in the initiation of tumors and therapies aiming at HIF-1α in AMB cases might show promising outcomes in the future.

Wavefront-guided PRK treatment of myopia using a refractive aberrometer.

PURPOSE: To evaluate the safety, effectiveness, and patient-reported outcomes of wavefront-guided photorefractive keratectomy (PRK) for the correction of myopic refractive errors with and without astigmatism. SETTING: U.S. multicenter study. DESIGN: Prospective, nonrandomized clinical investigation. METHODS: 334 eyes (167 patients) underwent wavefront-guided PRK with the STAR S4 IR Excimer Laser System. Patients had preoperative myopic refractive errors with sphere up to -8.00 diopters (D) and cylinder up to -4.00 D with a maximum spherical equivalent (SE) of -10.00 D. All eyes were targeted for emmetropia, and treatment plans were derived from the iDESIGN system wavefront measurements. RESULTS: At 6 months, the point of refractive stability, 99.4% of eyes achieved 20/20 or better uncorrected distance visual acuity (UDVA), 92% of eyes achieved 20/16 or better UDVA, 85.5% of eyes achieved manifest refraction SE (MRSE) within 0.50 D of target, mean SE was -0.06, and less than 1% of eyes lost more than 2 lines of corrected distance visual acuity. Glare and halos occurred with similar or lower frequencies at 6 months vs preoperative. Results from the National Eye Institute Refractive Error Quality of life questionnaire showed statistically significant improvements at 6 months vs preoperative across most measures of vision-related functioning and well-being. Approximately 98% of patients reported high satisfaction with their overall vision at 6 months. CONCLUSIONS: Wavefront-guided PRK with the iDESIGN aberrometer was safe, effective, and predictable for the correction of low to moderate myopia with and without astigmatism and led to high patient satisfaction.

Activation of the Ca2+/NFAT Pathway by Assembly of Hepatitis C Virus Core Protein into Nucleocapsid-like Particles.

Hepatitis C virus (HCV) is the primary pathogen responsible for liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been linked to several aspects of HCV pathology, including oncogenesis, immune evasion and stress responses. We and others have previously shown that C expression in various cell lines activates Ca2+ signaling and alters Ca2+ homeostasis. In this study, we identified two distinct C protein regions that are required for the activation of Ca2+/NFAT signaling. In the basic N-terminal domain, which has been implicated in self-association of C, amino acids 1-68 were critical for NFAT activation. Sedimentation analysis of four mutants in this domain revealed that association of the C protein into nucleocapsid-like particles correlated with NFAT-activated transcription. The internal, lipid droplet-targeting domain was not required for NFAT-activated transcription. Finally, the C-terminal ER-targeting domain was required in extenso for the C protein to function. Our results indicate that targeting of HCV C to the ER is necessary but not sufficient for inducing Ca2+/NFAT signaling. Taken together, our data are consistent with a model whereby proteolytic intermediates of C with an intact transmembrane ER-anchor assemble into pore-like structures in the ER membrane.

Next-Generation Sequencing Analysis of CpG Methylation of a Tumor Suppressor Gene SHP-1 Promoter in Stable Cell Lines and HCV-Positive Patients.

Hepatitis C virus (HCV) is the major causative pathogen associated with hepatocellular carcinoma and liver cirrhosis. The main virion component, the Core (C) protein, is involved in multiple aspects of HCV pathology including oncogenesis and immune evasion. In this study, we established a next-generation bisulfite sequencing (NGS-BS) protocol to analyze the CpG methylation profile at the tumor suppressor gene SHP-1 P2 promoter as a model system. Our data show that HCV C protein expression in the immortalized T cells correlated with a specific CpG methylation profile at the SHP-1 P2. The NGS-BS on HCV-positive (HCV+) patient-derived PBMCs revealed a considerably different CpG methylation profile compared to the HCV C protein immortalized T cells. Notably, the CpG methylation profile was very similar in healthy and HCV+ PBMCs, suggesting that the SHP-1 P2 CpG methylation profile is not altered in the HCV+ individuals. Collectively, the NGS-BS is a highly sensitive method that can be used to quantitatively characterize the CpG methylation status at the level of individual CpG position and also allows the characterization of cis-acting effects on epigenetic regulation.

Visual outcomes and safety of an extended depth-of-focus intraocular lens: results of a pivotal clinical trial.

PURPOSE: To compare the effectiveness and safety of the TECNIS Symfony intraocular lens (IOL; ZXR00) with the TECNIS 1-piece monofocal IOL (ZCB00). SETTING: 15 sites in the United States. DESIGN: Prospective, randomized, patient-masked/evaluator-masked clinical trial. METHODS: Randomized participants received either the ZXR00 or ZCB00 IOL bilaterally. The 6-month postoperative outcomes included monocular and binocular distance, intermediate, and near visual acuity (VA), spherical equivalent refraction and refractive cylinder, spectacle wear, and visual symptoms. RESULTS: Overall, 299 patients were implanted with a study IOL (ZXR00 IOL, n = 148; ZCB00 IOL control, n = 151). At the 6-month follow-up, mean binocular uncorrected distance VA was comparable between ZXR00 and ZCB00 IOL recipients (P = .1011). The ZXR00 IOL group had significantly better mean binocular uncorrected intermediate VA and uncorrected near VA (both P < .0001) than the ZCB00 IOL group. The mean binocular distance-corrected intermediate VA and distance-corrected near VA were also better in the ZXR00 IOL group (both P < .0001). More ZXR00 IOL recipients reported wearing spectacles none of the time or a little of the time for overall vision at 6 months compared with the ZCB00 IOL group (85.0% vs 59.9%, P < .0001). In the ZXR00 IOL-implanted patients, low incidence rates of night glare (mild to moderate, 2.7%), halo (mild to moderate, 13.6%; severe, 2.7%), and starbursts (mild to moderate, 7.5%; severe, 1.4%) were reported. CONCLUSIONS: The TECNIS Symfony IOL provided comparable distance vision and improved uncorrected and distance-corrected intermediate and near vision, along with decreased spectacle wear and low incidence rates of dysphotopsia, compared with the TECNIS 1-piece monofocal IOL.

Hepatitis C Virus Core Protein Down-Regulates Expression of Src-Homology 2 Domain Containing Protein Tyrosine Phosphatase by Modulating Promoter DNA Methylation.

Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been implicated in several aspects of HCV pathology including oncogenesis and immune subversion. Here we show that expression of the C protein induced specific tyrosine phosphorylation of the TCR-related signaling proteins ZAP-70, LAT and PLC-γ in the T cells. Stable expression of the C protein specifically reduced Src homology domain 2-containing protein tyrosine phosphatase 1 (SHP-1) mRNA and protein accumulation. Quantitative CpG methylation analysis revealed a distinct CpG methylation pattern at the SHP-1 gene promoter in the C protein expressing cells that included specific hypermethylation of the binding site for Sp1 transcription factor. Collectively, our results suggest that HCV may suppress immune responses and facilitate its own persistence by deregulating phosphotyrosine signaling via repressive epigenetic CpG modification at the SHP-1 promoter in the T cells.

Evaluation of Intraocular Lens Rotational Stability in a Multicenter Clinical Trial.

PURPOSE: To evaluate the postoperative rotational stability of two prototype intraocular lens (IOL) designs (subsequently termed version 1 and version 2). PATIENTS AND METHODS: A prospective, multicenter, randomized, paired-eye, 6-month study evaluated the version 1 and version 2 IOLs. Results were compared with a control IOL (TECNIS® toric 1-piece monofocal IOL) evaluated in a separate, similarly designed study. Participants aged ≥22 years and scheduled to undergo bilateral cataract extraction were randomly assigned 1:1 to receive the version 1 or version 2 IOL in the first operative eye; the alternate test IOL was then implanted in the second operative eye. RESULTS: Mean absolute IOL rotation at postoperative week 1 was the primary effectiveness end point. Additional end points included the percentage of eyes with postoperative IOL rotation >5°/>10°, direction of lens rotation, surgeon-reported ease of IOL handling during implantation, and safety. At postoperative week 1, mean (±standard deviation) absolute IOL rotation was significantly lower for both version 1 and version 2 versus control (0.88° [±0.94] and 0.71° [±0.69] vs 2.24° [±3.21], respectively; both P < 0.001). For both study lenses, absolute rotation was <5° for all eyes at postoperative week 1, and no cases of rotation >10° were observed at any postoperative time point. From postoperative week 1 onward, version 2 had a statistically significant clockwise bias in the direction of rotation (P = 0.03); similar findings were observed for version 1. Surgeons reported acceptable ease of IOL handling during implantation for both version 1 and version 2. No device-related adverse events were reported. CONCLUSION: Both the version 1 and version 2 IOLs, each with frosted, squared haptics, demonstrated improved postoperative rotational stability compared with a control lens without frosted haptics. Because version 2 had the same overall geometry as the current TECNIS toric IOL, this design was selected for commercialization. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015287.

CuO/C nanocomposite: Synthesis and optimization using sucrose as carbon source and its antifungal activity.

The synthesis of bioactive CuO/C nano composite using sucrose as a capping agent is achieved through simple green approach via Response Surface Methodology. The synthesis process was done in a green environment which prevents aggregation of sucrose and promotes nanoparticles formation. The innovative approach produces sucrose as a carbon source mediated copper oxide nanocomposites (CuO/C nanocomposite) with the particle size of 50 nm. Additionally, the produced CuO/C nanocomposite were characterized using microscopic techniques like SEM, TEM and spectroscopic techniques like UV-vis and X-ray diffraction. The antifungal activities of CuO/C nanocomposite were tested against Aspergillus niger and Aspergillus flavus species. At 1000 ppm of CuO/C nanocomposite, it showed 70% restraint on A. flavus and 90% hindrance on A. niger. The fungal inhibition mechanism of bioactive CuO/C nanocomposite was discussed in this research article. The particular high antifungal performance of CuO/C nanocomposite was found against Aspergillus niger while compare to Aspergillus flavus fungal strain.

Suction Cup Induced Palatal Fistula: Surgical Closure by Palatal Rotational Flap.

Construction of complete denture with adequate retention is a complex procedure. Use of suction cup in a maxillary denture is one of the techniques to improve retention. Palatal Suction cup, which provides high retention by inducing negative pressure on the mucosal surface, is not being recommended because of its pathological effect on the palatal tissues leading to palatal perforation. Surgical closure of palatal perforation is challenging, technique sensitive, and it can be achieved by different surgical methods depending on the size and location of the defect. In this case report, we present a patient with palatal perforation due to prolonged use of a denture with a suction cup for over 10 years, which was surgically closed by a palatal rotational flap. The result was good as the defect was successfully closed and the donor site healed uneventfully.