A universal recombinant adenovirus type 5 vector-based COVID-19 vaccine.

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Dihydroxyl modified UiO-66 as dispersive solid-phase extraction sorbent coupled with ultra-high performance liquid chromatography tandem mass spectrometry for detection of neonicotinoid insecticides.

The extensive usage of neonicotinoid insecticides (NIs) has raised many concerns about their potential harm to environment and human health. Thus, it is of great importance to develop an efficient and reliable method to determine NIs in food samples. In this work, three Zr4+-based metal-organic frameworks functionalized with various numbers of hydroxyl groups were fabricated with a facile one-pot solvothermal method. Among them, dihydroxy modified UiO-66 (UiO-66-(OH)2) exhibited best adsorption performance towards five target NIs. Then, a sensitive and efficient method for detection of NIs from vegetable and fruit samples was established based on dispersive solid phase extraction (dSPE) with UiO-66-(OH)2 as adsorbent coupled with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Key parameters affecting the dSPE procedure including amounts of adsorbent, adsorption time, eluent solvents and desorption time were investigated. Under the optimal conditions, rapid adsorption of NIs within five minutes was achieved due to the high affinity of UiO-66-(OH)2 towards NIs. The developed method exhibited high sensitivity with limits of detection (LODs) varied from 0.003 to 0.03 ng/mL and wide linearity range over 3-4 orders of magnitude from 0.01 to 500 ng/mL. Furthermore, the established method was applied for determining trace NIs from complex matrices with recoveries ranging from 74.6 to 99.6 % and 77.0-106.8 % for pear and tomato samples, respectively. The results indicate the potential of UiO-66-(OH)2 for efficient enrichment of trace NIs from complex matrices.

Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations.

BACKGROUND: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. METHODS: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. RESULTS: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients. CONCLUSION: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Effect of voltage gradients on EK-PRB remediation: Experimental and molecular dynamics simulations.

Electrokinetic-Permeable Reaction Barrier (EK-PRB) coupled remediation technology can effectively treat heavy metal-contaminated soil near coal mines. This study was conducted on cadmium (Cd), a widely present element in the soil of the mining area. To investigate the impact of the voltage gradient on the remediation effect of EK-PRB, the changes in current, power consumption, pH, and Cd concentration content during the macroscopic experiment were analyzed. A three-dimensional visualized kaolinite-heavy metal-water simulation system was constructed and combined with the Molecular Dynamics (MD) simulations to elucidate the migration mechanism and binding active sites of Cd on the kaolinite (001) crystalline surface at the microscopic scale. The results showed that the voltage gradient positively correlates with the current, power consumption, and Cd concentration during EK-PRB remediation, and the average removal efficiency increases non-linearly with increasing voltage gradient. Considering power consumption, average removal efficiency, and cost-effectiveness, the voltage range is between 1.5 and 3.0 V/cm, with 2.5 V/cm being the optimal value. The results of MD simulations and experiments correspond to each other. Cd2+ formed a highly stable adsorption structure in contrast to the Al-O sheet on the kaolinite (001) crystalline surface. The mean square displacement (MSD) curve of Cd2+ under the electric field exhibits anisotropy, the total diffusion coefficient DTotal increases and the Cd2+ migration rate accelerates. The electric field influences the microstructure of Cd2+ complexes. With the enhancement of the voltage gradient, the complexation between Cd2+ and water molecules is enhanced, and the interaction between Cd2+ and Cl－ in solution is weakened.

Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study.

Background/Aims: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. Methods: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. Results: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. Conclusions: In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Optical coherence tomography choroidal enhancement using generative deep learning.

Spectral-domain optical coherence tomography (SDOCT) is the gold standard of imaging the eye in clinics. Penetration depth with such devices is, however, limited and visualization of the choroid, which is essential for diagnosing chorioretinal disease, remains limited. Whereas swept-source OCT (SSOCT) devices allow for visualization of the choroid these instruments are expensive and availability in praxis is limited. We present an artificial intelligence (AI)-based solution to enhance the visualization of the choroid in OCT scans and allow for quantitative measurements of choroidal metrics using generative deep learning (DL). Synthetically enhanced SDOCT B-scans with improved choroidal visibility were generated, leveraging matching images to learn deep anatomical features during the training. Using a single-center tertiary eye care institution cohort comprising a total of 362 SDOCT-SSOCT paired subjects, we trained our model with 150,784 images from 410 healthy, 192 glaucoma, and 133 diabetic retinopathy eyes. An independent external test dataset of 37,376 images from 146 eyes was deployed to assess the authenticity and quality of the synthetically enhanced SDOCT images. Experts' ability to differentiate real versus synthetic images was poor (47.5% accuracy). Measurements of choroidal thickness, area, volume, and vascularity index, from the reference SSOCT and synthetically enhanced SDOCT, showed high Pearson's correlations of 0.97 [95% CI: 0.96-0.98], 0.97 [0.95-0.98], 0.95 [0.92-0.98], and 0.87 [0.83-0.91], with intra-class correlation values of 0.99 [0.98-0.99], 0.98 [0.98-0.99], and 0.95 [0.96-0.98], 0.93 [0.91-0.95], respectively. Thus, our DL generative model successfully generated realistic enhanced SDOCT data that is indistinguishable from SSOCT images providing improved visualization of the choroid. This technology enabled accurate measurements of choroidal metrics previously limited by the imaging depth constraints of SDOCT. The findings open new possibilities for utilizing affordable SDOCT devices in studying the choroid in both healthy and pathological conditions.

Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation has been proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel was proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protected BMSCs from shear force and mechanical stress before and after injection but also repaired the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD. This article is protected by copyright. All rights reserved.

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.

Correction: Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Correction for 'Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy' by Junyu Chen et al., Mater. Horiz., 2024, 11, 2010-2020, https://doi.org/10.1039/D3MH01884A.

Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia.

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease. CASE PRESENTATION: A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome. CONCLUSIONS: This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

Alternative splicing analysis of lignocellulose-degrading enzyme genes and enzyme variants in Aspergillus niger.

Alternative splicing (AS) greatly expands the protein diversity in eukaryotes. Although AS variants have been frequently reported existing in filamentous fungi, it remains unclear whether lignocellulose-degrading enzyme genes in industrially important fungi undergo AS events. In this work, AS events of lignocellulose-degrading enzymes genes in Aspergillus niger under two carbon sources (glucose and wheat straw) were investigated by RNA-Seq. The results showed that a total of 23 out of the 56 lignocellulose-degrading enzyme genes had AS events and intron retention was the main type of these AS events. The AS variant enzymes from the annotated endo-ß-1,4-xylanase F1 gene (xynF1) and the endo-ß-1,4-glucanase D gene (eglD), noted as XYNF1-AS and EGLD-AS, were characterized compared to their normal splicing products XYNF1 and EGLD, respectively. The AS variant XYNF1-AS displayed xylanase activity whereas XYNF1 did not. As for EGLD-AS and EGLD, neither of them showed annotated endo-ß-1,4-glucanase activity. Instead, both showed lytic polysaccharide monooxygenase (LPMO) activity with some differences in catalytic properties. Our work demonstrated that the AS variants in A. niger were good sources for discovering novel lignocellulose-degrading enzymes. KEY POINTS: • AS events were identified in the lignocellulose-degrading enzyme genes of A. niger. • New ß-1,4-xylanase and LPMO derived from AS events were characterized.

Visible Light-Catalyzed Reactions of Polysulfide (DBSPS) with Aryldiazonium.

A visible light-catalyzed radical coupling reaction of polysulfide reagents with aryldiazonium was developed, which gave thiosulfonates under mild conditions. In this reaction, the thiosulfonates were isolated in good yields with a broad tolerance to functional groups. And the synthesis of diaryl monosulfides were achieved through a step-by-step reaction of two molecular aryldiazonium with DBSPS, where the sulfur source was provided by DBSPS. It was worth noting that the reaction of this monosulfides could also be achieved by a one pot two-step process. The described polysulfide reagents were able to produce three new radicals: sulfonyl radicals, sulfur-sulfonyl radicals and sulfur-sulfur-sulfonyl radicals.

Metabolic characterization of sphere-derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance.

Alteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs. Urea cycle is the most significantly altered metabolic pathway in PCSCs, the key metabolites arginine and proline are evidently elevated. Proline promotes cancer stem-like characteristics via the JAK2/STAT3 signaling pathway. Meanwhile, the enzyme pyrroline-5-carboxylate reductase 1 (PYCR1), which catalyzes the conversion of pyrroline-5-carboxylic acid to proline, is highly expressed in PCSCs, and the inhibition of PYCR1 suppresses the stem-like characteristics of prostate cancer cells and tumor growth. In addition, carnitine and free fatty acid levels are significantly increased, indicating reprogramming of fatty acid metabolism in PCSCs. Reduced sphingolipid levels and increased triglyceride levels are also observed. Collectively, our data illustrate the comprehensive landscape of the metabolic reprogramming of PCSCs and provide potential therapeutic strategies for prostate cancer.

Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Effectiveness of prognostic nutritional index in predicting overall survival and evaluating immunotherapy response in anaplastic thyroid carcinoma.

BACKGROUND: The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS: We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS: A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION: PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.

Improving drug response prediction via integrating gene relationships with deep learning.

Predicting the drug response of cancer cell lines is crucial for advancing personalized cancer treatment, yet remains challenging due to tumor heterogeneity and individual diversity. In this study, we present a deep learning-based framework named Deep neural network Integrating Prior Knowledge (DIPK) (DIPK), which adopts self-supervised techniques to integrate multiple valuable information, including gene interaction relationships, gene expression profiles and molecular topologies, to enhance prediction accuracy and robustness. We demonstrated the superior performance of DIPK compared to existing methods on both known and novel cells and drugs, underscoring the importance of gene interaction relationships in drug response prediction. In addition, DIPK extends its applicability to single-cell RNA sequencing data, showcasing its capability for single-cell-level response prediction and cell identification. Further, we assess the applicability of DIPK on clinical data. DIPK accurately predicted a higher response to paclitaxel in the pathological complete response (pCR) group compared to the residual disease group, affirming the better response of the pCR group to the chemotherapy compound. We believe that the integration of DIPK into clinical decision-making processes has the potential to enhance individualized treatment strategies for cancer patients.